Unusual Cancers of Childhood Treatment (PDQ®)


Information for: Patients | Healthcare Professionals

General Information About Unusual Cancers of Childhood

Unusual cancers of childhood are cancers rarely seen in children.

Cancer in children and teenagers is rare. Since 1975, the number of new cases of childhood cancer has slowly increased. Since 1975, the number of deaths from childhood cancer has decreased by more than half.

Unusual cancers are so rare that most children's hospitals might see less than a handful of some types in several years. Because the unusual cancers are so rare, there is not a lot of information about what treatment works best. A child's treatment is often based on what has been learned from treating other children. Sometimes, information is available only from reports of the diagnosis, treatment, and follow-up of one child or a small group of children who were given the same type of treatment.

Many different cancers are covered in this summary. They are grouped by where they are found in the body.

Tests are used to detect (find), diagnose, and stage unusual cancers of childhood.

Tests are done to detect, diagnose, and stage cancer. The tests used depend on the type of cancer. After cancer is diagnosed, tests are done to find out if cancer cells have spread from where the cancer began to other parts of the body. The process used to find out if cancer cells have spread to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan the best treatment. The following tests and procedures may be used to detect, diagnose, and stage cancer:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. There are many different types of biopsy procedures. The most common types include the following:
    • Excisional biopsy: The removal of an entire lump or area of tissue that doesn’t look normal.
    • Incisional biopsy: The removal of part of a lump or a sample of tissue that doesn’t look normal.
    • Core biopsy: The removal of tissue using a wide needle.
    • Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle.
  • X-ray: An x-ray is a type of energy beam that can go through the body and onto film.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
    Computed tomography (CT) scan of the abdomen; drawing shows the patient on a table that slides through the CT machine, which takes x-ray pictures of the inside of the body.
    Computed tomography (CT) scan of the abdomen. The patient lies on a table that slides through the CT machine, which takes x-ray pictures of the inside of the body.
  • PET scan (positron emission tomography scan): A procedure to find malignanttumor cells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet and radio waves to make a series of detailed pictures of areas inside the body. The pictures are made by a computer. This procedure is also called nuclear magnetic resonance imaging (NMRI).
    Magnetic resonance imaging (MRI) of the abdomen; drawing shows the patient on a table that slides into the MRI machine, which takes pictures of the inside of the body. The pad on the patient’s abdomen helps make the pictures clearer.
    Magnetic resonance imaging (MRI) of the abdomen. The patient lies on a table that slides into the MRI machine, which takes pictures of the inside of the body. The pad on the patient’s abdomen helps make the pictures clearer.
  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.
    Abdominal ultrasound; drawing shows a woman on an exam table during an abdominal ultrasound procedure. A diagnostic sonographer (a person trained to perform ultrasound procedures) is shown passing a transducer (a device that makes sound waves that bounce off tissues inside the body) over the surface of the patient’s abdomen. A computer screen shows a sonogram (computer picture).
    Abdominal ultrasound. An ultrasound transducer connected to a computer is passed over the surface of the abdomen. The ultrasound transducer bounces sound waves off internal organs and tissues to make echoes that form a sonogram (computer picture).
  • Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. An endoscope is inserted through an incision (cut) in the skin or opening in the body, such as the mouth or rectum. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of disease.
    Upper endoscopy; shows endoscope inserted through the mouth and esophagus and into the stomach. Inset shows patient on table having an upper endoscopy.
    Upper endoscopy. A thin, lighted tube is inserted through the mouth to look for abnormal areas in the esophagus, stomach, and first part of the small intestine.
  • Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.
    Bone scan; drawing shows patient lying on a table that slides under the scanner, a technician operating the scanner, and a monitor that will show images made during the scan.
    Bone scan. A small amount of radioactive material is injected into the patient's bloodstream and collects in abnormal cells in the bones. As the patient lies on a table that slides under the scanner, the radioactive material is detected and images are made on a computer screen or film.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

Treatment Option Overview

There are different types of treatment for children with unusual cancers.

Different types of treatments are available for children with cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with unusual cancers should have their treatment planned by a team of health care providers with expertise in treating cancer in children.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatrichealth care providers who are experts in treating children with cancer and who specialize in certain areas of medicine. These may include the following specialists:

  • Pediatric surgeon.
  • Pediatric hematologist.
  • Neurosurgeon.
  • Neurologist.
  • Neuropathologist.
  • Neuroradiologist.
  • Radiation oncologist.
  • Pediatric nurse specialist.
  • Rehabilitation specialist.
  • Endocrinologist.
  • Social worker.
  • Psychologist.

Seven types of standard treatment are used:

Surgery

Surgery is a procedure used to find out whether cancer is present, to remove cancer from the body, or to repair a body part. Palliative surgery is done to relieve symptoms caused by cancer. Surgery is also called an operation.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance that is injected into the body or sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

Radiosurgery and proton beam therapy are two kinds of external radiation therapy used to treat childhood cancers:

  • Radiosurgery uses special equipment to aim one large dose of radiation directly at a tumor, causing less damage to nearby healthy tissue. It is also called stereotaxic radiosurgery, stereotactic radiosurgery, and radiation surgery. This procedure does not remove the tumor in an operation.
  • Proton beam radiation therapy is a type of high-energy radiation therapy that uses streams of protons (small, positively-charged particles of matter) to kill tumor cells.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can affect cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, a body cavity such as the abdomen, or an organ, the drugs mainly affect cancer cells in those areas. Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Hormone therapy

Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances that are made by glands in the body and flow through the bloodstream. Some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy is used to reduce the production of hormones or block them from working. Hormone therapy with drugs called corticosteroids may be used to treat thymoma or thymic carcinoma.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Interferon-beta is a type of biologic therapy used to treat nasopharyngeal cancer.

EBV-specific cytotoxic T-lymphocytes is another a type of biologic therapy used to treat nasopharyngeal cancer. White blood cells (T-lymphocytes) that are treated in the laboratory with Epstein-Barr virus are given to the patient to stimulate the immune system and fight cancer.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change. Watchful waiting may be a treatment option when the tumor is slow-growing or when it is possible the tumor may disappear without treatment.

Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Tyrosine kinase inhibitors (TKIs) are targeted therapy drugs that block signals needed for tumors to grow. Vascular endothelial growth factor (VEGF) inhibitors are another type of targeted therapy that prevents the growth of new blood vessels that tumors need to grow.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Some cancers and cancer treatments cause side effects months or years after treatment has ended.

Some cancers and cancer treatments cause side effects that continue or appear months or years after cancer treatment has ended. These are called late effects. Late effects may include the following:

  • Physical problems.
  • Changes in mood, feelings, thinking, learning, or memory.
  • Second cancers (new types of cancer).

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the possible late effects caused by some cancers and cancer treatments. (See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information).

Unusual Cancers of the Head and Neck

Nasopharyngeal Cancer

Nasopharyngeal cancer is a disease in which malignant (cancer) cells form in the lining of the nasalcavity (inside of the nose) and throat. It is rare in children younger than 10 and more common in teenagers.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of nasopharyngeal cancer is greatly increased by having an infection with the Epstein-Barr virus (EBV), which infects cells of the immune system.

Nasopharyngeal cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Painless lumps in the neck.
  • Nosebleeds.
  • Blocked or stuffy nose.
  • Ear infection.
  • Snoring.
  • Problems moving the jaw.
  • Hearing loss.
  • Double vision.

Other conditions that are not nasopharyngeal cancer may cause these same symptoms.

When nasopharyngeal is diagnosed, it usually has already spread to lymph nodes in the neck and bones of the skull. It may also spread to the nose, mouth, throat, bones, lung, and/or liver.

Tests to diagnose and stage nasopharyngeal cancer may include the following:

  • Physical exam and history.
  • MRI of the head and neck.
  • CT scan of the chest and abdomen .
  • Bone scan.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose or stage nasopharyngeal cancer include the following:

  • Nasoscopy: A procedure in which a doctor inserts a nasoscope (a thin, lighted tube) into the patient’s nose to look for abnormal areas.
  • Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
  • Epstein-Barr virus (EBV) tests: Blood tests to check for antibodies to the Epstein-Barr virus and DNA markers of the Epstein-Barr virus. These are found in the blood of patients who have been infected with EBV.

Prognosis

The prognosis (chance of recovery) for most young patients with nasopharyngeal cancer is very good. The prognosis and treatment options depend on the following:

  • The size of the tumor at diagnosis.
  • Whether the tumor has spread to nearby tissues, lymph nodes, or distant parts of the body.
  • How the cancer responds to the initial treatment.

Treatment

Treatment of nasopharyngeal cancer in children may include the following:

  • Radiation therapy.
  • Chemotherapy given before and at the same time as radiation therapy.
  • Chemotherapy and radiation therapy given with interferon-beta.
  • Chemotherapy and radiation therapy given with brachytherapy.
  • Surgery, in certain cases.
  • Biologic therapy using EBV-specific cytotoxic T-lymphocytes.

Young patients are more likely than adults to have problems caused by treatment, including second cancers.

See the PDQ summary on adult Nasopharyngeal Cancer Treatment for more information.

Esthesioneuroblastoma

Esthesioneuroblastoma (olfactoryneuroblastoma) is a tumor that begins in the olfactory bulb in the brain. The olfactory bulb connects to the nerve that is important to the sense of smell. Even though it is rare, esthesioneuroblastoma is the most common tumor of the nasalcavity in children.

Most children have a tumor in the nose or throat at the time of diagnosis. The tumor may spread into the bone around the eyes, sinuses, and the front part of the brain. The disease rarely spreads to other parts of the body. Esthesioneuroblastoma is more common in boys and usually appears during the teen years.

Symptoms

Esthesioneuroblastoma may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Blocked nose.
  • Nosebleeds.
  • Loss of the sense of smell.
  • Bulging of the eye.
  • Frequent sinusinfections.

Other conditions that are not esthesioneuroblastoma may cause these same symptoms.

Prognosis

The prognosis (chance of recovery) depends on whether the cancer is only in the nose or if it has spread to nearby lymph nodes or to other parts of the body.

Treatment

Treatment of esthesioneuroblastoma in children may include the following:

  • Surgery and radiation therapy. Newer treatments include sinus surgery done through an endoscope, radiosurgery, or proton beam radiation therapy.
  • Chemotherapy before or after surgery to remove the cancer, in children with advanced cancer.

Thyroid Tumors

Thyroidtumors form in the tissues of the thyroid gland, which is a butterfly-shaped gland at the base of the throat near the windpipe. The thyroid gland makes important hormones that help control growth, heart rate, body temperature, and how quickly food is changed into energy.

Most childhood thyroid tumors occur in girls and children aged 15 to 19 years. Thyroid tumors may be adenomas (noncancer) or carcinomas (cancer).

  • Adenoma: Adenomas can grow very large and sometimes make hormones. Adenomas may become malignant (cancer) and spread to the lungs or lymph nodes in the neck. Thyroid cancer usually grows and spreads slowly.
  • Carcinoma: There are 3 types of thyroid cancer:
    • Papillary.
    • Follicular.
    • Medullary.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of thyroid cancer is increased by being exposed to radiation and by certain geneticsyndromes, such as multiple endocrine neoplasia (MEN) type 2A syndrome or multiple endocrine neoplasia (MEN) type 2B syndrome. See the Multiple Endocrine Neoplasia Syndromes and Carney Complex section of this summary for more information.

Thyroid tumors may cause any of the following symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • A lump in the neck or near the collarbone.
  • Trouble breathing.
  • Trouble swallowing.
  • Hoarseness or a change in the voice.

Other conditions that are not thyroid tumors may cause these same symptoms.

Tests to diagnose and stage thyroid tumors may include the following:

  • Physical exam and history.
  • Fine-needle aspiration (FNA) biopsy.
  • Open biopsy or surgery to remove all or part of the thyroid.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose and stage thyroid tumors include the following:

  • Ultrasound: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later. This procedure can show the size of a thyroid tumor and whether it is solid or a fluid-filled cyst. Ultrasound may be used to guide a fine-needle aspiration (FNA) biopsy.
  • Thyroid function test: The blood is checked for abnormal levels of thyroid-stimulating hormone (TSH). TSH is made by the pituitary gland in the brain. It stimulates the release of thyroid hormone and controls how fast follicular thyroid cells grow. The blood may also be checked for high levels of the hormone calcitonin.
  • Thyroglobulin test: The blood is checked for the amount of thyroglobulin, a protein made by the thyroid gland. Thyroglobulin levels are low or absent with normal thyroid function but may be higher with thyroid cancer or other conditions.

Prognosis

The prognosis (chance of recovery) depends on the following:

  • Whether the tumor has spread to other parts of the body at diagnosis.
  • The size of the tumor.

Treatment

Treatment of thyroid tumors in children may include the following:

  • Surgery to remove most or all of the thyroid gland and lymph nodes with cancer, followed by radioactive iodine (RAI) to kill any thyroid cancer cells that are left. Hormone replacement therapy (HRT) is given to make up for the lost thyroid hormone.
  • Surgery to remove the lobe in which thyroid cancer is found, followed by HRT to make up for the lost thyroid hormone.
  • Radioactive iodine (RAI) for cancer that has recurred (come back).
  • Targeted therapy with tyrosine kinase inhibitors (TKIs) or vascular endothelial growth factor inhibitors (VEGFs) for cancer that has spread to other parts of the body or that has recurred.
  • A clinical trial of targeted therapy.

Four to six weeks after surgery a radioactive iodine scan (RAI scan) is done to find areas in the body where thyroid cancer cells that were not removed during surgery may be dividing quickly. RAI is used because only thyroid cells take up iodine. A very small amount of RAI is swallowed, travels through the blood, and collects in thyroid tissue and thyroid cancer cells anywhere in the body. If no cancer cells are found, a larger dose of RAI is given to destroy any remaining thyroid tissue. If cancer remains in the lymph nodes or has spread to other parts of the body, an even larger dose of RAI is given to destroy any remaining thyroid tissue and thyroid cancer cells.

It is common for thyroid cancer to recur, especially in children younger than 10 years and those with cancer in the lymph nodes. Lifelong follow-up of thyroid hormone levels in the blood is needed to make sure the right amount of hormone replacement therapy (HRT) is being given. It is possible that thyroid cancer will spread to the lung later. Tests are done to check for thyroid cancer in the lung.

See the PDQ summary on adult Thyroid Cancer Treatment for more information.

Oral Cancer

Oral cancer is a disease in which malignant (cancer) cells form in the tissues of the oral cavity. Most tumors in the oral cavity are benign (not cancer). The most common type of oral cancer in adults, squamous cell carcinoma (cancer of the thin, flat cells lining the mouth), is very rare in children. Malignant tumors in children include lymphomas and sarcomas.

The number of new cases of oral cancer in teenage girls and young women has increased since the mid-1990s with a similar increase in cases of oral human papilloma virus (HPV) infection.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of oral cancer is increased by the following:

  • Tobacco use: Using any tobacco product increases the risk of oral cancer. Use of smokeless tobacco may cause mouth cancer. Changes in the texture, color, and shape of tissue inside the mouth have been seen in more than half of all teenagers who use smokeless tobacco.
  • Previous radiation therapy: Oral cancer is more likely in people who have had other childhood tumors and were treated with radiation therapy to the oral cavity.
  • Having certain diseases or conditions, such as:
    • Fanconi anemia.
    • Dyskeratosis congenita (a rare bone marrowdisorder that affects red blood cells, white blood cells, and platelets).
    • A mutation in connexin genes (changes the way proteins that connect cells are made).
    • Chronicgraft-versus-host disease (GVHD).
    • Epidermolysis bullosa (an illness that causes the skin to be easily injured and causes painful blisters).
    • Xeroderma pigmentosum.
    • Human papillomavirus (HPV) infection.

Oral cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • A sore in the mouth that does not heal.
  • A lump or thickening in the oral cavity.
  • A white or red patch on the gums, tongue, tonsils, or lining of the mouth.
  • Bleeding, pain, or numbness in the mouth.

Other conditions that are not oral cancer may cause these same symptoms.

Tests to diagnose and stage oral cancer may include the following:

  • Physical exam and history.
  • X-ray.
  • MRI of the head and neck.
  • CT scan.
  • PET scan.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Treatment

Treatment of oral cancer in children may include the following:

  • Surgery for most benign tumors.
  • Surgery, chemotherapy, and radiation therapy for malignant tumors.

See the following PDQ summaries for more information:

  • Oropharyngeal Cancer Treatment
  • Lip and Oral Cavity Cancer Treatment
  • Langerhans Cell Histiocytosis Treatment

Salivary Gland Tumors

Salivary glandtumors form in the salivary glands, which are small organs in the mouth and throat that make saliva. Most salivary gland tumors form in the parotid glands (just in front of and below each ear) or in the salivary glands under the tongue or near the jaw.

In children, most salivary gland tumors are benign (noncancer). Some salivary gland tumors are malignant (cancer), especially in young children. Malignant tumors sometimes form after treatment with radiation therapy for leukemia or solid tumors.

Symptoms and Diagnostic and Staging Tests

Salivary gland tumors may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • A lump (usually painless) near the ear, cheek, jaw, or lip, or inside the mouth.
  • Fluid draining from the ear.
  • Trouble swallowing or opening the mouth widely.
  • Numbness or weakness in the face.
  • Pain in the face that does not go away.

Other conditions that are not salivary gland tumors may cause these same symptoms.

Tests to diagnose and stagesalivary gland cancer may include the following:

  • Physical exam and history.
  • MRI of the head and neck.
  • CT scan.
  • PET scan.
  • Ultrasound.

See the General Information section for a description of these tests and procedures.

Prognosis

The prognosis for salivary gland cancer is usually good.

Treatment

Treatment of salivary gland cancer in children is usually surgery to remove the cancer, with or without radiation therapy and chemotherapy.

See the PDQ summary on adult Salivary Gland Cancer Treatment for more information.

Laryngeal Cancer and Papillomatosis

Laryngeal Cancer

Laryngeal cancer is a disease in which malignant (cancer) cells form in the tissues of the larynx. The larynx is also called the voice box. It's the part of the throat that holds the vocal cords and is used in breathing, swallowing, and talking. Rhabdomyosarcoma (a malignant tumor of muscle) is the most common type of laryngeal cancer in children. Squamous cell carcinoma is a less common type of laryngeal cancer in children.

Symptoms and Diagnostic and Staging Tests for Laryngeal Cancer

Laryngeal cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Hoarseness or a change in the voice.
  • Trouble or pain when swallowing.
  • A lump in the neck or throat.
  • A sore throat or cough that does not go away.
  • Ear pain.

Other conditions that are not laryngeal cancer may cause these same symptoms.

Tests to diagnose and stage laryngeal cancer may include the following:

  • Physical exam and history.
  • MRI of the head and neck.
  • CT scan.
  • Ultrasound.
  • Endoscopy.
  • Fine-needle aspiration (FNA) biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose laryngeal cancer include the following:

  • Laryngoscopy: A procedure in which the doctor examines the larynx (voice box) with a mirror or with a laryngoscope (a thin, lighted tube).
  • Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metalliccompound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.

Treatment of Laryngeal Cancer

Treatment of laryngeal cancer in children may include the following:

  • Chemotherapy and radiation therapy after a biopsy, for rhabdomyosarcomas.
  • Laser surgery and radiation therapy for squamous cell cancer. Laser surgery uses a laser beam (a narrow beam of intense light) to turn the cancer cells into a gas that evaporates (dissolves into the air).

See the following PDQ summaries for more information:

  • Childhood Rhabdomyosarcoma Treatment
  • Laryngeal Cancer Treatment

Papillomatosis

Papillomatosis of the larynx is a condition that causes papillomas (benign tumors that look like warts) to form in the tissue that lines the larynx. Papillomatosis may be caused by the human papillomavirus (HPV). Papillomas in the larynx may block the airway and cause trouble breathing. These growths often recur (come back) after treatment and may become cancer of the larynx.

Treatment of Papillomatosis

Treatment of papillomatosis in children may include the following:

  • Lasersurgery for papillomatosis and other benign tumors.
  • Biologic therapy for papillomas that keep come back after being removed by surgery four times in one year.

Midline Tract Cancer with NUT Gene Changes (NUT Midline Carcinoma)

Midline tract cancer is a disease in which malignant (cancer) cells form in the respiratory tract and sometimes other places along the middle of the body. The respiratory tract is made up of the nose, throat, larynx, trachea, bronchi, and lungs. Cancer may also form in other places along the middle of the body, such as the thymus, the area between the lungs, the pancreas, liver, and bladder.

Midline tract cancer is caused by a change in a chromosome. Every cell in the body contains DNA (genetic material stored inside chromosomes) that controls how the cell looks and acts. Midline tract cancer may form when part of the DNA from chromosome 15 (called the NUTgene) moves to another chromosome, or when chromosome 15 is broken.

Prognosis

Midline tract cancer with NUT gene changes usually cannot be cured.

Treatment

There is no standard treatment for midline tract cancer with NUT gene changes. Taking part in a clinical trial should be considered.

Unusual Cancers of the Chest

Breast Cancer

Most breast tumors in children are fibroadenomas, which are benign (not cancer). Rarely, these tumors become large phyllodes tumors (cancer) and begin to grow quickly. If a benign tumor begins to grow quickly, a fine-needle aspiration (FNA) biopsy or an excisional biopsy will be done. The tissues removed during the biopsy will be viewed under a microscope by a pathologist to check for signs of cancer.

Breast cancer is a disease in which malignant (cancer) cells form in the tissues of the breast. Breast cancer may occur in both male and female children.

Breast cancer is the most common cancer among teenage and young adult women aged 15 to 39 years. Breast cancer in this age group is more aggressive and more difficult to treat successfully than in older women. Treatments for younger and older women are similar. Also, care for younger patients with breast cancer includes checking for familial cancersyndromes and considering possible fertility issues when choosing treatment.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of breast cancer is increased by the following:

  • Having a personal history of cancer that may spread to the breast, such as leukemia, rhabdomyosarcoma, soft tissue sarcoma, or lymphoma.
  • Past treatment for another cancer, such as Hodgkin lymphoma, with radiation therapy to the breast or chest.

Breast cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • A lump or thickening in or near the breast or in the underarm area.
  • A change in the size or shape of the breast.
  • A dimple or puckering in the skin of the breast.
  • A nipple turned inward into the breast.
  • Scaly, red, or swollen skin on the breast, nipple, or areola (the dark area of skin that is around the nipple).
  • Dimples in the breast that look like the skin of an orange, called peau d’orange.

Other conditions that are not breast cancer may cause these same symptoms.

Tests to diagnose and stage breast cancer may include the following:

  • Physical exam and history.
  • MRI.
  • Ultrasound.
  • PET scan.
  • Blood chemistry studies.
  • X-ray of the chest.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Another test used to diagnose breast cancer is the mammogram (an x-ray of the breast). When treatment for another cancer included radiation therapy to the breast or chest, it is important to have a mammogram and MRI of the breast to check for breast cancer beginning at age 25, or 10 years after finishing radiation therapy, whichever is later.

Treatment

Treatment of breast cancer in children may include the following:

  • Watchful waiting, for benign tumors.
  • Surgery to remove the tumor, but not the whole breast. Radiation therapy may also be given.

See the PDQ summary Breast Cancer Treatment for more information on the treatment of adolescents and young adults with breast cancer.

Lung Cancer

Lung cancer begins in the tissue of the lung. The lungs are a pair of cone-shaped breathing organs in the chest. The lungs bring oxygen into the body as you breathe in. They release carbon dioxide, a waste product of the body’s cells, as you breathe out. Each lung has sections called lobes. The left lung has two lobes. The right lung is slightly larger and has three lobes. Two tubes called bronchi lead from the trachea (windpipe) to the right and left lungs. Tiny air sacs called alveoli and small tubes called bronchioles make up the inside of the lungs.

In children, most lung tumors are malignant (cancer).

Symptoms and Diagnostic Tests

Lung cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Coughing.
  • Streaks of blood in sputum (mucus coughed up from the lungs).
  • Trouble breathing.
  • Chest discomfort.
  • Fever.
  • Weight loss for no known reason.

Tests to diagnose lung cancer may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.

See the General Information section for a description of these tests and procedures.

Treatment

Treatment for lung cancer in children is surgery to remove the tumor. More treatment may be given after surgery. It depends on the type of tumor and whether the tumor has spread.

Bronchial Tumors

Bronchialtumors begin in the cells that line the surface of the lung. Most bronchial tumors in children are benign, slow-growing tumors in the trachea or large bronchi, which are the large airways of the lung. Sometimes, a slow-growing bronchial tumor becomes cancer that may spread to other parts of the body.

Respiratory anatomy; drawing shows right lung with upper, middle, and lower lobes; left lung with upper and lower lobes; and the trachea, bronchi, lymph nodes, and diaphragm. Inset shows bronchioles, alveoli, artery, and vein.
Anatomy of the respiratory system, showing the trachea and both lungs and their lobes and airways. Lymph nodes and the diaphragm are also shown. Oxygen is inhaled into the lungs and passes through the thin membranes of the alveoli and into the bloodstream (see inset).

Symptoms and Diagnostic and Staging Tests

Bronchial tumors may cause any of the following signs and symptoms:

  • Coughing.
  • Wheezing.
  • Trouble breathing.
  • Spitting up blood from the airways or lung.
  • Frequent infections in the lung, such as pneumonia.

Other conditions that are not bronchial tumors may cause these same symptoms. For example, symptoms of bronchial tumors are a lot like the symptoms of asthma, and that can make it hard to diagnose the tumor.

Tests to diagnose and stage bronchial tumors may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.

See the General Information section for a description of these tests and procedures.

A biopsy of the abnormal area is usually not done because it can cause severe bleeding.

Other tests used to diagnose bronchial tumors include the following:

  • Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer. A contrast dye may be put through the bronchoscope to make the larynx, trachea, and airways show up clearer on x-ray film.
  • Octreotide scan: A type of radionuclide scan used to find tumors. A small amount of radioactiveoctreotide (a hormone that attaches to carcinoid tumors) is injected into a vein and travels through the bloodstream. The radioactive octreotide attaches to the tumor and a special camera that detects radioactivity is used to show where the tumors are in the body.

Prognosis

Bronchial cancer in children can usually be cured, even when it has spread to nearby areas. The prognosis (chance of recovery) depends on how the cells look under a microscope and the stage of the cancer.

Treatment

Treatment of bronchial tumors in children may include the following:

  • Surgery to remove the tumor. Sometimes a type of surgery called a sleeve resection is used. The lymph nodes and vessels where cancer has spread are also removed.
  • Chemotherapy or radiation therapy, for cancer that has spread to other parts of the body.

Pleuropulmonary Blastoma

Pleuropulmonary blastomas (PPBs) form in the tissue of the lung and pleura (tissue that covers the lungs and lines the inside of the chest). PPBs can also form in the organs between the lungs including the heart, aorta, and pulmonaryartery, or in the diaphragm (the main breathing muscle below the lungs).

There are three stages of PPB that are described as types:

  • Type I tumors are cyst-like tumors in the lung. They are most common in children aged 2 years and younger and can usually be cured.
  • Type II tumors are cyst-like with some solid parts. These tumors sometimes spread to the brain.
  • Type III tumors are solid. These tumors often spread to the brain.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of PPB is increased by the following:

  • Having a family history of any type of cancer in close relatives.
  • Having a brother or sister with PPB.
  • Having a personal history of other types of cancer.

PPB may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • A cough that doesn’t go away.
  • Trouble breathing.
  • Chest discomfort.
  • Wheezing.
  • Streaks of blood in sputum (mucus coughed up from the lungs).
  • Hoarseness.
  • Pain under the rib cage.
  • Pain, swelling, or lumps in the abdomen.
  • Loss of appetite.
  • Weight loss for no known reason.
  • Feeling very tired.

Other conditions that are not PPB may cause these same symptoms.

Tests to diagnose and stage PPB may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • PET scan.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose PPB include the following:

  • Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.
  • Thoracoscopy: A surgical procedure to look at the organs inside the chest to check for abnormal areas. An incision (cut) is made between two ribs, and a thoracoscope is inserted into the chest. A thoracoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. In some cases, this procedure is used to remove part of the esophagus or lung. If the thoracoscope cannot reach certain tissues, organs, or lymph nodes, a thoracotomy may be done. In this procedure, a larger incision is made between the ribs and the chest is opened.

PPBs may spread or recur (come back) even after being removed by surgery.

Treatment

Treatment of pleuropulmonary blastomas in children is usually surgery to remove the whole lobe of the lung the tumor is in, with or without chemotherapy.

Esophageal Tumors

Esophagealtumors may be benign (not cancer) or malignant (cancer). Esophageal cancer is a disease in which malignant cells form in the tissues of the esophagus. The esophagus is the hollow, muscular tube that moves food and liquid from the throat to the stomach. Most esophageal tumors in children begin in the thin, flat cells that line the esophagus.

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, large intestine, and small intestine.
The stomach and esophagus are part of the upper digestive system.

Symptoms and Diagnostic and Staging Tests

Esophageal cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Trouble swallowing.
  • Weight loss.
  • Pain behind the breastbone.
  • Hoarseness and cough.
  • Indigestion and heartburn.

Other conditions that are not esophageal cancer may cause these same symptoms.

Tests to diagnose and stage esophageal cancer may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • PET scan.
  • Ultrasound.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose esophageal cancer include the following:

  • Esophagoscopy: A procedure to look inside the esophagus to check for abnormal areas. An esophagoscope is inserted through the mouth or nose and down the throat into the esophagus. An esophagoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer. A biopsy is usually done during an esophagoscopy. Sometimes a biopsy shows changes in the esophagus that are not cancer but may lead to cancer.
  • Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.
  • Thoracoscopy: A surgical procedure to look at the organs inside the chest to check for abnormal areas. An incision (cut) is made between two ribs and a thoracoscope is inserted into the chest. A thoracoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. Sometimes this procedure is used to remove part of the esophagus or lung.
  • Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples to be checked under a microscope for signs of disease.

Prognosis

Esophageal cancer is hard to cure because it usually is not possible to remove the whole tumor by surgery.

Treatment

Treatment for esophageal cancer in children may include the following:

  • Surgery to remove all or part of the tumor.
  • Radiation therapy given through a plastic or metal tube placed through the mouth into the esophagus.
  • Chemotherapy.

See the PDQ summary on adult Esophageal Cancer for more information.

Thymoma and Thymic Carcinoma

Thymomas and thymic carcinomas are tumors of the cells that cover the outside surface of the thymus. The thymus is a small organ in the upper chest under the breastbone. It is part of the lymph system and makes white blood cells, called lymphocytes, that help fight infection. Thymomas and thymic carcinomas usually form in the front part of the chest and are often found during a chest x-ray that is done for another reason.

Anatomy of the thymus gland; drawing shows the thymus gland in the upper chest under the breastbone. Also shown are the ribs, lungs, and heart.
Anatomy of the thymus gland. The thymus gland is a small organ that lies in the upper chest under the breastbone. It makes white blood cells, called lymphocytes, which protect the body against infections.

Thymoma and thymic carcinoma are slow-growing cancers that may spread to the lymph nodes or to other parts of the body.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

People who develop thymomas often have one of the following immune system diseases or hormonedisorders:

  • Myasthenia gravis.
  • Polymyositis.
  • Lupus.
  • Rheumatoid arthritis.
  • Thyroiditis.
  • Isaac syndrome.
  • Pure red cell aplasia.
  • Hyperthyroidism.
  • Addison disease.
  • Panhypopituitarism.

Thymoma and thymic carcinoma may cause any of the following symptoms Check with your child’s doctor if you see any of the following problems in your child:

  • Coughing.
  • Trouble swallowing.
  • Pain or a tight feeling in the chest.
  • Trouble breathing.

Other conditions that are not thymoma and thymic carcinoma may cause these same symptoms.

Tests to diagnose and stage thymoma and thymic carcinoma may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • PET scan.
  • MRI.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Prognosis

The prognosis (chance of recovery) is better when the tumor has not spread.

Treatment

Treatment for thymomas and thymic carcinoma in children may include the following:

  • Surgery to remove as much of the tumor as possible, followed by radiation therapy for tumors that have spread.
  • Chemotherapy.

Heart Tumors

Most tumors that form in the heart are benign (not cancer). Benign heart tumors that may appear in children include the following:

  • Rhabdomyoma: A tumor that forms in muscle made up of long fibers.
  • Fibroma: A tumor that forms in fiber-like tissue that holds bones, muscles, and other organs in place.
  • Myxoma: A tumor that may be part of an inheritedsyndrome called Carney complex. (See the Multiple Endocrine Neoplasia Syndromes section for more information.)
  • Histiocytoid cardiomyopathy tumor: A tumor that forms in the heart cells that control heart rhythm.
  • Teratomas: A type of germ cell tumor. In the heart, these tumors form most often in the pericardium (the sac that covers the heart). Some teratomas are malignant (cancer).
  • Hemangiomas: A tumor that forms in the cells that line blood vessels.
  • Neurofibroma: A tumor that forms in the cells and tissues that cover nerves.

In children, the most common benign heart tumors are rhabdomyomas and fibromas. Before birth and in newborns, the most common benign heart tumors are teratomas. An inherited disorder called tuberous sclerosis can cause heart tumors to form in a fetus or newborn.

Malignant tumors that begin in the heart are even more rare than benign tumors in children. Some of these include:

  • Malignant teratoma.
  • Rhabdomyosarcoma: A cancer that forms in muscle made up of long fibers.
  • Chondrosarcoma: A type of cancer that usually forms in bone cartilage but very rarely can begin in the heart.
  • Infantile fibrosarcoma.

Some cancers, such as rhabdomyosarcoma, melanoma, and leukemia, spread to the heart from other parts of the body. These tumors are malignant.

Symptoms and Diagnostic and Staging Tests

Heart tumors may cause any of the following symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Change in the heart's normal rhythm.
  • Trouble breathing, particularly when you are lying down.
  • Pain in the middle of the chest that feels better when you are sitting up.
  • Coughing.
  • Fainting.
  • Feeling dizzy, tired, or weak.
  • Fast heart rate.
  • Swelling in the legs, ankles, or abdomen.
  • Feeling anxious.

Heart tumors sometimes cause sudden death without causing any symptoms.

Other conditions that are not heart tumors may cause these same symptoms. Sometimes heart tumors do not cause any symptoms at all.

Tests to diagnose and stage heart tumors may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • MRI.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose or stage heart tumors include the following:

  • Echocardiogram: A procedure in which high-energy sound waves (ultrasound) are bounced off the heart and nearby tissues or organs and make echoes. A moving picture is made of the heart and heart valves as blood is pumped through the heart.
  • Electrocardiogram (EKG): A recording of the heart's electrical activity to evaluate its rate and rhythm. A number of small pads (electrodes) are placed on the patient’s chest, arms, and legs, and are connected by wires to the EKG machine. Heart activity is then recorded as a line graph on paper. Electrical activity that is faster or slower than normal may be a sign of heart disease or damage.

Treatment

Treatment for heart tumors in children may include the following:

  • Watchful waiting for benign tumors of heart muscle (rhabdomyomas), which usually shrink and go away on their own.
  • Surgery (which may include a heart transplant) and chemotherapy for tumors that spread to the heart from other places in the body.

Mesothelioma

Malignant mesothelioma is a disease in which malignant (cancer) cells are found in the pleura (the thin layer of tissue that lines the chest cavity and covers the lungs) or the peritoneum (the thin layer of tissue that lines the abdomen and covers most of the organs in the abdomen). The tumors often spread over the surface of organs without spreading into the organ. They may spread to lymph nodes nearby or in other parts of the body.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

Mesothelioma is sometimes a late effect of treatment for an earlier cancer, especially after treatment with radiation therapy. In adults, mesothelioma has been linked to being exposed to asbestos, which was once used as building insulation. There is no information about the risk of mesothelioma in children exposed to asbestos.

Mesothelioma may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Trouble breathing.
  • Pain under the rib cage.
  • Weight loss for no known reason.

Other conditions that are not mesothelioma may cause these same symptoms.

Tests to diagnose and stage mesothelioma may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • PET scan.
  • Fine-needle aspiration (FNA) biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose mesothelioma include the following:

  • Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.
  • Thoracoscopy: A surgical procedure to look at the organs inside the chest to check for abnormal areas. An incision (cut) is made between two ribs and a thoracoscope is inserted into the chest. A thoracoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. In some cases, this procedure is used to remove part of the esophagus or lung.
  • Thoracotomy: An incision (cut) is made between two ribs to check inside the chest for signs of disease.
  • Cytologic exam: An exam of cells under a microscope (by a pathologist) to check for anything abnormal. For mesothelioma, fluid is taken from around the lungs or from the abdomen. A pathologist checks the cells in the fluid.

Prognosis

The prognosis (chance of recovery) is better when the tumor has not spread or come back after treatment.

Treatment

Treatment for mesothelioma in children may include one or more of the following:

  • Surgery to remove the part of the chest lining with cancer and some of the healthy tissue around it.
  • Chemotherapy.
  • Radiation therapy, as palliative therapy, to relieve pain and improve quality of life.

See the PDQ summary on adult Malignant Mesothelioma Treatment for more information.

Unusual Cancers of the Abdomen

Cancer of the Adrenal Cortex

There are two adrenal glands. The adrenal glands are small and shaped like a triangle. One adrenal gland sits on top of each kidney. Each adrenal gland has two parts. The outer layer of the adrenal gland is the adrenal cortex. The center of the adrenal gland is the adrenal medulla. Cancer of the adrenal cortex is also called adrenocortical carcinoma.

Childhood cancer of the adrenal cortex occurs most commonly in patients younger than 6 years or in the teen years, and more often in females.

The adrenal cortex makes important hormones that do the following:

  • Balance the water and salt in the body.
  • Help keep blood pressure normal.
  • Help control the body's use of protein, fat, and carbohydrates.
  • Cause the body to have male or female characteristics.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of cancer of the adrenal cortex is increased by having any of the following syndromes:

  • Li-Fraumeni syndrome.
  • Beckwith-Wiedemann syndrome.
  • Hemihypertrophy.

A tumor of the adrenal cortex may be functioning (makes more hormones than normal) or nonfunctioning (does not make hormones). The hormones made by functioning tumors may cause certain signs or symptoms of disease and these depend on the type of hormone made by the tumor. For example, extra androgen hormone may cause both male and female children to develop masculine traits, such as body hair or a deep voice, grow faster, and have acne. (See the PDQ summary on adult Adrenocortical Carcinoma Treatment for more information on the symptoms of cancer of the adrenal cortex.)

The tests and procedures used to diagnose and stage adrenocortical carcinoma depend on the patient's symptoms. They may include:

  • Physical exam and history.
  • Blood chemistry studies.
  • CT scan.
  • MRI.
  • PET scan.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose cancer of the adrenal cortex include the following:

  • Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of cortisol or 17-ketosteroids. A higher than normal amount of these substances in the urine may be a sign of disease in the adrenal cortex.
  • Low-dosedexamethasone suppression test: A test in which one or more small doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
  • High-dose dexamethasone suppression test: A test in which one or more high doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
  • Blood tests: Tests to measure the levels of testosterone or estrogen in the blood. A higher than normal amount of these hormones that may be a sign of adrenocortical carcinoma.
  • Adrenal angiography: A procedure to look at the arteries and the flow of blood near the adrenal gland. A contrast dye is injected into the adrenal arteries. As the dye moves through the blood vessel, a series of x-rays are taken to see if any arteries are blocked.
  • Adrenal venography: A procedure to look at the adrenal veins and the flow of blood near the adrenal glands. A contrast dye is injected into an adrenal vein. As the contrast dye moves through the vein, a series of x-rays are taken to see if any veins are blocked. A catheter (very thin tube) may be inserted into the vein to take a blood sample, which is checked for abnormal hormone levels.

Prognosis

The prognosis (chance of recovery) is good for patients who have small tumors that have been completely removed by surgery. The cancer is harder to treat when the tumor is large or when the cancer has spread to other parts of the body when it was diagnosed. These tumors can spread to the kidneys, lungs, bones, and brain.

Treatment

Treatment for cancer of the adrenal cortex in children may include the following:

  • Surgery with or without chemotherapy.
  • A second surgery for tumors that come back and for tumors that spread to other parts of the body.
  • A clinical trial of surgery with or without chemotherapy.

See the PDQ summary on adult Adrenocortical Carcinoma Treatment for more information.

Stomach (Gastric) Cancer

Stomach cancer is a disease in which malignant (cancer) cells form in the lining of the stomach. The stomach is a J-shaped organ in the upper abdomen. It is part of the digestive system, which processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) in foods that are eaten and helps pass waste material out of the body. Food moves from the throat to the stomach through a hollow, muscular tube called the esophagus. After leaving the stomach, partly-digested food passes into the small intestine and then into the large intestine.

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, large intestine, and small intestine.
The stomach and esophagus are part of the upper digestive system.

The risk of stomach cancer is increased by having an infection with Helicobacter pylori (H.pylori)bacterium, which is found in the stomach.

Symptoms and Diagnostic and Staging Tests

Many patients will have anemia (a lower than normal number of red blood cells), but have no symptoms before the cancer spreads. Stomach cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Stomach pain.
  • Loss of appetite.
  • Weight loss for no known reason.
  • Nausea.
  • Vomiting.
  • Constipation or diarrhea.
  • Weakness.

Other conditions that are not stomach cancer may cause these same symptoms.

Tests to diagnose and stage stomach cancer may include the following:

  • Physical exam and history.
  • X-ray of the abdomen.
  • Blood chemistry studies.
  • CT scan.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose stomach cancer include the following:

  • Upper endoscopy: A procedure to look inside the esophagus, stomach, and duodenum (first part of the small intestine) to check for abnormal areas. An endoscope is passed through the mouth and down the throat into the esophagus. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of disease
  • Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metalliccompound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.
  • Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells, white blood cells, and platelets.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the blood sample made up of red blood cells.

Prognosis

Prognosis (chance of recovery) depends on whether the cancer has spread at the time of diagnosis.

Treatment

Treatment of stomach cancer in children may include the following:

  • Surgery to remove the cancer and some healthy tissue around it.
  • Surgery to remove as much of the cancer as possible, followed by radiation therapy and/or chemotherapy.

See the PDQ summary on adult Gastric Cancer Treatment for more information.

Pancreatic Cancer

Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas. The pancreas is a pear-shaped gland about 6 inches long. The wide end of the pancreas is called the head, the middle section is called the body, and the narrow end is called the tail. Many different kinds of tumors can form in the pancreas. Some tumors are benign (not cancer).

Anatomy of the pancreas; drawing shows the pancreas, stomach, spleen, liver, gallbladder, bile ducts, colon, and small intestine. An inset shows the head, body, and tail of the pancreas. The bile duct and pancreatic duct are also shown.
Anatomy of the pancreas. The pancreas has three areas: head, body, and tail. It is found in the abdomen near the stomach, intestines, and other organs.

The pancreas has two main jobs in the body:

  • To make juices that help digest (break down) food. These juices are secreted into the small intestine.
  • To make hormones that help control the sugar and salt levels in the blood. These hormones are secreted into the bloodstream.

The risk of pancreatic cancer is increased by having Beckwith-Wiedemann syndrome or Cushing syndrome.

Symptoms and Diagnostic and Staging Tests

Most pancreatic tumors do not secrete hormones and there are no symptoms of disease. This makes it difficult to diagnose pancreatic cancer early.

Pancreatic tumors that do secrete hormones may cause symptoms. The symptoms depend on the type of hormone being made.

If the tumor secretes insulin, symptoms that may occur include the following:

  • Weakness.
  • Feeling very tired.
  • Low blood sugar. This can cause blurred vision, headache, and feeling lightheaded, tired, weak, shaky, nervous, irritable, sweaty, confused, or hungry.
  • Coma.

Other symptoms caused by tumors that make hormones include the following:

  • Watery diarrhea.
  • Abnormalsodium (salt) level in the blood: Having a low sodium level can cause confusion, sleepiness, muscle weakness, and seizures. Having a high sodium level may cause weakness, tiredness, confusion, paralysis, coma, and seizures.
  • A lump in the abdomen.
  • Weight loss for no known reason.
  • Pain in the abdomen.

If cancer is in the head of the pancreas, the bile duct or blood flow to the stomach may be blocked and the following symptoms may occur:

  • Jaundice (yellowing of the skin and whites of the eyes).
  • Blood in the stool or vomit.

Check with your child’s doctor if you see any of these problems in your child. Other conditions that are not pancreatic cancer may cause these same symptoms.

Tests to diagnose and stage pancreatic cancer may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • MRI.
  • PET scan.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose pancreatic cancer include the following:

  • Endoscopic ultrasound (EUS): A procedure in which an endoscope is inserted into the body, usually through the mouth or rectum. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography.
  • Endoscopic retrograde cholangiopancreatography (ERCP): A procedure used to x-ray the ducts (tubes) that carry bile from the liver to the gallbladder and from the gallbladder to the small intestine. Sometimes pancreatic cancer causes these ducts to narrow and block or slow the flow of bile, causing jaundice. An endoscope (a thin, lighted tube) is passed through the mouth, esophagus, and stomach into the first part of the small intestine. A catheter (a smaller tube) is then inserted through the endoscope into the pancreatic ducts. A dye is injected through the catheter into the ducts and an x-ray is taken. If the ducts are blocked by a tumor, a fine tube may be inserted into the duct to unblock it. This tube, called a stent, may be left in place to keep the duct open. Tissue samples may also be taken and checked under a microscope for signs for cancer.
  • Percutaneous transhepatic cholangiography (PTC): A procedure used to x-ray the liver and bile ducts. A thin needle is inserted through the skin below the ribs and into the liver. Dye is injected into the liver or bile ducts and an x-ray is taken. If a blockage is found, a thin, flexible tube called a stent is sometimes left in the liver to drain bile into the small intestine or a collection bag outside the body. This test is done only if ERCP cannot be done.
  • Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples to be checked under a microscope for signs of disease.
  • Laparotomy: A surgical procedure in which an incision (cut) is made in the wall of the abdomen to check the inside of the abdomen for signs of disease. The size of the incision depends on the reason the laparotomy is being done. Sometimes organs are removed or tissue samples are taken and checked under a microscope for signs of disease.

Treatment

Treatment for children with pancreatic cancer may include the following:

  • Surgery to remove all or part of the pancreas and part of the small intestine.
  • Chemotherapy.

See the PDQ summary on adult Pancreatic Cancer Treatment for more information.

Colorectal Cancer

Colorectal cancer is a disease in which malignant (cancer) cells form in the tissues of the colon or the rectum. The colon is part of the body’s digestive system. The digestive system removes and processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) from foods and helps pass waste material out of the body. The digestive system is made up of the esophagus, stomach, and the small and large intestines. The first 6 feet of the large intestine are called the large bowel or colon. The last 6 inches are the rectum and the anal canal. The anal canal ends at the anus (the opening of the large intestine to the outside of the body).

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, colon, small intestine, rectum, and anus.
Anatomy of the lower digestive system, showing the colon and other organs.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

Childhood colon cancer is often part of an inheritedsyndrome that causes the disease. Some colorectal cancers in young people are linked to a genemutation that causes polyps (growths in the mucous membrane that lines the colon) to form that may turn into cancer later.

The risk of colorectal cancer is increased by having inherited certain conditions, such as:

  • Attenuated familial adenomatous polyposis.
  • Familial adenomatous polyposis.
  • Lynch syndrome.
  • Li-Fraumeni syndrome.
  • MYH-associated polyposis.
  • Turcot syndrome.
  • Cowden syndrome.
  • Juvenile polyposis syndrome.
  • Peutz-Jeghers syndrome.

Colon polyps that form in children who do not have an inherited syndrome are not linked to an increased risk of cancer.

Symptoms of childhood colorectal cancer usually depend on where the tumor forms. Colorectal cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Tumors of the rectum or lower colon may cause pain in the abdomen, constipation, or diarrhea.
  • Tumors in the part of the colon on the right side of the body may cause:
    • A lump in the abdomen.
    • Weight loss for no known reason.
    • Loss of appetite.
    • Blood in the stool.

Other conditions that are not colorectal cancer may cause these same symptoms.

Tests to diagnose and stage colorectal cancer may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • PET scan.
  • MRI.
  • Bone scan.
  • Biopsy.

Other tests used to diagnose colorectal cancer include the following:

  • Colonoscopy: A procedure to look inside the rectum and colon for polyps, abnormal areas, or cancer. A colonoscope is inserted through the rectum into the colon. A colonoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove polyps or tissue samples, which are checked under a microscope for signs of cancer.
  • Barium enema: A series of x-rays of the lower gastrointestinal tract. A liquid that contains barium (a silver-white metalliccompound) is put into the rectum. The barium coats the lower gastrointestinal tract and x-rays are taken. This procedure is also called a lower GI series.
  • Fecal occult blood test: A test to check stool (solid waste) for blood that can only be seen with a microscope. Small samples of stool are placed on special cards and returned to the doctor or laboratory for testing.
  • Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells, white blood cells, and platelets.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the blood sample made up of red blood cells.
  • Kidney function test: A test in which blood or urine samples are checked for the amounts of certain substances released by the kidneys. A higher or lower than normal amount of a substance can be a sign that the kidneys are not working the way they should. This is also called a renal function test.
  • Liver function test: A blood test to measure the blood levels of certain substances released by the liver. A high or low level of certain substances can be a sign of liver disease.
  • Carcinoembryonic antigen (CEA) assay: A test that measures the level of CEA in the blood. CEA is released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, it can be a sign of colon cancer or other conditions.

Prognosis

The prognosis (chance of recovery) depends on the following:

  • Whether the entire tumor was removed by surgery.
  • Whether the cancer has spread to other parts of the body, such as the lymph nodes, liver, pelvis, or ovaries.

Treatment

Treatment for colorectal cancer in children may include the following:

  • Surgery to remove the tumor when it has not spread.
  • Radiation therapy and chemotherapy for tumors in the rectum or lower colon.
  • Combination chemotherapy.

Children with certain familial colon cancer syndromes may be treated with:

  • Surgery to remove the colon before cancer forms.
  • Medicine to decrease the number of polyps in the colon.

See the following PDQ summaries on adult cancer for more information:

  • Colon Cancer Treatment
  • Rectal Cancer Treatment

Carcinoid Tumors

Carcinoid tumors usually form in the lining of the stomach or intestines, but they can form in other organs, such as the lungs or liver. These tumors are usually small, slow-growing, and benign (not cancer). Some carcinoid tumors are malignant (cancer) and spread to other places in the body. Sometimes carcinoid tumors in children form in the appendix (a pouch that sticks out from the first part of the large intestine near the end of the small intestine). The tumor is often found during surgery to remove the appendix.

Symptoms and Diagnostic and Staging Tests

Some carcinoid tumors release hormones and other substances. If the tumor is in the liver, high amounts of these hormones may remain in the body and cause a group of symptoms called carcinoid syndrome. Carcinoid syndrome caused by the hormone somatostatin may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Redness and a warm feeling in the face and neck.
  • A fast heartbeat.
  • Trouble breathing.
  • Sudden drop in blood pressure.
  • Diarrhea.

Other conditions that are not carcinoid tumors may cause these same symptoms.

Tests that check for signs of cancer are used to diagnose and stage carcinoid tumors. They may include:

  • Physical exam and history.
  • Blood chemistry studies.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose carcinoid tumors include the following:

  • Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells, white blood cells, and platelets.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the blood sample made up of red blood cells.
  • Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of certain substances, such as hormones. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. The urine sample is checked to see if it contains a hormone made by carcinoid tumors. This test is used to help diagnose carcinoid syndrome.

Treatment

Treatment for carcinoid tumors in the appendix in children may include the following:

  • Surgery to remove the appendix, when the tumor is small and only in the appendix.
  • Surgery to remove the appendix, lymph nodes, and part of the large intestine, when the tumor is larger, has spread to nearby lymph nodes, and is in the appendix.
  • Surgery, chemotherapy, and/or radiation therapy for tumors that have spread.

Treatment for carcinoid tumors that have spread to the large intestine or stomach is the same as treatment for colorectal cancer.

For tumors that make hormones that cause symptoms, medicine can be given to help relieve the symptoms.

See the PDQ summary on adult Gastrointestinal Carcinoid Tumors Treatment for more information.

Gastrointestinal Stromal Tumors

Gastrointestinalstromal celltumors (GIST) usually begin in cells in the wall of the stomach or intestines. GISTs may be benign (not cancer) or malignant (cancer). Childhood GISTs are more common in girls, and usually appear in the teen years.

Risk Factors and Symptoms

GISTs in children are not the same as GISTs in adults. Patients should be seen at centers that specialize in the treatment of GISTs and the tumors should be tested for genetic changes. A small number of children have tumors with genetic changes like those found in adult patients. The risk of GIST is increased by the following genetic disorders:

  • Carney triad.
  • Carney-Stratakis syndrome.

Most children with GIST have tumors in the stomach and develop anemia caused by bleeding. Symptoms of anemia include the following:

  • Feeling tired.
  • Dizziness.
  • A fast or irregular heartbeat.
  • Shortness of breath.
  • Pale skin.

Other conditions that are not anemia caused by GIST may cause these same symptoms.

Treatment

Treatment for children who have tumors with genetic changes like those found in adult patients is targeted therapy with a tyrosine kinase inhibitor.

Treatment for children whose tumors do not show genetic changes may include the following:

  • Surgery to remove the tumor and check nearby lymph nodes for signs of cancer. If cancer is in the lymph nodes, the lymph nodes are removed.
  • Watchful waiting for tumors that come back in the same place or cannot be removed, but do not cause symptoms.

Unusual Cancers of the Reproductive and Urinary Systems

Bladder Cancer

Bladder cancer is a disease in which malignant (cancer) cells form in the tissues of the bladder. The bladder is a hollow organ in the lower part of the abdomen. It is shaped like a small balloon and has a muscle wall that allows it to get bigger or smaller. The bladder stores urine until it is passed out of the body. Urine is the liquid waste that is made by the kidneys when they clean the blood. The urine passes from the two kidneys into the bladder through two tubes called ureters. When the bladder is emptied during urination, the urine goes from the bladder to the outside of the body through another tube called the urethra.

Anatomy of the female urinary system; drawing shows a front view of the right and left kidneys, the ureters,  urethra, and bladder filled with urine. The inside of the left kidney shows the renal pelvis. An inset shows the renal tubules and urine. The spine, adrenal glands, and uterus are also shown.
Anatomy of the female urinary system showing the kidneys, adrenal glands, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis of each kidney. The urine flows from the kidneys through the ureters to the bladder. The urine is stored in the bladder until it leaves the body through the urethra.

The most common type of bladder cancer is transitional cell cancer. Squamous cell and other more aggressive types of bladder cancer are less common.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

In teenagers who were treated with certain anticancer drugs for leukemia, the risk of bladder cancer is increased.

Bladder cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Blood in the urine (slightly rusty to bright red in color).
  • Frequent urination or feeling the need to urinate without being able to do so.
  • Pain during urination.
  • Lower back pain.

Other conditions that are not bladder cancer may cause the same symptoms.

Tests to diagnose and stage bladder cancer may include the following:

  • Physical exam and history.
  • CT scan.
  • Ultrasound of the bladder.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Other tests used to diagnose bladder cancer include the following:

  • Urinalysis: A test to check the color of urine and its contents, such as sugar, protein, red blood cells, and white blood cells.
  • Urine cytology: Examination of urine under a microscope to check for abnormal cells.
  • Cystoscopy: A procedure to look inside the bladder and urethra to check for abnormal areas. A cystoscope is inserted through the urethra into the bladder. A cystoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.

Prognosis

In children, bladder cancer is usually low grade (not likely to spread) and the prognosis is usually good following surgery to remove the tumor.

Treatment

Treatment for bladder cancer in children is usually transurethral resection (TUR). This is a surgical procedure to remove tissue from the bladder using a resectoscope inserted into the bladder through the urethra. A resectoscope is a thin, tube-like instrument with a light, a lens for viewing, and a tool to remove tissue and burn away any remaining tumor cells. Tissue samples are checked under a microscope for signs of cancer.

See the PDQ summary on adult Bladder Cancer Treatment for more information.

Testicular Cancer

Testicular cancer is a disease in which malignant (cancer) cells form in the tissues of one or both testicles. The testicles are 2 egg-shaped glands located inside the scrotum (a sac of loose skin that lies directly below the penis). The testicles are held within the scrotum by the spermatic cord, which also contains the vas deferens and vessels and nerves of the testicles.

Anatomy of the  male reproductive and urinary systems; drawing shows front and side views of ureters, lymph nodes, rectum, bladder, prostate gland, vas deferens,  penis, testicles, urethra, seminal vesicle, and ejaculatory duct.
Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs.

There are two types of testicular tumors:

  • Germ cell tumors: Tumors that start in sperm cells in males. Testicular germ cell tumors may be benign (not cancer) or malignant (cancer). The most common testicular germ cell tumors in young boys are benign teratomas and malignant nonseminomas. Seminomas usually occur in young men and are rare in boys.
  • Non-germ cell tumors: Tumors that begin in the tissues that surround and support the testicles. These tumors may be benign or malignant.

Symptoms and Diagnostic and Staging Tests

A testicular tumor may cause a painless lump in the testicles. Other conditions may also cause a lump in the testicles.

Tests to diagnose and stage non-germ cell testicular cancer may include the following:

  • Physical exam and history.
  • CT scan.
  • Ultrasound.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Treatment

Treatment for non-germ cell testicular cancer in children may be surgery.

See the PDQ summary on Childhood Extracranial Germ Cell Tumors Treatment for more information on testicular germ cell tumors.

Ovarian Cancer

Ovarian cancer is a disease in which malignant (cancer) cells form in the ovary. The ovaries are a pair of organs in the female reproductive system. They are located in the pelvis, one on each side of the uterus (the hollow, pear-shaped organ where a fetus grows). Each ovary is about the size and shape of an almond. The ovaries produce eggs and female hormones (chemicals that control the way certain cells or organs function).

Anatomy of the female reproductive system; drawing shows the uterus, myometrium (muscular outer layer of the uterus), endometrium (inner lining of the uterus), ovaries, fallopian tubes, cervix, and vagina.
Anatomy of the female reproductive system. The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium.

Most ovariantumors in children are benign (not cancer). They occur most often in females aged 15 to 19 years.

There are several common types of malignant ovarian tumors:

  • Germ cell tumors: Tumors that start in egg cells in females. These are the most common ovarian tumors in girls. (See the PDQ summary on Childhood Extracranial Germ Cell Tumors Treatment for more information on ovarian germ cell tumors.)
  • Epithelial tumors: Tumors that start in the tissue covering the ovary. These are the second most common ovarian tumors in girls.
  • Stromal tumors: Tumors that begin in stromal cells, which make up tissues that surround and support the ovaries.
  • Other tumors, such as Burkitt lymphoma and small cell carcinoma of the ovary (a very rare tumor).

Risk Factors, Symptoms, and Diagnostic and Staging Tests

The risk of ovarian cancer is increased by having one of the following conditions:

  • Ollier disease (a disorder that causes abnormal growth of cartilage at the end of long bones).
  • Maffucci syndrome (a disorder that causes abnormal growth of cartilage at the end of long bones and of blood vessels in the skin).
  • Peutz-Jeghers syndrome.

Ovarian cancer may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Painful menstrual periods.
  • A lump in the abdomen.
  • Pain or swelling in the abdomen.
  • Having male sex traits, such as body hair or a deep voice.
  • Early signs of puberty.

Other conditions that are not ovarian cancer may cause these same symptoms.

Tests to diagnose and stage ovarian cancer may include the following:

  • Physical exam and history.
  • CT scan.
  • Ultrasound.
  • Biopsy.

See the General Information section for a description of these tests and procedures.

Prognosis

Ovarian epithelial cancer is usually found at an early stage in children and is easier to treat than in adult patients.

Treatment

Treatment of ovarian epithelial cancer may include the following:

  • Surgery.
  • Radiation therapy.
  • Combination chemotherapy.

Treatment of ovarian stromal tumors may include the following:

  • Surgery to remove one ovary and one fallopian tube, for early cancer.
  • Surgery followed by chemotherapy for cancer that is advanced.
  • Chemotherapy for cancer that has recurred (come back).

See the following PDQ summaries for more information:

  • Childhood Extracranial Germ Cell Tumors Treatment
  • Ovarian Epithelial Cancer Treatment
  • Ovarian Germ Cell Tumors Treatment

Cervical and Vaginal Cancer

Cervical cancer is a disease in which malignant (cancer) cells form in the cervix. The cervix is the lower, narrow end of the uterus (the hollow, pear-shaped organ where a fetus grows). The cervix leads from the uterus to the vagina (birth canal). Vaginal cancer forms in the vagina. The vagina is the canal leading from the cervix to the outside of the body. At birth, a baby passes out of the body through the vagina (also called the birth canal).

Anatomy of the female reproductive system; drawing shows the uterus, myometrium (muscular outer layer of the uterus), endometrium (inner lining of the uterus), ovaries, fallopian tubes, cervix, and vagina.
Anatomy of the female reproductive system. The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium.

The most common symptom of cervical and vaginal cancer is bleeding from the vagina. Other conditions may also cause vaginal bleeding.

Treatment

Treatment for childhood cervical and vaginal cancer may include surgery to remove as much of the cancer as possible, followed by radiation therapy. Chemotherapy may also be used but it is not yet known if this is an effective treatment.

Other Rare Unusual Cancers of Childhood

Multiple Endocrine Neoplasia Syndromes

Multiple endocrine neoplasia (MEN) syndromes

Multiple endocrine neoplasia (MEN) syndromes are inheriteddisorders that affect the endocrine system. The endocrine system is made up of glands and cells that make hormones and release them into the blood. MEN syndromes may cause hyperplasia (the growth of too many normal cells) or tumors that may be benign (not cancer) or malignant (cancer).

There are several types of MEN syndrome and each type may cause different conditions or cancers. Patients and family members with an increased risk of these syndromes should have genetic counseling and tests to check for the syndromes.

The two main types of MEN syndromes are MEN1 and MEN2:

  • MEN1 syndrome is also called Werner syndrome. This syndrome can cause tumors in the parathyroid, pancreas, and pituitary glands. A diagnosis of MEN1 syndrome is usually made when tumors are found in two or three of these glands. MEN1 syndrome may also cause tumors in the adrenal glands, gastrointestinal tract, fibroustissue, and fat cells. The prognosis (chance of recovery) is usually good.

    The most common sign of MEN1 syndrome is hypercalcemia. Hypercalcemia may cause weakness, feeling very tired, nausea and vomiting, loss of appetite, being very thirsty and urinating more than usual, and constipation.

    Children who are diagnosed with MEN1 syndrome are checked for signs of cancer starting at age 5 and continuing for the rest of their life. Talk to your doctor about the tests and procedures that should be done to check for signs of cancer and how often they should be done.

  • MEN2 syndrome includes three subgroups:
    • MEN2A syndrome

      MEN2A syndrome is also called Sipple syndrome. A diagnosis of MEN2A syndrome may be made when the patient or the patient's parents, brothers, sisters, or children have two or more of the following tumors:

      • Medullary thyroid cancer.
      • Pheochromocytoma (a tumor of the adrenal gland).
      • Parathyroid gland cancer.

      Symptoms of medullary thyroid cancer may include the following:

      • A lump in the neck.
      • Trouble breathing.
      • Trouble swallowing.
      • Hoarseness.

      Symptoms of pheochromocytoma may include:

      • Pain in the abdomen or chest.
      • Fast or irregular heart beat.
      • Being irritable or nervous.
      • Headache.

      Symptoms of parathyroid gland cancer may include:

      • Hypercalcemia.
      • Pain in the abdomen, side, or back that doesn't go away.
      • Pain in the bones.
      • A broken bone.
      • A lump in the neck.
      • Change in voice, such as hoarseness.
      • Trouble swallowing.

      Family members of patients with the MEN2A syndrome should have genetic counseling and be tested in early childhood, before age 5, for the gene changes that lead to this type of cancer.

      A small number of medullary thyroid cancers may occur at the same time as Hirschsprung disease (chronic constipation that begins when a child is an infant), which has been found in some families with MEN2A syndrome. Hirschsprung disease may appear before other signs of MEN2A syndrome do. Patients who are diagnosed with Hirschsprung disease should be checked for certain gene changes that cause MEN2A syndrome.

    • MEN2B syndrome

      Patients with MEN2B syndrome may have a slender body build with long, thin arms and legs. The lips may appear thick and bumpy because of benign tumors in the mucous membranes. MEN2B syndrome may cause the following conditions:

      • Medullary thyroid cancer.
      • Parathyroid hyperplasia.
      • Adenomas.
      • Pheochromocytoma.
      • Nerve cell tumors in the mucous membranes or other places.
    • Familial medullary carcinoma of the thyroid (FMTC)

      This type of MEN2 syndrome causes medullary thyroid cancer. A diagnosis of FMTC may be made when 2 or more family members have medullary thyroid cancer and no family members have parathyroid or adrenal gland problems.

Tests used to diagnose and stage MEN syndromes depend on the symptoms and the patient's family history. They may include:

  • Physical exam and history.
  • Blood chemistry studies.
  • Ultrasound.
  • MRI.
  • CT scan.
  • PET scan.
  • Fine-needle aspiration (FNA) or surgical biopsy.

See the General Information section for a description of these tests and procedures.

Other tests and procedures used to diagnose MEN syndromes include the following:

  • Genetic testing: A test to analyze DNA and check for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder.
  • Blood hormone studies: A procedure in which a blood sample is checked to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of thyroid-stimulating hormone (TSH). TSH is made by the pituitary gland in the brain. It stimulates the release of thyroid hormone and controls how fast follicular thyroid cells grow. The blood may also be checked for high levels of the hormone calcitonin or parathyroid hormone (PTH).
  • Radioactive iodinescan (RAI scan): A procedure to find areas in the body where thyroid cancer cells may be dividing quickly. Radioactive iodine (RAI) is used because only thyroid cells take up iodine. A very small amount of RAI is swallowed, travels through the blood, and collects in thyroid tissue and thyroid cancer cells anywhere in the body. Abnormal thyroid cells take up less iodine than normal thyroid cells do. Areas that do not take up the iodine normally are called cold spots. Cold spots show up lighter in the picture made by the scan. They can be either benign (not cancer) or malignant, so a biopsy is done to find out if they are cancer.
  • Sestamibi scan: A type of radionuclide scan used to find an overactive parathyroid gland. A small amount of a radioactive substance called technetium 99 is injected into a vein and travels through the bloodstream to the parathyroid gland. The radioactive substance will collect in the overactive gland and show up brightly on a special camera that detects radioactivity.
  • Angiogram: A procedure to look at blood vessels and the flow of blood. A contrast dye is injected into a blood vessel. As the contrast dye moves through the blood vessel, x-rays are taken to see if there are any blockages.
  • Venous sampling for an overactive parathyroid gland: A procedure in which a sample of blood is taken from veins near the parathyroid glands. The sample is checked to measure the amount of parathyroid hormone released into the blood by each gland. Venous sampling may be done if blood tests show there is an overactive parathyroid gland but imaging tests don’t show which one it is.
  • Somatostatin receptor scintigraphy: A type of radionuclide scan that may be used to find tumors. A small amount of radioactive octreotide (a hormone that attaches to tumors) is injected into a vein and travels through the blood. The radioactive octreotide attaches to the tumor and a special camera that detects radioactivity is used to show where the tumors are in the body. This procedure is also called octreotide scan and SRS.
  • MIBG scan: A procedure used to find neuroendocrine tumors, such as pheochromocytoma. A very small amount of a substance called radioactive MIBG is injected into a vein and travels through the bloodstream. Neuroendocrine tumor cells take up the radioactive MIBG and are detected by a scanner. Scans may be taken over 1-3 days. An iodine solution may be given before or during the test to keep the thyroid gland from absorbing too much of the MIBG.
  • Blood catecholamine studies: A procedure in which a blood sample is checked to measure the amount of certain catecholamines released into the blood. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher- or lower-than-normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts may be a sign of pheochromocytoma.
  • Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of catecholamines in the urine. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher- or lower-than-normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts may be a sign of pheochromocytoma.
  • Pentagastrin stimulation test: A test in which blood samples are checked to measure the amount of calcitonin in the blood. Calcium gluconate and pentagastrin are injected into the blood and then several blood samples are taken over the next 5 minutes. If the level of calcitonin in the blood increases, it may be a sign of medullary thyroid cancer.

Treatment

There are several types of MEN syndrome, and each type may need different treatment:

  • Patients with the MEN1 syndrome are treated for parathyroid, pancreatic and pituitary tumors.
  • Patients with the MEN2A syndrome usually have surgery to remove the thyroid by age 5 or earlier if genetic tests show certain gene changes. The surgery is done to diagnose cancer or to prevent cancer from forming or spreading.
  • Infants with the MEN2B syndrome may have the thyroid removed to prevent cancer.
  • Patients with Hirschsprung disease and certain gene changes may have the thyroid removed to prevent cancer.
  • A clinical trial of targeted therapy with a tyrosine kinase inhibitor for medullary thyroid cancer.

Pheochromocytoma and Paraganglioma

Pheochromocytoma and paraganglioma are rare tumors that come from the same type of nervetissue.

  • Pheochromocytoma forms in the adrenal glands. There are two adrenal glands, one on top of each kidney in the back of the upper abdomen. Each adrenal gland has two parts. The outer layer of the adrenal gland is the adrenal cortex. The center of the adrenal gland is the adrenal medulla. Pheochromocytoma is a tumor of the adrenal medulla. The adrenal glands make important hormones called catecholamines. Adrenaline (epinephrine) and noradrenaline (norepinephrine) are two types of catecholamines that help control heart rate, blood pressure, blood sugar, and the way the body reacts to stress. Some pheochromocytomas release extra adrenaline and noradrenaline into the blood and cause symptoms of disease.
  • Paraganglioma forms outside the adrenal glands near the carotid artery, along nerve pathways in the head and neck, and in other parts of the body. Some paragangliomas make extra catecholamines called adrenaline and noradrenaline. The release of extra adrenaline and noradrenaline into the blood may cause symptoms of disease.

Risk Factors, Symptoms, and Diagnostic and Staging Tests

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor doesn't mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your child’s doctor if you think your child may be at risk.

The risk of pheochromocytoma or paraganglioma is increased by having any of the following inheritedsyndromes or gene changes:

  • Multiple endocrine neoplasia 1 syndrome.
  • Multiple endocrine neoplasia 2 syndrome (MEN2A and MEN2B).
  • von Hippel-Lindau disease (VHL).
  • Neurofibromatosis type 1 (NF1).
  • Carney-Stratakis dyad (paraganglioma and gastrointestinal stromal tumor [GIST]).
  • Carney triad (paraganglioma, GIST, and pulmonary chondroma).
  • Changes in certain genes including SDHD, SDHB, SDHA, and TMEM127.

More than half of the children and adolescents diagnosed with pheochromocytoma or paraganglioma have an inherited syndrome or gene change that increased the risk of cancer. Genetic counseling (a discussion with a trained professional about inherited diseases) and testing is an important part of the treatment plan.

Some tumors do not make extra adrenaline or noradrenaline and do not cause symptoms. These tumors may be found when a lump forms in the neck or when a test or procedure is done for another reason. Symptoms of pheochromocytoma and paraganglioma occur when too much adrenaline or noradrenaline is released into the blood. These and other symptoms may be caused by pheochromocytoma and paraganglioma. Other conditions may cause the same symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • High blood pressure.
  • Headache.
  • Heavy sweating for no known reason.
  • A strong, fast, or irregular heartbeat.
  • Being shaky.
  • Being extremely pale.

These symptoms may come and go but high blood pressure is more likely to occur for long periods of time in young patients. These symptoms may also occur with physical activity, injury, anesthesia, surgery to remove the tumor, eating foods such as chocolate and cheese, or passing urine (if the tumor is in the bladder).

Tests used to diagnose and stage pheochromocytoma and paraganglioma depend on the symptoms and the patient's family history. They may include:

  • Physical exam and history.
  • PET scan.
  • CT scan (CAT scan).
  • MRI (magnetic resonance imaging).

See the General Information section for a description of these tests and procedures.

Other tests and procedures used to diagnose pheochromocytoma and paraganglioma include the following:

  • Plasma-free metanephrines test: A blood test that measures the amount of metanephrines in the blood. Metanephrines are substances that are made when the body breaks down adrenaline or noradrenaline. Pheochromocytomas and paragangliomas can make large amounts of adrenaline and noradrenaline and cause high levels of metanephrines in both the blood and urine.
  • Blood catecholamine studies: A procedure in which a blood sample is checked to measure the amount of certain catecholamines (adrenaline or noradrenaline) released into the blood. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher- or lower-than-normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts may be a sign of pheochromocytoma or paraganglioma.
  • Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of catecholamines (adrenaline or noradrenaline) or metanephrines in the urine. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher- or lower-than-normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts may be a sign of pheochromocytoma or paraganglioma.
  • MIBG scan: A procedure used to find neuroendocrine tumors, such as pheochromocytoma and paraganglioma. A very small amount of a substance called radioactive MIBG is injected into a vein and travels through the bloodstream. Neuroendocrine tumor cells take up the radioactive MIBG and are detected by a scanner. Scans may be taken over 1-3 days. An iodine solution may be given before or during the test to keep the thyroid gland from absorbing too much of the MIBG.
  • Somatostatin receptor scintigraphy: A type of radionuclide scan that may be used to find tumors. A small amount of radioactive octreotide (a hormone that attaches to tumors) is injected into a vein and travels through the blood. The radioactive octreotide attaches to the tumor and a special camera that detects radioactivity is used to show where the tumors are in the body. This procedure is also called octreotide scan and SRS.

Treatment

Treatment of pheochromocytoma and paraganglioma in children may include the following:

  • Surgery to completely removed the tumor.
  • Combination chemotherapy or treatment with high-dose131I-MIBG for tumors that have spread.

Before surgery, drug therapy with alpha-blockers to control blood pressure and beta-blockers to control heart rate are given. If both adrenal glands are removed, life-long hormone therapy to replace hormones made by the adrenal glands is needed after surgery.

Skin Cancer (Melanoma, Squamous Cell Cancer, Basal Cell Cancer)

Skin cancer is a disease in which malignant (cancer) cells form in the tissues of the skin. The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. Skin also helps control body temperature and stores water, fat, and vitamin D. The skin has several layers, but the two main layers are the epidermis (upper or outer layer) and the dermis (lower or inner layer). Skin cancer begins in the epidermis, which is made up of three kinds of cells:

  • Squamous cells: Thin, flat cells that form the top layer of the epidermis.
  • Basal cells: Round cells under the squamous cells.
  • Melanocytes: Found in the lower part of the epidermis, these cells make melanin, the pigment that gives skin its natural color. When skin is exposed to the sun, melanocytes make more pigment and cause the skin to darken.
Anatomy of the skin with melanocytes; drawing shows normal skin anatomy, including the epidermis, dermis, hair follicles, sweat glands, hair shafts, veins, arteries, fatty tissue, nerves, lymph vessels, oil glands, and subcutaneous tissue. The pullout shows a close-up of the squamous cell and basal cell layers of the epidermis above the dermis with blood vessels. Melanin is shown in the cells. A melanocyte is shown in the layer of basal cells at the deepest part of the epidermis.
Anatomy of the skin, showing the epidermis, dermis, and subcutaneous tissue. Melanocytes are in the layer of basal cells at the deepest part of the epidermis.

There are three types of skin cancer:

  • Melanoma.
  • Squamous cell skin cancer.
  • Basal cell skin cancer.

Melanoma

Even though melanoma is rare, it is the most common skin cancer in children. It occurs more often in children aged 10 to 19 years. Melanoma rates in the United States have slowly increased since 1975.

The risk of having melanoma is increased by the following:

  • Giant melanocytic nevi (large black spots, which may cover the trunk and thigh).
  • Xeroderma pigmentosum.
  • Certain disorders of the immune system.
  • Multiple endocrine neoplasia Type I (MEN1) syndrome (Werner syndrome).
  • A personal history of retinoblastoma.

Risk factors for melanoma in all age groups include:

  • Having a fair complexion, which includes the following:
    • Fair skin that freckles and burns easily, does not tan, or tans poorly.
    • Blue or green or other light-colored eyes.
    • Red or blond hair.
  • Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time.
  • Having a history of many blistering sunburns as a child.
  • Having several large or many small moles.
  • Having a family history or personal history of unusual moles (atypical nevus syndrome).
  • Having a family or personal history of melanoma.

Symptoms of melanoma include the following:

  • A mole that:
    • changes in size, shape, or color.
    • has irregular edges or borders.
    • is more than one color.
    • is asymmetrical (if the mole is divided in half, the 2 halves are different in size or shape).
    • itches.
    • oozes, bleeds, or is ulcerated (a hole forms in the skin when the top layer of cells breaks down and the tissue below shows through).
  • Change in pigmented (colored) skin.
  • Satellite moles (new moles that grow near an existing mole).

Tests to diagnose and stage melanoma may include the following:

  • Physical exam and history.
  • X-ray of the chest.
  • CT scan.
  • MRI.
  • PET scan.

See the General Information section for a description of these tests and procedures.

Other tests and procedures used to diagnose melanoma include the following:

  • Skin exam: A doctor or nurse checks the skin for bumps or spots that look abnormal in color, size, shape, or texture.
  • Biopsy: All or part of the abnormal-looking growth is cut from the skin and viewed under a microscope by a pathologist to see if cancer cells are present. There are 4 main types of skin biopsies:
    • Shave biopsy: A sterile razor blade is used to “shave-off” the abnormal-looking growth.
    • Punch biopsy: A special instrument called a punch or a trephine is used to remove a circle of tissue from the abnormal-looking growth.
    • Excisional biopsy: A scalpel is used to remove the entire growth.
    • Wide local excision: A scalpel is used to remove some of the normal tissue around the area where melanoma was found, to check for cancer cells. Skin grafting may be needed to cover the area where tissue was removed.
  • Sentinel lymph node biopsy: The removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It is the first lymph node the cancer is likely to spread to from the tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes.
  • Lymph node dissection: A surgical procedure in which lymph nodes are removed and a sample of tissue is checked under a microscope for signs of cancer. For a regional lymph node dissection, some of the lymph nodes in the tumor area are removed. For a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed. This procedure is also called a lymphadenectomy.
  • FISH (fluorescence in situ hybridization): A laboratory test used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA attach to certain genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light. This test is done to tell the difference between melanoma and melanocytic tumors of unknown metastatic potential (MELTUMP).
  • Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.

Treatment of Melanoma

Treatment for melanoma is surgery to remove the tumor and some tissue around the tumor. If cancer has spread to nearby lymph nodes, treatment is surgery to remove the lymph nodes with cancer. Biologic therapy with high-doseinterferon alpha-2b may also be given.

Treatment for melanoma that has spread beyond the lymph nodes may include the following:

  • Chemotherapy and/or biologic therapy.
  • A clinical trial of high-dose biologic therapy or targeted therapy.

See the PDQ summary on adult Melanoma Treatment for more information.

Squamous Cell and Basal Cell Skin Cancer

The risk of squamous cell or basal cell cancer is increased by the following:

  • Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time.
  • Having a fair complexion, which includes the following:
    • Fair skin that freckles and burns easily, does not tan, or tans poorly.
    • Blue or green or other light-colored eyes.
    • Red or blond hair.
  • Having actinic keratosis.
  • Past treatment with radiation.
  • Having a weakened immune system.

Symptoms of squamous cell and basal cell skin cancer include the following:

  • A sore that does not heal.
  • Areas of the skin that are:
    • Small, raised, smooth, shiny, and waxy.
    • Small, raised, and red or reddish-brown.
    • Flat, rough, red or brown, and scaly.
    • Scaly, bleeding, or crusty.
    • Similar to a scar and firm.

Tests to diagnose squamous cell and basal cell skin cancer include the following:

  • Skin exam: A doctor or nurse checks the skin for bumps or spots that look abnormal in color, size, shape, or texture.
  • Biopsy: All or part of a growth that doesn't look normal is cut from the skin and viewed under a microscope by a pathologist to check for signs of cancer. There are three main types of skin biopsies:
    • Shave biopsy: A sterile razor blade is used to “shave-off” the growth that does not look normal.
    • Punch biopsy: A special instrument called a punch or a trephine is used to remove a circle of tissue from the growth that does not look normal.
    • Excisional biopsy: A scalpel is used to remove the entire growth.

Treatment of Squamous Cell and Basal Cell Skin Cancer

Treatment for squamous cell and basal cell cancer is usually surgery to remove the tumor.

See the PDQ summary on adult Skin Cancer Treatment for more information.

Chordoma

Chordoma is a very rare type of bone tumor that forms anywhere along the spine from the base of the skull to the tailbone. In children and teenagers, chordomas develop more often in the base of the skull, making them hard to remove completely with surgery.

Childhood chordoma is linked to the conditiontuberous sclerosis, a geneticdisorder in which tumors that are benign (not cancer) form in the kidneys, brain, eyes, heart, lungs, and skin.

Symptoms

Chordoma may cause any of the following signs and symptoms. Check with your child’s doctor if you see any of the following problems in your child:

  • Headache.
  • Neck or back pain.
  • Double vision.
  • Paralysis of the muscles in the face.
  • Numbness, tingling, or weakness of the arms and legs.
  • A change in bowel or bladder habits.

Other conditions that are not chordoma may cause these same symptoms.

Chordomas may recur (come back), usually in the same place, but sometimes they recur in other areas of bone or in the lungs.

Treatment

Treatment for chordoma in children is usually surgery to remove as much of the tumor as possible, followed by radiation therapy. Proton beam radiation therapy may be used.

Cancer of Unknown Primary Site

Carcinoma of unknown primary is a rare disease in which malignant (cancer) cells are found in the body but the place the cancer began is not known. Cancer can form in any tissue of the body. The primary cancer (the cancer that first formed) can spread to other parts of the body. This process is called metastasis. Cancer cells usually look like the cells in the type of tissue in which the cancer began. For example, breast cancer cells may spread to the lung. Because the cancer began in the breast, the cancer cells in the lung look like breast cancer cells.

Sometimes doctors find where the cancer has spread but cannot find where in the body the cancer first began to grow. This type of cancer is called a cancer of unknown primary or occult primary tumor.

Tests are done to find where the primary cancer began and to get information about where the cancer has spread. When tests are able to find the primary cancer, the cancer is no longer a cancer of unknown primary and treatment is based on the type of primary cancer.

Because the place where the cancer started is not known, many different tests and procedures may be needed to find out what type of cancer it is. If tests show there may be cancer, a biopsy is done. A biopsy is the removal of cells or tissues so they can be viewed under a microscope by a pathologist. The pathologist views the tissue under a microscope to look for cancer cells and to find out the type of cancer. The type of biopsy that is done depends on the part of the body being tested for cancer. One of the following types of biopsies may be used:

  • Excisional biopsy: The removal of an entire lump of tissue.
  • Incisional biopsy: The removal of part of a lump or a sample of tissue.
  • Core biopsy: The removal of tissue using a wide needle.
  • Fine-needle aspiration (FNA) biopsy: The removal tissue or fluid using a thin needle.

When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found, a diagnosis of cancer of unknown primary may be made. The cells in the body have a certain look that depends on the type of tissue they come from. For example, a sample of cancer tissue taken from the breast is expected to be made up of breast cells. However, if the sample of tissue is a different type of cell (not made up of breast cells), it is likely that the cells have spread to the breast from another part of the body.

Adenocarcinomas, melanomas, and embryonal tumors are common tumor types that appear and it is not known where the cancer first formed. Embryonal tumors such as rhabdomyosarcomas and neuroblastomas are most common in children.

Treatment

Treatment depends on what the cancer cells look like under a microscope, the patient's age and symptoms, and where the cancer has spread in the body. Treatment is usually chemotherapy or radiation therapy.

To Learn More About Childhood Cancer

For more childhood cancer information and other general cancer resources, see the following:

About PDQ

PDQ is a comprehensive cancer database available on NCI's Web site.

PDQ is the National Cancer Institute's (NCI's) comprehensive cancer information database. Most of the information contained in PDQ is available online at NCI's Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government's focal point for biomedical research.

PDQ contains cancer information summaries.

The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions provide current and accurate cancer information.

Images in the PDQ summaries are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in the PDQ summaries, along with many other cancer-related images, are available in Visuals Online, a collection of over 2,000 scientific images.

The PDQ cancer information summaries are developed by cancer experts and reviewed regularly.

Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary ("Date Last Modified") indicates the time of the most recent change.

PDQ also contains information on clinical trials.

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." In the United States, about two-thirds of children with cancer are treated in a clinical trial at some point in their illness.

Listings of clinical trials are included in PDQ and are available online at NCI's Web site. Descriptions of the trials are available in health professional and patient versions. For additional help in locating a childhood cancer clinical trial, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The PDQ database contains listings of groups specializing in clinical trials.

The Children's Oncology Group (COG) is the major group that organizes clinical trials for childhood cancers in the United States. Information about contacting COG is available on the NCI Web site or from the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).


This information is provided by the National Cancer Institute.

This information was last updated on March 7, 2013.


General Information About Unusual Cancers of Childhood

Introduction

Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. (Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%.[1] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Childhood cancer is a rare disease with less than 13,000 cases diagnosed before the age of 20 years each year in the United States.[3] The Rare Disease Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons in the United States and thus, by definition, all pediatric cancers would be considered rare. The designation of a pediatric rare tumor is not uniform; for example, the Italian cooperative project on rare pediatric tumors (Tumori Rari in Eta Pediatrica [TREP]) defines a pediatric rare tumor as one with an incidence of less than two per 1 million population per year and is not the subject of specific clinical trials.[4] Yet, this definition excludes common histologic subtypes such as melanoma and thyroid carcinoma, both of which have an incidence rate in excess of five per 1 million per year.[3]

Most diagnoses included in this summary of rare cancers are in the subset of malignancies listed in the International Classification of Childhood Cancer (ICCC) subgroup XI, including thyroid cancer, melanoma and nonmelanoma skin cancers, as well as multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.). These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed for adolescents aged 15 to 19 years (see Figure 1). The majority of cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers within adolescents aged 15 to 19 years. The very low incidence of patients with any individual diagnosis, as well as their age distribution, makes these rare cancers extremely challenging to study.

Age-adjusted and age-specific cancer incidence rates for patients 0-19 years of age (SEER 2005-2009); chart shows leukemia, lymphoma, central nervous system (CNS) tumors, neuroblastoma, retinoblastoma, renal tumors, hepatic tumors, bone tumors, soft tissue tumors, germ cell tumors, carcinomas and melanomas, and other cancer incidence by percent.
Figure 1. Cancer incidence rates for patients aged 0 to 14 years and 15 to 19 years in the Surveillance Epidemiology and End Results (SEER) program from 2005 to 2009. Incidence rates are age-adjusted and age-specific and are shown for leukemia, lymphoma, central nervous system (CNS) tumors, neuroblastoma, retinoblastoma, renal tumors, hepatic tumors, bone tumors, soft tissue tumors, germ cell tumors, carcinomas and melanomas, and other cancers. Retinoblastoma occurs infrequently in adolescents aged 15 to 19 years.

Several initiatives to study rare pediatric cancers have been developed by the Children's Oncology Group (COG) as well as international groups. The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) rare tumor project was founded in Germany in 2006.[6] The TREP project was launched in Italy in 2000,[4] and the Polish Pediatric Rare Tumor Study Group was launched in 2002.[7] Within the COG, efforts have concentrated on increasing accrual to the COG registry and the rare tumor bank, as well as developing single-arm clinical trials and increasing cooperation with adult cooperative group trials. The accomplishments and challenges of this initiative are described in detail.[8]

The tumors discussed in this summary are very diverse; they are arranged in descending anatomic order, from infrequent tumors of the head and neck to rare tumors of the urogenital tract and skin. All of these cancers are rare enough that most pediatric hospitals might see less than a handful of some histologies in several years. The majority of the histologies described here occur more frequently in adults. Information about these tumors may also be found in sources relevant to adults with cancer.

References:

  1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.

  2. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.

  3. Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Also available online. Last accessed January 23, 2013.

  4. Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.

  5. Howlader N, Noone AM, Krapcho M, et al., eds.: Childhood cancer by the ICCC. In: Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda, Md: National Cancer Institute, 2012, Section 29. Also available online. Last accessed December 03, 2012.

  6. Brecht IB, Graf N, Schweinitz D, et al.: Networking for children and adolescents with very rare tumors: foundation of the GPOH Pediatric Rare Tumor Group. Klin Padiatr 221 (3): 181-5, 2009 May-Jun.

  7. Balcerska A, Godziński J, Bień E, et al.: [Rare tumours--are they really rare in the Polish children population?]. Przegl Lek 61 (Suppl 2): 57-61, 2004.

  8. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.

Head and Neck Cancers

Childhood sarcomas often occur in the head and neck area and they are described in other sections. Unusual pediatric head and neck cancers include nasopharyngeal carcinoma, esthesioneuroblastoma, thyroid tumors, oral cancer, salivary gland cancer, laryngeal carcinoma, papillomatosis, and respiratory tract carcinoma involving the NUT gene on chromosome 15.[1] The prognosis, diagnosis, classification, and treatment of these head and neck cancers are discussed below. It must be emphasized that these cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Nasopharyngeal Carcinoma

Incidence

Nasopharyngeal carcinoma arises in the lining of the nasal cavity and pharynx.[2][3] This tumor accounts for about one-third of all cancers of the upper airways. Nasopharyngeal carcinoma is very uncommon in children younger than 10 years but increases in incidence to 0.8 and 1.3 per 1 million per year in children aged 10 to 14 years and in children aged 15 to 19 years, respectively.[4][5] The incidence of nasopharyngeal carcinoma is characterized by racial and geographic variations, with an endemic distribution among well-defined ethnic groups, such as inhabitants of some areas in North Africa and Southeast Asia. In the United States, nasopharyngeal carcinoma is overrepresented in black children when compared with other malignancies.[6]

Risk factor

Nasopharyngeal carcinoma is strongly associated with Epstein-Barr virus (EBV) infection. In addition to the serological evidence of infection, EBV DNA is present as a monoclonal episome in the nasopharyngeal carcinoma cells, and tumor cells can have EBV antigens on their cell surface.[7] The circulating levels of EBV DNA, as well as serologic documentation of EBV infection, may aid in the diagnosis.[8]

Histology

Three histologic subtypes of nasopharyngeal carcinoma are recognized by the World Health Organization (WHO). Type 1 is squamous cell carcinoma; type 2 is nonkeratinizing squamous cell carcinoma; and type 3 is undifferentiated carcinoma. Children with nasopharyngeal carcinoma are more likely to have WHO type 2 or type 3 disease.[5]

Clinical Presentation

Nasopharyngeal carcinoma commonly presents as nosebleeds, nasal congestion and obstruction, or otitis media. Given the rich lymphatic drainage of the nasopharynx, bilateral cervical lymphadenopathies are often the first sign of disease. The tumor spreads locally to adjacent areas of the oropharynx and may invade the skull base, resulting in cranial nerve palsy or difficulty with movements of the jaw (trismus). Distant metastatic sites may include the bones, lungs, and liver.

Diagnostic Evaluation

Diagnostic tests should determine the extent of the primary tumor and whether there are metastases. Visualization of the nasopharynx by an ear-nose-throat specialist using nasal endoscopy, examination by a neurologist, and magnetic resonance imaging of the head and neck can be used to determine the extent of the primary tumor. A diagnosis can be made from a biopsy of the primary tumor or of enlarged lymph nodes of the neck. Nasopharyngeal carcinomas must be distinguished from all other cancers that can present with enlarged lymph nodes and from other types of cancer in the head and neck area. Thus, diseases such as thyroid cancer, rhabdomyosarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, and Burkitt lymphoma must be considered, as should benign conditions such as nasal angiofibroma, which usually presents with epistaxis in adolescent males, and infectious lymphadenitis. Evaluation of the chest and abdomen by computed tomography and bone scan should also be performed to determine whether there is metastatic disease.

Staging

Tumor staging is performed utilizing the tumor-node-metastasis classification system of the American Joint Committee on Cancer (AJCC).[9] The majority (>90%) of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[6][10][11] Metastatic disease at diagnosis is uncommon (stage IVC). A retrospective analysis of data from the Surveillance Epidemiology and End Results (SEER) program reported that patients younger than 20 years had a higher incidence of advanced-stage disease than did older patients, higher risk of developing a second malignancy, and a superior outcome after controlling for stage.[5]

Prognosis

The overall survival of children and adolescents with nasopharyngeal carcinoma has improved over the last four decades; with state-of-the-art multimodal treatment, 5-year survival rates are in excess of 80%.[5][6][11][12] However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities.[6][11]

Treatment

Treatment of nasopharyngeal carcinoma is multimodal:

  1. Combined-modality therapy with chemotherapy and radiation: High-dose radiation therapy alone has had a role in the management of low-stage nasopharyngeal carcinoma, but studies in both children and adults show that combined modality therapy with chemotherapy and radiation is the most effective way to treat nasopharyngeal carcinoma.[6][11][12][13][14][15][16]
    1. Many randomized studies have investigated the role of chemotherapy in the treatment of adult nasopharyngeal carcinoma. In a meta-analysis of ten randomized studies and 2,450 patients, the use of concomitant chemoradiation therapy was associated with a significant survival benefit, including improved locoregional disease control and reduction in distant metastases.[15] Neoadjuvant chemotherapy resulted in a significant reduction in locoregional recurrence only, while postradiation chemotherapy did not offer any benefit.
    2. In children, four studies utilizing preradiation chemotherapy with different combinations of methotrexate, cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without recombinant interferon-beta have reported response rates of more than 90%.[11][12][17][18]
      • Neoadjuvant chemotherapy with cisplatin and 5-FU (with or without leucovorin), followed by chemoradiation with single-agent cisplatin yield 5-year overall survival rates consistently above 80%.[11][12]
      • A preliminary analysis of the NPC-2003-GPOH study, which included a 6-month maintenance therapy phase with interferon-beta, reported a 30-month overall survival estimate of 97.1%.[12]
    3. While nasopharyngeal carcinoma is a very chemosensitive neoplasm, high radiation doses to the nasopharynx and neck (approximately 60 Gy) are required for optimal locoregional control.[6][11][12] The combination of cisplatin-based chemotherapy and high doses of radiation therapy to the nasopharynx and neck are associated with a high probability of hearing loss, hypothyroidism and panhypopituitarism, trismus, xerostomia, dental problems, and chronic sinusitis or otitis.[6][11]
    4. Additional drug combinations that have been used in children with nasopharyngeal carcinoma include bleomycin with epirubicin and cisplatin and cisplatin with methotrexate and bleomycin.[3]
    5. Other approaches to the management of nasopharyngeal carcinoma in children have been evaluated and include the following:
      • Incorporation of high-dose-rate brachytherapy into the chemoradiation therapy approach.[19][20]
      • Following adult data, taxanes have been incorporated into the treatment of childhood nasopharyngeal carcinoma; studies have shown good objective response rates and favorable outcomes with the use of docetaxel in combination with cisplatin.[21][Level of evidence: 3iiiDiv]
  2. Surgery: Surgery has a limited role in the management of nasopharyngeal carcinoma because the disease is usually considered unresectable due to extensive local spread.
  3. EBV-specific cytotoxic T-lymphocytes: The use of EBV-specific cytotoxic T-lymphocytes has shown to be a very promising approach with minimal toxicity and evidence of significant antitumor activity in patients with relapsed or refractory nasopharyngeal carcinoma.[22]

(Refer to the PDQ summary on Nasopharyngeal Cancer Treatment for more information.)

Esthesioneuroblastoma

Esthesioneuroblastoma (olfactory neuroblastoma) is a small round-cell tumor arising from the nasal neuroepithelium that is distinct from primitive neuroectodermal tumors.[23][24][25][26] In children, esthesioneuroblastoma is a very rare malignancy with an estimated incidence of 0.1 per 100,000 children younger than 15 years.[27] Despite its rarity, esthesioneuroblastoma is the most common cancer of the nasal cavity in pediatric patients, accounting for 28% of all cases.[27][28] In a series of 511 patients from the SEER database, there was a slight male predominance, the mean age at presentation was 53 years, and only 8% of cases were younger than 25 years.[29] Most patients were white (81%) and the most common tumor sites were the nasal cavity (72%) and ethmoid sinus (13%).[29]

Most children present in the second decade of life with symptoms that include nasal obstruction, epistaxis, hyposmia, exophthalmos, or a nasopharyngeal mass, which may have local extension into the orbits, sinuses, or frontal lobe. Most patients present with advanced-stage disease (Kadish stages B and C).[27][28]

A meta-analysis of 26 studies with a total of 390 patients, largely adults with esthesioneuroblastoma, indicates that higher histopathologic grade and metastases to the cervical lymph nodes may correlate with adverse prognostic factors.[30]

The mainstay of treatment has been surgery and radiation.[31] Newer techniques such as endoscopic sinus surgery may offer similar short-term outcomes to open craniofacial resection.[29] Other techniques such as stereotactic radiosurgery and proton-beam therapy (charged-particle radiation therapy) may also play a role in the management of this tumor.[32] Nodal metastases are seen in about 5% of patients. Routine neck dissection and nodal exploration are not indicated in the absence of clinical or radiological evidence of disease.[33] Management of cervical lymph node metastases has been addressed in a review article.[33]

Reports indicate the increasing use of neoadjuvant or adjuvant chemotherapy in patients with advanced-stage disease with promising results.[23][24][34][35][36]; [37][Level of evidence: 3iii] Chemotherapy regimens that have been used with efficacy include etoposide with ifosfamide and cisplatin;[38] vincristine, actinomycin D, and cyclophosphamide with and without doxorubicin; ifosfamide/etoposide; cisplatin plus etoposide or doxorubicin; [34] and irinotecan plus docetaxel.[39][Level of evidence: 3iiA]

The use of multimodal therapy optimizes the chances for survival with over 70% of children expected to survive 5 or more years following initial diagnosis.[27][34]

Thyroid Tumors

Incidence

The annual incidence of thyroid cancers is low in children younger than 15 years (2.0 per 1 million people), accounting for approximately 1.5% of all cancers in this age group.[4] Thyroid cancer incidence is higher in children aged 15 to 19 years (17.6 per 1 million people), and it accounts for approximately 8% of cancers arising in this older age group.[4] Most thyroid carcinomas occur in girls.[40]

There is an excessive frequency of thyroid adenoma and carcinoma in patients who previously received radiation to the neck.[41][42] In the decade following the Chernobyl nuclear incident, there was a tenfold increase in the incidence of thyroid cancer compared to the previous and following decades.[43] In this group of patients with exposure to low-dose radiation, tumors commonly show a gain of 7q11.[44] When occurring in patients with the multiple endocrine neoplasia syndromes, thyroid cancer may be associated with the development of other types of malignant tumors. (Refer to the Multiple Endocrine Neoplasia (MEN) Syndromes and Carney Complex section of this summary for more information.)

Histology

Tumors of the thyroid are classified as adenomas or carcinomas.[45][46][47][48][49] Adenomas are benign growths that may cause enlargement of all or part of the gland, which extends to both sides of the neck and can be quite large; some tumors may secrete hormones. Transformation to a malignant carcinoma may occur in some cells, which then may grow and spread to lymph nodes in the neck or to the lungs. Approximately 20% of thyroid nodules in children are malignant.[45][50]

Various histologies account for the general diagnostic category of carcinoma of the thyroid:[42][51]

  • Papillary carcinoma (60%–75%): Papillary carcinoma often has multicentric origin and a very high rate of lymph node metastasis (70%–90%).[51] Papillary carcinoma (often referred to as differentiated thyroid cancer) generally has a benign course, with a 10-year survival rate of more than 95%.[52][53] Overall, long-term outcomes for children and adolescents with papillary thyroid cancer are excellent, with 2% cause-specific mortality at 40 years.[53]
  • Follicular carcinoma (10%–20%): Follicular carcinoma is usually encapsulated and has a higher incidence of bone and lung metastases.[51] It may be sporadic or familial.[54] Follicular carcinoma (often referred to as differentiated thyroid cancer) generally has a benign course, with a 10-year survival rate of more than 95%.[52]
  • Medullary carcinoma (5%–10%): Medullary carcinoma is usually familial.[54]
  • Anaplastic carcinoma (<1%).

Studies have shown subtle differences in the genetic profiling of childhood differentiated thyroid carcinomas compared with adult tumors. A higher prevalence of RET/PTC rearrangements is seen in pediatric papillary carcinoma (45%–65% vs. 3%–34% in adults). Conversely, BRAF V600E mutations, which are seen in more than 50% of adults with papillary thyroid carcinoma, are extremely rare in children.[55]

Table 1. Characteristics of Thyroid Carcinoma in Children and Adolescents Versus Adultsa

Characteristic

Children and Adolescents (%)

Adults (%)

Histologic subtype:

Papillary

67–98

85–90

Follicular

4–23

<10

Medullary

2–8

3

Poorly differentiated

<0.1

2–7

Gene rearrangements:

RET/PTC

38–87

0–35

NTRK 1

5–11

5–13

AKAP9-BRAF

11

1

PAX8-PPARG

Unknown

0–50

Point mutations:

BRAF

0–6

0–43

RAS family

0–16

25–69

GNAS

0

11

TP53

0–23

0–20

Other:

Multicentric

30–50

40–56

Lymph node involvement

30–90

5–55

Extrathyroid extension

24–51

16–46

Vascular invasion

<31

14–37

Distant metastases

10–20

5–10

aAdapted from Yamashita et al.[56]

Clinical presentation

Patients with thyroid cancer usually present with a thyroid mass with or without cervical adenopathy.[57][58][59][60] Younger age is associated with a more aggressive clinical presentation in differentiated thyroid carcinoma. Compared with adults, children have a higher proportion of nodal involvement (40%–90% vs. 20%–50%) and lung metastases (20%–30% vs. 2%).[55] Likewise, when compared to pubertal adolescents, prepubertal children have a more aggressive presentation with a greater degree of extrathyroid extension, lymph node involvement, and lung metastases. However, outcome is similar in the prepubertal and adolescent groups.[61]

Diagnostic evaluation

Initial evaluation of a child or adolescent with a thyroid nodule should include the following:

  • Ultrasound of the thyroid.
  • Serum thyrotropin (TSH) level.
  • Serum thyroglobulin level.

Tests of thyroid function are usually normal, but thyroglobulin can be elevated.

Fine-needle aspiration as an initial diagnostic approach is sensitive and useful. However, in doubtful cases, open biopsy or resection should be considered.[62][63][64][65] Open biopsy or resection may be preferable for young children as well.

Table 2. Thyroid Carcinomas in Children

Histology

Associated Chromosomal Abnormality

Presentation

Diagnosis

Treatment

Papillary thyroid carcinoma (differentiated with generally a benign course)

RET/PTC more common in children. BRAF V600E mutations seen in adults are rare in children.

Thyroid mass. Prepubertal children more often with nodal and lung metastases.

Ultrasound, TSH, thyroglobulin. Fine needle or open biopsy.

Total or near-total thyroidectomy; I-131; thyroid hormone. In metastatic or recurrent disease, tyrosine kinase or EGF receptor inhibitors may be of benefit.

Follicular thyroid carcinoma (differentiated with generally benign course)

Sporadic or familial

Thyroid mass. Prepubertal children more often with nodal and lung metastases.

Ultrasound, TSH, thyroglobulin. Fine needle or open biopsy.

Total or near-total thyroidectomy; I-131; thyroid hormone. In metastatic or recurrent disease, tyrosine kinase or EGF receptor inhibitors may be of benefit.

Medullary thyroid carcinoma

MEN2

Aggressive. 50% with metastases at presentation.

In familial MEN2, RET testing.

Aggressive surgical intervention. Prophylactic thyroidectomy is indicated in familial cases.

EGF = epidermal growth factor; MEN2 = multiple endocrine neoplasia type 2; TSH = thyroid-stimulating hormone.

Treatment of papillary and follicular thyroid carcinoma

The management of differentiated thyroid cancer in children has been reviewed in detail.[50] Also, the American Thyroid Association Taskforce [66] has developed guidelines for management of thyroid nodules and differentiated thyroid cancer in older adolescents and adults; however, it is not yet known how to apply these guidelines to thyroid nodules in children.[45]

Surgery performed by an experienced thyroid surgeon is the treatment required for all thyroid neoplasms.[52][55] For patients with papillary or follicular carcinoma, total or near-total thyroidectomy plus cervical lymph node dissection is the recommended surgical approach.[52][57][67] This aggressive approach is indicated for several reasons:

  • Up to 40% of children with differentiated thyroid carcinoma have multifocal disease and a higher recurrence risk if less than a total thyroidectomy is performed.
  • Many children have disseminated disease and require radioactive iodine therapy.
  • Sensitive assays for serum thyroglobulin are used as a marker for active disease and are most useful after total thyroidectomy.[45][50][52]

However, for patients with a small (<1 cm) unifocal nodule, treatment may involve only a lobectomy.[50][57][68]

The use of radioactive iodine ablation for the treatment of children with differentiated thyroid carcinoma has increased over the years. Despite surgery, most children have a significant radioactive iodine uptake in the thyroid bed,[52] and studies have shown increased local recurrence rates for patients who did not receive radioactive iodine after total thyroidectomy compared with those who did receive radioactive iodine.[69] Thus, it is currently recommended that children receive an ablative dose after initial surgery.[45][50][55] For successful remnant ablation, serum TSH levels must be elevated to allow for maximal radioactive iodine uptake; this can usually be achieved with thyroid hormone withdrawal for 3 to 4 weeks after thyroidectomy.[45] A radioactive iodine (I-131) scan is then performed to search for residual, functionally active neoplasm. If there is no disease outside of the thyroid bed, an ablative dose of I-131 (approximately 30 mCi) is administered for total thyroid destruction. If there is evidence of nodal or disseminated disease, higher doses (100–200 mCi) of I-131 are required.[70][Level of evidence: 3iDiv] In younger children, the I-131 dose may be adjusted for weight (1–1.5 mCi/kg).[45][71][72] After surgery and radioactive iodine therapy, hormone replacement therapy must be given to compensate for the lost thyroid hormone and to suppress TSH production.[73]

Initial treatment (defined as surgery plus one radioactive iodine ablation plus thyroid replacement) is effective in inducing remission for 70% of patients. Extensive disease at diagnosis and larger tumor size predict failure to remit. With additional treatment, 89% of patients achieve remission.[74]

Periodic evaluations are required to determine whether there is metastatic disease involving the lungs. Lifelong follow-up is necessary.[75] T4 and TSH levels should be evaluated periodically to determine whether replacement hormone is appropriately dosed. If thyroglobulin levels rise above postthyroidectomy baseline levels, recurrence of the disease is possible, and physical examination and imaging studies should be repeated.[45] The use of various tyrosine kinase inhibitors or vascular endothelial growth factor receptor inhibitors has shown promising results in patients with metastatic or recurrent thyroid cancer in adults.[76][77][78][79]

Treatment of recurrent papillary and follicular thyroid carcinoma

Patients with differentiated thyroid cancer generally have an excellent survival with relatively few side effects.[75][80][81] Recurrence is common (35%–45%), however, and is seen more often in children younger than 10 years and in those with palpable cervical lymph nodes at diagnosis.[47][82][83] Even patients with a tumor that has spread to the lungs may expect to have no decrease in life span after appropriate treatment.[84] Of note, the sodium-iodide symporter (a membrane-bound glycoprotein cotransporter), essential for uptake of iodide and thyroid hormone synthesis, is expressed in 35% to 45% of thyroid cancers in children and adolescents. Patients with expression of the sodium-iodide symporter have a lower risk of recurrence.[85]

Recurrent papillary thyroid cancer is usually responsive to treatment with radioactive iodine ablation.[86] Tyrosine kinase inhibitors such as sorafenib have shown to induce responses in up to 15% of adult patients with metastatic disease.[76] Responses to sorafenib have also been documented in pediatric cases.[87] Given the high incidence of BRAF mutations in older patients with papillary thyroid carcinoma, the use of selective RAF/MEK inhibitors is being investigated.[76][88][89]

Treatment of medullary thyroid carcinoma

Medullary thyroid carcinomas are commonly associated with the MEN2 syndrome (refer to the Multiple Endocrine Neoplasia (MEN) Syndromes and Carney Complex section of this summary for more information). They present with a more aggressive clinical course; 50% of the cases have hematogenous metastases at diagnosis.[90] Patients with medullary carcinoma of the thyroid have a guarded prognosis, unless they have very small tumors (microcarcinoma, defined as <1.0 cm in diameter), which carry a good prognosis.[91]

Treatment for children with medullary thyroid carcinoma is mainly surgical. A recent review of 430 patients aged 0 to 21 years with medullary thyroid cancer reported older age (16–21 years) at diagnosis, tumor diameter greater than 2 cm, positive margins after total thyroidectomy, and lymph node metastases were associated with a worse prognosis.[92] This suggests that central neck node dissection and dissection of nearby positive nodes should improve the 10-year survival for these patients. Most cases of medullary thyroid carcinoma occur in the context of the MEN 2A and MEN 2B syndromes. In those familial cases, early genetic testing and counseling is indicated, and prophylactic surgery is recommended in children with the RET germline mutation. Strong genotype-phenotype correlations have facilitated the development of guidelines for intervention, including screening and age at which prophylactic thyroidectomy should occur.[90] A natural history study of children and young adults with medullary thyroid cancer is being conducted by the National Cancer Institute (NCT01660984).

A number of tyrosine kinase inhibitors have been evaluated for patients with unresectable medullary thyroid cancer. Vandetanib (an inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling) is FDA-approved for the treatment of symptomatic or progressive medullary thyroid cancer in adult patients with unresectable, locally advanced, or metastatic disease. Approval was based on a randomized, placebo-controlled, phase III trial that showed a marked progression-free survival improvement for patients randomly assigned to receive vandetanib (hazard ratio, 0.35); the trial also showed an objective response rate advantage for patients receiving vandetanib (44% vs. 1% for the placebo arm).[93][94] A phase I trial of vandetanib for children has been completed.[95] Cabozantinib (an inhibitor of the RET and MET kinases and vascular endothelial growth factor receptor) has also shown activity against unresectable medullary thyroid cancer (10 of 35 patients [29%] had a partial response).[96]

(Refer to the Multiple Endocrine Neoplasia (MEN) Syndromes and Carney Complex section of this summary for more information.)

Treatment options under clinical evaluation

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

  • NCI-07-C-0189 (NCT00514046) (Vandetanib to Treat Children and Adolescents With Medullary Thyroid Cancer): This phase I/II trial of children and adolescents (aged 5–18 years) with medullary thyroid cancer whose tumor cannot be surgically removed, has grown back after treatment, or has metastasized (spread beyond the thyroid gland) is evaluating the activity, safety, and tolerability of vandetanib given once daily.

Oral Cancers

Incidence

The vast majority (>90%) of tumors and tumor-like lesions in the oral cavity are benign.[97][98][99][100] Cancer of the oral cavity is extremely rare in children and adolescents. According to the SEER Stat Fact Sheets, only 0.6% of all cases are diagnosed in patients younger than 20 years, and in 2008, the age-adjusted incidence for this population was 0.24 per 100,000.[101][102]

The incidence of cancer of the oral cavity has increased in adolescent and young adult females, and this pattern is consistent with the national increase in orogenital sexual intercourse in younger females and human papilloma virus (HPV) infection.[103] It is currently estimated that the prevalence of oral HPV infection in the United States is 6.9% in people aged 14 to 69 years and that HPV causes about 30,000 oropharyngeal cancers. Furthermore, the incidence rates for HPV-related oropharyngeal cancer from 1999 to 2008 have increased by 4.4% per year in white men and 1.9% in white women.[104][105][106] Current practices to increase HPV immunization rates in both boys and girls may reduce the burden of HPV-related noncervical cancers.[107]

Histology

Benign odontogenic neoplasms include odontoma and ameloblastoma. The most common nonodontogenic neoplasms are fibromas, hemangiomas, and papillomas. Tumor-like lesions include lymphangiomas, granulomas, and eosinophilic granuloma (Langerhans cell histiocytosis; refer to the Oral mucosa subsection in the PDQ summary on Langerhans Cell Histiocytosis Treatment for more information).

Malignant lesions were found in 0.1% to 2% of a series of oral biopsies performed in children [97][98] and 3% to 13% of oral tumor biopsies.[99][100] Malignant tumor types include lymphomas (especially Burkitt) and sarcomas (including rhabdomyosarcoma and fibrosarcoma). Mucoepidermoid carcinomas have rarely been reported in the pediatric and adolescent age group. Most are low grade and have a high cure rate with surgery alone.[108]; [109][Level of evidence: 3iiA]

The most common type of primary oral cancer in adults, squamous cell carcinoma (SCC), is extremely rare in children. Review of the SEER database identified 54 patients younger than 20 years with oral cavity SCC between 1973 and 2006. Pediatric patients with oral cavity SCC were more often female and had better survival than adult patients. When differences in patient, tumor, and treatment-related characteristics are adjusted for, the two groups experienced equivalent survival.[108][Level of evidence: 3iA] Diseases that can be associated with the development of oral SCC include Fanconi anemia, dyskeratosis congenita, connexin mutations, chronic graft-versus-host disease, epidermolysis bullosae, xeroderma pigmentosum, and HPV infection.[110][111][112][113][114][115][116][117]

Treatment

Treatment of benign oral tumors is surgical. Management of malignant tumors is dependent on histology and may include surgery, chemotherapy, and radiation.[118] Langerhans cell histiocytosis may require other treatment besides surgery. (Refer to the PDQ summaries on adult Oropharyngeal Cancer Treatment; Lip and Oral Cavity Cancer Treatment; and Langerhans Cell Histiocytosis Treatment for more information.)

Most reported cases of SCC managed with surgery alone have done well without recurrence.[108][119]

Salivary Gland Tumors

Incidence

Salivary gland tumors are rare and account for 0.5% of all malignancies in children and adolescents.[120] Most salivary gland neoplasms arise in the parotid gland.[121][122][123][124][125] About 15% of these tumors may arise in the submandibular glands or in the minor salivary glands under the tongue and jaw. These tumors are most frequently benign but may be malignant, especially in young children.[126] Overall 5-year survival in the pediatric age group is approximately 95%.[127]

Histology

The most common malignant lesion is mucoepidermoid carcinoma.[120][128][129] Less common malignancies include acinic cell carcinoma, rhabdomyosarcoma, adenocarcinoma, adenoid cystic carcinoma, and undifferentiated carcinoma. These tumors may occur after radiation therapy and chemotherapy are given for treatment of primary leukemia or solid tumors.[130][131] Mucoepidermoid carcinoma is the most common type of treatment-related salivary gland tumor, and with standard therapy, the 5-year survival is about 95%.[132][133]

Treatment

Radical surgical removal is the treatment of choice for salivary gland tumors whenever possible, with additional use of radiation therapy and chemotherapy for high-grade tumors or tumors that have spread from their site of origin.[127][129][134][135]

(Refer to the PDQ summary on adult Salivary Gland Cancer Treatment for more information.)

Sialoblastomas

Sialoblastomas are usually benign tumors presenting in the neonatal period and rarely metastasize.[136] Chemotherapy regimens with carboplatin, epirubicin, vincristine, etoposide, dactinomycin, doxorubicin, and ifosfamide have produced responses in two children with sialoblastoma.[137]; [138][Level of evidence: 3iiiDiv]

Laryngeal Cancer and Papillomatosis

Tumors of the larynx are rare. The most common benign tumor is subglottic hemangioma.[139] Malignant tumors, which are especially rare, may be associated with benign tumors such as polyps and papillomas.[140][141] These tumors may cause hoarseness, difficulty swallowing, and enlargement of the lymph nodes of the neck.

Rhabdomyosarcoma is the most common malignant tumor of the larynx in the pediatric age group and is usually managed with chemotherapy and radiation therapy following biopsy, rather than laryngectomy.[142] SCC of the larynx should be managed in the same manner as in adults with carcinoma at this site, with surgery and radiation.[143] Laser surgery may be the first type of treatment utilized for these lesions.

Papillomatosis of the larynx is a benign overgrowth of tissues lining the larynx and is associated with the HPV, most commonly HPV-6 and HPV-11.[144] The presence of HPV-11 appears to correlate with a more aggressive clinical course than HPV-6.[145] These tumors can cause hoarseness because of their association with wart-like nodules on the vocal cords and may rarely extend into the lung, producing significant morbidity.[146] Malignant degeneration may occur with development of cancer in the larynx and squamous cell lung cancer.

Papillomatosis is not cancerous, and primary treatment is surgical ablation with laser vaporization.[147] Frequent recurrences are common. Lung involvement, though rare, can occur.[146] If a patient requires more than four surgical procedures per year, treatment with interferon may be considered.[148] A pilot study of immunotherapy with HspE7, a recombinant fusion protein that has shown activity in other HPV-related diseases, has suggested a marked increase in the amount of time between surgeries.[149] These results, however, must be confirmed in a larger randomized trial.

(Refer to the PDQ summary on adult Laryngeal Cancer Treatment for more information.)

Midline Tract Carcinoma Involving the NUT Gene (NUT Midline Carcinoma)

NUT midline carcinoma is a very rare and aggressive malignancy genetically defined by rearrangements of the gene NUT. In the majority (75%) of cases, the NUT gene on chromosome 15q14 is fused with BRD4 on chromosome 19p13, creating chimeric genes that encode the BRD-NUT fusion proteins. In the remaining cases, NUT is fused to BRD3 on chromosome 9q34 or an unknown partner gene; these tumors are termed NUT-variant.[150]

The tumors arise in midline epithelial structures, typically mediastinum and upper aerodigestive track, and present as very aggressive undifferentiated carcinomas, with or without squamous differentiation.[151] Although the original description of this neoplasm was made in children and young adults, patients of all ages can be affected.[150] The outcome is very poor, with an average survival of less than 1 year. Preliminary data seem to indicate that NUT-variant tumors may have a more protracted course.[150][151]

Preclinical studies have shown that NUT-BRD4 is associated with globally decreased histone acetylation and transcriptional repression; studies have also shown that this acetylation can be restored with histone deacetylase inhibitors, resulting in squamous differentiation and arrested growth in vitro and growth inhibition in xenograft models. Response to vorinostat has been reported in a case of a child with refractory disease, thus suggesting a potential role for this class of agents in the treatment of this malignancy.[152]

References:

  1. Gil Z, Patel SG, Cantu G, et al.: Outcome of craniofacial surgery in children and adolescents with malignant tumors involving the skull base: an international collaborative study. Head Neck 31 (3): 308-17, 2009.

  2. Vasef MA, Ferlito A, Weiss LM: Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein-Barr virus. Ann Otol Rhinol Laryngol 106 (4): 348-56, 1997.

  3. Ayan I, Kaytan E, Ayan N: Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 4 (1): 13-21, 2003.

  4. Horner MJ, Ries LA, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2006. Bethesda, Md: National Cancer Institute, 2009. Also available online. Last accessed November 20, 2012.

  5. Sultan I, Casanova M, Ferrari A, et al.: Differential features of nasopharyngeal carcinoma in children and adults: a SEER study. Pediatr Blood Cancer 55 (2): 279-84, 2010.

  6. Cheuk DK, Billups CA, Martin MG, et al.: Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 117 (1): 197-206, 2011.

  7. Dawson CW, Port RJ, Young LS: The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol 22 (2): 144-53, 2012.

  8. Lo YM, Chan LY, Lo KW, et al.: Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res 59 (6): 1188-91, 1999.

  9. Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010.

  10. Casanova M, Ferrari A, Gandola L, et al.: Undifferentiated nasopharyngeal carcinoma in children and adolescents: comparison between staging systems. Ann Oncol 12 (8): 1157-62, 2001.

  11. Casanova M, Bisogno G, Gandola L, et al.: A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project. Cancer 118 (10): 2718-25, 2012.

  12. Buehrlen M, Zwaan CM, Granzen B, et al.: Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG. Cancer 118 (19): 4892-900, 2012.

  13. Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16 (4): 1310-7, 1998.

  14. Wolden SL, Steinherz PG, Kraus DH, et al.: Improved long-term survival with combined modality therapy for pediatric nasopharynx cancer. Int J Radiat Oncol Biol Phys 46 (4): 859-64, 2000.

  15. Langendijk JA, Leemans ChR, Buter J, et al.: The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol 22 (22): 4604-12, 2004.

  16. Venkitaraman R, Ramanan SG, Sagar TG: Nasopharyngeal cancer of childhood and adolescence: a single institution experience. Pediatr Hematol Oncol 24 (7): 493-502, 2007 Oct-Nov.

  17. Mertens R, Granzen B, Lassay L, et al.: Treatment of nasopharyngeal carcinoma in children and adolescents: definitive results of a multicenter study (NPC-91-GPOH). Cancer 104 (5): 1083-9, 2005.

  18. Rodriguez-Galindo C, Wofford M, Castleberry RP, et al.: Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma. Cancer 103 (4): 850-7, 2005.

  19. Nakamura RA, Novaes PE, Antoneli CB, et al.: High-dose-rate brachytherapy as part of a multidisciplinary treatment of nasopharyngeal lymphoepithelioma in childhood. Cancer 104 (3): 525-31, 2005.

  20. Louis CU, Paulino AC, Gottschalk S, et al.: A single institution experience with pediatric nasopharyngeal carcinoma: high incidence of toxicity associated with platinum-based chemotherapy plus IMRT. J Pediatr Hematol Oncol 29 (7): 500-5, 2007.

  21. Varan A, Ozyar E, Corapçioğlu F, et al.: Pediatric and young adult nasopharyngeal carcinoma patients treated with preradiation Cisplatin and docetaxel chemotherapy. Int J Radiat Oncol Biol Phys 73 (4): 1116-20, 2009.

  22. Straathof KC, Bollard CM, Popat U, et al.: Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes. Blood 105 (5): 1898-904, 2005.

  23. Kumar M, Fallon RJ, Hill JS, et al.: Esthesioneuroblastoma in children. J Pediatr Hematol Oncol 24 (6): 482-7, 2002 Aug-Sep.

  24. Theilgaard SA, Buchwald C, Ingeholm P, et al.: Esthesioneuroblastoma: a Danish demographic study of 40 patients registered between 1978 and 2000. Acta Otolaryngol 123 (3): 433-9, 2003.

  25. Dias FL, Sa GM, Lima RA, et al.: Patterns of failure and outcome in esthesioneuroblastoma. Arch Otolaryngol Head Neck Surg 129 (11): 1186-92, 2003.

  26. Nakao K, Watanabe K, Fujishiro Y, et al.: Olfactory neuroblastoma: long-term clinical outcome at a single institute between 1979 and 2003. Acta Otolaryngol Suppl (559): 113-7, 2007.

  27. Bisogno G, Soloni P, Conte M, et al.: Esthesioneuroblastoma in pediatric and adolescent age. A report from the TREP project in cooperation with the Italian Neuroblastoma and Soft Tissue Sarcoma Committees. BMC Cancer 12: 117, 2012.

  28. Benoit MM, Bhattacharyya N, Faquin W, et al.: Cancer of the nasal cavity in the pediatric population. Pediatrics 121 (1): e141-5, 2008.

  29. Soler ZM, Smith TL: Endoscopic versus open craniofacial resection of esthesioneuroblastoma: what is the evidence? Laryngoscope 122 (2): 244-5, 2012.

  30. Dulguerov P, Allal AS, Calcaterra TC: Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol 2 (11): 683-90, 2001.

  31. Ozsahin M, Gruber G, Olszyk O, et al.: Outcome and prognostic factors in olfactory neuroblastoma: a rare cancer network study. Int J Radiat Oncol Biol Phys 78 (4): 992-7, 2010.

  32. Unger F, Haselsberger K, Walch C, et al.: Combined endoscopic surgery and radiosurgery as treatment modality for olfactory neuroblastoma (esthesioneuroblastoma). Acta Neurochir (Wien) 147 (6): 595-601; discussion 601-2, 2005.

  33. Zanation AM, Ferlito A, Rinaldo A, et al.: When, how and why to treat the neck in patients with esthesioneuroblastoma: a review. Eur Arch Otorhinolaryngol 267 (11): 1667-71, 2010.

  34. Eich HT, Müller RP, Micke O, et al.: Esthesioneuroblastoma in childhood and adolescence. Better prognosis with multimodal treatment? Strahlenther Onkol 181 (6): 378-84, 2005.

  35. Loy AH, Reibel JF, Read PW, et al.: Esthesioneuroblastoma: continued follow-up of a single institution's experience. Arch Otolaryngol Head Neck Surg 132 (2): 134-8, 2006.

  36. Porter AB, Bernold DM, Giannini C, et al.: Retrospective review of adjuvant chemotherapy for esthesioneuroblastoma. J Neurooncol 90 (2): 201-4, 2008.

  37. Benfari G, Fusconi M, Ciofalo A, et al.: Radiotherapy alone for local tumour control in esthesioneuroblastoma. Acta Otorhinolaryngol Ital 28 (6): 292-7, 2008.

  38. Kim DW, Jo YH, Kim JH, et al.: Neoadjuvant etoposide, ifosfamide, and cisplatin for the treatment of olfactory neuroblastoma. Cancer 101 (10): 2257-60, 2004.

  39. Kiyota N, Tahara M, Fujii S, et al.: Nonplatinum-based chemotherapy with irinotecan plus docetaxel for advanced or metastatic olfactory neuroblastoma: a retrospective analysis of 12 cases. Cancer 112 (4): 885-91, 2008.

  40. Shapiro NL, Bhattacharyya N: Population-based outcomes for pediatric thyroid carcinoma. Laryngoscope 115 (2): 337-40, 2005.

  41. Cotterill SJ, Pearce MS, Parker L: Thyroid cancer in children and young adults in the North of England. Is increasing incidence related to the Chernobyl accident? Eur J Cancer 37 (8): 1020-6, 2001.

  42. Kaplan MM, Garnick MB, Gelber R, et al.: Risk factors for thyroid abnormalities after neck irradiation for childhood cancer. Am J Med 74 (2): 272-80, 1983.

  43. Demidchik YE, Saenko VA, Yamashita S: Childhood thyroid cancer in Belarus, Russia, and Ukraine after Chernobyl and at present. Arq Bras Endocrinol Metabol 51 (5): 748-62, 2007.

  44. Hess J, Thomas G, Braselmann H, et al.: Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation. Proc Natl Acad Sci U S A 108 (23): 9595-600, 2011.

  45. Dinauer C, Francis GL: Thyroid cancer in children. Endocrinol Metab Clin North Am 36 (3): 779-806, vii, 2007.

  46. Vasko V, Bauer AJ, Tuttle RM, et al.: Papillary and follicular thyroid cancers in children. Endocr Dev 10: 140-72, 2007.

  47. Grigsby PW, Gal-or A, Michalski JM, et al.: Childhood and adolescent thyroid carcinoma. Cancer 95 (4): 724-9, 2002.

  48. Skinner MA: Cancer of the thyroid gland in infants and children. Semin Pediatr Surg 10 (3): 119-26, 2001.

  49. Halac I, Zimmerman D: Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am 34 (3): 725-44, x, 2005.

  50. Waguespack SG, Francis G: Initial management and follow-up of differentiated thyroid cancer in children. J Natl Compr Canc Netw 8 (11): 1289-300, 2010.

  51. Feinmesser R, Lubin E, Segal K, et al.: Carcinoma of the thyroid in children--a review. J Pediatr Endocrinol Metab 10 (6): 561-8, 1997 Nov-Dec.

  52. Hung W, Sarlis NJ: Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid 12 (8): 683-702, 2002.

  53. Hay ID, Gonzalez-Losada T, Reinalda MS, et al.: Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg 34 (6): 1192-202, 2010.

  54. Skinner MA: Management of hereditary thyroid cancer in children. Surg Oncol 12 (2): 101-4, 2003.

  55. Rivkees SA, Mazzaferri EL, Verburg FA, et al.: The treatment of differentiated thyroid cancer in children: emphasis on surgical approach and radioactive iodine therapy. Endocr Rev 32 (6): 798-826, 2011.

  56. Yamashita S, Saenko V: Mechanisms of Disease: molecular genetics of childhood thyroid cancers. Nat Clin Pract Endocrinol Metab 3 (5): 422-9, 2007.

  57. Thompson GB, Hay ID: Current strategies for surgical management and adjuvant treatment of childhood papillary thyroid carcinoma. World J Surg 28 (12): 1187-98, 2004.

  58. Harness JK, Sahar DE, et al.: Childhood thyroid carcinoma. In: Clark O, Duh Q-Y, Kebebew E, eds.: Textbook of Endocrine Surgery. 2nd ed. Philadelphia, PA: Elsevier Saunders Company, 2005., pp 93-101.

  59. Rachmiel M, Charron M, Gupta A, et al.: Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma. J Pediatr Endocrinol Metab 19 (12): 1377-93, 2006.

  60. Wada N, Sugino K, Mimura T, et al.: Treatment strategy of papillary thyroid carcinoma in children and adolescents: clinical significance of the initial nodal manifestation. Ann Surg Oncol 16 (12): 3442-9, 2009.

  61. Lazar L, Lebenthal Y, Steinmetz A, et al.: Differentiated thyroid carcinoma in pediatric patients: comparison of presentation and course between pre-pubertal children and adolescents. J Pediatr 154 (5): 708-14, 2009.

  62. Flannery TK, Kirkland JL, Copeland KC, et al.: Papillary thyroid cancer: a pediatric perspective. Pediatrics 98 (3 Pt 1): 464-6, 1996.

  63. Willgerodt H, Keller E, Bennek J, et al.: Diagnostic value of fine-needle aspiration biopsy of thyroid nodules in children and adolescents. J Pediatr Endocrinol Metab 19 (4): 507-15, 2006.

  64. Stevens C, Lee JK, Sadatsafavi M, et al.: Pediatric thyroid fine-needle aspiration cytology: a meta-analysis. J Pediatr Surg 44 (11): 2184-91, 2009.

  65. Bargren AE, Meyer-Rochow GY, Sywak MS, et al.: Diagnostic utility of fine-needle aspiration cytology in pediatric differentiated thyroid cancer. World J Surg 34 (6): 1254-60, 2010.

  66. Cooper DS, Doherty GM, Haugen BR, et al.: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19 (11): 1167-214, 2009.

  67. Raval MV, Bentrem DJ, Stewart AK, et al.: Utilization of total thyroidectomy for differentiated thyroid cancer in children. Ann Surg Oncol 17 (10): 2545-53, 2010.

  68. Newman KD, Black T, Heller G, et al.: Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group. Ann Surg 227 (4): 533-41, 1998.

  69. Chow SM, Law SC, Mendenhall WM, et al.: Differentiated thyroid carcinoma in childhood and adolescence-clinical course and role of radioiodine. Pediatr Blood Cancer 42 (2): 176-83, 2004.

  70. Verburg FA, Biko J, Diessl S, et al.: I-131 activities as high as safely administrable (AHASA) for the treatment of children and adolescents with advanced differentiated thyroid cancer. J Clin Endocrinol Metab 96 (8): E1268-71, 2011.

  71. Luster M, Lassmann M, Freudenberg LS, et al.: Thyroid cancer in childhood: management strategy, including dosimetry and long-term results. Hormones (Athens) 6 (4): 269-78, 2007 Oct-Dec.

  72. Parisi MT, Mankoff D: Differentiated pediatric thyroid cancer: correlates with adult disease, controversies in treatment. Semin Nucl Med 37 (5): 340-56, 2007.

  73. Yeh SD, La Quaglia MP: 131I therapy for pediatric thyroid cancer. Semin Pediatr Surg 6 (3): 128-33, 1997.

  74. Powers PA, Dinauer CA, Tuttle RM, et al.: Tumor size and extent of disease at diagnosis predict the response to initial therapy for papillary thyroid carcinoma in children and adolescents. J Pediatr Endocrinol Metab 16 (5): 693-702, 2003.

  75. Vassilopoulou-Sellin R, Goepfert H, Raney B, et al.: Differentiated thyroid cancer in children and adolescents: clinical outcome and mortality after long-term follow-up. Head Neck 20 (6): 549-55, 1998.

  76. Kloos RT, Ringel MD, Knopp MV, et al.: Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 27 (10): 1675-84, 2009.

  77. Cohen EE, Rosen LS, Vokes EE, et al.: Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26 (29): 4708-13, 2008.

  78. Schlumberger MJ, Elisei R, Bastholt L, et al.: Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol 27 (23): 3794-801, 2009.

  79. Cabanillas ME, Waguespack SG, Bronstein Y, et al.: Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: the M. D. Anderson experience. J Clin Endocrinol Metab 95 (6): 2588-95, 2010.

  80. Wiersinga WM: Thyroid cancer in children and adolescents--consequences in later life. J Pediatr Endocrinol Metab 14 (Suppl 5): 1289-96; discussion 1297-8, 2001.

  81. Jarzab B, Handkiewicz-Junak D, Wloch J: Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review. Endocr Relat Cancer 12 (4): 773-803, 2005.

  82. Alessandri AJ, Goddard KJ, Blair GK, et al.: Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma. Med Pediatr Oncol 35 (1): 41-6, 2000.

  83. Borson-Chazot F, Causeret S, Lifante JC, et al.: Predictive factors for recurrence from a series of 74 children and adolescents with differentiated thyroid cancer. World J Surg 28 (11): 1088-92, 2004.

  84. Biko J, Reiners C, Kreissl MC, et al.: Favourable course of disease after incomplete remission on (131)I therapy in children with pulmonary metastases of papillary thyroid carcinoma: 10years follow-up. Eur J Nucl Med Mol Imaging 38 (4): 651-5, 2011.

  85. Patel A, Jhiang S, Dogra S, et al.: Differentiated thyroid carcinoma that express sodium-iodide symporter have a lower risk of recurrence for children and adolescents. Pediatr Res 52 (5): 737-44, 2002.

  86. Powers PA, Dinauer CA, Tuttle RM, et al.: Treatment of recurrent papillary thyroid carcinoma in children and adolescents. J Pediatr Endocrinol Metab 16 (7): 1033-40, 2003.

  87. Waguespack SG, Sherman SI, Williams MD, et al.: The successful use of sorafenib to treat pediatric papillary thyroid carcinoma. Thyroid 19 (4): 407-12, 2009.

  88. Falchook GS, Long GV, Kurzrock R, et al.: Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 379 (9829): 1893-901, 2012.

  89. Hayes DN, Lucas AS, Tanvetyanon T, et al.: Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res 18 (7): 2056-65, 2012.

  90. Waguespack SG, Rich TA, Perrier ND, et al.: Management of medullary thyroid carcinoma and MEN2 syndromes in childhood. Nat Rev Endocrinol 7 (10): 596-607, 2011.

  91. Krueger JE, Maitra A, Albores-Saavedra J: Inherited medullary microcarcinoma of the thyroid: a study of 11 cases. Am J Surg Pathol 24 (6): 853-8, 2000.

  92. Raval MV, Sturgeon C, Bentrem DJ, et al.: Influence of lymph node metastases on survival in pediatric medullary thyroid cancer. J Pediatr Surg 45 (10): 1947-54, 2010.

  93. Wells SA Jr, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012.

  94. Thornton K, Kim G, Maher VE, et al.: Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res 18 (14): 3722-30, 2012.

  95. Broniscer A, Baker JN, Tagen M, et al.: Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol 28 (31): 4762-8, 2010.

  96. Kurzrock R, Sherman SI, Ball DW, et al.: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 29 (19): 2660-6, 2011.

  97. Das S, Das AK: A review of pediatric oral biopsies from a surgical pathology service in a dental school. Pediatr Dent 15 (3): 208-11, 1993 May-Jun.

  98. Ulmansky M, Lustmann J, Balkin N: Tumors and tumor-like lesions of the oral cavity and related structures in Israeli children. Int J Oral Maxillofac Surg 28 (4): 291-4, 1999.

  99. Tröbs RB, Mader E, Friedrich T, et al.: Oral tumors and tumor-like lesions in infants and children. Pediatr Surg Int 19 (9-10): 639-45, 2003.

  100. Tanaka N, Murata A, Yamaguchi A, et al.: Clinical features and management of oral and maxillofacial tumors in children. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88 (1): 11-5, 1999.

  101. Young JL Jr, Miller RW: Incidence of malignant tumors in U. S. children. J Pediatr 86 (2): 254-8, 1975.

  102. Berstein L, Gurney JG: Carcinomas and other malignant epithelial neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649., Chapter 11, pp 139-148. Also available online. Last accessed November 20, 2012.

  103. Bleyer A: Cancer of the oral cavity and pharynx in young females: increasing incidence, role of human papilloma virus, and lack of survival improvement. Semin Oncol 36 (5): 451-9, 2009.

  104. D'Souza G, Dempsey A: The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med 53 (Suppl 1): S5-S11, 2011.

  105. Gillison ML, Broutian T, Pickard RK, et al.: Prevalence of oral HPV infection in the United States, 2009-2010. JAMA 307 (7): 693-703, 2012.

  106. Simard EP, Ward EM, Siegel R, et al.: Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin : , 2012.

  107. Gillison ML, Chaturvedi AK, Lowy DR: HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 113 (10 Suppl): 3036-46, 2008.

  108. Morris LG, Ganly I: Outcomes of oral cavity squamous cell carcinoma in pediatric patients. Oral Oncol 46 (4): 292-6, 2010.

  109. Perez DE, Pires FR, Alves Fde A, et al.: Juvenile intraoral mucoepidermoid carcinoma. J Oral Maxillofac Surg 66 (2): 308-11, 2008.

  110. Oksüzoğlu B, Yalçin S: Squamous cell carcinoma of the tongue in a patient with Fanconi's anemia: a case report and review of the literature. Ann Hematol 81 (5): 294-8, 2002.

  111. Reinhard H, Peters I, Gottschling S, et al.: Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia. J Pediatr Hematol Oncol 29 (7): 488-91, 2007.

  112. Ragin CC, Modugno F, Gollin SM: The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res 86 (2): 104-14, 2007.

  113. Fine JD, Johnson LB, Weiner M, et al.: Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol 60 (2): 203-11, 2009.

  114. Kraemer KH, Lee MM, Scotto J: Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol 123 (2): 241-50, 1987.

  115. Alter BP: Cancer in Fanconi anemia, 1927-2001. Cancer 97 (2): 425-40, 2003.

  116. Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J, et al.: Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol 156 (5): 1015-9, 2007.

  117. Alter BP, Giri N, Savage SA, et al.: Cancer in dyskeratosis congenita. Blood 113 (26): 6549-57, 2009.

  118. Sturgis EM, Moore BA, Glisson BS, et al.: Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: a case series. Head Neck 27 (9): 748-56, 2005.

  119. Woo VL, Kelsch RD, Su L, et al.: Gingival squamous cell carcinoma in adolescence. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107 (1): 92-9, 2009.

  120. Sultan I, Rodriguez-Galindo C, Al-Sharabati S, et al.: Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 33 (10): 1476-81, 2011.

  121. Ethunandan M, Ethunandan A, Macpherson D, et al.: Parotid neoplasms in children: experience of diagnosis and management in a district general hospital. Int J Oral Maxillofac Surg 32 (4): 373-7, 2003.

  122. da Cruz Perez DE, Pires FR, Alves FA, et al.: Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 68 (7): 895-902, 2004.

  123. Shapiro NL, Bhattacharyya N: Clinical characteristics and survival for major salivary gland malignancies in children. Otolaryngol Head Neck Surg 134 (4): 631-4, 2006.

  124. Ellies M, Schaffranietz F, Arglebe C, et al.: Tumors of the salivary glands in childhood and adolescence. J Oral Maxillofac Surg 64 (7): 1049-58, 2006.

  125. Muenscher A, Diegel T, Jaehne M, et al.: Benign and malignant salivary gland diseases in children A retrospective study of 549 cases from the Salivary Gland Registry, Hamburg. Auris Nasus Larynx 36 (3): 326-31, 2009.

  126. Laikui L, Hongwei L, Hongbing J, et al.: Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases. J Oral Pathol Med 37 (4): 201-5, 2008.

  127. Rutt AL, Hawkshaw MJ, Lurie D, et al.: Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 90 (4): 174-84, 2011.

  128. Rahbar R, Grimmer JF, Vargas SO, et al.: Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience. Arch Otolaryngol Head Neck Surg 132 (4): 375-80, 2006.

  129. Kupferman ME, de la Garza GO, Santillan AA, et al.: Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol 17 (12): 3301-7, 2010.

  130. Kaste SC, Hedlund G, Pratt CB: Malignant parotid tumors in patients previously treated for childhood cancer: clinical and imaging findings in eight cases. AJR Am J Roentgenol 162 (3): 655-9, 1994.

  131. Whatley WS, Thompson JW, Rao B: Salivary gland tumors in survivors of childhood cancer. Otolaryngol Head Neck Surg 134 (3): 385-8, 2006.

  132. Verma J, Teh BS, Paulino AC: Characteristics and outcome of radiation and chemotherapy-related mucoepidermoid carcinoma of the salivary glands. Pediatr Blood Cancer 57 (7): 1137-41, 2011.

  133. Védrine PO, Coffinet L, Temam S, et al.: Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms. Head Neck 28 (9): 827-33, 2006.

  134. Kamal SA, Othman EO: Diagnosis and treatment of parotid tumours. J Laryngol Otol 111 (4): 316-21, 1997.

  135. Ryan JT, El-Naggar AK, Huh W, et al.: Primacy of surgery in the management of mucoepidermoid carcinoma in children. Head Neck 33 (12): 1769-73, 2011.

  136. Williams SB, Ellis GL, Warnock GR: Sialoblastoma: a clinicopathologic and immunohistochemical study of 7 cases. Ann Diagn Pathol 10 (6): 320-6, 2006.

  137. Prigent M, Teissier N, Peuchmaur M, et al.: Sialoblastoma of salivary glands in children: chemotherapy should be discussed as an alternative to mutilating surgery. Int J Pediatr Otorhinolaryngol 74 (8): 942-5, 2010.

  138. Scott JX, Krishnan S, Bourne AJ, et al.: Treatment of metastatic sialoblastoma with chemotherapy and surgery. Pediatr Blood Cancer 50 (1): 134-7, 2008.

  139. Bitar MA, Moukarbel RV, Zalzal GH: Management of congenital subglottic hemangioma: trends and success over the past 17 years. Otolaryngol Head Neck Surg 132 (2): 226-31, 2005.

  140. McGuirt WF Jr, Little JP: Laryngeal cancer in children and adolescents. Otolaryngol Clin North Am 30 (2): 207-14, 1997.

  141. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatr Clin North Am 43 (6): 1385-401, 1996.

  142. Wharam MD Jr, Foulkes MA, Lawrence W Jr, et al.: Soft tissue sarcoma of the head and neck in childhood: nonorbital and nonparameningeal sites. A report of the Intergroup Rhabdomyosarcoma Study (IRS)-I. Cancer 53 (4): 1016-9, 1984.

  143. Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003.

  144. Kashima HK, Mounts P, Shah K: Recurrent respiratory papillomatosis. Obstet Gynecol Clin North Am 23 (3): 699-706, 1996.

  145. Maloney EM, Unger ER, Tucker RA, et al.: Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 132 (7): 711-5, 2006.

  146. Gélinas JF, Manoukian J, Côté A: Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature. Int J Pediatr Otorhinolaryngol 72 (4): 433-52, 2008.

  147. Andrus JG, Shapshay SM: Contemporary management of laryngeal papilloma in adults and children. Otolaryngol Clin North Am 39 (1): 135-58, 2006.

  148. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 112 (2): 197-202, 1995.

  149. Derkay CS, Smith RJ, McClay J, et al.: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial. Ann Otol Rhinol Laryngol 114 (9): 730-7, 2005.

  150. French CA: NUT midline carcinoma. Cancer Genet Cytogenet 203 (1): 16-20, 2010.

  151. French CA, Kutok JL, Faquin WC, et al.: Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22 (20): 4135-9, 2004.

  152. Schwartz BE, Hofer MD, Lemieux ME, et al.: Differentiation of NUT midline carcinoma by epigenomic reprogramming. Cancer Res 71 (7): 2686-96, 2011.

Thoracic Cancers

Thoracic cancers include breast cancer, bronchial adenomas, bronchial carcinoid tumors, pleuropulmonary blastoma, esophageal tumors, thymomas, thymic carcinomas, cardiac tumors, and mesothelioma. The prognosis, diagnosis, classification, and treatment of these thoracic cancers are discussed below. It must be emphasized that these cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.[1]

Breast Cancer

Fibroadenoma

The most frequent breast tumor seen in children is a fibroadenoma.[2][3] These tumors can be observed and many will regress without a need for biopsy. However, rare malignant transformation leading to phyllodes tumors has been reported.[4] Sudden rapid enlargement of a suspected fibroadenoma is an indication for needle biopsy or excision. Phyllodes tumors can be managed by wide local excision without mastectomy.[4]

Malignant breast tumors

Breast cancer has been reported in both males and females younger than 21 years.[5][6][7][8][9][10] A review of the Surveillance, Epidemiology, and End Results (SEER) database shows that 75 cases of malignant breast tumors in females 19 years or younger were identified from 1973 to 2004.[11] Fifteen percent of these patients had in situ disease, 85% had invasive disease, 55% of the tumors were carcinomas, and 45% of the tumors were sarcomas—most of which were phyllodes tumors. Only three patients in the carcinoma group presented with metastatic disease, while 11 patients (27%) had regionally advanced disease. All patients with sarcomas presented with localized disease. Of the carcinoma patients, 85% underwent surgical resection, and 10% received adjuvant radiation therapy. Of the sarcoma patients, 97% had surgical resection, and 9% received radiation. The 5- and 10-year survival rates for patients with sarcomatous tumors were both 90%; for patients with carcinomas, the 5-year survival rate was 63% and the 10-year survival rate was 54%.

Breast cancer is the most frequently diagnosed cancer among adolescent and young adult (AYA) women aged 15 to 39 years, accounting for about 14% of all AYA cancer diagnoses.[12] Breast cancer in this age group has a more aggressive course and worse outcome than in older women. Expression of hormone receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2) on breast cancer in the AYA group is also different than in older women and correlates with a worse prognosis.[13] Treatment in the AYA group is similar to that in older women. However, unique aspects of management must include attention to genetic implications (i.e., familial breast cancer syndromes) and fertility.[14]

There is an increased lifetime risk of breast cancer in female survivors of Hodgkin lymphoma who were treated with radiation to the chest area; however, breast cancer is also seen in patients who were treated for any cancer that was treated with chest irradiation.[9][15][16][17][18] Carcinomas are more frequent than sarcomas. Mammograms with adjunctive breast magnetic resonance imaging (MRI) should start at age 25 years or 10 years postexposure to radiation therapy (whichever came last). (Refer to the PDQ summary on the Late Effects of Treatment for Childhood Cancer for more information about secondary breast cancers.) Breast tumors may also occur as metastatic deposits from leukemia, rhabdomyosarcoma, other sarcomas, or lymphoma (particularly in patients who are infected with the human immunodeficiency virus).

(Refer to the PDQ summary on adult Breast Cancer Treatment for more information.)

Lung Cancer

Primary lung tumors are rare in children and histologically quite diverse.[1] When epithelial cancers of the lung occur, they tend to be of advanced stage with prognosis dependent on both histology and stage.[19] The majority of pulmonary malignant neoplasms in children are due to metastatic disease, with an approximate ratio of primary malignant tumors to metastatic disease of 1:5.[20] While primary pulmonary tumors are rare in children, the majority of these tumors are malignant. In a review of 383 primary pulmonary neoplasms in children, 76% were malignant and 24% were benign.[21] These tumors may respond to the ALK inhibitor crizotinib in the presence of ALK translocations.[22][Level of evidence: 3iiiDiv]

The most common malignant primary tumors of the lung, bronchial tumors and pleuropulmonary blastoma, are discussed below.

Bronchial Tumors

Bronchial tumors are a heterogeneous group of primary endobronchial lesions, and though adenoma implies a benign process, all varieties of bronchial tumors on occasion display a malignant behavior. There are three histologic types:[23][24][25][26][27][28]

  • Carcinoid tumor (most frequent). Carcinoid tumors account for 80% to 85% of all bronchial tumors in children.[23][24][25][26][27]
  • Mucoepidermoid carcinoma.
  • Adenoid cystic carcinoma (least frequent).

Bronchial tumors of all histologic types are associated with an excellent prognosis in children, even in the presence of local invasion.[29][30]

The presenting symptoms of a cough, recurrent pneumonitis, and hemoptysis are usually due to an incomplete bronchial obstruction. Because of difficulties in diagnosis, symptoms are frequently present for months and occasionally children with wheezing have been treated for asthma with delays in diagnosis as long as 4 to 5 years.[31]

Metastatic lesions are reported in approximately 6% of carcinoid tumors and recurrences are reported in 2% of cases. Atypical carcinoid tumors are rare but more aggressive with 50% of patients presenting with metastatic disease at diagnosis.[19][32] There is a single report of a child with a carcinoid tumor and metastatic disease who developed the classic carcinoid syndrome.[33] Octreotide nuclear scans may demonstrate uptake of radioactivity by the tumor or lymph nodes, suggesting metastatic spread.

The management of bronchial tumors is somewhat controversial because bronchial tumors are usually visible endoscopically. Biopsy in these lesions may be hazardous because of hemorrhage, and endoscopic resection is not recommended. Bronchography or computed tomography scan may be helpful to determine the degree of bronchiectasis distal to the obstruction since the degree of pulmonary destruction may influence surgical therapy.[34]

Conservative pulmonary resection, including sleeve segmental resection when feasible, with the removal of the involved lymphatics, is the treatment of choice.[35][36] Adenoid cystic carcinomas (cylindroma) have a tendency to spread submucosally, and late local recurrence or dissemination has been reported. In addition to en bloc resection with hilar lymphadenectomy, a frozen section examination of the bronchial margins should be carried out in children with this lesion. Neither chemotherapy nor radiation therapy is indicated for bronchial tumors, unless evidence of metastasis is documented.

Pleuropulmonary Blastoma

Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in children. Pleuropulmonary blastoma appears to progress through the following stages:

  • Type I: A purely lung cystic neoplasm with subtle malignant changes that typically occurs in the first 2 years of life and has a good prognosis. However, there have been reports of Type I transitioning directly to Type III.[37][38]
  • Type II: A cystic and solid neoplasm. Cerebral metastasis may occur in 11% of patients.[39]
  • Type III: A purely solid neoplasm.[40][41] Cerebral metastasis occurs in up to 50% of patients with Type III tumors.[39]

The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the heart/great vessels, mediastinum, diaphragm, and/or pleura.[42][43] The International Pleuropulmonary Blastoma Registry identified 11 cases of Type II and Type III pleuropulmonary blastoma with tumor extension into the thoracic great vessels or the heart. Radiographic evaluation of the central circulation should be performed in children with suspected or diagnosed pleuropulmonary blastoma to identify potentially fatal embolic complications.[44]

Approximately one-third of families affected by pleuropulmonary blastoma manifest a number of dysplastic and/or neoplastic conditions comprising the Pleuropulmonary blastoma Family Tumor and Dysplasia Syndrome. Germline mutations in the DICER1 gene are considered the major genetic determinant of the complex.[45][46] A family history of cancer in close relatives has been noted for many young patients affected by this tumor.[47][48] In addition, pleuropulmonary blastoma has been reported in siblings.[49] There has been a reported association between pleuropulmonary blastoma and cystic nephroma, ciliary body medulloepithelioma of the eye, and primary ovarian neoplasms, particularly ovarian sex cord–stromal tumors.[46][50][51][52][53] Importantly, while DICER1 mutations cause a wide range of phenotypes, pleuropulmonary blastoma does not occur in all families with DICER1 mutations; therefore, the term DICER1 syndrome is generally used for these families. Also, most mutation carriers are unaffected, indicating that tumor risk is modest.[46]

Achieving total resection of the tumor at any time during treatment is associated with improved prognosis.[43] The tumors may recur or metastasize, in spite of primary resection.[38][41] The cerebral parenchyma is the most common metastatic site.[39] Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma, and adjuvant chemotherapy may benefit patients with Type I pleuropulmonary blastoma by reducing the risk of recurrence.[40][54] Chemotherapeutic agents may include vincristine, cyclophosphamide, dactinomycin, doxorubicin, and irinotecan.[55] High-dose chemotherapy with stem cell rescue has been used without success.[56] Radiation, either external beam or P-32, may be used when the tumor cannot be surgically removed. Data from the International Pleuropulmonary Blastoma Registry suggest that adjuvant chemotherapy may reduce the risk of recurrence.[40]

There are no standard treatment options. Current treatment regimens have been informed by consensus conferences. The rare occurrence of these tumors makes recommending treatment difficult. Some general treatment considerations from the Pleuropulmonary Blastoma Registry include:[57]

  • Type I: Surgery alone for select cases; adjuvant chemotherapy may decrease recurrences.[40][57] Evidence suggests a close histologic relationship between a Type 4 cystic adenomatoid malformation and a Type I pleuropulmonary blastoma.[58][59] Complete surgical lobectomy is adequate treatment for these patients, but close observation is recommended.
  • Type II and Type III: Surgery followed by chemotherapy.[55]

An independent group of researchers has established a registry and resource Web site for this rare tumor.[57]

Esophageal Tumors

Esophageal cancer is rare in the pediatric age group, although it is relatively common in older adults.[60][61] Most of these tumors are squamous cell carcinomas, although sarcomas can also arise in the esophagus. The most common benign tumor is leiomyoma.

Symptoms are related to difficulty in swallowing and associated weight loss. Diagnosis is made by histologic examination of biopsy tissue.

Treatment options for esophageal carcinoma include either external-beam intracavitary radiation therapy or chemotherapy agents commonly used to treat carcinomas: platinum derivatives, paclitaxel, and etoposide. Prognosis is generally poor for this cancer, which rarely can be completely resected.

(Refer to the PDQ summary on adult Esophageal Cancer Treatment for more information.)

Thymoma and Thymic Carcinoma

A cancer of the thymus is not considered a thymoma or a thymic carcinoma unless there are neoplastic changes of the epithelial cells that cover the organ.[62][63][64] The term thymoma is customarily used to describe neoplasms that show no overt atypia of the epithelial component. Thymic carcinomas have a higher incidence of capsular invasion and metastases. A thymic epithelial tumor that exhibits clear-cut cytologic atypia and histologic features no longer specific to the thymus is known as thymic carcinoma, also known as type C thymoma. Other tumors that involve the thymus gland include lymphomas, germ cell tumors, carcinomas, carcinoids, and thymomas. Hodgkin lymphoma and non-Hodgkin lymphoma may also involve the thymus and must be differentiated from true thymomas and thymic carcinomas.

Thymoma and thymic carcinomas are very rare in children.[65][66] In the Tumori Rari in Età Pediatrica (TREP) registry, only eight cases were identified over a 9-year period.[67] Various diseases and syndromes are associated with thymoma, including myasthenia gravis, polymyositis, systemic lupus erythematosus, rheumatoid arthritis, thyroiditis, Isaacs syndrome or neuromyotonia (continuous muscle stiffness resulting from persistent muscle activity as a consequence of antibodies against voltage-gated potassium channels), and pure red-cell aplasia.[68][69] Endocrine (hormonal) disorders including hyperthyroidism, Addison disease, and panhypopituitarism can also be associated with a diagnosis of thymoma.[70]

These neoplasms are usually located in the anterior mediastinum and are usually discovered during a routine chest x-ray. Symptoms can include cough, difficulty with swallowing, tightness of the chest, chest pain, and shortness of breath, although nonspecific symptoms may occur. These tumors generally are slow growing but are potentially invasive, with metastases to distant organs or lymph nodes. Staging is related to invasiveness.

Surgery is performed with the goal of a complete resection and is the mainstay of therapy. Radiation therapy is used in patients with invasive thymoma or thymic carcinoma,[70] and chemotherapy is usually reserved for patients with advanced-stage disease who have not responded to radiation therapy or corticosteroids. Agents that have been effective include doxorubicin, cyclophosphamide, etoposide, cisplatin, ifosfamide, and vincristine.[64][67][70][71][72][73] Responses to regimens containing combinations of some of these agents have ranged from 26% to 100% and survival rates have been as high as 50%.[73][74] Response rates are lower for patients with thymic carcinoma, but 2-year survival rates have been reported to be as high as 50%.[75] Sunitinib has yielded clinical responses in four patients with adult thymic carcinoma.[76]

Cardiac Tumors

The most common primary tumors of the heart are benign. In adults, myxoma is the most common tumor; however, these tumors are rare in children.[77] The most common primary heart tumors in children are rhabdomyomas and fibromas.[78][79][80][81] Other benign tumors include myxomas (as noted above), histiocytoid cardiomyopathy tumors, teratomas, hemangiomas, and neurofibromas (i.e., tumors of the nerves that innervate the muscles).[78][80][82][83][84] Myxomas are the most common noncutaneous finding in Carney complex, a rare syndrome characterized by lentigines, cardiac myxomas or other myxoid fibromas, and endocrine abnormalities.[85][86][87] A mutation of the PRKAR1A gene is noted in more than 90% of the cases of Carney complex.[85][88] Primary malignant pediatric heart tumors are rare but may include malignant teratomas, rhabdomyosarcomas, chondrosarcomas, infantile fibrosarcoma, and other sarcomas.[78][89]

The utilization of new cardiac MRI techniques can identify the likely tumor type in the majority of children.[90] However, histologic diagnosis remains the standard for diagnosing cardiac tumors.

The distribution of cardiac tumors in the fetal and neonatal period is different, with more benign teratomas occurring.[82] Multiple cardiac tumors noted in the fetal or neonatal period are highly associated with a diagnosis of tuberous sclerosis.[82] A retrospective review of 94 patients with cardiac tumors detected by prenatal or neonatal echocardiography shows that 68% of the patients exhibited features of tuberous sclerosis.[91] In another study, 79% (15 out of 19) of patients with rhabdomyomas discovered prenatally had tuberous sclerosis, while 96% of those diagnosed postnatally had tuberous sclerosis. Most rhabdomyomas, whether diagnosed prenatally or postnatally, will spontaneously regress.[92]

Secondary tumors of the heart include metastatic spread of rhabdomyosarcoma, melanoma, leukemia, and carcinoma of other sites.[78] Patients may be asymptomatic for long periods. Symptoms may include abnormalities of heart rhythm, enlargement of the heart, fluid in the pericardial sac, and congestive heart failure. Some patients present with sudden death. Successful treatment may require surgery, including transplantation, and chemotherapy appropriate for the type of cancer that is present.[93][94][95]; [77][Level of evidence: 3iiA]

Mesothelioma

Mesothelioma is extremely rare in childhood, with only 2% to 5% of patients presenting during the first two decades of life.[96] Fewer than 300 cases in children have been reported.[97]

This tumor can involve the membranous coverings of the lung, the heart, or the abdominal organs.[98][99][100] These tumors can spread over the surface of organs, without invading far into the underlying tissue, and may spread to regional or distant lymph nodes. Mesothelioma may develop after successful treatment of an earlier cancer, especially after treatment with radiation.[101][102] In adults, these tumors have been associated with exposure to asbestos, which was used as building insulation.[103] The amount of exposure required to develop cancer is unknown, and there is no information about the risk for children exposed to asbestos.

Benign and malignant mesotheliomas cannot be differentiated using histologic criteria. A poor prognosis is associated with lesions that are diffuse and invasive or for those that recur. In general, the course of the disease is slow, and long-term survival is common. Diagnostic thoracoscopy should be considered in suspicious cases to confirm diagnosis.[96]

Radical surgical resection has been attempted with mixed results.[104] Treatment with various chemotherapeutic agents used for carcinomas or sarcomas may result in partial responses.[100][105] Pain is an infrequent symptom; however, radiation therapy may be used for palliation of pain.

Papillary serous carcinoma of the peritoneum is sometimes mistaken for mesothelioma.[106] This tumor generally involves all surfaces lining the abdominal organs, including the surfaces of the ovary. Treatment includes surgical resection whenever possible and use of chemotherapy with agents such as cisplatin, carboplatin, and paclitaxel.

(Refer to the PDQ summary on adult Malignant Mesothelioma Treatment for more information.)

References:

  1. Yu DC, Grabowski MJ, Kozakewich HP, et al.: Primary lung tumors in children and adolescents: a 90-year experience. J Pediatr Surg 45 (6): 1090-5, 2010.

  2. Chung EM, Cube R, Hall GJ, et al.: From the archives of the AFIP: breast masses in children and adolescents: radiologic-pathologic correlation. Radiographics 29 (3): 907-31, 2009 May-Jun.

  3. Jayasinghe Y, Simmons PS: Fibroadenomas in adolescence. Curr Opin Obstet Gynecol 21 (5): 402-6, 2009.

  4. Valdes EK, Boolbol SK, Cohen JM, et al.: Malignant transformation of a breast fibroadenoma to cystosarcoma phyllodes: case report and review of the literature. Am Surg 71 (4): 348-53, 2005.

  5. Serour F, Gilad A, Kopolovic J, et al.: Secretory breast cancer in childhood and adolescence: report of a case and review of the literature. Med Pediatr Oncol 20 (4): 341-4, 1992.

  6. Drukker BH: Breast disease: a primer on diagnosis and management. Int J Fertil Womens Med 42 (5): 278-87, 1997 Sep-Oct.

  7. Rogers DA, Lobe TE, Rao BN, et al.: Breast malignancy in children. J Pediatr Surg 29 (1): 48-51, 1994.

  8. Rivera-Hueto F, Hevia-Vázquez A, Utrilla-Alcolea JC, et al.: Long-term prognosis of teenagers with breast cancer. Int J Surg Pathol 10 (4): 273-9, 2002.

  9. Kaste SC, Hudson MM, Jones DJ, et al.: Breast masses in women treated for childhood cancer: incidence and screening guidelines. Cancer 82 (4): 784-92, 1998.

  10. Costa NM, Rodrigues H, Pereira H, et al.: Secretory breast carcinoma--case report and review of the medical literature. Breast 13 (4): 353-5, 2004.

  11. Gutierrez JC, Housri N, Koniaris LG, et al.: Malignant breast cancer in children: a review of 75 patients. J Surg Res 147 (2): 182-8, 2008.

  12. Keegan TH, DeRouen MC, Press DJ, et al.: Occurrence of breast cancer subtypes in adolescent and young adult women. Breast Cancer Res 14 (2): R55, 2012.

  13. Anders CK, Hsu DS, Broadwater G, et al.: Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26 (20): 3324-30, 2008.

  14. Gabriel CA, Domchek SM: Breast cancer in young women. Breast Cancer Res 12 (5): 212, 2010.

  15. Metayer C, Lynch CF, Clarke EA, et al.: Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence. J Clin Oncol 18 (12): 2435-43, 2000.

  16. Swerdlow AJ, Barber JA, Hudson GV, et al.: Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 18 (3): 498-509, 2000.

  17. van Leeuwen FE, Klokman WJ, Veer MB, et al.: Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood. J Clin Oncol 18 (3): 487-97, 2000.

  18. Henderson TO, Amsterdam A, Bhatia S, et al.: Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152 (7): 444-55; W144-54, 2010.

  19. Lal DR, Clark I, Shalkow J, et al.: Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer 45 (5): 683-6, 2005.

  20. Weldon CB, Shamberger RC: Pediatric pulmonary tumors: primary and metastatic. Semin Pediatr Surg 17 (1): 17-29, 2008.

  21. Hancock BJ, Di Lorenzo M, Youssef S, et al.: Childhood primary pulmonary neoplasms. J Pediatr Surg 28 (9): 1133-6, 1993.

  22. Kim SJ, Kim DW, Kim TM, et al.: Remarkable tumor response to crizotinib in a 14-year-old girl with ALK-positive non-small-cell lung cancer. J Clin Oncol 30 (16): e147-50, 2012.

  23. Vadasz P, Palffy G, Egervary M, et al.: Diagnosis and treatment of bronchial carcinoid tumors: clinical and pathological review of 120 operated patients. Eur J Cardiothorac Surg 7 (1): 8-11, 1993.

  24. Kulke MH, Mayer RJ: Carcinoid tumors. N Engl J Med 340 (11): 858-68, 1999.

  25. Oliaro A, Filosso PL, Donati G, et al.: Atypical bronchial carcinoids. Review of 46 patients. J Cardiovasc Surg (Torino) 41 (1): 131-5, 2000.

  26. Moraes TJ, Langer JC, Forte V, et al.: Pediatric pulmonary carcinoid: a case report and review of the literature. Pediatr Pulmonol 35 (4): 318-22, 2003.

  27. Al-Qahtani AR, Di Lorenzo M, Yazbeck S: Endobronchial tumors in children: Institutional experience and literature review. J Pediatr Surg 38 (5): 733-6, 2003.

  28. Roby BB, Drehner D, Sidman JD: Pediatric tracheal and endobronchial tumors: an institutional experience. Arch Otolaryngol Head Neck Surg 137 (9): 925-9, 2011.

  29. Soga J, Yakuwa Y: Bronchopulmonary carcinoids: An analysis of 1,875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 5 (4): 211-9, 1999.

  30. Fauroux B, Aynie V, Larroquet M, et al.: Carcinoid and mucoepidermoid bronchial tumours in children. Eur J Pediatr 164 (12): 748-52, 2005.

  31. Abuzetun JY, Hazin R, Suker M, et al.: Primary squamous cell carcinoma of the lung with bony metastasis in a 13-year-old boy: case report and review of literature. J Pediatr Hematol Oncol 30 (8): 635-7, 2008.

  32. Rizzardi G, Marulli G, Calabrese F, et al.: Bronchial carcinoid tumours in children: surgical treatment and outcome in a single institution. Eur J Pediatr Surg 19 (4): 228-31, 2009.

  33. Lack EE, Harris GB, Eraklis AJ, et al.: Primary bronchial tumors in childhood. A clinicopathologic study of six cases. Cancer 51 (3): 492-7, 1983.

  34. Ahel V, Zubovic I, Rozmanic V: Bronchial adenoid cystic carcinoma with saccular bronchiectasis as a cause of recurrent pneumonia in children. Pediatr Pulmonol 12 (4): 260-2, 1992.

  35. Gaissert HA, Mathisen DJ, Grillo HC, et al.: Tracheobronchial sleeve resection in children and adolescents. J Pediatr Surg 29 (2): 192-7; discussion 197-8, 1994.

  36. Jalal A, Jeyasingham K: Bronchoplasty for malignant and benign conditions: a retrospective study of 44 cases. Eur J Cardiothorac Surg 17 (4): 370-6, 2000.

  37. Shivastava R, Saha A, Mehera B, et al.: Pleuropulmonary blastoma: transition from type I (cystic) to type III (solid). Singapore Med J 48 (7): e190-2, 2007.

  38. Hill DA, Jarzembowski JA, Priest JR, et al.: Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol 32 (2): 282-95, 2008.

  39. Priest JR, Magnuson J, Williams GM, et al.: Cerebral metastasis and other central nervous system complications of pleuropulmonary blastoma. Pediatr Blood Cancer 49 (3): 266-73, 2007.

  40. Priest JR, Hill DA, Williams GM, et al.: Type I pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 24 (27): 4492-8, 2006.

  41. Miniati DN, Chintagumpala M, Langston C, et al.: Prenatal presentation and outcome of children with pleuropulmonary blastoma. J Pediatr Surg 41 (1): 66-71, 2006.

  42. Indolfi P, Casale F, Carli M, et al.: Pleuropulmonary blastoma: management and prognosis of 11 cases. Cancer 89 (6): 1396-401, 2000.

  43. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007.

  44. Priest JR, Andic D, Arbuckle S, et al.: Great vessel/cardiac extension and tumor embolism in pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. Pediatr Blood Cancer 56 (4): 604-9, 2011.

  45. Hill DA, Ivanovich J, Priest JR, et al.: DICER1 mutations in familial pleuropulmonary blastoma. Science 325 (5943): 965, 2009.

  46. Slade I, Bacchelli C, Davies H, et al.: DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48 (4): 273-8, 2011.

  47. Priest JR, McDermott MB, Bhatia S, et al.: Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 80 (1): 147-61, 1997.

  48. Cross SF, Arbuckle S, Priest JR, et al.: Familial pleuropulmonary blastoma in Australia. Pediatr Blood Cancer 55 (7): 1417-9, 2010.

  49. Gutweiler JR, Labelle J, Suh MY, et al.: A familial case of pleuropulmonary blastoma. Eur J Pediatr Surg 18 (3): 192-4, 2008.

  50. Bouron-Dal Soglio D, Harvey I, Yazbeck S, et al.: An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association. Pediatr Dev Pathol 9 (1): 61-4, 2006 Jan-Feb.

  51. Boman F, Hill DA, Williams GM, et al.: Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry. J Pediatr 149 (6): 850-854, 2006.

  52. Priest JR, Williams GM, Manera R, et al.: Ciliary body medulloepithelioma: four cases associated with pleuropulmonary blastoma--a report from the International Pleuropulmonary Blastoma Registry. Br J Ophthalmol 95 (7): 1001-5, 2011.

  53. Schultz KA, Pacheco MC, Yang J, et al.: Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol 122 (2): 246-50, 2011.

  54. Schmaltz C, Sauter S, Opitz O, et al.: Pleuro-pulmonary blastoma: a case report and review of the literature. Med Pediatr Oncol 25 (6): 479-84, 1995.

  55. Ohta Y, Fujishima M, Hasegawa H, et al.: High therapeutic effectiveness of postoperative irinotecan chemotherapy in a typical case of radiographically and pathologically diagnosed pleuropulmonary blastoma. J Pediatr Hematol Oncol 31 (5): 355-8, 2009.

  56. de Castro CG Jr, de Almeida SG, Gregianin LJ, et al.: High-dose chemotherapy and autologous peripheral blood stem cell rescue in a patient with pleuropulmonary blastoma. J Pediatr Hematol Oncol 25 (1): 78-81, 2003.

  57. Pleuropulmonary Blastoma Registry. St. Paul, Minn: Children's Hospitals and Clinics of St. Paul. Available online. Last accessed November 20, 2012.

  58. MacSweeney F, Papagiannopoulos K, Goldstraw P, et al.: An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol 27 (8): 1139-46, 2003.

  59. Hill DA, Dehner LP: A cautionary note about congenital cystic adenomatoid malformation (CCAM) type 4. Am J Surg Pathol 28 (4): 554-5; author reply 555, 2004.

  60. Gangopadhyay AN, Mohanty PK, Gopal SC, et al.: Adenocarcinoma of the esophagus in an 8-year-old boy. J Pediatr Surg 32 (8): 1259-60, 1997.

  61. Issaivanan M, Redner A, Weinstein T, et al.: Esophageal carcinoma in children and adolescents. J Pediatr Hematol Oncol 34 (1): 63-7, 2012.

  62. Verley JM, Hollmann KH: Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. Cancer 55 (5): 1074-86, 1985.

  63. Hsueh C, Kuo TT, Tsang NM, et al.: Thymic lymphoepitheliomalike carcinoma in children: clinicopathologic features and molecular analysis. J Pediatr Hematol Oncol 28 (12): 785-90, 2006.

  64. Stachowicz-Stencel T, Bien E, Balcerska A, et al.: Thymic carcinoma in children: a report from the Polish Pediatric Rare Tumors Study. Pediatr Blood Cancer 54 (7): 916-20, 2010.

  65. Furman WL, Buckley PJ, Green AA, et al.: Thymoma and myasthenia gravis in a 4-year-old child. Case report and review of the literature. Cancer 56 (11): 2703-6, 1985.

  66. Yaris N, Nas Y, Cobanoglu U, et al.: Thymic carcinoma in children. Pediatr Blood Cancer 47 (2): 224-7, 2006.

  67. Carretto E, Inserra A, Ferrari A, et al.: Epithelial thymic tumours in paediatric age: a report from the TREP project. Orphanet J Rare Dis 6: 28, 2011.

  68. Souadjian JV, Enriquez P, Silverstein MN, et al.: The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med 134 (2): 374-9, 1974.

  69. Coulter D, Gold S: Thymoma in the offspring of a patient with Isaacs syndrome. J Pediatr Hematol Oncol 29 (11): 797-8, 2007.

  70. Cowen D, Richaud P, Mornex F, et al.: Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 34 (1): 9-16, 1995.

  71. Carlson RW, Dorfman RF, Sikic BI: Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Cancer 66 (10): 2092-4, 1990.

  72. Niehues T, Harms D, Jürgens H, et al.: Treatment of pediatric malignant thymoma: long-term remission in a 14-year-old boy with EBV-associated thymic carcinoma by aggressive, combined modality treatment. Med Pediatr Oncol 26 (6): 419-24, 1996.

  73. Casey EM, Kiel PJ, Loehrer PJ Sr: Clinical management of thymoma patients. Hematol Oncol Clin North Am 22 (3): 457-73, 2008.

  74. Giaccone G, Ardizzoni A, Kirkpatrick A, et al.: Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 14 (3): 814-20, 1996.

  75. Loehrer PJ Sr, Jiroutek M, Aisner S, et al.: Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 91 (11): 2010-5, 2001.

  76. Ströbel P, Bargou R, Wolff A, et al.: Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. Br J Cancer 103 (2): 196-200, 2010.

  77. Wu KH, Mo XM, Liu YL: Clinical analysis and surgical results of cardiac myxoma in pediatric patients. J Surg Oncol 99 (1): 48-50, 2009.

  78. Burke A, Virmani R: Pediatric heart tumors. Cardiovasc Pathol 17 (4): 193-8, 2008 Jul-Aug.

  79. Becker AE: Primary heart tumors in the pediatric age group: a review of salient pathologic features relevant for clinicians. Pediatr Cardiol 21 (4): 317-23, 2000 Jul-Aug.

  80. Bruce CJ: Cardiac tumours: diagnosis and management. Heart 97 (2): 151-60, 2011.

  81. Miyake CY, Del Nido PJ, Alexander ME, et al.: Cardiac tumors and associated arrhythmias in pediatric patients, with observations on surgical therapy for ventricular tachycardia. J Am Coll Cardiol 58 (18): 1903-9, 2011.

  82. Isaacs H Jr: Fetal and neonatal cardiac tumors. Pediatr Cardiol 25 (3): 252-73, 2004 May-Jun.

  83. Elderkin RA, Radford DJ: Primary cardiac tumours in a paediatric population. J Paediatr Child Health 38 (2): 173-7, 2002.

  84. Uzun O, Wilson DG, Vujanic GM, et al.: Cardiac tumours in children. Orphanet J Rare Dis 2: 11, 2007.

  85. Boikos SA, Stratakis CA: Carney complex: the first 20 years. Curr Opin Oncol 19 (1): 24-9, 2007.

  86. Carney JA, Young WF: Primary pigmented nodular adrenocortical disease and its associated conditions. Endocrinologist 2: 6-21, 1992.

  87. Stratakis CA, Kirschner LS, Carney JA: Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 86 (9): 4041-6, 2001.

  88. Boikos SA, Stratakis CA: Carney complex: pathology and molecular genetics. Neuroendocrinology 83 (3-4): 189-99, 2006.

  89. Kogon B, Shehata B, Katzenstein H, et al.: Primary congenital infantile fibrosarcoma of the heart: the first confirmed case. Ann Thorac Surg 91 (4): 1276-80, 2011.

  90. Beroukhim RS, Prakash A, Buechel ER, et al.: Characterization of cardiac tumors in children by cardiovascular magnetic resonance imaging: a multicenter experience. J Am Coll Cardiol 58 (10): 1044-54, 2011.

  91. Tworetzky W, McElhinney DB, Margossian R, et al.: Association between cardiac tumors and tuberous sclerosis in the fetus and neonate. Am J Cardiol 92 (4): 487-9, 2003.

  92. Bader RS, Chitayat D, Kelly E, et al.: Fetal rhabdomyoma: prenatal diagnosis, clinical outcome, and incidence of associated tuberous sclerosis complex. J Pediatr 143 (5): 620-4, 2003.

  93. Michler RE, Goldstein DJ: Treatment of cardiac tumors by orthotopic cardiac transplantation. Semin Oncol 24 (5): 534-9, 1997.

  94. Stiller B, Hetzer R, Meyer R, et al.: Primary cardiac tumours: when is surgery necessary? Eur J Cardiothorac Surg 20 (5): 1002-6, 2001.

  95. Günther T, Schreiber C, Noebauer C, et al.: Treatment strategies for pediatric patients with primary cardiac and pericardial tumors: a 30-year review. Pediatr Cardiol 29 (6): 1071-6, 2008.

  96. Nagata S, Nakanishi R: Malignant pleural mesothelioma with cavity formation in a 16-year-old boy. Chest 127 (2): 655-7, 2005.

  97. Rosas-Salazar C, Gunawardena SW, Spahr JE: Malignant pleural mesothelioma in a child with ataxia-telangiectasia. Pediatr Pulmonol 48 (1): 94-7, 2013.

  98. Kelsey A: Mesothelioma in childhood. Pediatr Hematol Oncol 11 (5): 461-2, 1994 Sep-Oct.

  99. Moran CA, Albores-Saavedra J, Suster S: Primary peritoneal mesotheliomas in children: a clinicopathological and immunohistochemical study of eight cases. Histopathology 52 (7): 824-30, 2008.

  100. Cioffredi LA, Jänne PA, Jackman DM: Treatment of peritoneal mesothelioma in pediatric patients. Pediatr Blood Cancer 52 (1): 127-9, 2009.

  101. Hofmann J, Mintzer D, Warhol MJ: Malignant mesothelioma following radiation therapy. Am J Med 97 (4): 379-82, 1994.

  102. Pappo AS, Santana VM, Furman WL, et al.: Post-irradiation malignant mesothelioma. Cancer 79 (1): 192-3, 1997.

  103. Hyers TM, Ohar JM, Crim C: Clinical controversies in asbestos-induced lung diseases. Semin Diagn Pathol 9 (2): 97-101, 1992.

  104. Maziak DE, Gagliardi A, Haynes AE, et al.: Surgical management of malignant pleural mesothelioma: a systematic review and evidence summary. Lung Cancer 48 (2): 157-69, 2005.

  105. Milano E, Pourroy B, Rome A, et al.: Efficacy of a combination of pemetrexed and multiple redo-surgery in an 11-year-old girl with a recurrent multifocal abdominal mesothelioma. Anticancer Drugs 17 (10): 1231-4, 2006.

  106. Wall JE, Mandrell BN, Jenkins JJ 3rd, et al.: Effectiveness of paclitaxel in treating papillary serous carcinoma of the peritoneum in an adolescent. Am J Obstet Gynecol 172 (3): 1049-52, 1995.

Abdominal Cancers

Abdominal cancers include adrenocortical tumors, carcinomas of the stomach, cancer of the pancreas, colorectal carcinomas, carcinoid tumors, and gastrointestinal stromal tumors. The prognosis, diagnosis, classification, and treatment of these abdominal cancers are discussed below. It must be emphasized that these cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series. (Refer to the Renal Cell Carcinoma section in the PDQ summary on Wilms Tumor and Other Childhood Kidney Tumors for more information.)

Carcinoma of the Adrenal Cortex

Incidence

Adrenocortical tumors encompass a spectrum of diseases with often seamless transition from benign (adenoma) to malignant (carcinoma) behavior. Their incidence in children is extremely low (only 0.2% of pediatric cancers).[1] Adrenocortical tumors appear to follow a bimodal distribution, with peaks during the first and fourth decades.[2][3] In children, 25 new cases are expected to occur annually in the United States, for an estimated annual incidence of 0.2 to 0.3 cases per 1 million.[4] Internationally, however, the incidence of adrenocortical tumors appear to vary substantially. The incidence of adrenocortical tumors is particularly high in southern Brazil, where it is approximately 10 to 15 times that observed in the United States.[5][6][7] Childhood adrenocortical tumors typically present during the first 5 years of life (median age, 3–4 years), although there is a second, smaller peak during adolescence.[8][9][10][11] Female gender is consistently predominant in most studies, with a female to male ratio of 1.6 to 1.[12]

Risk factors

Predisposing genetic factors have been implicated in more than 50% of the cases in North America and Europe, and in 95% of the Brazilian cases. Germline TP53 mutations are almost always the predisposing factor. In the non-Brazilian cases, relatives of children with adrenocortical tumors often, though not invariably, have a high incidence of other non-adrenal cancers (Li-Fraumeni syndrome), and germline mutations usually occur within the region coding for the TP53 DNA-binding domain (exons 5 to 8, primarily at highly conserved amino acid residues).[7] In the Brazilian cases, in contrast, the patients’ families do not exhibit a high incidence of cancer, and a single, unique mutation at codon 337 in exon 10 of the TP53 gene is consistently observed.[13] Patients with Beckwith-Wiedemann and hemihypertrophy syndromes have a predisposition to cancer, and as many as 16% of their neoplasms are adrenocortical tumors.[14] However, less than 1% of children with adrenocortical tumors have these syndromes.[15] The distinctive genetic features of pediatric adrenocortical carcinoma have been reviewed.[16]

Histology

Unlike adult adrenocortical tumors, histologic differentiation of adenomas and carcinomas is difficult. However, approximately 10% to 20% of pediatric cases are adenomas.[2][9] The distinction between benign (adenomas) and malignant (carcinomas) tumors can be problematic. In fact, adenoma and carcinoma appear to share multiple genetic aberrations and may represent points on a continuum of cellular transformation.[17] Macroscopically, adenomas tend to be well defined and spherical, and they never invade surrounding structures. They are typically small (usually <200 cm3), and some studies have included size as a criterion for adenoma. By contrast, carcinomas have macroscopic features suggestive of malignancy; they are larger, and they show marked lobulation with extensive areas of hemorrhage and necrosis. Microscopically, carcinomas comprise larger cells with eosinophilic cytoplasm, arranged in alveolar clusters. Several authors have proposed histologic criteria that may help to distinguish the two types of neoplasm.[18][19] However, morphologic criteria may not allow reliable distinction of benign and malignant adrenocortical tumors. Mitotic rate is consistently reported as the most important determinant of aggressive behavior.[20]IGF2 expression also appears to discriminate between carcinomas and adenomas in adults, but not in children.[21][22] Other histopathologic variables are also important, and risk groups may be identified on the basis of a score derived from characteristics, such as venous, capsular, or adjacent organ invasion; tumor necrosis; mitotic rate; and the presence of atypical mitoses.[20]

Clinical presentation

Because pediatric adrenocortical tumors are almost universally functional, they cause endocrine disturbances, and a diagnosis is usually made 5 to 8 months after the first signs and symptoms emerge.[3][9] Virilization (pubic hair, accelerated growth, enlarged penis, clitoromegaly, hirsutism, and acne) due to excess of androgen secretion is seen, alone or in combination with hypercortisolism, in more than 80% of patients. Isolated Cushing syndrome is very rare (5% of patients), and it appears to occur more frequently in older children.[3][9][23] Likewise, nonfunctional tumors are rare (<10%) and tend to occur in older children.[3] Because of the hormone hypersecretion, it is possible to establish an endocrine profile for each particular tumor, which may facilitate the evaluation of response to treatment and monitor for tumor recurrence.

Prognostic factors

In patients with localized disease, age between 0 and 3 years, virilization alone, normal blood pressure, disease stage I, absence of spillage during surgery, and tumor weight no greater than 200 grams were associated with a greater probability of survival. In a Cox regression model analysis, only stage I, virilization alone, and age 0 to 3 years were independently associated with a better outcome.[3] Available data suggest that tumor size is especially important in children; patients with small tumors have an excellent outcome with surgery alone, regardless of histologic features.[24] The overall probability of 5-year survival for children with adrenocortical tumors is reported to be 54% to 74%.[3][9][10][23][24]

Treatment of adrenocortical tumors

At the time of diagnosis, two-thirds of pediatric patients have limited disease (tumors can be completely resected), and the remaining patients have either unresectable or metastatic disease.[3]

Treatment of childhood adrenocortical tumors has evolved from the data derived from the adult studies, and the same guidelines are used; surgery is the most important mode of therapy, and mitotane and cisplatin-based regimens, usually incorporating doxorubicin and etoposide, are recommended for patients with advanced disease.[7][25][26] An aggressive surgical approach of the primary tumor and all metastatic sites is recommended when feasible.[27] Because of tumor friability, rupture of the capsule with resultant tumor spillage is frequent (approximately 20% of initial resections and 43% of resections after recurrence).[3][10] When the diagnosis of adrenocortical tumor is suspected, laparotomy and a curative procedure are recommended rather than fine-needle aspiration, to avoid the risk of tumor rupture.[28] Laparoscopic resection is associated with a high risk of rupture and peritoneal carcinomatosis; thus, open adrenalectomy remains the standard of care.[29]

Little information is available about the use of mitotane in children, although response rates appear to be similar to those seen in adults.[1][25] A retrospective analysis in Italy and Germany identified 177 adult patients with adrenocortical carcinoma. Recurrence-free survival was significantly prolonged by the use of adjuvant mitotane. Benefit was present with 1 to 3 g per day of mitotane and was associated with fewer toxic side effects than doses of 3 to 5 g per day.[30] In a review of 11 children with advanced adrenocortical tumors treated with mitotane and a cisplatin-based chemotherapeutic regimen, measurable responses were seen in seven patients. The mitotane daily dose required for therapeutic levels was around 4 g/m2, and therapeutic levels were achieved after 4 to 6 months of therapy.[25]

The use of radiation therapy in pediatric patients with adrenocortical tumors has not been consistently investigated. Adrenocortical tumors are generally considered to be radioresistant. Furthermore, because many children with adrenocortical tumors carry germline TP53 mutations that predispose to cancer, radiation may increase the incidence of secondary tumors. One study reported three of five long-term survivors of pediatric adrenocortical tumors died of secondary sarcoma that arose within the radiation field.[31]

(Refer to the PDQ summary on adult Adrenocortical Carcinoma Treatment for more information.)

Treatment options under clinical evaluation

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

  • COG-ARAR0332 (Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor): This Children's Oncology Group trial is evaluating the treatment of adrenocortical tumors with surgery and lymph node dissection. Patients with advanced disease will receive multiagent chemotherapy. Patients with stage I or stage II disease will have resection and retroperitoneal lymph node sampling (stage I) or dissection (stage II). Patients with stage III and stage IV disease will receive chemotherapy before resection. The chemotherapy regimen is cisplatin, doxorubicin, etoposide, and oral mitotane.

Carcinoma of the Stomach

Primary gastric tumors in children are rare, and carcinoma of the stomach is even more unusual.[32] In one series, gastric cancer in children younger than 18 years accounted for 0.11% of all gastric cancer cases seen over an 18-year period.[33] The frequency and death rate from stomach cancer has declined worldwide for the past 50 years with the introduction of food preservation practices such as refrigeration.[34]

The tumor must be distinguished from other conditions such as non-Hodgkin lymphoma, malignant carcinoid, leiomyosarcoma, and various benign conditions or tumors of the stomach.[32] Symptoms include vague upper abdominal pain, which can be associated with poor appetite and weight loss. Other symptoms may include nausea, vomiting, change in bowel habits, poor appetite, weakness, and Helicobacter pylori infection.[33][35] Many individuals become anemic but otherwise show no symptoms before the development of metastatic spread. Fiberoptic endoscopy can be used to visualize the tumor or to take a biopsy sample to confirm the diagnosis. Confirmation can also involve an x-ray examination of the upper gastrointestinal tract.

Treatment should include surgical excision with wide margins. For individuals who cannot have a complete surgical resection, radiation therapy may be used along with chemotherapeutic agents such as fluorouracil (5-FU) and irinotecan.[36] Other agents that may be of value are the nitrosoureas with or without cisplatin, etoposide, doxorubicin, or mitomycin C.

Prognosis depends on the extent of the disease at the time of diagnosis and the success of treatment that is appropriate for the clinical situation.[33] Because of the rarity of stomach cancer in the pediatric age group, little information exists regarding the treatment outcomes of children.

(Refer to the PDQ summary on adult Gastric Cancer Treatment for more information.)

Cancer of the Pancreas

Malignant pancreatic tumors are rare in children and adolescents with an incidence of 0.46 cases per 1 million (younger than 30 years).[37][38][39][40] Tumors included in this general category can arise at any site within the pancreas. Cancers of the pancreas may be classified as adenocarcinomas, squamous cell carcinomas, acinic cell carcinomas, liposarcomas, lymphomas, papillary-cystic carcinomas, pancreatoblastomas, malignant insulinomas, glucagonomas, and gastrinomas.[41][42][43][44][45] Several cases of primitive neuroectodermal tumor of the pancreas have been reported in children and young adults.[46] Pancreatoblastoma is reported to be associated with Beckwith-Wiedemann syndrome and Cushing syndrome.[47][48]

Most malignant pancreatic tumors are carcinomas and do not secrete hormones, although some tumors secrete insulin, which can lead to symptoms of weakness, fatigue, hypoglycemia, and coma.[40][41][49] If the tumor interferes with the normal function of the islet cells, patients may have watery diarrhea or abnormalities of salt balance. Both carcinoma of the pancreas and pancreatoblastoma can produce active hormones and can be associated with an abdominal mass, wasting, and pain.[50][51][52] At times, there is obstruction of the head of the pancreas, which is associated with jaundice and gastrointestinal bleeding. Elevation of alpha-fetoprotein has been seen in pancreatoblastoma and acinar cell carcinoma.[44][53][54][55]

Diagnosis of pancreatic tumors is usually established by biopsy, using laparotomy or a minimally invasive surgery (e.g., laparoscopy). A diagnosis can be achieved only after ruling out various benign and cancerous lesions.

Solid pseudopapillary neoplasm of the pancreas is a rare tumor of borderline malignancy that has been reported in children but more commonly occurs in young women.[56][57][58][59] Treatment consists of complete tumor resection (ideally without biopsy). Metastases may occur, but in general, prognosis is good following surgery alone.[45][60][61]; [62][Level of evidence: 3iiA]; [63][Level of evidence: 3iiDi]

Treatment includes various surgical procedures to remove the pancreas and duodenum or removal of part of the pancreas. Complete resection is usually possible and long-term survival is likely, though pancreatoblastoma has a high recurrence rate.[42][53]; [64][Level of evidence: 3iiA] For pediatric patients, the effectiveness of radiation therapy is not known. Chemotherapy may be useful for treatment of localized or metastatic pancreatic carcinoma. The combination of cisplatin and doxorubicin has produced responses in pancreatoblastoma prior to tumor resection.[65][66] Postoperative treatment with cisplatin, doxorubicin, ifosfamide, and etoposide has also produced responses in patients with pancreatoblastoma, although surgery is the mainstay of therapy.[55]; [67][Level of evidence: 3iiiA] Other agents that may be of value include 5-FU, streptozotocin, mitomycin C, carboplatin, gemcitabine, and irinotecan. Response rates and survival rates generally are not good.

(Refer to the PDQ summary on adult Pancreatic Cancer Treatment for more information.)

Colorectal Carcinoma

Incidence

Carcinoma of the large bowel is rare in the pediatric age group. It is seen in one per 1 million persons younger than 20 years in the United States annually, and fewer than 100 cases are diagnosed in children each year in the United States.[68] From 1973 to 2006, the SEER database recorded 174 cases of colorectal cancer in patients younger than 19 years.[69]

Histology

In children, 40% to 60% of tumors arise on the right side of the colon, in contrast to adults who have a prevalence of tumors on the left side.[70] Most reports also suggest that children present with more advanced disease and have a worse outcome.[68][70][71][72][73][74][75][76][77][78][79][80][81][82]

Most tumors in the pediatric age group are poorly differentiated mucin-producing carcinomas and many are of the signet ring cell type,[68][71][75] whereas only about 15% of adult lesions are of this histology. The tumors of younger patients with this histologic variant may be less responsive to chemotherapy. In the adolescent and young adult population, colorectal cancers have a higher incidence of mucinous histology, signet ring cells, microsatellite instability, and mutations in the mismatch repair genes.[83] These tumors arise from the surface of the bowel, usually at the site of an adenomatous polyp. The tumor may extend into the muscle layer surrounding the bowel, or the tumor may perforate the bowel entirely and seed through the spaces around the bowel, including intra-abdominal fat, lymph nodes, liver, ovaries, and the surface of other loops of bowel. A high incidence of metastasis involving the pelvis, ovaries, or both may be present in girls.[84] Colorectal cancers in younger patients have a high incidence of microsatellite instability, and noninherited sporadic tumors in younger patients often lack KRAS mutations and other cytogenetic anomalies seen in older patients.[85]

Genetic syndromes associated with colorectal cancer

About 20% to 30% of adult patients with colorectal cancer have a significant history of familial cancer; of these, about 5% have a well-defined genetic syndrome.[86] The incidence of these syndromes in children has not been well defined. In one review, 16% of patients younger than 40 years had a predisposing factor for the development of colorectal cancer.[87] A later study documented immunohistochemical evidence of mismatch repair deficiency in 31% of colorectal carcinoma samples in patients aged 30 years or younger.[88] The most common genetic syndromes associated with the development of colorectal cancer are shown in Tables 3 and 4.

Table 3. Common Genetic Syndromes Associated With Adenomatous Polyposis

Syndrome

Gene

Gene Function

Hereditary Pattern

Attenuated familial adenomatous polyposis

APC (5’ mutations), AXIN2

Tumor suppressor

Dominant

Familial adenomatous polyposis (Gardner syndrome)

APC

Tumor suppressor

Dominant

Lynch syndrome (hereditary nonpolyposis colorectal cancer)

MSH2, MLH1, MSH6, PMS2, EPCAM

Repair/stability

Dominant

Li-Fraumeni syndrome

TP53 (p53)

Tumor suppressor

Dominant

MYH-associated polyposis

MYH (MUTYH)

Repair/stability

Recessive

Turcot syndrome

APC

Tumor suppressor

Dominant

MLH1

Repair/stability

Dominant

Table 4. Common Genetic Syndromes Associated With Hamartomatous Polyps

Syndrome

Gene

Gene Function

Hereditary Pattern

Cowden syndrome

PTEN

Tumor suppressor

Dominant

Juvenile polyposis syndrome

BMPR1A, SMAD4, ENG

Tumor suppressor

Dominant

Peutz-Jeghers syndrome

STK11

Tumor suppressor

Dominant

Familial polyposis is inherited as a dominant trait, which confers a high degree of risk. Early diagnosis and surgical removal of the colon eliminates the risk of developing carcinomas of the large bowel.[89] Some colorectal carcinomas in young people, however, may be associated with a mutation of the adenomatous polyposis coli (APC) gene, which also is associated with an increased risk of brain tumors and hepatoblastoma.[90] The familial APC syndrome is caused by mutation of a gene on chromosome 5q, which normally suppresses proliferation of cells lining the intestine and later development of polyps.[91] A double-blind, placebo-controlled, randomized phase I trial in children aged 10 to 14 years with familial adenomatous polyposis (FAP) reported that celecoxib at a dose of 16 mg/kg/day is safe for administration for up to 3 months. At this dose, there was a significant decrease in the number of polyps detected on colonoscopy.[92][Level of evidence: 1iiDiv] The role of celecoxib in the management of FAP is not known.

Another tumor suppressor gene on chromosome 18 is associated with progression of polyps to malignant form. Multiple colon carcinomas have been associated with neurofibromatosis type I and several other rare syndromes.[93]

Clinical features

Presenting symptoms are nonspecific and include abdominal pain, weight loss, change in bowel habits, anemia, and bleeding; the median duration of symptoms was about 3 months in one series.[68][71][94] Changes in bowel habits may be associated with tumors of the rectum or lower colon. Tumors of the right colon may cause more subtle symptoms but are often associated with an abdominal mass, weight loss, decreased appetite, and blood in the stool. Any tumor that causes complete obstruction of the large bowel can cause bowel perforation and spread of the tumor cells within the abdominal cavity.

Diagnostic evaluation

Diagnostic studies that may be of value include examination of the stool for blood, studies of liver and kidney function, measurement of carcinoembryonic antigen, and various medical imaging studies, including direct examination using colonoscopy to detect polyps in the large bowel. Other conventional radiographic studies include barium enema or video-capsule endoscopy followed by computed tomography of the chest and bone scans.[81][84][95]

Treatment

Most patients present with evidence of metastatic disease,[71] either as gross tumor or as microscopic deposits in lymph nodes, on the surface of the bowel, or on intra-abdominal organs.[73][75] Complete surgical excision is the most important prognostic factor and should be the primary aim of the surgeon, but in most instances this is impossible; removal of large portions of tumor provides little benefit for the individuals with extensive metastatic disease.[68] Most patients with microscopic metastatic disease generally develop gross metastatic disease, and few individuals with metastatic disease at diagnosis become long-term survivors.

Current therapy includes the use of radiation for rectal and lower colon tumors, in conjunction with chemotherapy using 5-FU with leucovorin.[96] Other agents, including irinotecan, may be of value.[71][Level of evidence: 3iiiA] No significant benefit has been determined for interferon-alpha given in conjunction with 5-FU/leucovorin.[97] A recent review of nine clinical trials comprising 138 patients younger than 40 years demonstrated that the use of combination chemotherapy improved progression-free and overall survival (OS) in these patients. Furthermore, OS and response rates to chemotherapy were similar to those observed in older patients.[98]

(Refer to the PDQ summaries on adult Colon Cancer Treatment and Rectal Cancer Treatment for more information.)

Carcinoid Tumors

These tumors, like bronchial adenomas, may be benign or malignant and can involve the lining of the lung, large or small bowel, or liver.[99][100][101][102][103][104] Most lung lesions are benign; however, some metastasize.[105]

Most carcinoid tumors of the appendix are discovered incidentally at the time of appendectomy, and are small, localized tumors; simple appendectomy is the therapy of choice.[106][107] For larger (>2 cm) tumors or tumors that have spread to local nodes, cecectomy or rarely, right hemicolectomy, is the usual treatment. It has become accepted practice to remove the entire right colon in patients with large carcinoid tumors of the appendix (>2 cm in diameter) or with tumors that have spread to the nodes; however, this practice remains controversial.[108] A MEDLINE search did not find any documented cases of childhood localized appendiceal carcinoid in children younger than 18 years with complete resection who relapsed.[109] Treatment of metastatic carcinoid tumors of the large bowel or stomach becomes more complicated and requires treatment similar to that given for colorectal carcinoma. (Refer to the PDQ summary on adult Gastrointestinal Carcinoid Tumors for therapeutic options in patients with malignant carcinoid tumors.)

The carcinoid syndrome of excessive excretion of somatostatin is characterized by flushing, labile blood pressure, and metastatic spread of the tumor to the liver.[105] Symptoms may be lessened by giving somatostatin analogs, which are available in short-acting and long-acting forms.[110] Occasionally, carcinoids may produce ectopic ACTH and cause Cushing disease.[111]

Gastrointestinal Stromal Tumors (GIST)

Incidence

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract in adults.[112] These tumors are rare in children.[113] Approximately 2% of all GIST occur in children and young adults;[114][115][116] in one series, pediatric GIST accounted for 2.5% of all pediatric nonrhabdomyosarcomatous soft tissue sarcomas.[117] Previously, these tumors were diagnosed as leiomyomas, leiomyosarcomas, and leiomyoblastomas. In pediatric patients, GIST are most commonly located in the stomach and usually occur in adolescent females.[118][119]

Risk factors

Pediatric GIST can arise within the context of tumor predisposition syndromes. Approximately 10% of pediatric cases of GIST are associated with Carney triad or Carney-Stratakis syndrome.[118][120]

  • Carney triad is a syndrome characterized by the occurrence of GIST, lung chondromas, and paragangliomas. In addition, about 20% of patients have adrenal adenomas and 10% have esophageal leiomyomas. GIST are the most common (75%) presenting lesions in these patients. To date, no coding sequence mutations of KIT, PDGFR, or the succinate dehydrogenase (SDH) genes have been found in these patients.[116][120][121]
  • Carney-Stratakis syndrome is characterized by paraganglioma and GIST due to germline mutations of the SDH genes B, C, and D.[122][123]

Familial GIST and neurofibromatosis 1–associated GIST occur in patients older than 40 years.[119][124][125]

Histology and molecular genetics

Histologically, pediatric GIST have a predominance of epithelioid or epithelioid/spindle cell morphology and, unlike adult GIST, their mitotic rate does not appear to accurately predict clinical behavior.[118][126] Most pediatric patients with GIST present during the second decade of life with anemia-related gastrointestinal bleeding. In addition, pediatric GIST have a high propensity for multifocality (23%) and nodal metastases.[118][127] These features may account for the high incidence of local recurrence seen in this patient population.

Pediatric GIST is biologically different from adult GIST. Activating mutations of KIT and PDGFA, which are seen in 90% of adult GIST, are present in only 11% of pediatric GIST.[118][127][128] In addition, unlike adult KIT mutant GIST, pediatric GIST have minimal large-scale chromosomal changes and the expression of insulin-like growth factor 1 receptor (IGF1R) expression is significantly higher and amplified in these patients, suggesting that administration of an IGF1R inhibitor might be therapeutically beneficial in these patients.[128][129]

Recent studies have revealed that about 12% of patients with wild-type GIST and a negative history of paraganglioma have germline mutations in the SDHB or C gene. In addition, using immunohistochemistry, SDHB expression is absent in all pediatric wild-type GIST, implicating cellular respiration defects in the pathogenesis of this disease. Furthermore, these findings support the notion that pediatric patients with wild-type GIST should be offered testing for constitutional mutations for the SDH complex.[130] The routine use of immunohistochemistry has documented lack of SDHB expression in 94% of children younger than 20 years with wild-type GIST and some investigators now favor the term SDH-deficient GIST. This group of patients lack KIT, PDGFR, and BRAF mutations in the primary tumor and lack SDHB immunoreactivity in the tumor. SDH-deficient GIST more commonly affects females, has an indolent clinical course, and occurs in the stomach.[123]

Treatment of GIST

Once the diagnosis of pediatric GIST is established, it is recommended that patients be seen at centers with expertise in the treatment of GIST and that all samples be subjected to mutational analysis for KIT (exons 9, 11, 13, 17), PDGFR (exons 12, 14, 18), and BRAF (V600E).[131][132]

Treatment of GIST varies based on whether a mutation is detected:

  • GIST with a KIT or PDGFR mutation: Pediatric patients who harbor KIT or PDGFR mutations should be managed according to adult guidelines.
  • Wild-type GIST (no mutation): For most pediatric patients with wild-type GIST complete surgical resection of localized disease is recommended as long as it can be accomplished without significant morbidity (i.e., gastrectomy). When feasible, wedge resections are an acceptable surgical option. Since lymph node involvement is relatively common in younger patients, searching for overt or occult nodal involvement should be encouraged. Given the indolent course of the disease in pediatric patients, it is reasonable to withhold extensive and mutilative surgeries and to carefully observe children with locally recurrent or unresectable asymptomatic disease.[113][118]

    A randomized clinical trial in adults demonstrated that administration of adjuvant imatinib mesylate improved event-free survival in adult patients with GIST but this benefit was restricted to those with KIT exon 11 and PDGFR mutations, and thus the use of this agent in the adjuvant setting in pediatric wild-type GIST cannot be recommended.[133] Responses to imatinib and sunitinib in pediatric patients with wild-type GIST are uncommon and consist mainly of disease stabilization.[118][134][135] In a review of ten patients who were treated with imatinib mesylate, one patient experienced a partial response and three patients had stable disease.[118] In another study, the clinical activity of sunitinib in six children with imatinib-resistant GIST was reported as one partial response and five stable disease.[136]

References:

  1. Ribeiro RC, Figueiredo B: Childhood adrenocortical tumours. Eur J Cancer 40 (8): 1117-26, 2004.

  2. Wooten MD, King DK: Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 72 (11): 3145-55, 1993.

  3. Michalkiewicz E, Sandrini R, Figueiredo B, et al.: Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. J Clin Oncol 22 (5): 838-45, 2004.

  4. Berstein L, Gurney JG: Carcinomas and other malignant epithelial neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649., Chapter 11, pp 139-148. Also available online. Last accessed November 20, 2012.

  5. Figueiredo BC, Sandrini R, Zambetti GP, et al.: Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation. J Med Genet 43 (1): 91-6, 2006.

  6. Pianovski MA, Maluf EM, de Carvalho DS, et al.: Mortality rate of adrenocortical tumors in children under 15 years of age in Curitiba, Brazil. Pediatr Blood Cancer 47 (1): 56-60, 2006.

  7. Rodriguez-Galindo C, Figueiredo BC, Zambetti GP, et al.: Biology, clinical characteristics, and management of adrenocortical tumors in children. Pediatr Blood Cancer 45 (3): 265-73, 2005.

  8. Ribeiro RC, Sandrini Neto RS, Schell MJ, et al.: Adrenocortical carcinoma in children: a study of 40 cases. J Clin Oncol 8 (1): 67-74, 1990.

  9. Wieneke JA, Thompson LD, Heffess CS: Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol 27 (7): 867-81, 2003.

  10. Sandrini R, Ribeiro RC, DeLacerda L: Childhood adrenocortical tumors. J Clin Endocrinol Metab 82 (7): 2027-31, 1997.

  11. Bugg MF, Ribeiro RC, Roberson PK, et al.: Correlation of pathologic features with clinical outcome in pediatric adrenocortical neoplasia. A study of a Brazilian population. Brazilian Group for Treatment of Childhood Adrenocortical Tumors. Am J Clin Pathol 101 (5): 625-9, 1994.

  12. Michalkiewicz EL, Sandrini R, Bugg MF, et al.: Clinical characteristics of small functioning adrenocortical tumors in children. Med Pediatr Oncol 28 (3): 175-8, 1997.

  13. Ribeiro RC, Sandrini F, Figueiredo B, et al.: An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci U S A 98 (16): 9330-5, 2001.

  14. Hoyme HE, Seaver LH, Jones KL, et al.: Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 79 (4): 274-8, 1998.

  15. Steenman M, Westerveld A, Mannens M: Genetics of Beckwith-Wiedemann syndrome-associated tumors: common genetic pathways. Genes Chromosomes Cancer 28 (1): 1-13, 2000.

  16. El Wakil A, Doghman M, Latre De Late P, et al.: Genetics and genomics of childhood adrenocortical tumors. Mol Cell Endocrinol 336 (1-2): 169-73, 2011.

  17. Figueiredo BC, Stratakis CA, Sandrini R, et al.: Comparative genomic hybridization analysis of adrenocortical tumors of childhood. J Clin Endocrinol Metab 84 (3): 1116-21, 1999.

  18. Weiss LM: Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 8 (3): 163-9, 1984.

  19. van Slooten H, Schaberg A, Smeenk D, et al.: Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 55 (4): 766-73, 1985.

  20. Stojadinovic A, Ghossein RA, Hoos A, et al.: Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 20 (4): 941-50, 2002.

  21. Almeida MQ, Fragoso MC, Lotfi CF, et al.: Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors. J Clin Endocrinol Metab 93 (9): 3524-31, 2008.

  22. West AN, Neale GA, Pounds S, et al.: Gene expression profiling of childhood adrenocortical tumors. Cancer Res 67 (2): 600-8, 2007.

  23. Hanna AM, Pham TH, Askegard-Giesmann JR, et al.: Outcome of adrenocortical tumors in children. J Pediatr Surg 43 (5): 843-9, 2008.

  24. Klein JD, Turner CG, Gray FL, et al.: Adrenal cortical tumors in children: factors associated with poor outcome. J Pediatr Surg 46 (6): 1201-7, 2011.

  25. Zancanella P, Pianovski MA, Oliveira BH, et al.: Mitotane associated with cisplatin, etoposide, and doxorubicin in advanced childhood adrenocortical carcinoma: mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 28 (8): 513-24, 2006.

  26. Hovi L, Wikström S, Vettenranta K, et al.: Adrenocortical carcinoma in children: a role for etoposide and cisplatin adjuvant therapy? Preliminary report. Med Pediatr Oncol 40 (5): 324-6, 2003.

  27. Stewart JN, Flageole H, Kavan P: A surgical approach to adrenocortical tumors in children: the mainstay of treatment. J Pediatr Surg 39 (5): 759-63, 2004.

  28. Kardar AH: Rupture of adrenal carcinoma after biopsy. J Urol 166 (3): 984, 2001.

  29. Gonzalez RJ, Shapiro S, Sarlis N, et al.: Laparoscopic resection of adrenal cortical carcinoma: a cautionary note. Surgery 138 (6): 1078-85; discussion 1085-6, 2005.

  30. Terzolo M, Angeli A, Fassnacht M, et al.: Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356 (23): 2372-80, 2007.

  31. Driver CP, Birch J, Gough DC, et al.: Adrenal cortical tumors in childhood. Pediatr Hematol Oncol 15 (6): 527-32, 1998 Nov-Dec.

  32. Curtis JL, Burns RC, Wang L, et al.: Primary gastric tumors of infancy and childhood: 54-year experience at a single institution. J Pediatr Surg 43 (8): 1487-93, 2008.

  33. Subbiah V, Varadhachary G, Herzog CE, et al.: Gastric adenocarcinoma in children and adolescents. Pediatr Blood Cancer 57 (3): 524-7, 2011.

  34. American Cancer Society.: Cancer Facts and Figures-2000. Atlanta, Ga: American Cancer Society, 2000.

  35. Rowland M, Drumm B: Helicobacter pylori infection and peptic ulcer disease in children. Curr Opin Pediatr 7 (5): 553-9, 1995.

  36. Ajani JA: Current status of therapy for advanced gastric carcinoma. Oncology (Huntingt) 12 (8 Suppl 6): 99-102, 1998.

  37. Chung EM, Travis MD, Conran RM: Pancreatic tumors in children: radiologic-pathologic correlation. Radiographics 26 (4): 1211-38, 2006 Jul-Aug.

  38. Perez EA, Gutierrez JC, Koniaris LG, et al.: Malignant pancreatic tumors: incidence and outcome in 58 pediatric patients. J Pediatr Surg 44 (1): 197-203, 2009.

  39. Dall'igna P, Cecchetto G, Bisogno G, et al.: Pancreatic tumors in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 54 (5): 675-80, 2010.

  40. Brecht IB, Schneider DT, Klöppel G, et al.: Malignant pancreatic tumors in children and young adults: evaluation of 228 patients identified through the Surveillance, Epidemiology, and End Result (SEER) database. Klin Padiatr 223 (6): 341-5, 2011.

  41. Vossen S, Goretzki PE, Goebel U, et al.: Therapeutic management of rare malignant pancreatic tumors in children. World J Surg 22 (8): 879-82, 1998.

  42. Shorter NA, Glick RD, Klimstra DS, et al.: Malignant pancreatic tumors in childhood and adolescence: The Memorial Sloan-Kettering experience, 1967 to present. J Pediatr Surg 37 (6): 887-92, 2002.

  43. Raffel A, Cupisti K, Krausch M, et al.: Therapeutic strategy of papillary cystic and solid neoplasm (PCSN): a rare non-endocrine tumor of the pancreas in children. Surg Oncol 13 (1): 1-6, 2004.

  44. Ellerkamp V, Warmann SW, Vorwerk P, et al.: Exocrine pancreatic tumors in childhood in Germany. Pediatr Blood Cancer 58 (3): 366-71, 2012.

  45. van den Akker M, Angelini P, Taylor G, et al.: Malignant pancreatic tumors in children: a single-institution series. J Pediatr Surg 47 (4): 681-7, 2012.

  46. Movahedi-Lankarani S, Hruban RH, Westra WH, et al.: Primitive neuroectodermal tumors of the pancreas: a report of seven cases of a rare neoplasm. Am J Surg Pathol 26 (8): 1040-7, 2002.

  47. Muguerza R, Rodriguez A, Formigo E, et al.: Pancreatoblastoma associated with incomplete Beckwith-Wiedemann syndrome: case report and review of the literature. J Pediatr Surg 40 (8): 1341-4, 2005.

  48. Kletter GB, Sweetser DA, Wallace SF, et al.: Adrenocorticotropin-secreting pancreatoblastoma. J Pediatr Endocrinol Metab 20 (5): 639-42, 2007.

  49. Karachaliou F, Vlachopapadopoulou E, Kaldrymidis P, et al.: Malignant insulinoma in childhood. J Pediatr Endocrinol Metab 19 (5): 757-60, 2006.

  50. Schwartz MZ: Unusual peptide-secreting tumors in adolescents and children. Semin Pediatr Surg 6 (3): 141-6, 1997.

  51. Murakami T, Ueki K, Kawakami H, et al.: Pancreatoblastoma: case report and review of treatment in the literature. Med Pediatr Oncol 27 (3): 193-7, 1996.

  52. Imamura A, Nakagawa A, Okuno M, et al.: Pancreatoblastoma in an adolescent girl: case report and review of 26 Japanese cases. Eur J Surg 164 (4): 309-12, 1998.

  53. Dhebri AR, Connor S, Campbell F, et al.: Diagnosis, treatment and outcome of pancreatoblastoma. Pancreatology 4 (5): 441-51; discussion 452-3, 2004.

  54. Bendell JC, Lauwers GY, Willett C, et al.: Pancreatoblastoma in a teenage patient. Clin Adv Hematol Oncol 4 (2): 150-3; discussion 154, 2006.

  55. Bien E, Godzinski J, Dall'igna P, et al.: Pancreatoblastoma: a report from the European cooperative study group for paediatric rare tumours (EXPeRT). Eur J Cancer 47 (15): 2347-52, 2011.

  56. Papavramidis T, Papavramidis S: Solid pseudopapillary tumors of the pancreas: review of 718 patients reported in English literature. J Am Coll Surg 200 (6): 965-72, 2005.

  57. Choi SH, Kim SM, Oh JT, et al.: Solid pseudopapillary tumor of the pancreas: a multicenter study of 23 pediatric cases. J Pediatr Surg 41 (12): 1992-5, 2006.

  58. Nakahara K, Kobayashi G, Fujita N, et al.: Solid-pseudopapillary tumor of the pancreas showing a remarkable reduction in size over the 10-year follow-up period. Intern Med 47 (14): 1335-9, 2008.

  59. Soloni P, Cecchetto G, Dall'igna P, et al.: Management of unresectable solid papillary cystic tumor of the pancreas. A case report and literature review. J Pediatr Surg 45 (5): e1-6, 2010.

  60. Moholkar S, Sebire NJ, Roebuck DJ: Solid-pseudopapillary neoplasm of the pancreas: radiological-pathological correlation. Pediatr Radiol 35 (8): 819-22, 2005.

  61. Peng CH, Chen DF, Zhou GW, et al.: The solid-pseudopapillary tumor of pancreas: the clinical characteristics and surgical treatment. J Surg Res 131 (2): 276-82, 2006.

  62. Park M, Koh KN, Kim BE, et al.: Pancreatic neoplasms in childhood and adolescence. J Pediatr Hematol Oncol 33 (4): 295-300, 2011.

  63. Lee SE, Jang JY, Hwang DW, et al.: Clinical features and outcome of solid pseudopapillary neoplasm: differences between adults and children. Arch Surg 143 (12): 1218-21, 2008.

  64. Yu DC, Kozakewich HP, Perez-Atayde AR, et al.: Childhood pancreatic tumors: a single institution experience. J Pediatr Surg 44 (12): 2267-72, 2009.

  65. Défachelles AS, Martin De Lassalle E, Boutard P, et al.: Pancreatoblastoma in childhood: clinical course and therapeutic management of seven patients. Med Pediatr Oncol 37 (1): 47-52, 2001.

  66. Yonekura T, Kosumi T, Hokim M, et al.: Aggressive surgical and chemotherapeutic treatment of advanced pancreatoblastoma associated with tumor thrombus in portal vein. J Pediatr Surg 41 (3): 596-8, 2006.

  67. Lee YJ, Hah JO: Long-term survival of pancreatoblastoma in children. J Pediatr Hematol Oncol 29 (12): 845-7, 2007.

  68. Saab R, Furman WL: Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 10 (3): 177-92, 2008.

  69. Ferrari A, Casanova M, Massimino M, et al.: Peculiar features and tailored management of adult cancers occurring in pediatric age. Expert Rev Anticancer Ther 10 (11): 1837-51, 2010.

  70. Sharma AK, Gupta CR: Colorectal cancer in children: case report and review of literature. Trop Gastroenterol 22 (1): 36-9, 2001 Jan-Mar.

  71. Hill DA, Furman WL, Billups CA, et al.: Colorectal carcinoma in childhood and adolescence: a clinicopathologic review. J Clin Oncol 25 (36): 5808-14, 2007.

  72. Andersson A, Bergdahl L: Carcinoma of the colon in children: a report of six new cases and a review of the literature. J Pediatr Surg 11 (6): 967-71, 1976.

  73. Chantada GL, Perelli VB, Lombardi MG, et al.: Colorectal carcinoma in children, adolescents, and young adults. J Pediatr Hematol Oncol 27 (1): 39-41, 2005.

  74. Durno C, Aronson M, Bapat B, et al.: Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma. Gut 54 (8): 1146-50, 2005.

  75. Ferrari A, Rognone A, Casanova M, et al.: Colorectal carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy. Pediatr Blood Cancer 50 (3): 588-93, 2008.

  76. Karnak I, Ciftci AO, Senocak ME, et al.: Colorectal carcinoma in children. J Pediatr Surg 34 (10): 1499-504, 1999.

  77. LaQuaglia MP, Heller G, Filippa DA, et al.: Prognostic factors and outcome in patients 21 years and under with colorectal carcinoma. J Pediatr Surg 27 (8): 1085-9; discussion 1089-90, 1992.

  78. MIDDELKAMP JN, HAFFNER H: CARCINOMA OF THE COLON IN CHILDREN. Pediatrics 32: 558-71, 1963.

  79. Radhakrishnan CN, Bruce J: Colorectal cancers in children without any predisposing factors. A report of eight cases and review of the literature. Eur J Pediatr Surg 13 (1): 66-8, 2003.

  80. Taguchi T, Suita S, Hirata Y, et al.: Carcinoma of the colon in children: a case report and review of 41 Japanese cases. J Pediatr Gastroenterol Nutr 12 (3): 394-9, 1991.

  81. Pratt CB, Rao BN, Merchant TE, et al.: Treatment of colorectal carcinoma in adolescents and young adults with surgery, 5-fluorouracil/leucovorin/interferon-alpha 2a and radiation therapy. Med Pediatr Oncol 32 (6): 459-60, 1999.

  82. Sultan I, Rodriguez-Galindo C, El-Taani H, et al.: Distinct features of colorectal cancer in children and adolescents: a population-based study of 159 cases. Cancer 116 (3): 758-65, 2010.

  83. Tricoli JV, Seibel NL, Blair DG, et al.: Unique characteristics of adolescent and young adult acute lymphoblastic leukemia, breast cancer, and colon cancer. J Natl Cancer Inst 103 (8): 628-35, 2011.

  84. Kauffman WM, Jenkins JJ 3rd, Helton K, et al.: Imaging features of ovarian metastases from colonic adenocarcinoma in adolescents. Pediatr Radiol 25 (4): 286-8, 1995.

  85. Bleyer A, Barr R, Hayes-Lattin B, et al.: The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer 8 (4): 288-98, 2008.

  86. Gatalica Z, Torlakovic E: Pathology of the hereditary colorectal carcinoma. Fam Cancer 7 (1): 15-26, 2008.

  87. O'Connell JB, Maggard MA, Livingston EH, et al.: Colorectal cancer in the young. Am J Surg 187 (3): 343-8, 2004.

  88. Goel A, Nagasaka T, Spiegel J, et al.: Low frequency of Lynch syndrome among young patients with non-familial colorectal cancer. Clin Gastroenterol Hepatol 8 (11): 966-71, 2010.

  89. Erdman SH: Pediatric adenomatous polyposis syndromes: an update. Curr Gastroenterol Rep 9 (3): 237-44, 2007.

  90. Turcot J, Despres JP, St. Pierre F: Malignant tumors of the central nervous system associated with familial polyposis of the colon: Report of two cases. Dis Colon Rectum 2: 465-468, 1959.

  91. Vogelstein B, Fearon ER, Hamilton SR, et al.: Genetic alterations during colorectal-tumor development. N Engl J Med 319 (9): 525-32, 1988.

  92. Lynch PM, Ayers GD, Hawk E, et al.: The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol 105 (6): 1437-43, 2010.

  93. Pratt CB, Jane JA: Multiple colorectal carcinomas, polyposis coli, and neurofibromatosis, followed by multiple glioblastoma multiforme. J Natl Cancer Inst 83 (12): 880-1, 1991.

  94. Pappo A, Rodriguez-Galindo C, Furman W: Management of infrequent cancers of childhood. In: Pizzo PA, Poplack DG: Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams and Wilkins, 2010, pp 1098-1123.

  95. Postgate A, Hyer W, Phillips R, et al.: Feasibility of video capsule endoscopy in the management of children with Peutz-Jeghers syndrome: a blinded comparison with barium enterography for the detection of small bowel polyps. J Pediatr Gastroenterol Nutr 49 (4): 417-23, 2009.

  96. Madajewicz S, Petrelli N, Rustum YM, et al.: Phase I-II trial of high-dose calcium leucovorin and 5-fluorouracil in advanced colorectal cancer. Cancer Res 44 (10): 4667-9, 1984.

  97. Wolmark N, Bryant J, Smith R, et al.: Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J Natl Cancer Inst 90 (23): 1810-6, 1998.

  98. Blanke CD, Bot BM, Thomas DM, et al.: Impact of young age on treatment efficacy and safety in advanced colorectal cancer: a pooled analysis of patients from nine first-line phase III chemotherapy trials. J Clin Oncol 29 (20): 2781-6, 2011.

  99. Modlin IM, Sandor A: An analysis of 8305 cases of carcinoid tumors. Cancer 79 (4): 813-29, 1997.

  100. Deans GT, Spence RA: Neoplastic lesions of the appendix. Br J Surg 82 (3): 299-306, 1995.

  101. Doede T, Foss HD, Waldschmidt J: Carcinoid tumors of the appendix in children--epidemiology, clinical aspects and procedure. Eur J Pediatr Surg 10 (6): 372-7, 2000.

  102. Quaedvlieg PF, Visser O, Lamers CB, et al.: Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol 12 (9): 1295-300, 2001.

  103. Broaddus RR, Herzog CE, Hicks MJ: Neuroendocrine tumors (carcinoid and neuroendocrine carcinoma) presenting at extra-appendiceal sites in childhood and adolescence. Arch Pathol Lab Med 127 (9): 1200-3, 2003.

  104. Foley DS, Sunil I, Debski R, et al.: Primary hepatic carcinoid tumor in children. J Pediatr Surg 43 (11): e25-8, 2008.

  105. Tormey WP, FitzGerald RJ: The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid. Postgrad Med J 71 (839): 542-5, 1995.

  106. Pelizzo G, La Riccia A, Bouvier R, et al.: Carcinoid tumors of the appendix in children. Pediatr Surg Int 17 (5-6): 399-402, 2001.

  107. Hatzipantelis E, Panagopoulou P, Sidi-Fragandrea V, et al.: Carcinoid tumors of the appendix in children: experience from a tertiary center in northern Greece. J Pediatr Gastroenterol Nutr 51 (5): 622-5, 2010.

  108. Dall'Igna P, Ferrari A, Luzzatto C, et al.: Carcinoid tumor of the appendix in childhood: the experience of two Italian institutions. J Pediatr Gastroenterol Nutr 40 (2): 216-9, 2005.

  109. Cernaianu G, Tannapfel A, Nounla J, et al.: Appendiceal carcinoid tumor with lymph node metastasis in a child: case report and review of the literature. J Pediatr Surg 45 (11): e1-5, 2010.

  110. Delaunoit T, Rubin J, Neczyporenko F, et al.: Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumors. Mayo Clin Proc 80 (4): 502-6, 2005.

  111. More J, Young J, Reznik Y, et al.: Ectopic ACTH syndrome in children and adolescents. J Clin Endocrinol Metab 96 (5): 1213-22, 2011.

  112. Corless CL, Fletcher JA, Heinrich MC: Biology of gastrointestinal stromal tumors. J Clin Oncol 22 (18): 3813-25, 2004.

  113. Pappo AS, Janeway K, Laquaglia M, et al.: Special considerations in pediatric gastrointestinal tumors. J Surg Oncol 104 (8): 928-32, 2011.

  114. Prakash S, Sarran L, Socci N, et al.: Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol 27 (4): 179-87, 2005.

  115. Miettinen M, Lasota J, Sobin LH: Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol 29 (10): 1373-81, 2005.

  116. Benesch M, Wardelmann E, Ferrari A, et al.: Gastrointestinal stromal tumors (GIST) in children and adolescents: A comprehensive review of the current literature. Pediatr Blood Cancer 53 (7): 1171-9, 2009.

  117. Cypriano MS, Jenkins JJ, Pappo AS, et al.: Pediatric gastrointestinal stromal tumors and leiomyosarcoma. Cancer 101 (1): 39-50, 2004.

  118. Pappo AS, Janeway KA: Pediatric gastrointestinal stromal tumors. Hematol Oncol Clin North Am 23 (1): 15-34, vii, 2009.

  119. Benesch M, Leuschner I, Wardelmann E, et al.: Gastrointestinal stromal tumours in children and young adults: a clinicopathologic series with long-term follow-up from the database of the Cooperative Weichteilsarkom Studiengruppe (CWS). Eur J Cancer 47 (11): 1692-8, 2011.

  120. Otto C, Agaimy A, Braun A, et al.: Multifocal gastric gastrointestinal stromal tumors (GISTs) with lymph node metastases in children and young adults: a comparative clinical and histomorphological study of three cases including a new case of Carney triad. Diagn Pathol 6: 52, 2011.

  121. Carney JA: Carney triad: a syndrome featuring paraganglionic, adrenocortical, and possibly other endocrine tumors. J Clin Endocrinol Metab 94 (10): 3656-62, 2009.

  122. Pasini B, McWhinney SR, Bei T, et al.: Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 16 (1): 79-88, 2008.

  123. Miettinen M, Wang ZF, Sarlomo-Rikala M, et al.: Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol 35 (11): 1712-21, 2011.

  124. Miettinen M, Fetsch JF, Sobin LH, et al.: Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 30 (1): 90-6, 2006.

  125. Li FP, Fletcher JA, Heinrich MC, et al.: Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol 23 (12): 2735-43, 2005.

  126. Miettinen M, Lasota J: Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 130 (10): 1466-78, 2006.

  127. Agaram NP, Laquaglia MP, Ustun B, et al.: Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res 14 (10): 3204-15, 2008.

  128. Janeway KA, Liegl B, Harlow A, et al.: Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res 67 (19): 9084-8, 2007.

  129. Tarn C, Rink L, Merkel E, et al.: Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proceedings of the National Academy of Sciences 105 (24): 8387-92, 2008. Also available online. Last accessed November 20, 2012.

  130. Janeway KA, Kim SY, Lodish M, et al.: Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A 108 (1): 314-8, 2011.

  131. Demetri GD, Benjamin RS, Blanke CD, et al.: NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 5 (Suppl 2): S1-29; quiz S30, 2007.

  132. Janeway KA, Weldon CB: Pediatric gastrointestinal stromal tumor. Semin Pediatr Surg 21 (1): 31-43, 2012.

  133. Dematteo RP, Ballman KV, Antonescu CR, et al.: Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373 (9669): 1097-104, 2009.

  134. Demetri GD, van Oosterom AT, Garrett CR, et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368 (9544): 1329-38, 2006.

  135. Demetri GD, von Mehren M, Blanke CD, et al.: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347 (7): 472-80, 2002.

  136. Janeway KA, Albritton KH, Van Den Abbeele AD, et al.: Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer 52 (7): 767-71, 2009.

Genital/Urinary Tumors

Genital/urinary tumors include carcinoma of the bladder, non-germ cell testicular cancer, non-germ cell ovarian cancer, and carcinoma of the cervix and vagina. The prognosis, diagnosis, classification, and treatment of these genital/urinary tumors are discussed below. It must be emphasized that these tumors are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Carcinoma of the Bladder

Carcinoma of the bladder is extremely rare in children. The most common carcinoma to involve the bladder is papillary urothelial neoplasm of low malignant potential, which generally presents with hematuria.[1][2] In contrast to adults, most pediatric bladder carcinomas are low grade, superficial, and have a good prognosis following transurethral resection.[2][3][4][5][6] Squamous cell and more aggressive carcinomas, however, have been reported and may require a more aggressive surgical approach.[7][8] Bladder cancer in adolescents may develop as a consequence of alkylating-agent chemotherapy given for other childhood tumors or leukemia.[9][10] The association between cyclophosphamide and bladder cancer is the only established relationship between a specific anticancer drug and a solid tumor.[9]

(Refer to the PDQ summary on adult Bladder Cancer Treatment for more information.)

Testicular Cancer (Non-Germ Cell)

Testicular tumors are very rare in young boys and account for an incidence of 1% to 2% of all childhood tumors.[11][12] The most common testicular tumors are benign teratomas followed by malignant non-seminomatous germ cell tumors. (Refer to the PDQ summary on Childhood Extracranial Germ Cell Tumors for more information.) Non-germ cell tumors such as sex cord–stromal tumors are exceedingly rare in prepubertal boys. In a small series, gonadal stromal tumors accounted for 8% to 13% of pediatric testicular tumors.[13]; [14] In newborns and infants, juvenile granulosa cell tumors are the most common stromal cell tumor.[15] In older males, Leydig cell tumors are more common. Stromal cell tumors have been described as benign in young boys.[16][17][18]

There are conflicting data about malignant potential in older males. Most case reports suggest that in the pediatric patients, these tumors can be treated with surgery alone.[16][Level of evidence: 3iii]; [19][Level of evidence: 3iiiA]; [18][Level of evidence: 3iiiDii] However, given the rarity of this tumor, the surgical approach in pediatrics has not been well studied.

Ovarian Cancer (Non-Germ Cell)

The majority of ovarian masses in children are not malignant. The most common neoplasms are germ cell tumors, followed by epithelial tumors, stromal tumors, and then miscellaneous tumors such as Burkitt lymphoma.[20][21][22][23] The majority of ovarian tumors occur in girls aged 15 to 19 years.[24]

Epithelial ovarian neoplasia

Ovarian tumors derived from malignant epithelial elements include: adenocarcinomas, cystadenocarcinomas, endometrioid tumors, clear cell tumors, and undifferentiated carcinomas.[25] In one series of 19 patients younger than 21 years with epithelial ovarian neoplasms, the average age at diagnosis was 19.7 years. Dysmenorrhea and abdominal pain were the most common presenting symptoms; 79% of the patients had stage I disease with a 100% survival rate, and only those who had small cell anaplastic carcinoma died. Girls with ovarian carcinoma (epithelial ovarian neoplasia) fare better than adults with similar histology, probably because girls usually present with low-stage disease.[26]

Treatment is stage-related and may include surgery, radiation, and chemotherapy with cisplatin, carboplatin, etoposide, topotecan, paclitaxel, and other agents.

Sex cord–stromal tumors

Ovarian sex cord–stromal tumors are a heterogeneous group of rare tumors that derive from the gonadal non-germ cell component.[27] Histologic subtypes display some areas of gonadal differentiation and include juvenile granulosa cell tumors, Sertoli-Leydig cell tumors, and sclerosing stromal tumors. Ovarian sex-cord stromal tumors in children and adolescents are commonly associated with the presence of germline DICER1 mutations and may be a manifestation of the familial pleuropulmonary blastoma syndrome.[28]

The most common histologic subtype in girls younger than 18 years is juvenile granulosa cell tumors (median age, 7.6 years; range, birth to 17.5 years).[29][30] Juvenile granulosa cell tumors represent about 5% of ovarian tumors in children and adolescents and are distinct from the granulosa cell tumors seen in adults.[27][31][32][33] Most patients with juvenile granulosa cell tumors present with precocious puberty.[34] Other presenting symptoms include abdominal pain, abdominal mass, and ascites. Juvenile granulosa cell tumors has been reported in children with Ollier disease and Maffucci syndrome.[35]

As many as 90% of children with juvenile granulosa cell tumors will have low-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I) and are usually curable with unilateral salpingo-oophorectomy alone. Patients with advanced disease (FIGO stage II–IV) and those with high mitotic activity tumors have a poorer prognosis. Use of a cisplatin-based chemotherapy regimen has been reported in both the adjuvant and recurrent disease settings with some success.[29][33][36][37][38]

Sertoli-Leydig cell tumors are rare in young girls but may present with virilization [39] or precocious puberty.[40][41] These tumors may also be associated with Peutz-Jeghers syndrome.[42]

Small cell carcinomas of the ovary are exceedingly rare and aggressive tumors and may be associated with hypercalcemia.[43] Successful treatment with aggressive therapy has been reported in a few cases.[43][Level of evidence: 3iiB]; [44][45][Level of evidence: 3iiiA]

Carcinoma of the Cervix and Vagina

Adenocarcinoma of the cervix and vagina is rare in childhood and adolescence with fewer than 50 reported cases.[23][46] Two-thirds of the cases are related to the exposure of diethylstilbestrol in utero. The median age at presentation is 15 years, with a range of 7 months to 18 years, and with most patients presenting with vaginal bleeding.

Adults with adenocarcinoma of the cervix or vagina will present with stage I or stage II disease 90% of the time. In children and adolescents, there is a high incidence of stage III and stage IV disease (24%). This difference may be explained by the practice of routine pelvic examinations in adults and the hesitancy to perform pelvic exams in children.

The treatment of choice is surgical resection,[47] followed by radiation therapy for residual microscopic disease or lymphatic metastases. The role of chemotherapy in management is unknown, although drugs commonly used in the treatment of gynecologic malignancies, carboplatin and paclitaxel, have been used. The 3-year event-free survival (EFS) for all stages is 71% ± 11%; for stage I and stage II, the EFS is 82% ± 11%, and for stage III and stage IV, the EFS is 57% ± 22%.[46]

References:

  1. Alanee S, Shukla AR: Bladder malignancies in children aged <18 years: results from the Surveillance, Epidemiology and End Results database. BJU Int 106 (4): 557-60, 2010.

  2. Paner GP, Zehnder P, Amin AM, et al.: Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. Adv Anat Pathol 18 (1): 79-89, 2011.

  3. Hoenig DM, McRae S, Chen SC, et al.: Transitional cell carcinoma of the bladder in the pediatric patient. J Urol 156 (1): 203-5, 1996.

  4. Serrano-Durbá A, Domínguez-Hinarejos C, Reig-Ruiz C, et al.: Transitional cell carcinoma of the bladder in children. Scand J Urol Nephrol 33 (1): 73-6, 1999.

  5. Fine SW, Humphrey PA, Dehner LP, et al.: Urothelial neoplasms in patients 20 years or younger: a clinicopathological analysis using the world health organization 2004 bladder consensus classification. J Urol 174 (5): 1976-80, 2005.

  6. Lerena J, Krauel L, García-Aparicio L, et al.: Transitional cell carcinoma of the bladder in children and adolescents: six-case series and review of the literature. J Pediatr Urol 6 (5): 481-5, 2010.

  7. Sung JD, Koyle MA: Squamous cell carcinoma of the bladder in a pediatric patient. J Pediatr Surg 35 (12): 1838-9, 2000.

  8. Lezama-del Valle P, Jerkins GR, Rao BN, et al.: Aggressive bladder carcinoma in a child. Pediatr Blood Cancer 43 (3): 285-8, 2004.

  9. Johansson SL, Cohen SM: Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13 (5): 291-8, 1997 Sep-Oct.

  10. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. International Agency for Research on Cancer.: Overall evaluations of carcinogenicity: an updating of IARC monographs, volumes 1 to 42. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Supplement 7. Lyon, France: International Agency for Research on Cancer, 1987.

  11. Hartke DM, Agarwal PK, Palmer JS: Testicular neoplasms in the prepubertal male. J Mens Health Gend 3 (2): 131-8, 2006.

  12. Ahmed HU, Arya M, Muneer A, et al.: Testicular and paratesticular tumours in the prepubertal population. Lancet Oncol 11 (5): 476-83, 2010.

  13. Pohl HG, Shukla AR, Metcalf PD, et al.: Prepubertal testis tumors: actual prevalence rate of histological types. J Urol 172 (6 Pt 1): 2370-2, 2004.

  14. Schwentner C, Oswald J, Rogatsch H, et al.: Stromal testis tumors in infants. a report of two cases. Urology 62 (6): 1121, 2003.

  15. Carmignani L, Colombo R, Gadda F, et al.: Conservative surgical therapy for leydig cell tumor. J Urol 178 (2): 507-11; discussion 511, 2007.

  16. Agarwal PK, Palmer JS: Testicular and paratesticular neoplasms in prepubertal males. J Urol 176 (3): 875-81, 2006.

  17. Dudani R, Giordano L, Sultania P, et al.: Juvenile granulosa cell tumor of testis: case report and review of literature. Am J Perinatol 25 (4): 229-31, 2008.

  18. Cecchetto G, Alaggio R, Bisogno G, et al.: Sex cord-stromal tumors of the testis in children. A clinicopathologic report from the Italian TREP project. J Pediatr Surg 45 (9): 1868-73, 2010.

  19. Thomas JC, Ross JH, Kay R: Stromal testis tumors in children: a report from the prepubertal testis tumor registry. J Urol 166 (6): 2338-40, 2001.

  20. Morowitz M, Huff D, von Allmen D: Epithelial ovarian tumors in children: a retrospective analysis. J Pediatr Surg 38 (3): 331-5; discussion 331-5, 2003.

  21. Schultz KA, Sencer SF, Messinger Y, et al.: Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer 44 (2): 167-73, 2005.

  22. Aggarwal A, Lucco KL, Lacy J, et al.: Ovarian epithelial tumors of low malignant potential: a case series of 5 adolescent patients. J Pediatr Surg 44 (10): 2023-7, 2009.

  23. You W, Dainty LA, Rose GS, et al.: Gynecologic malignancies in women aged less than 25 years. Obstet Gynecol 105 (6): 1405-9, 2005.

  24. Brookfield KF, Cheung MC, Koniaris LG, et al.: A population-based ana