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Non-Hodgkin Lymphoma Diagnosis: What You Need To Know

Posted on July 28, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Aminah Wali, Ph.D.

Doctors may conduct a variety of tests if they suspect that you have non-Hodgkin lymphoma (NHL). Non-Hodgkin lymphoma is cancer that affects lymphocytes, a type of white blood cell of the immune system that helps the body fight infection. There are T lymphocytes (T cells) and B lymphocytes (B cells). NHL can arise from either type, but it most commonly forms in B cells. Genetic changes can cause lymphocytes to divide out of control, giving rise to lymphoma.

NHL usually forms in the lymph nodes, but it may also be extranodal, meaning cancer occurs in other tissues of the lymphatic system, such as the spleen, bone marrow, liver, and gastrointestinal tract. Tests for diagnosis and staging may take such presentations into account.

Diagnostic Tests for Non-Hodgkin Lymphoma

Several medical and laboratory tests help doctors diagnose NHL. Other tests also help to identify what particular subtype of NHL a person has.

Medical History and Physical Examination

Initial evaluation starts with a history and physical examination. People with non-Hodgkin lymphoma often experience B symptoms — fevers, night sweats, and rapid weight loss — along with other signs and symptoms of lymphoma like swollen lymph nodes, fatigue, and bloating. A doctor will check externally for swollen lymph nodes (particularly in the neck, groin, and armpits) and other signs of NHL. They will examine the spleen. They will also look into a person’s medical history and determine if there are any risk factors for NHL.

Lymph Node Biopsy

To confirm a diagnosis of NHL, a doctor will likely order a lymph node biopsy. This procedure involves surgical removal of lymph node tissue. The lymph node biopsy is typically either an excisional biopsy (an entire lymph node is removed) or an incisional biopsy (a portion of a lymph node is removed).

The doctor may also do a less invasive procedure called a needle biopsy. A needle biopsy uses a small needle to remove a tissue sample from a lymph node. There are two types of needle biopsy procedures: core needle biopsy, which uses a small hollow needle, and fine needle aspiration biopsy, which uses an even smaller needle.

Needle biopsies are not often used to diagnose lymphoma because they usually don’t remove enough tissue for proper analysis. Needle biopsies may, however, be used to determine if the cancer is spreading to other parts of the body.

You may be given either local or general anesthesia before a biopsy, depending on the location of the lymph node. After your doctor obtains the sample, the tissue will be analyzed under a microscope for the presence of lymphoma cells. The appearance of non-Hodgkin lymphoma cells can be distinguished from cells of Hodgkin lymphoma — the other main type of lymphoma that is less common than NHL. A pathologist’s analysis of the biopsy sample can also help determine the specific subtype of NHL.

Other Laboratory Tests

Laboratory tests such as immunohistochemistry and flow cytometry identify cancer cells based on specific protein markers on the cell surface. These tests may be recommended to help identify which subtype of NHL you have.

Staging Tests for Non-Hodgkin Lymphoma

NHL can be classified as stages 1 through stage 4. Stages 1 and 2 indicate early-stage disease, whereas stages 3 and 4 indicate advanced, more widespread disease. After a diagnosis is confirmed, doctors may use several tests to determine what stage the cancer is. Staging is important to understand the prognosis and select treatment.

Blood Tests

Blood tests are routinely performed after an NHL diagnosis and can measure different factors affected by the stage, or extent, of disease.

Complete Blood Cell Count

A complete blood cell count measures the levels of red blood cells, white blood cells, and platelets in the blood. Advanced-stage NHL can cause low blood cell counts due to higher numbers of lymphoma cells in the blood and bone marrow.

Protein Levels

Blood tests can measure levels of lactate dehydrogenase (LDH), a protein that is released into the blood when cells are damaged. Higher levels of LDH in the blood indicate more cell damage caused by NHL. NHL may also cause high blood levels of another protein called beta-2 microglobulin.

Viral Infection

A doctor may also recommend blood tests to look for evidence of viral infection, particularly hepatitis B virus, Epstein-Barr virus, hepatitis C virus, and HIV. These viruses may affect treatment options.

Other Measurements

Blood tests can measure indicators of liver and kidney function, which may be affected by NHL. Women of reproductive age should also undergo a pregnancy test, because many cancer treatments can be harmful to a fetus. You may also consider sperm or ovary preservation if you want to have children after treatment.

Bone Marrow Test

A bone marrow aspiration and biopsy can determine if there are lymphoma cells in the bone marrow. A doctor uses a small needle to remove liquid bone marrow for aspiration or to collect a tissue sample for a biopsy. It is not uncommon to experience pain during the procedure. Bone marrow tests may be performed for aggressive or advanced-stage cases of NHL, but they may not be recommended in all cases of early-stage disease.

Imaging Tests

Imaging tests use different techniques to take images of organs in the body. These tests are useful for looking for:

  • Enlarged lymph nodes
  • Spread to other tissues
  • Large tumors present at one or a few sites

X-Ray

A chest X-ray may be recommended to view enlarged lymph nodes in the chest.

Computerized Tomography

Computerized tomography (CT) scans use many X-rays to take detailed images of tissues. A CT scan can look for enlarged lymph nodes or other affected organs, such as the spleen or liver.

Positron Emission Tomography

Positron emission tomography (PET) scans use radioactive sugar to detect cancer cells. A PET scan is useful for finding small numbers of cancer cells in areas that may look normal on a CT scan. Sometimes, a PET scan and CT scan can be performed at the same time, known as a PET-CT scan. PET scans may be repeated after two or more treatment cycles to assess response, which provides information about prognosis and subsequent treatment.

Magnetic Resonance Imaging

MRI uses magnets and radio waves to take images of tissues. An MRI may be recommended to see if there’s involvement of the brain or spinal cord, but overall, MRI is less commonly used for NHL than CT and PET-CT.

Lumbar Puncture

Also known as a spinal tap, a lumbar puncture involves using a thin needle to remove a sample of cerebrospinal fluid from the spinal cord for analysis. As with an MRI, a lumbar puncture is usually only recommended in rare cases of NHL that have spread to the central nervous system, or the less common types that have the potential to do so.

Other Tests

Some additional tests are only required if a specific subtype of NHL is suspected. For example, a colonoscopy or endoscopy may be recommended if you have mantle cell lymphoma or gastric mucosa-associated lymphoid tissue (MALT) lymphoma. If you have MALT, a Helicobacter pylori test may be done.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. On MyLymphomaTeam, more than 8,500 members understand what it’s like to face lymphoma and can provide support and answers.

Are you or a loved one newly diagnosed with non-Hodgkin lymphoma? Share your experience in the comments below, or start a conversation by posting on MyLymphomaTeam.

All updates must be accompanied by text or a picture.
Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here.

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