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

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. There are many different types of B-cell lymphoma and each has different characteristics, prognosis, and therapy. Several classification systems have been used to describe them. The most recent is from the World Health Organization (for more on this, see the Lymphoma article).

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

• Full Blood Count (FBC) 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 the presence of abnormal lymphocytes.
• Pathology evaluation of blood film, bone marrow, lymph node and/or other tissue biopsy samples. These samples are examined under a microscope by a specialist pathologist or scientist.
• If indicated, immunophenotyping is performed on blood, bone marrow, or other tissue (e.g., enlarged lymph node, tumour) using a method such as flow cytometry or immunohistochemistry. This test detects the presence or absence of certain markers on the outer 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.

A proliferation 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.

Testing may 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.

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

Findings from a FBC 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 FBC and a blood film 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
• In the vast majority of cases, B cell lymphoma can be clearly diagnosed with immunophenotyping or special staining of biopsy specimens, so B cell gene rearrangement studies are only required in rare and difficult to diagnose cases.
   

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.

Results of testing are typically interpreted by a pathologist and/or clinician who specialises in dealing with blood, blood cells, and bone marrow cells (haematologist). Results must be interpreted in conjunction with clinical findings, other test results including 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:

• B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma
• Burkitt lymphoma
• Diffuse large B-cell lymphoma
• Follicular lymphoma
• Hairy cell leukaemia
• Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinaemia
• Mantle cell lymphoma
• Marginal zone B-cell lymphoma

Each year in Australia, about 3,500 people are diagnosed with a type of B-cell or T-cell lymphoma making them the most common type of blood cancer diagnosed. Overall, they represent the sixth most common type of cancer in men, and the fifth most common type of cancer in women.

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 does not always indicate the presence of B-cell lymphoma. Someone 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. 

If someone is negative for a clonal B-cell immunoglobulin gene rearrangement, they 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 have mutations that are not detected by the test.

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.

No. This testing is only required if routine diagnostic procedures are not sufficient to make an accurate diagnosis.

No. A positive test 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.

B-cell immunoglobulin genes are rearranged in each B-cell 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 visualise 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 customisation process can be used to produce a large number of unique B-cell gene arrangements.