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Adrenocortical carcinoma is a rare cancer that forms in the outer layer of the adrenal gland, which release hormones such as adrenaline to control heart rate, blood pressure, and other body functions. Learn about adrenocortical carcinoma and find information on how we support and care for children and teens with this rare cancer before, during, and after treatment.
The Solid Tumor Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center treats children and teens with a variety of solid malignancies, including bone and soft tissue tumors, liver and kidney tumors, neuroblastomas, retinoblastomas and rare tumors. Our doctors provide unparalleled expertise in the diagnosis, treatment and management of these diseases.
Your child's care team will include pediatric oncologists, radiation oncologists, surgeons, pathologists, radiologists, and nurses with expertise in treating your child's specific type of cancer.
Our physicians are focused on family-centered care: From your first visit, you'll work with a team of professionals who are committed to supporting your family's needs. We consider you and your child integral parts of the care team. Our specialists will collaborate with you to customize a treatment plan that takes the needs of your child and your family into account.
As well as providing access to a range of innovative clinical trials through Dana-Farber/Boston Children's, we are New England's Phase I referral center for the Children's Oncology Group, which means we're able to offer clinical trials unavailable at other regional centers.
Your child will have access to long-term treatment and childhood cancer survivor support through Dana-Farber's David B. Perini, Jr. Quality of Life Clinic.
From diagnosis through treatment and survivorship, our team will be able to answer all of your questions about your child's care.
Find out more about our Solid Tumor Center, including the diseases we treat and our specialized programs for bone and soft tissue tumors, liver tumors, neuroblastoma, rare tumors, and retinoblastoma.
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 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:
Cancer can spread through tissue, the lymph system, and the blood:
When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if thyroid cancer spreads to the lung, the cancer cells in the lung are actually thyroid cancer cells. The disease is metastatic thyroid cancer, not lung cancer.
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.
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:
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 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:
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 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 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 is closely monitoring a patient’s condition without giving any treatment until signs or 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 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.
Information about clinical trials is available from the NCI Web site.
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.
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.
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 that continue or appear months or years after cancer treatment has ended. These are called late effects. Late effects may include the following:
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).
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, Signs and 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 your child has any of the following:
Other conditions that are not nasopharyngeal cancer may cause these same signs and 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:
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:
The prognosis (chance of recovery) for most young patients with nasopharyngeal cancer is very good. The prognosis and treatment options depend on the following:
Treatment of nasopharyngeal cancer in children may include the following:
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 (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.
Signs and Symptoms and Staging Tests
Esthesioneuroblastoma may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not esthesioneuroblastoma may cause these same signs and symptoms.
Esthesioneuroblastoma has usually spread by the time it is diagnosed. Tests to stage esthesioneuroblastoma may include the following:
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 of esthesioneuroblastoma in children may include the following:
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).
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 signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not thyroid tumors may cause these same signs and symptoms.
Tests to diagnose and stage thyroid tumors may include the following:
Other tests used to diagnose and stage thyroid tumors include the following:
The prognosis (chance of recovery) depends on the following:
Treatment of thyroid tumors in children may include the following:
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 cavity cancer is a disease in which malignant (cancer) cells form in the tissues of the mouth. Most tumors in the oral cavity are benign (not cancer). The most common type of oral cavity 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.
Signs and Symptoms, and Diagnostic and Staging Tests
Oral cavity cancer may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not oral cavity cancer may cause these same signs and symptoms.
Tests to diagnose and stage oral cavity cancer may include the following:
Treatment of oral cavity cancer in children may include the following:
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.
Signs and Symptoms
Salivary gland tumors may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not salivary gland tumors may cause these same signs and symptoms.
Diagnostic and Staging Tests
Tests to diagnose and stagesalivary gland cancer may include the following:
The prognosis for salivary gland cancer is usually good.
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 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.
Signs and Symptoms for Laryngeal Cancer
Laryngeal cancer may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not laryngeal cancer may cause these same signs and symptoms.
Diagnostic and Staging Tests for Laryngeal Cancer
Tests to diagnose and stage laryngeal cancer may include the following:
Other tests used to diagnose laryngeal cancer include the following:
Treatment of Laryngeal Cancer
Treatment of laryngeal cancer in children may include the following:
See the following PDQ summaries for more information:
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:
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.
Midline tract cancer with NUT gene changes usually cannot be cured.
There is no standard treatment for midline tract cancer with NUT gene changes. Treatment may include surgery to remove the tumor and radiation therapy. Taking part in a clinical trial should be considered.
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, Signs, and Diagnostic and Staging Tests
The risk of breast cancer is increased by the following:
Breast cancer may cause any of the following signs. Check with your child’s doctor if your child has any of the following:
Other conditions that are not breast cancer may cause these same signs.
Tests to diagnose and stage breast cancer may include the following:
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 of breast cancer in children may include the following:
See the PDQ summary Breast Cancer Treatment for more information on the treatment of adolescents and young adults with breast 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).
Signs and Symptoms and Diagnostic Tests
Lung cancer may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not lung cancer may cause these same signs and symptoms.
Tests to diagnose lung cancer may include the following:
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.
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.
Bronchial tumors may cause any of the following signs and symptoms. Check with your child's doctor if your child has any of the following:
Other conditions that are not bronchial tumors may cause these same signs and 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:
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:
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 of bronchial tumors in children may include the following:
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:
The risk of PPB is increased by the following:
PPB may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not PPB may cause these same signs and symptoms.
Tests to diagnose and stage PPB may include the following:
Other tests used to diagnose PPB include the following:
PPBs may spread or recur (come back) even after being removed by surgery.
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.
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.
Esophageal cancer may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not esophageal cancer may cause these same signs and symptoms.
Tests to diagnose and stage esophageal cancer may include the following:
Other tests used to diagnose esophageal cancer include the following:
Esophageal cancer is hard to cure because it usually is not possible to remove the whole tumor by surgery.
Treatment for esophageal cancer in children may include the following:
See the PDQ summary on adult Esophageal Cancer for more information.
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.
Thymoma and thymic carcinoma are slow-growing cancers that may spread to the lymph nodes or to other parts of the body.
People who develop thymomas often have one of the following immune system diseases or hormonedisorders:
Thymoma and thymic carcinoma may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not thymoma or thymic carcinoma may cause these same signs and symptoms.
Tests to diagnose and stage thymoma and thymic carcinoma may include the following:
The prognosis (chance of recovery) is better when the tumor has not spread.
Treatment for thymomas and thymic carcinoma in children may include the following:
Most tumors that form in the heart are benign (not cancer). Benign heart tumors that may appear in children include the following:
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:
Some cancers, such as rhabdomyosarcoma, melanoma, leukemia, thymoma, and carcinomas, spread to the heart from other parts of the body. These tumors are malignant.
Heart tumors may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Sometimes heart tumors do not cause any signs or symptoms at all and sudden death may occur.
Other conditions that are not heart tumors may cause these same signs and symptoms.
Tests to diagnose and stage heart tumors may include the following:
Other tests used to diagnose or stage heart tumors include the following:
Treatment for heart tumors in children may include the following:
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.
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 your child has any of the following:
Other conditions that are not mesothelioma may cause these same signs and symptoms.
Tests to diagnose and stage mesothelioma may include the following:
Other tests used to diagnose mesothelioma include the following:
The prognosis (chance of recovery) is better when the tumor has not spread or come back after treatment.
Treatment for mesothelioma in children may include one or more of the following:
See the PDQ summary on adult Malignant Mesothelioma Treatment for more information.
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:
The risk of cancer of the adrenal cortex is increased by having any of the following syndromes:
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. Extra estrogen hormone may cause the growth of breasttissue in male children. (See the PDQ summary on adult Adrenocortical Carcinoma Treatment for more information on the signs and 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:
Other tests used to diagnose cancer of the adrenal cortex include the following:
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 for cancer of the adrenal cortex in children may include the following:
See the PDQ summary on adult Adrenocortical Carcinoma Treatment for more information.
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.
The risk of stomach cancer is increased by having an infection with Helicobacter pylori (H.pylori)bacterium, which is found in the stomach.
Many patients will have anemia (a lower than normal number of red blood cells), but have no signs or symptoms before the cancer spreads. Stomach cancer may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not stomach cancer may cause these same signs and symptoms.
Tests to diagnose and stage stomach cancer may include the following:
Other tests used to diagnose stomach cancer include the following:
Prognosis (chance of recovery) depends on whether the cancer has spread at the time of diagnosis.
Treatment of stomach cancer in children may include the following:
See the PDQ summary on adult Gastric Cancer Treatment for more information.
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).
The pancreas has two main jobs in the body:
The risk of pancreatic cancer is increased by having Beckwith-Wiedemann syndrome or Cushing syndrome.
Most pancreatic tumors do not secrete hormones and there are no signs or symptoms of disease. This makes it difficult to diagnose pancreatic cancer early.
Pancreatic tumors that do secrete hormones may cause signs and symptoms. The signs and symptoms depend on the type of hormone being made.
If the tumor secretes insulin, signs and symptoms that may occur include the following:
Other signs and symptoms caused by tumors that make hormones include the following:
If cancer is in the head of the pancreas, the bile duct or blood flow to the stomach may be blocked and the following signs may occur:
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 signs and symptoms.
Tests to diagnose and stage pancreatic cancer may include the following:
Other tests used to diagnose pancreatic cancer include the following:
Treatment for children with pancreatic cancer may include the following:
See the PDQ summary on adult Pancreatic Cancer Treatment for more information.
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).
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:
Colon polyps that form in children who do not have an inherited syndrome are not linked to an increased risk of cancer.
Signs and 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 your child has any of the following:
Other conditions that are not colorectal cancer may cause these same signs and symptoms.
Tests to diagnose and stage colorectal cancer may include the following:
Other tests used to diagnose colorectal cancer include the following:
Treatment for colorectal cancer in children may include the following:
Children with certain familial colon cancer syndromes may be treated with:
See the following PDQ summaries on adult cancer for more information:
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.
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 signs and 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 your child has any of the following:
Other conditions that are not carcinoid tumors may cause these same signs and symptoms.
Tests that check for signs of cancer are used to diagnose and stage carcinoid tumors. They may include:
Other tests used to diagnose carcinoid tumors include the following:
Treatment for carcinoid tumors in the appendix in children may include the following:
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.
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 Signs 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:
Most children with GIST have tumors in the stomach and develop anemia caused by bleeding. Signs and symptoms of anemia include the following:
Other conditions that are not anemia caused by GIST may cause these same signs and symptoms.
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:
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.
The most common type of bladder cancer is transitional cell cancer. Squamous cell and other more aggressive types of bladder cancer are less common.
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 your child has any of the following:
Other conditions that are not bladder cancer may cause the same signs and symptoms.
Tests to diagnose and stage bladder cancer may include the following:
Other tests used to diagnose bladder cancer include the following:
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 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 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.
There are two types of testicular tumors:
Signs and Diagnostic and Staging Tests
A painless lump in the testicles may be a sign of a testicular tumor. Other conditions may also cause a lump in the testicles.
Tests to diagnose and stage non-germ cell testicular cancer may include the following:
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 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).
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:
The risk of ovarian cancer is increased by having one of the following conditions:
Ovarian cancer may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not ovarian cancer may cause these same signs and symptoms.
Tests to diagnose and stage ovarian cancer may include the following:
Ovarian epithelial cancer is usually found at an early stage in children and is easier to treat than in adult patients.
Treatment of ovarian epithelial cancer may include the following:
Treatment of ovarian stromal tumors may include the following:
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).
The most common sign of cervical and vaginal cancer is bleeding from the vagina. Other conditions may also cause vaginal bleeding.
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.
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:
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.
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:
Signs and symptoms of medullary thyroid cancer may include:
Signs and symptoms of pheochromocytoma may include:
Signs and symptoms of parathyroid gland cancer may include:
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.
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:
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 signs and symptoms and the patient's family history. They may include:
Other tests and procedures used to diagnose MEN syndromes include the following:
There are several types of MEN syndrome, and each type may need different treatment:
Pheochromocytoma and paraganglioma are rare tumors that come from the same type of nervetissue.
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:
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. Signs and 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, paraganglioma, or other conditions. Check with your child’s doctor if your child has any of the following:
These signs and symptoms may come and go but high blood pressure is more likely to occur for long periods of time in young patients. These signs and 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 signs and symptoms and the patient's family history. They may include:
Other tests and procedures used to diagnose pheochromocytoma and paraganglioma include the following:
Treatment of pheochromocytoma and paraganglioma in children may include the following:
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 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:
There are three types of skin cancer:
Even though melanoma is rare, it is the most common skin cancer in children. It occurs more often in children aged 15 to 19 years. Melanoma rates in the United States have slowly increased since 1975.
The risk of having melanoma is increased by the following:
Risk factors for melanoma in all age groups include:
Signs and symptoms of melanoma include the following:
Tests to diagnose and stage melanoma may include the following:
Other tests and procedures used to diagnose melanoma include the following:
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:
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:
Signs of squamous cell and basal cell skin cancer include the following:
Tests to diagnose squamous cell and basal cell skin cancer include the following:
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 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.
Chordoma may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Other conditions that are not chordoma may cause these same signs and 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 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.
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:
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 depends on what the cancer cells look like under a microscope, the patient's age, signs and symptoms, and where the cancer has spread in the body. Treatment is usually chemotherapy or radiation therapy.
For more information from the National Cancer Institute about unusual cancers of childhood, see the following:
For more childhood cancer information and other general cancer resources, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on August 15, 2014.
Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. 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. 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%. 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. 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. 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.
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, in addition to 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, and their age distribution, makes these rare cancers extremely challenging to study.
Several initiatives to study rare pediatric cancers have been developed by the Children's Oncology Group (COG) and international groups. The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) rare tumor project was founded in Germany in 2006. The TREP project was launched in Italy in 2000, and the Polish Pediatric Rare Tumor Study Group was launched in 2002. Within the COG, efforts have concentrated on increasing accrual to the COG registry and the rare tumor bank and developing single-arm clinical trials and increasing cooperation with adult cooperative group trials. The accomplishments and challenges of this initiative are described in detail.
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.
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.
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.
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 August 15, 2014.
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.
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 January 29, 2014.
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.
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.
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.
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. 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 arises in the lining of the nasal cavity and pharynx. 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. 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.
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. The circulating levels of EBV DNA, and serologic documentation of EBV infection, may aid in the diagnosis.
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.
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 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.
Tumor staging is performed utilizing the tumor-node-metastasis classification system of the American Joint Committee on Cancer (AJCC). The majority (>90%) of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4). 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.
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%. However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities.
Treatment of nasopharyngeal carcinoma is multimodal:
(Refer to the PDQ summary on Nasopharyngeal Cancer Treatment for more information.)
Esthesioneuroblastoma (olfactory neuroblastoma) is a small round-cell tumor arising from the nasal neuroepithelium that is distinct from primitive neuroectodermal tumors. In children, esthesioneuroblastoma is a very rare malignancy with an estimated incidence of 0.1 per 100,000 children younger than 15 years. Despite its rarity, esthesioneuroblastoma is the most common cancer of the nasal cavity in pediatric patients, accounting for 28% of all cases. 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. Most patients were white (81%) and the most common tumor sites were the nasal cavity (72%) and ethmoid sinus (13%).
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). Recent reports suggest that positron emission tomography–computed tomography may aid in staging the disease.
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.
The mainstay of treatment has been surgery and radiation. Newer techniques such as endoscopic sinus surgery may offer similar short-term outcomes to open craniofacial resection.; [Level of evidence: 3iiiDii] 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. 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. Management of cervical lymph node metastases has been addressed in a review article.
Reports indicate the increasing use of neoadjuvant or adjuvant chemotherapy in patients with advanced-stage disease with promising results.; [Level of evidence: 3iii] Chemotherapy regimens that have been used with efficacy include etoposide with ifosfamide and cisplatin; vincristine, actinomycin D, and cyclophosphamide with and without doxorubicin; ifosfamide/etoposide; cisplatin plus etoposide or doxorubicin;  and irinotecan plus docetaxel.[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.
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. 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. Most thyroid carcinomas occur in girls.
There is an excessive frequency of thyroid adenoma and carcinoma in patients who previously received radiation to the neck. In the decade following the Chernobyl nuclear incident, there was a tenfold increase in the incidence of thyroid cancer compared with the previous and following decades. In this group of patients with exposure to low-dose radiation, tumors commonly show a gain of 7q11. 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.)
Tumors of the thyroid are classified as adenomas or carcinomas. 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.
Various histologies account for the general diagnostic category of carcinoma of the thyroid:
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.
Children and Adolescents (%)
Lymph node involvement
aAdapted from Yamashita et al.
Patients with thyroid cancer usually present with a thyroid mass with or without cervical adenopathy. 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%). Likewise, when compared with 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. In well-differentiated thyroid cancer, male gender, large tumor size, and distant metastases have been found to have prognostic significance for early mortality; however, even patients in the highest risk group who had distant metastases had excellent survival at 90%.
Initial evaluation of a child or adolescent with a thyroid nodule should include the following:
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. Open biopsy or resection may be preferable for young children as well.
Associated Chromosomal Abnormality
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
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.
The management of differentiated thyroid cancer in children has been reviewed in detail. Also, the American Thyroid Association Taskforce  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.
Surgery performed by an experienced thyroid surgeon is the treatment required for all thyroid neoplasms. For patients with papillary or follicular carcinoma, total or near-total thyroidectomy plus cervical lymph node dissection is the recommended surgical approach. This aggressive approach is indicated for several reasons:
However, for patients with a small (<1 cm) unifocal nodule, treatment may involve only a lobectomy.
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, 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. Thus, it is currently recommended that children receive an ablative dose after initial surgery. 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. 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.[Level of evidence: 3iDiv] In younger children, the I-131 dose may be adjusted for weight (1–1.5 mCi/kg). After surgery and radioactive iodine therapy, hormone replacement therapy must be given to compensate for the lost thyroid hormone and to suppress TSH production.
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.
Periodic evaluations are required to determine whether there is metastatic disease involving the lungs. Lifelong follow-up is necessary. 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. 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.
Patients with differentiated thyroid cancer generally have an excellent survival with relatively few side effects. 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. Even patients with a tumor that has spread to the lungs may expect to have no decrease in life span after appropriate treatment. 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.
Recurrent papillary thyroid cancer is usually responsive to treatment with radioactive iodine ablation. Tyrosine kinase inhibitors such as sorafenib have shown to induce responses in up to 15% of adult patients with metastatic disease. Responses to sorafenib have also been documented in pediatric cases. Given the high incidence of BRAF mutations in older patients with papillary thyroid carcinoma, the use of selective RAF/MEK inhibitors is being investigated.
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. 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.
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. 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. 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 approved by the U.S. Food and Drug Administration 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). A phase I trial of vandetanib for children has been completed. 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).
(Refer to the Multiple Endocrine Neoplasia (MEN) Syndromes and Carney Complex section of this summary for more information.)
The vast majority (>90%) of tumors and tumor-like lesions in the oral cavity are benign. 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.
The incidence of cancer of the oral cavity and pharynx 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. 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. Current practices to increase HPV immunization rates in both boys and girls may reduce the burden of HPV-related noncervical cancers.
Benign odontogenic neoplasms of the oral cavity include odontoma and ameloblastoma. The most common nonodontogenic neoplasms of the oral cavity are fibromas, hemangiomas, and papillomas. Tumor-like lesions of the oral cavity include lymphangiomas, granulomas, and eosinophilic granuloma (Langerhans cell histiocytosis) (refer to the Oral cavity subsection in the PDQ summary on Langerhans Cell Histiocytosis Treatment for more information about Langerhans cell histiocytosis).
Malignant lesions of the oral cavity were found in 0.1% to 2% of a series of oral biopsies performed in children  and 3% to 13% of oral tumor biopsies. Malignant tumor types include lymphomas (especially Burkitt) and sarcomas (including rhabdomyosarcoma and fibrosarcoma). Mucoepidermoid carcinomas of the oral cavity have rarely been reported in the pediatric and adolescent age group. Most are low grade and have a high cure rate with surgery alone.; [Level of evidence: 3iiA]
The most common type of primary oral cavity 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.[Level of evidence: 3iA] Diseases that can be associated with the development of oral cavity and/or head and neck SCC include Fanconi anemia, dyskeratosis congenita, connexin mutations, chronic graft-versus-host disease, epidermolysis bullosa, xeroderma pigmentosum, and HPV infection.
Treatment of benign oral cavity tumors is surgical.
Management of malignant tumors of the oral cavity is dependent on histology and may include surgery, chemotherapy, and radiation. Most reported cases of oral cavity SCC managed with surgery alone have done well without recurrence. Langerhans cell histiocytosis of the oral cavity may require treatment in addition to surgery. (Refer to the PDQ summary on Langerhans Cell Histiocytosis Treatment for more information.)
Salivary gland tumors are rare and account for 0.5% of all malignancies in children and adolescents. Most salivary gland neoplasms arise in the parotid gland. 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. Overall 5-year survival in the pediatric age group is approximately 95%.
The most common malignant lesion is mucoepidermoid carcinoma. 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. Mucoepidermoid carcinoma is the most common type of treatment-related salivary gland tumor, and with standard therapy, the 5-year survival is about 95%.
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.; [Level of evidence: 3iiiA]
(Refer to the PDQ summary on adult Salivary Gland Cancer Treatment for more information.)
Sialoblastoma is a usually benign tumor presenting in the neonatal period and rarely metastasizes. Chemotherapy regimens with carboplatin, epirubicin, vincristine, etoposide, dactinomycin, doxorubicin, and ifosfamide have produced responses in two children with sialoblastoma.; [Level of evidence: 3iiiDiv]
Tumors of the larynx are rare. The most common benign tumor is subglottic hemangioma. Malignant tumors, which are especially rare, may be associated with benign tumors such as polyps and papillomas. 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. SCC of the larynx should be managed in the same manner as in adults with carcinoma at this site, with surgery and radiation. 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. The presence of HPV-11 appears to correlate with a more aggressive clinical course than HPV-6. 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. 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. Frequent recurrences are common. Lung involvement, although rare, can occur. If a patient requires more than four surgical procedures per year, treatment with interferon may be considered. 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. These results, however, must be confirmed in a larger randomized trial.
(Refer to the PDQ summary on adult Laryngeal Cancer Treatment for more information.)
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.
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. Although the original description of this neoplasm was made in children and young adults, patients of all ages can be affected. A retrospective series with clinicopathologic correlation found that the median age at diagnosis of 54 patients was 16 years (range, 0.1–78 years). 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.
Although gross complete resection and early radiation therapy may be of benefit, there is no proven benefit of chemotherapy.[Level of evidence: 3iiiB]
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.
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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.
The most frequent breast tumor seen in children is a fibroadenoma. 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. 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.
Breast cancer has been reported in both males and females younger than 21 years. 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. 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. 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. 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.
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. 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.)
Primary lung tumors are rare in children and histologically quite diverse. When epithelial cancers of the lung occur, they tend to be of advanced stage with prognosis dependent on both histology and stage.
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. 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. These tumors may respond to the ALK inhibitor crizotinib in the presence of ALK translocations.[Level of evidence: 3iiiDiv]
The most common malignant primary tumors of the lung, bronchial tumors and pleuropulmonary blastoma, are discussed below.
Bronchial tumors are a heterogeneous group of primary endobronchial lesions, and although adenoma implies a benign process, all varieties of bronchial tumors on occasion display a malignant behavior. There are three histologic types:
Bronchial tumors of all histologic types are associated with an excellent prognosis in children, even in the presence of local invasion.
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.
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. There is a single report of a child with a carcinoid tumor and metastatic disease who developed the classic carcinoid syndrome. 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 of 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.
Conservative pulmonary resection, including sleeve segmental resection, when feasible, with the removal of the involved lymphatics, is the treatment of choice. 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 performed in children with this lesion. Neither chemotherapy nor radiation therapy is indicated for bronchial tumors, unless evidence of metastasis is documented.
Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in children. Pleuropulmonary blastoma appears to progress through the following stages:
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. 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.
A family history of cancer in close relatives has been noted for many young patients affected by this tumor. In addition, pleuropulmonary blastoma has been reported in siblings.
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.
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. 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.
Achieving total resection of the tumor at any time during treatment is associated with improved prognosis. The tumors may recur or metastasize, in spite of primary resection. The cerebral parenchyma is the most common metastatic site.
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. Chemotherapeutic agents may include vincristine, cyclophosphamide, dactinomycin, doxorubicin, and irinotecan. Data from the International Pleuropulmonary Blastoma Registry suggest that adjuvant chemotherapy may reduce the risk of recurrence.
Radiation, either external beam or P-32, may be used when the tumor cannot be surgically removed.
High-dose chemotherapy with stem cell rescue has been used without success.
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 the following:
An independent group of researchers has established a registry and resource Web site for this rare tumor.
Esophageal cancer is rare in the pediatric age group, although it is relatively common in older adults. 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.)
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. 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. In the Tumori Rari in Età Pediatrica registry, only eight cases were identified over a 9-year period. A review of 73 cases of anterior mediastinal tumors using the SEER Registry of the National Cancer Institute identified thymic epithelial tumors as having the worst survival rate at 10 years from diagnosis; better survival rates occurred in patients with lymphomas and germ cell tumors.
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. Endocrine (hormonal) disorders including hyperthyroidism, Addison disease, and panhypopituitarism can also be associated with a diagnosis of thymoma.
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.
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. 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%. Response rates are lower for patients with thymic carcinoma, but 2-year survival rates have been reported to be as high as 50%.
Sunitinib has yielded clinical responses in four adult patients with thymic carcinoma.
Cardiac tumors are rare, with an autopsy frequency of 0.001% to 0.30%; in one report, the percentage of cardiac surgeries performed as a result of cardiac tumors was 0.093%. The most common primary tumors of the heart are benign and include rhabdomyoma, myxoma, teratoma, and fibroma. Other benign tumors include histiocytoid cardiomyopathy tumors, hemangiomas, and neurofibromas (i.e., tumors of the nerves that innervate the muscles).
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. A mutation of the PRKAR1A gene is noted in more than 90% of the cases of Carney complex.
Primary malignant pediatric heart tumors are rare but may include malignant teratoma, lymphoma, and various sarcomas such as rhabdomyosarcoma, angiosarcoma, chondrosarcoma, and infantile fibrosarcoma.
Secondary tumors of the heart include metastatic spread of rhabdomyosarcoma, melanoma, leukemia, thymoma, and carcinomas of various sites.
The distribution of cardiac tumors in the fetal and neonatal period is different when compared with older patients, with two-thirds of teratomas occurring during this period of life. Multiple cardiac tumors noted in the fetal or neonatal period are highly associated with a diagnosis of tuberous sclerosis. A retrospective review of 94 patients with cardiac tumors detected by prenatal or neonatal echocardiography showed that 68% of the patients exhibited features of tuberous sclerosis. 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.
Patients may be asymptomatic but about two-thirds of patients have symptoms that may include abnormalities of heart rhythm, enlargement of the heart, fluid in the pericardial sac, congestive heart failure, syncope, stroke, and respiratory distress. Some patients present with sudden death.[Level of evidence: 3iiiA]
The utilization of new cardiac MRI techniques can identify the likely tumor type in the majority of children. However, histologic diagnosis remains the standard for diagnosing cardiac tumors.
Successful treatment may require surgery, debulking for progressive symptoms, cardiac transplantation, and chemotherapy that is appropriate for the type of cancer that is present.; [Level of evidence: 3iiA] Although some lesions such as rhabdomyomas can regress spontaneously, some practitioners recommend prophylactic resection to prevent mass-related complications.; [Level of evidence: 3iiDiii] Treatment with the mTOR inhibitor everolimus has been reported to be associated with a decrease in the size of rhabdomyomas in patients with tuberous sclerosis. Complete surgical excision of other lesions offers the best chance for cure, with postoperative complications seen in about one-third of patients and postoperative mortality rates in less than 10% of patients. In one series, 95% of patients were free from cardiac tumor recurrence at 10 years. Cardiac sarcomas have a poor outcome and can be treated with multimodal therapy; the use of preoperative chemotherapy may be of value in reducing tumor volume prior to surgery.
Mesothelioma is extremely rare in childhood, with only 2% to 5% of patients presenting during the first two decades of life. Fewer than 300 cases in children have been reported.
This tumor can involve the membranous coverings of the lung, the heart, or the abdominal organs. 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. In adults, these tumors have been associated with exposure to asbestos, which was used as building insulation. 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 and with 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.
Radical surgical resection has been attempted with mixed results. Treatment with various chemotherapeutic agents used for carcinomas or sarcomas may result in partial responses. 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. 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.)
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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 Standard Treatment Options for Renal Cell Carcinoma (RCC) section in the PDQ summary on Wilms Tumor and Other Childhood Kidney Tumors for more information.)
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). Adrenocortical tumors appear to follow a bimodal distribution, with peaks during the first and fourth decades. 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. 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. 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. Female gender is consistently predominant in most studies, with a female to male ratio of 1.6 to 1.
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, although not invariably, have a high incidence of other non-adrenal cancers (Li-Fraumeni syndrome); 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). 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. In a Brazilian study, neonatal screening for the TP53 R337H mutation, which is prevalent in the region, identified 461 (0.27%) carriers among 171,649 of the newborns who were screened. Carriers and relatives younger than 15 years were offered clinical screening. Adrenocortical tumors identified in the screening participants were smaller and more curable than the tumors found in carriers who did not elect to participate in screening.
Patients with Beckwith-Wiedemann and hemihypertrophy syndromes have a predisposition to cancer, and as many as 16% of their neoplasms are adrenocortical tumors. Hypomethylation of the KCNQ1OT1 gene has also been associated with the development of adrenocortical tumors in patients without the phenotypic features of Beckwith-Wiedemann syndrome. However, less than 1% of children with adrenocortical tumors have these syndromes. The distinctive genetic features of pediatric adrenocortical carcinoma have been reviewed.
Unlike adult adrenocortical tumors, histologic differentiation of adenomas and carcinomas is difficult. However, approximately 10% to 20% of pediatric cases are adenomas. 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. 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. 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.IGF2 expression also appears to discriminate between carcinomas and adenomas in adults, but not in children. 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.
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. 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. Hyperestrogenism can also occur. Isolated Cushing syndrome is very rare (5% of patients), and it appears to occur more frequently in older children. Likewise, nonfunctional tumors are rare (<10%) and tend to occur in older children. 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.
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. 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. The overall probability of 5-year survival for children with adrenocortical tumors is reported to be 54% to 74%.
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.
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.; [Level of evidence: 3iiiA] An aggressive surgical approach of the primary tumor and all metastatic sites is recommended when feasible. 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). 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. Laparoscopic resection is associated with a high risk of rupture and peritoneal carcinomatosis; thus, open adrenalectomy remains the standard of care.
Little information is available about the use of mitotane in children, although response rates appear to be similar to those seen in adults. 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. 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. In the GPOH-MET 97 trial, mitotane levels greater than 14 mg/L correlated with better survival.
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.
(Refer to the PDQ summary on adult Adrenocortical Carcinoma Treatment for more information.)
Primary gastric tumors in children are rare, and carcinoma of the stomach is even more unusual. 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. 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.
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. 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. 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. 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. 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.)
Malignant pancreatic tumors are rare in children and adolescents with an incidence of 0.46 cases per 1 million (younger than 30 years). 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. Several cases of primitive neuroectodermal tumor of the pancreas have been reported in children and young adults. Pancreatoblastoma is reported to be associated with Beckwith-Wiedemann syndrome and Cushing syndrome.
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. 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. 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.
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. Treatment consists of complete tumor resection (ideally without biopsy). Metastases may occur, but in general, prognosis is good following surgery alone.; [Level of evidence: 3iiA]; [Level of evidence: 3iiDi]; [Level of evidence: 3iiDiii]
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, although pancreatoblastoma has a high recurrence rate.; [Level of evidence: 3iiA] A series of 31 patients aged 4 to 18.7 years included 21 patients with solid pseudopapillary tumor, four with neuroendocrine tumor, four with pancreatoblastoma, and one with an unclassified spindle-cell tumor. Treatment was surgical removal in 29 patients. The 3-year survival rate for patients with pseudopapillary tumor was 100%.[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. Postoperative treatment with cisplatin, doxorubicin, ifosfamide, and etoposide has also produced responses in patients with pancreatoblastoma, although surgery is the mainstay of therapy.; [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.)
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. From 1973 to 2006, the Surveillance, Epidemiology, and End Results database recorded 174 cases of colorectal cancer in patients younger than 19 years.
The most common presenting symptom in children is abdominal pain. Other signs and symptoms include rectal bleeding, change in bowel habits, weight loss, and nausea and vomiting; the median duration of symptoms before diagnosis was about 3 months in one series. 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.
Colorectal tumors can occur in any location in the large bowel. Larger series and reviews suggest that ascending and descending colon tumors are each seen in approximately 30% of cases, with rectal tumors occurring in approximately 25% of cases.
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.
Most reports also suggest that children present with more advanced disease than do adults, with 80% to 90% of patients presenting with Duke stage C/D or TNM stage III/IV disease (refer to the Stage Information for Colon Cancer section of the PDQ summary on adult Colon Cancer Treatment for more information about staging).
There is a higher incidence of mucinous adenocarcinoma in the pediatric and adolescent age group (40%–50%), with many lesions being the signet ring cell type, 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 with the mucinous histology, there is a higher incidence of signet ring cells, microsatellite instability, and mutations in the mismatch repair genes. 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. Colorectal cancers in younger patients with noninherited sporadic tumors often lack KRAS mutations and other cytogenetic anomalies seen in older patients.
Most patients present with evidence of metastatic disease, either as gross tumor or as microscopic deposits in lymph nodes, on the surface of the bowel, or on intra-abdominal organs. 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 those with extensive metastatic disease. 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. Other agents, including irinotecan, may be of value.[Level of evidence: 3iiiA] No significant benefit has been determined for interferon-alpha given in conjunction with 5-FU/leucovorin. A recent review of nine clinical trials comprising 138 patients younger than 40 years demonstrated that the use of combination chemotherapy improved progression-free survival and overall survival (OS) in these patients. Furthermore, OS and response rates to chemotherapy were similar to those observed in older patients.
Survival is consistent with the advanced stage of disease observed in most children with colorectal cancer, with an overall mortality rate of approximately 70%. For patients with a complete surgical resection or for those with low-stage/localized disease, survival is significantly prolonged, with curative potential.
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. 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. A later study documented immunohistochemical evidence of mismatch repair deficiency in 31% of colorectal carcinoma samples in patients aged 30 years or younger. The most common genetic syndromes associated with the development of colorectal cancer are shown in Tables 3 and 4.
Attenuated familial adenomatous polyposis
APC (5’ mutations), AXIN2
Familial adenomatous polyposis (Gardner syndrome)
Lynch syndrome (hereditary nonpolyposis colorectal cancer)
MSH2, MLH1, MSH6, PMS2, EPCAM
Juvenile polyposis syndrome
BMPR1A, SMAD4, ENG
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. 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. 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. 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.[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.
These tumors, like bronchial adenomas, may be benign or malignant and can involve the lining of the lung, large or small bowel, or liver. Most lung lesions are benign; however, some metastasize.
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. 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.
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. 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. Symptoms may be lessened by giving somatostatin analogs, which are available in short-acting and long-acting forms. Occasionally, carcinoids may produce ectopic ACTH and cause Cushing disease.
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract in adults. These tumors are rare in children. Approximately 2% of all GIST occur in children and young adults; in one series, pediatric GIST accounted for 2.5% of all pediatric nonrhabdomyosarcomatous soft tissue sarcomas. 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.
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.
Familial GIST and neurofibromatosis 1–associated GIST occur in patients older than 40 years.
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. 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. 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. 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.
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. 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.
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).
Treatment of GIST varies based on whether a mutation is detected:
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. Responses to imatinib and sunitinib in pediatric patients with wild-type GIST are uncommon and consist mainly of disease stabilization. In a review of ten patients who were treated with imatinib mesylate, one patient experienced a partial response and three patients had stable disease. 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.
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