How We Diagnose Non-Hodgkin Lymphoma

Accurate diagnosis of your non-Hodgkin lymphoma subtype is crucial in determining the proper course of treatment, so it is important to be seen at — or consult with — a large lymphoma treatment center like ours, which diagnoses and cares for many patients with all forms of this kind of cancer.

Data from our program shows that in 10 to 15 percent cases, a second opinion from Dana-Farber renders a different diagnosis from what was given by a referring doctor. Our hematopathologists and radiologists conduct and study these diagnostic test results on a daily basis, which has given us a tremendous amount of expertise in this area.

Until recently, non-Hodgkin lymphoma patients were often treated with very similar chemotherapy regimens, regardless of the cancer subtype. Advances in research have revealed subtleties in the various forms, leading to nuanced treatment protocols. Correctly identifying the subtype of lymphoma is particularly important in determining:

  • If immediate treatment is needed and the aggressiveness of the plan.
  • The correct chemotherapy regimen.
  • Whether to integrate radiation therapy into the treatment plan.
  • The timing of components of treatment, possibly including a stem cell transplant.

We use a variety of highly specialized tests — including genetic and molecular profiling — to distinguish between the different subtypes. This is crucial, since even within the same diagnosis, the specific mutation "profile" of a cancer can predict very different outcomes.

We take findings from all of these tests and integrate them to make an accurate diagnosis.

Lymphoma Program leaders Margaret Shipp, MD, and Philippe Armand, MD, PhD

Initial Diagnosis


A biopsy of involved tissue or lymph nodes is essential to make a diagnosis. Our surgeons have expertise in performing lymph node biopsies that ensure adequate tissue is gathered to make a precise diagnosis. Generally, the removal of all or a big part of a lymph node is the preferred method, in order to ensure an adequate sample.

  • A pathologist then examines the lymph node tissue to look for the malignant cells.
  • Immunophenotyping may be done on tissue that was removed to study the protein expressed by cells. This is used to diagnose the specific type of lymphoma by comparing the cancer cells to normal cells.

Radiographic Studies

Your doctor may conduct imaging studies, such as CT scans, X-rays, and PET scans. Radiologists look for an enlarged spleen or lymph nodes, or abnormal retinal veins.

Genetic and Molecular Analysis

We have unique expertise in interpreting molecular and genomic tests and translating the data into an action plan.

Our scientists are creating one of the world's largest databases on the genetic abnormalities that drive the development of tumors across all cancer types with OncoPanel. More than 43,000 patients have consented to have their tumor tissue analyzed for mutations and other cancer-related DNA abnormalities. The results from this can be especially useful in differentiating among the many kinds of T-cell non-Hodgkin lymphomas.

Blood Tests

Your doctor may decide to run blood tests, including a blood chemistry study. This is a procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

Your doctor may check for lactate dehydrogenase (LDH), which can be used to predict prognosis and response to treatment.

Lumbar Puncture

In some cases, this procedure is done to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.

Flow Cytometry

This blood test measures:

  • The number of cells in a sample.
  • The percentage of live cells in a sample.
  • Certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface.

The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light.

If cancer is found, the following tests may be done to study the cancer cells:


This is a test that uses antibodies to check for certain antigens in a sample of tissue.

Bone Marrow Aspiration and Biopsy

This procedure involves the removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist examines the bone marrow, blood, and bone to look for signs of cancer. This procedure is not needed in all cases. Your physician will review with you whether a bone marrow biopsy is necessary.

FISH (Fluorescence In Situ Hybridization)

This test looks at genes or chromosomes in cells and tissues. It is used to detect certain chromosomal abnormalities.

Cytogenetic Analysis

This is a test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.


This imaging serves to help determine the disease stage of cancer and to provide a baseline from which to determine your response to treatment. The procedure combines the pictures from a positron emission tomography (PET) scan and a computed tomography (CT) scan. The pictures from both scans are combined to create a more detailed picture than either test would produce by itself. The procedure is done to find tumor cells.


This test is used to identify cells, based on the types of antigens or markers on the surface of the cell. This process helps diagnose the specific type of non-Hodgkin lymphoma by comparing the cancer cells to normal cells of the immune system.


Patients with mantle cell non-Hodgkin lymphoma may have this procedure because this type of cancer can sometimes invade the GI tract.



Additional criteria are used to further identify subgroups within each stage, identified as A, B, E, and S:

  • A: The patient does not have B symptoms (fever, weight loss, or night sweats).
  • B: The patient has B symptoms.
  • E: Cancer is in an organ or tissue outside the lymph system but may be next to an affected area of the lymph system.
  • S: Cancer is in the spleen.

Stage I

Stage I is divided into stage I and stage IE.

  • Stage I: Cancer is found in one lymph node group.
  • Stage IE: Cancer is found outside the lymph system in one organ or area.

Stage II

Stage II is divided into stage II and stage IIE.

  • Stage II: Cancer is in two or more lymph node groups, either above or below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).
  • Stage IIE: Cancer is in one or more lymph node groups either above or below the diaphragm and outside the lymph nodes in a nearby organ or area.

Stage III

Stage III is divided into stage III, stage IIIE, stage IIIS, and stage IIIE+S.

  • Stage III: Cancer is in lymph node groups above and below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).
  • Stage IIIE: Cancer is in lymph node groups above and below the diaphragm and outside the lymph nodes in a nearby organ or area.
  • Stage IIIS: Cancer is in lymph node groups above and below the diaphragm, and in the spleen.
  • Stage IIIE+S: Cancer is in lymph node groups above and below the diaphragm, outside the lymph nodes in a nearby organ or area, and in the spleen.

Stage IV

In stage IV, the cancer is:

  • Outside the lymph nodes throughout one or more organs, with or without lymph node involvement.
  • In the lung, liver, bone marrow, or cerebrospinal fluid (CSF).

Second Opinions

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Consultations and Second Opinions

We believe there is great value for patients with suspected or diagnosed non-Hodgkin lymphoma to receive a second opinion. Many times, our pathologists render a different diagnosis from that of the referring doctor.

We routinely evaluate specimens sent to us from outside centers. These specimens are evaluated by our entire team, including our expert hematopathologists.

Reasons to consider a second opinion include:

  • To confirm your diagnosis.
  • If you have received a diagnosis elsewhere and want to be treated at Dana-Farber Brigham Cancer Center.
  • To determine the optimal therapy and timing of treatment.
  • To learn more about your cancer from specialists who are world leaders in this disease, and who have treated hundreds of other patients like you.
  • To learn if you're eligible for a clinical trial.

Scheduling Your Appointment

To schedule your second opinion appointment:

Call 617-632-6028 or 617-632-5138
Online: Complete the Appointment Request Form

Can't travel to Boston in person? Take advantage of our Online Second Opinion service.

For Referring Physicians

Because you, the referring physician, are an integral part of your patient's care team, we are committed to collaborating with you to provide the best care for your patient.