T-cell receptor gene rearrangement testing is used to help diagnose T-cell lymphomas and to evaluate for residual or recurrent disease after treatment.

Lymphomas arise when an abnormal T-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 T-cell lymphoma and each has different characteristics, prognosis, and a likely response to therapy. Several classification systems have been used to describe them. The most recent is the World Health Organization's. (For more on this, see the Lymphoma condition page.)

Testing for T-cell lymphomas is done in a step-wise fashion and typically starts with:

1. 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 presence of abnormal lymphocytes.
2. A pathology evaluation of blood film, bone marrow, lymph node, skin and/or other tissue biopsy samples is performed. These samples are examined under a microscope by a specialist pathologist or scientist.
3. If indicated, immunophenotyping is performed on blood, bone marrow, or other tissue (such as an enlarged lymph node or tumour) using a method such as flow cytometry or immunohistochemistry. 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 T-cells are clones (monoclonal) and can further help classify a T-cell lymphoma.

A proliferation of T-cells can be benign or malignant. If, after the above tests are performed, there is still no conclusion as to whether a person has a benign or malignant T-cell population, a T-cell receptor gene rearrangement test can be performed.

Testing may sometimes be performed to evaluate the effectiveness of lymphoma treatment - to detect residual or recurrent disease as evidenced by the continued presence of abnormal monoclonal T-cells.
 

• 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.
• Skin lesions
• Enlarged spleen and/or liver
• Fatigue
• Fever
• Night sweats
• Unexplained weight loss

Findings from a FBC and WBC differential may be the first indication that a person might have a lymphoma as symptoms 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 T-cell lymphoma, or when the doctor wants to confirm a diagnosis of lymphoma based on histopathology and immunophenotyping

Results of testing are typically interpreted by a haematologist – a pathologist who specialises in blood, blood cells, and bone marrow cells (haematopathology). Results must be interpreted in the context of clinical findings, and other test results including histopathology, immunophenotyping information. They must take into account the range of findings that can be found in a "normal" lymphocyte cell population.

This testing helps confirm whether a clonal population of T-cell lymphocytes is present and helps confirm and/or clarify a person's diagnosis. In general, if a significant clonal T-cell population is detected and other associated tests are in agreement, it is likely that the person tested has a T-cell lymphoma or that lymphoma has recurred.

Examples of lymphomas that may be detected by this testing include:

• Adult T-cell leukemia/lymphoma (ATLL)
• Anaplastic large-cell lymphoma
• Angioimmunoblastic T-cell lymphoma
• Enteropathy-associated T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Mycosis fungoides
• Peripheral T-cell lymphoma, unspecified
• Precursor T-cell neoplasm (T lymphoblastic leukemia/lymphoma)
• Sézary syndrome
• T-cell large granular lymphocytic leukemia
• T-cell prolymphocytic leukemia

In 2011, 5237 new cases of lymphoma were diagnosed in Australia. Non-Hodgkin lymphoma is more common, with 4631 new cases diagnosed in 2011, compared with 606 cases of Hodgkin lymphoma. The risk of being diagnosed with non-Hodgkin lymphoma by age 85 is 1 in 41. The risk of being diagnosed with Hodgkin lymphoma by age 85 is 1 in 412. The majority of these cases (about 85 per cent) will be due to B-cell lymphomas; almost 15 per cent will be T-cell lymphomas.

Testing may need to be repeated when the sample does not contain enough DNA to test or if the sample is not suitable for testing.

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

If someone is negative for a clonal T-cell receptor 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, or if the lymphoma is of the B-cell type.

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