At a Glance

Why Get Tested?

To help diagnose a T-cell lymphoma; sometimes to detect and evaluate residual lymphoma cells

When To Get Tested?

When a health care practitioner thinks that you may have a T-cell lymphoma; when a healthcare practitioner would like to assess whether treatment has been effective and/or whether lymphoma has recurred

Sample Required?

A bone marrow, tissue such as a lymph node (biopsy), or body fluid sample; sometimes a blood sample drawn from a vein in your arm

Test Preparation Needed?


What is being tested?

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

T-cells are a type of lymphocyte (a kind of white blood cell, WBC) that helps to protect the body from infection. Rearrangements in certain parts of their DNA called receptor genes are a normal part of their development. These rearrangements are associated with the development of a large repertoire of diverse T-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 T-cells, the cells and their gene rearrangement profiles are very diverse.

In lymphoma, the T-cells in affected tissue (such as blood, lymph node, or skin) are identical and their gene rearrangement profiles are likewise identical. 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.

A T-cell receptor gene rearrangement test evaluates the T-cells in a person’s sample to determine whether the majority of T-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 for persistent, residual, or recurrent lymphoma.

Most non-Hodgkin lymphomas in the U.S. are B-cell lymphomas (about 85%), according to the American Cancer Society. Close to 15% are T-cell lymphomas. There are many different types of T-cell lymphomas, but each is rare.

For additional details about T-cells and this testing, see Common Questions below.

How is the sample collected for testing?

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


Common Questions

How is it used?

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

There are many different types of T-cell lymphoma and each has different characteristics, prognosis, and likely response to therapy. Several classification systems have been used to describe them. The most recent is the World Health Organization’s.

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

  1. 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.
  2. A pathology evaluation of blood smear, bone marrow, lymph node, skin and/or other tissue biopsy samples is performed. These samples are examined under a microscope by a trained laboratorian, usually a pathologist.
  3. If indicated, immunophenotyping is performed on blood, bone marrow, or other tissue (such as an enlarged lymph node or tumor) 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.

This testing may also sometimes be performed to evaluate the effectiveness of lymphoma treatment — to detect residual or recurrent disease, the continued presence of abnormal monoclonal T-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.
  • Skin lesions
  • Enlarged spleen and/or liver
  • 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 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 with similar appearance, 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 T-cell lymphoma, or when the healthcare practitioner 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 and to detect residual or recurrent disease.

What does the test result mean?

Results of testing are typically interpreted by a healthcare practitioner 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 histopathology, immunophenotyping information, an understanding of the strengths and limitations of different testing methods.

This testing helps confirm whether a cloned 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 individual 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
  • Extranodal NK/T-cell lymphoma, nasal type
  • Mycosis fungoides
  • Sézary syndrome
  • Peripheral T-cell lymphoma, unspecified
  • Precursor T-cell neoplasm (T lymphoblastic leukemia/lymphoma)
  • T-cell large granular lymphocytic leukemia
  • T-cell prolymphocytic leukemia

A negative result on this test does not necessarily rule out a lymphoma. A person with a negative result for a clonal T-cell receptor gene rearrangement 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, or if the lymphoma is of the B-cell type.

What are some other details about T cells?

During an immune response, it is important that T-cells be able to distinguish between a person’s own cells and tissues (self) and foreign and/or infected cells (non-self) as the T-cells are responsible for targeting harmful cells for destruction and for signaling B-cell lymphocytes (another type of WBC) to begin producing antibodies.

Receptors are protein structures on the surface of T-cells that allow them to identify and evaluate self and non-self cells and other substances that can produce an immune response (antigens). There are two types of T-cell receptors, each containing two different subunits. The T-cell receptor genes control the development of these receptor subunits. Rearrangements in these genes are a normal part of T-cell development. The purpose of the rearrangements is to produce a wide variety of receptors within the T-cell population to recognize and address the vast number of antigens that a person may encounter. This means that the receptor gene rearrangements and the receptors in a normal T-cell lymphocyte population are usually very diverse (polyclonal).

With a T-cell lymphoma, an abnormal T-cell lymphocyte begins to clone itself, producing numerous identical cells. The identical, cloned (monoclonal) cells do not function normally, their replication is not regulated, and they may not die as normal cells do. A cancerous monoclonal population of T-cells accumulates, begins to crowd out normal cells, and may eventually spread throughout the lymphatic system and blood to other lymph nodes and tissue, including the bone marrow.

All of the monoclonal cells produced will have identical T-cell receptor gene rearrangement profiles. The cancerous (neoplastic) clones are generally large and therefore the clonal cells are the predominant T-cells present in affected tissue. Detection of a predominant T-cell receptor gene rearrangement profile often indicates the presence of a neoplastic T-cell population. This can help to establish the diagnosis of a T-cell lymphoma or to evaluate for residual or recurrent disease after treatment.

Is there anything else I should know?

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. An individual 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.

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.

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. It requires specialized equipment and interpretation. 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 (prognosis)?

No. A positive testing result only helps to confirm a diagnosis of T-cell lymphoma. The cancer progression and response to treatment is generally determined by the type of a person’s lymphoma, but will also vary from person to person.

How common are T-cell lymphomas?

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. The majority of these cases (about 85%) will be due to B-cell lymphomas; close to 15% will be T-cell lymphomas.



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