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Lymphoma — The Path to Diagnosis

Posted on July 27, 2020
Medically reviewed by
Todd Gersten, M.D.
Article written by
Alison Channon

Lymphoma is a blood cancer where lymphocytes (certain types of white blood cells) develop abnormally and crowd out healthy cells. Hodgkin lymphoma (HL, also called Hodgkin disease) and non-Hodgkin lymphoma (NHL, also called non-Hodgkin’s lymphoma) are the two primary categories of lymphoma.

Hodgkin and non-Hodgkin lymphoma are cancers that originate in the lymphatic system, a key component of the body’s immune system. The lymphatic system consists of the bone marrow; organs including the spleen, lymph nodes, and thymus; and vessels that transport fluids throughout the body. A healthy lymphatic system removes bacteria, excess fluid, and waste material from old and damaged cells. Lymphoma is related to other blood cancers, including leukemia, myeloma, and myeloproliferative neoplasms (MPNs).

A person may start on the path to a lymphoma diagnosis because they are experiencing general symptoms consistent with Hodgkin lymphoma or non-Hodgkin lymphoma. These symptoms include:

  • Fever
  • Night sweats
  • Unexplained weight loss
  • Abdominal pain
  • Cough
  • Fatigue
  • Swollen or enlarged lymph nodes

Fever, night sweats, and weight loss are considered “B symptoms.” B symptoms are systemic, meaning they affect the entire body. The presence of B symptoms influences staging and prognosis for lymphoma.

Sometimes people don’t exhibit any obvious symptoms of lymphoma, and the cancer is found when routine blood work or other tests return abnormal results.

Who Gets Lymphoma?

Most cases of NHL occur in people in their 60s or older. Hodgkin lymphoma frequently occurs in young adults, but can also impact older adults. Overall, HL and NHL occur more often in men than women. In the United States, lymphoma is more common among white Americans than Black or Asian Americans.

Tests Used to Diagnose Lymphoma

A variety of medical tests can be used to diagnose and stage Hodgkin and non-Hodgkin lymphoma. Many of the tests for HL and NHL overlap. Some tests are used to confirm a diagnosis, while others are used to determine the type of lymphoma and the stage of the illness.

There are two primary types of Hodgkin lymphoma and dozens of types of non-Hodgkin lymphoma. The subtypes of NHL are divided into two categories based on the type of lymphocyte — white blood cell — that has become cancerous. The two main varieties of lymphocytes are B cells (also called B lymphocytes) and T cells (also called T lymphocytes). Most cases of NHL are B-cell lymphomas, but there are also T-cell lymphomas.

Medical History and Physical Examination

If you have symptoms consistent with lymphoma, a medical history is likely the first step toward diagnosing both HL and NHL. Your physician will conduct an in-depth medical history and ask you about the presence of lymphoma symptoms and any disease risk factors you may have. Your provider may also conduct a physical exam to assess the lymph nodes in your neck, underarms, and groin. Swollen lymph nodes are a common symptom of both HL and NHL. They may also assess your spleen and liver to identify any enlargement.

Lymph Node Biopsy

If your health care provider identifies swollen lymph nodes during a physical exam, they may call for a lymph node biopsy. This involves removing part of or an entire enlarged lymph node. Depending on the location of the lymph node being biopsied, you will receive a local anesthetic or general anesthesia. A lymph node biopsy can help identify the type and subtype of lymphoma you have and help your care team develop a treatment plan.

A hematopathologist — a doctor who specializes in diagnosing blood, bone marrow, and lymphatic diseases — will evaluate your biopsy sample. When assessing a lymph node sample, a hematopathologist will look for cell structures that are consistent with the different types of lymphoma.

In the case of Hodgkin lymphoma, Reed-Sternberg (RS) cells and Hodgkin cells will likely be present. Reed-Sternberg cells are large, abnormal B cells with a double nucleus. Hodgkin cells are smaller than RS cells but larger than normal lymphocytes.

In the case of NHL, the sample from the biopsy will be used to help determine if B cells or T cells have become cancerous. B-cell and T-cell are the two primary categories of NHL.

There are three main types of lymph node biopsies used to diagnose Hodgkin and non-Hodgkin lymphoma.

Excisional or Incisional Biopsy

In an excisional biopsy, a surgeon removes an entire lymph node. In an incisional biopsy, a surgeon removes a large portion of a lymph node. A larger tissue sample size allows for greater accuracy in diagnosis. Local anesthetic is used for lymph nodes close to the surface of the skin. General anesthesia is used for lymph nodes in the chest or stomach.

Core Needle Biopsy

A core needle biopsy uses a needle to collect a small sample of tissue from a lymph node. This method is usually used for lymph nodes in areas that are difficult to reach using excisional or incisional biopsy. The amount of tissue collected may not be sufficient for diagnosis.

Fine Needle Aspirate Biopsy

A fine needle aspirate (FNA) biopsy uses a very small needle to collect cells from a lymph node. The very small sample of cells is insufficient to confirm an HL or NHL diagnosis. FNA biopsy is often used to test for cancer relapse.

Immunophenotyping and Chromosome Tests

Immunophenotyping looks for certain cell markers in a blood sample and lymph node sample. The presence of certain cell markers or proteins can help to diagnose the subtype of HL or NHL. Immunophenotyping is particularly important for NHL. This technique can help doctors determine if the cancer cells are B cells or T cells and identify other important characteristics.

Chromosome tests are used to evaluate the DNA of cancer cells for specific genetic mutations. This is another tool for identifying the subtype of lymphoma. These additional tests are often not needed for Hodgkin lymphoma.

Immunophenotyping and chromosome tests can be very important for evaluating prognosis and determining the best treatment plan for certain types of non-Hodgkin lymphoma.

Lumbar Puncture

A lumbar puncture, also called a spinal tap, may be used in cases of NHL to determine if the cancer cells have spread to the cerebrospinal fluid (CSF). This test is usually only done if there are symptoms that indicate that lymphoma has spread to the brain.

Staging Hodgkin Lymphoma and Non-Hodgkin Lymphoma

After receiving a diagnosis of Hodgkin or non-Hodgkin lymphoma, you may undergo additional testing to confirm the subtype or stage (extent) of your lymphoma. HL and NHL can each be classified into four stages (stage I through IV). In both illnesses, stage I is the most localized and stage IV is the most widespread.

Bone Marrow Aspiration and Biopsy

After receiving a diagnosis of Hodgkin or non-Hodgkin lymphoma, you may undergo a bone marrow aspiration and bone marrow biopsy to see if lymphoma cells have spread to the bone marrow. These two tests are usually done at the same time. A bone marrow aspiration uses a smaller needle and removes liquid bone marrow. A bone marrow biopsy uses a larger needle to remove solid bone marrow.

Bone marrow samples are usually taken from the hip. You will receive a local anesthetic to numb the site of the biopsy. Your doctor may provide a mild sedative upon request to help you stay relaxed. You may experience pain at the site of the biopsy for a few days after the procedure.

Imaging Tests: X-Ray, PET Scan, CT Scan

Imaging tests can be used to stage HL or NHL. They can also be used to identify the cause of certain symptoms, check if treatment is working, or check for cancer recurrence.

Chest X-Ray

A chest X-ray can be used to identify swollen lymph nodes in the chest for both Hodgkin lymphoma and non-Hodgkin lymphoma.

CT Scan

A computed tomography (CT) scan can help identify cancer in the stomach, chest, head, or pelvis. CT scans are also sometimes used to help guide biopsies.

PET Scan

A positron emission tomography (PET) scan may be used to determine if a swollen lymph node contains lymphoma cells or check for small areas of cancer. PET scans are also used to evaluate the effectiveness of chemotherapy or monitor lymph nodes after treatment.

Blood Tests

Blood tests are often used to evaluate the extent of a person’s lymphoma. They can also assist in diagnosing both types of lymphoma.

Complete Blood Count (CBC)

A CBC test measures the number of red blood cells, white blood cells, and platelets in a blood sample. Low blood cell counts could be a sign that lymphoma has spread to the bone marrow. This could indicate a more advanced stage of lymphoma. CBC tests are used for HL and NHL.

Erythrocyte Sedimentation Rate (ESR)

An ESR test measures how quickly red blood cells settle in a test tube. Faster than normal settling can indicate inflammation. This test is usually used for Hodgkin lymphoma.

Other Blood Tests

Whether you have Hodgkin or non-Hodgkin lymphoma, you may undergo additional blood tests to evaluate liver and kidney function. Blood tests may also be used to check for conditions like HIV or hepatitis B or C. The presence of these viruses could impact your treatment plan.

Lymphoma Condition Guide

A MyLymphomaTeam Member said:

Does anyone know what the progression of symptoms are with CLL?

posted 21 days ago

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Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Alison Channon has nearly a decade of experience writing about chronic health conditions, mental health, and women's health. Learn more about her here.

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