At a Glance

Why Get Tested?

To help diagnose a B-cell lymphoma; to detect and evaluate residual cancer cells

When To Get Tested?

When a health care practitioner thinks that you may have a B-cell lymphoma; sometimes to evaluate the effectiveness of treatment or to evaluate for recurrent disease

Sample Required?

A bone marrow or other tissue biopsy procedure is performed by a doctor or other trained specialist. Body fluid samples are obtained by inserting a needle into the body cavity and withdrawing a portion of the fluid with a syringe. Sometimes, a blood sample is obtained by inserting a needle into a vein in the arm.

Test Preparation Needed?


What is being tested?

This test detects characteristic changes (rearrangements) in specific genes in B-cells. This information can be helpful in diagnosing a B-cell lymphoma.

B-cells are a type of lymphocyte (a kind of white blood cell, WBC) that produces antibodies in response to infections or other “foreign invaders.” Rearrangements in certain parts of their DNA called immunoglobulin genes are a normal part of their development. These rearrangements are associated with the development of a large repertoire of diverse B-cells, allowing them to protect against many different kinds of infections. The final order in which the genes are rearranged is called a gene rearrangement profile. Within any normal population (sample) of B cells, the cells and their gene rearrangement profiles are very diverse.

In a B-cell lymphoma, the lymphoma cells are virtually identical and their gene rearrangement profiles are likewise identical. Lymphomas arise when an abnormal B cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells.

A B-cell immunoglobulin gene rearrangement test evaluates the cells in a person’s sample to determine whether the majority of B-cell rearrangement profiles are diverse or identical. This information, along with clinical signs and symptoms and results of other laboratory tests, can help clarify a person’s diagnosis, or evaluate the persistence or recurrence of lymphoma.

About 85% of non-Hodgkin lymphomas in the U.S. are B-cell lymphomas, according to the American Cancer Society (ACS).

Common Questions

How is it used?

B-cell immunoglobulin gene rearrangement tests are used to help diagnose non-Hodgkin B-cell lymphomas and evaluate for residual or recurrent disease after treatment.

There are many different types of B-cell lymphoma and each has different characteristics, prognoses, and a likely response to therapy. Several classification systems have been used to describe them. The most recent is the World Health Organization’s.

Testing for B-cell lymphomas involves several types of tests:

  • Complete Blood Count (CBC) and a WBC differential to evaluate the number, types, and maturity of white blood cells present in the blood. Results may reveal an increased number of lymphocytes and/or presence of abnormal lymphocytes.
  • Pathology evaluation of blood smear, bone marrow, lymph node and/or other tissue biopsy samples. These samples are examined under a microscope by a trained laboratorian, usually a pathologist.
  • If indicated, immunophenotyping is performed on blood, bone marrow, or other tissue (e.g., enlarged lymph node, tumor). This test detects the presence or absence of certain markers on the membrane of the cells or inside the cells. These commonly used markers are called clusters of differentiation (CD) and are listed numerically. Patterns of antigens (presence or absence) can provide information as to whether the B cells are clones (monoclonal) and can further help classify a B-cell lymphoma.

An excess of B cells can be benign or malignant. If, at this point, there is still no conclusion whether a person has a benign or malignant lymphocyte population, B-cell immunoglobulin gene rearrangement testing can be performed.

This testing may also sometimes be performed to evaluate the effectiveness of lymphoma treatment, that is, to detect residual or recurrent disease, the continued presence of abnormal monoclonal B cells.

When is it ordered?

Testing is performed when a person has signs and symptoms that suggest a lymphoma, such as:

  • One or more swollen but painless lymph nodes—depending on the site of the affected lymph node, symptoms may involve areas of the chest, armpit, neck, abdomen, or groin area, for example
  • Fatigue
  • Fever
  • Night sweats
  • Unexplained weight loss
  • Neurologic symptoms that may suggest central nervous system involvement

Findings from a CBC and differential may be the first indication that a person might have a blood cell cancer as symptoms of early lymphoma may be absent, mild, or nonspecific.

Testing may be done when other laboratory tests indicate that a lymphoma may be present and/or when other tests are inconclusive. Some examples include:

  • An increased number of lymphocytes, especially abnormal-looking lymphocytes, as determined with a CBC and a blood smear examination
  • Signs of lymphoma in a tissue biopsy, body fluid or bone marrow sample
  • With immunophenotyping (e.g., flow cytometry, immunohistochemistry), antigen groupings that are inconclusive for a B-cell lymphoma, or when the doctor wants to confirm a diagnosis of lymphoma based on histopathology and immunophenotyping

Testing may also be ordered when a person has been treated for a lymphoma to evaluate the effectiveness of treatment, that is, to detect residual or recurrent disease.

What does the test result mean?

Results of testing are typically interpreted by a doctor who specializes in pathology, in particular, pathology dealing with blood, blood cells, and bone marrow cells (hematopathology). Results must be interpreted in conjunction with clinical findings, other test results including pathology immunophenotyping information, an understanding of the strengths and limitations of different testing methods, and with an understanding of the range of findings in a “normal” lymphocyte cell population.

In general, if a significant clonal B-cell population is detected and other associated tests are in agreement, then it is likely that the individual tested has a B-cell lymphoma.

Examples of lymphomas that may be detected by gene rearrangement testing include:

  • Chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Burkitt lymphoma
  • Diffuse large B-cell lymphoma
  • Follicular lymphoma
  • Hairy cell leukemia
  • Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia
  • Mantle cell lymphoma
  • Marginal zone lymphoma

A negative result on this test does not necessarily rule out a lymphoma. A person can be negative for a clonal B-cell immunoglobulin gene rearrangement but may still have lymphoma. A test may also be negative if the test method is not sensitive enough to detect the rearrangement, or if the clonal lymphocytes from the person tested have mutations that are not detected by the test.

What are some other details about B cells?

B cells contain specific areas (genes) in their DNA that code for the production of antibodies (also known as immunoglobulins).The immunoglobulin genes consist of numerous, discontinuous coding segments. As B cells develop and mature, these DNA segments are rearranged in a controlled fashion such that each mature B cell has a unique rearrangement profile. When the body is exposed to antigen, such as bacteria or viruses, the B-cell immunoglobulin genes undergo a permanent rearrangement in order to produce antibodies directed against that threat. For instance, if a person is exposed to a rubella virus, then some of the B cells change and become rubella antibody-secreting cells. If a person is exposed to a hepatitis B virus, then some of the B cells become hepatitis B antibody-secreting cells.

The body maintains a library of antibody “blueprints” so that the next time it is exposed to a threat, it can use the B-cell blueprint to rapidly produce large quantities of a specific antibody. This means that the population of mature B cells is normally diverse (polyclonal) with small amounts of many different kinds of antibodies and temporary increases in specific antibodies as needed to counter an exposure. In this setting, B-cell expansions are polyclonal, with each clone containing relatively few cells and no one clone predominating.

With a B-cell lymphoma, an abnormal B cell is formed and begins to clone itself. The identical, cloned (monoclonal) cells do not function normally, their replication is not controlled by the immune system, and they may not die as normal cells do. A monoclonal population of B cells accumulates, begins to crowd out normal cells, and may eventually spread through the lymphatic system and blood to other lymph nodes or tissue, including bone marrow.

All of the monoclonal B cells produced will have an identical immunoglobulin gene rearrangement profile. The neoplastic clones are generally large, and therefore the clonal cells are the predominant B cells present in involved tissue (e.g., lymph node, bone marrow, blood, body fluid). Detection of a predominant immunoglobulin gene rearrangement profile often indicates the presence of a clonal B-cell population. This can help establish the diagnosis of a B-cell lymphoma or evaluate for residual or recurrent disease after treatment.

Is there anything else I should know?

According to the American Cancer Society (ACS), non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States. ACS estimates that about 72,240 people will be diagnosed with NHL in 2017 and as many as 20,140 will die of it.

Sample collection and testing may need to be repeated when the initial sample does not contain enough DNA to test.

The detection of a clonal immunoglobulin gene rearrangement is not synonymous with the presence of B-cell lymphoma. An individual may have a clonal B-cell population and not have cancer. Conditions such as autoimmune disorders, immune suppression, and immune deficiencies are sometimes associated with small clonal B-cell populations. This means that one or more groups of cloned B-cells may be present in a person’s lymphocyte population without it being considered a lymphoma.

Since false positive and false negative results can be associated with this testing, the results must be interpreted in the context of other clinical and pathologic findings.

Since plasma cells are terminally differentiated B cells, immunoglobulin gene rearrangement testing can also be seen in plasma cell neoplasms, such as multiple myeloma and plasmacytoma.

How long will it take for results?

That depends on the laboratory performing the testing. It is not a routine test and not every laboratory offers it. Your sample may be sent to a reference laboratory and it may be several days before results are available.

Can results of testing be used to determine the course of my cancer?

No. A positive testing result only helps to confirm a diagnosis of B-cell lymphoma and does not point to a specific subtype of B-cell lymphoma. The clinical course and response to treatment are generally determined by the subtype of a person’s lymphoma, along with certain genetic abnormalities.

How common are B-cell gene rearrangements?

B-cell immunoglobulin genes are constantly rearranging themselves to produce unique immunoglobulins. These rearrangements are normal. The immunoglobulin genes consist of numerous, discontinuous coding segments. As B cells develop and mature, a portion of DNA that contains one full DNA sequence of one of the genes breaks into pieces. After rearrangement, only some of the pieces are kept, which are joined back together in a specific set of steps. To visualize this, imagine that you have a piece of paper with a set of instructions on it, several paragraphs long and containing hundreds of words. Now imagine that you pick and choose words from multiple locations on the page – a sufficient number to form a sentence. Then you get rid of the rest of the words and put together your sentence. You started with a page and ended up with a sentence, but both make sense as you read them and, in this case, both represent “functional genes.” It is not hard to see that many different sentences could have been constructed from the same set of instructions. In a similar fashion, the B-cell customization process can be used to produce a large number of unique B-cell gene arrangements.

Elsewhere on the Web

American Cancer Society: Non-Hodgkin Lymphoma
National Cancer Institute: Lymphoma
MedlinePlus Medical Encyclopedia: Non-Hodgkin lymphoma
Leukemia & Lymphoma Society


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