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Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia

Last updated Oct. 22, 2017


What are other Names for this Test? (Equivalent Terms)

  • Gene Mutation Analysis for Indolent T-Cell Large Granular Lymphocyte Leukemia
  • Test for Molecular Diagnosis of Indolent T-Cell Large Granular Lymphocyte Leukemia 

What is Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia? (Background Information)

  • Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia is a genetic test that is helpful in aiding a diagnosis of indolent T-cell large granular lymphocyte leukemia. The lab test results may also be subsequently useful in taking appropriate treatment decisions
  • Indolent T-cell large granular lymphocyte leukemia is the most common form of large granular lymphocyte leukemia, a type of blood cancer. It is typically seen in middle-aged and older adults
  • Large granular lymphocyte (LGL) leukemia represents a type of lymphoproliferative disorder. Lymphoproliferative disorders are disorders in which there is uncontrolled production of (excess) lymphocytes that occurs due to several reasons
  • Indolent T-cell LGL leukemia does not present with symptoms in over 30% of the patients. In others, it can cause signs and symptoms that include fever, weight loss, and appetite loss, reduced blood cell counts with a variety of symptoms, and swollen spleen and/or liver

The cause of indolent T-cell large granular lymphocyte leukemia may be due to genetic mutations. Many cases of indolent T-cell LGL leukemia have a normal karyotype. Only, less than 10% of the individuals show chromosomal abnormalities that may include:

  • Inversion of 12p
  • Inversion of 14q
  • Deletion of 5q
  • Trisomy of chromosome 3
  • Trisomy of chromosome 8
  • Trisomy of chromosome 14

Also, the presence of a clonal population of T-cells as evidenced by TCR-β/γ (T-cell receptor-beta/gamma) gene rearrangement is essential for a diagnosis.

The above genetic abnormalities can be detected using molecular studies, which may play a significant role in identifying the tumor type, and in some cases, helping the healthcare provider take appropriate treatment decisions.

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for indolent T-cell LGL leukemia may vary from one laboratory to another.

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia Test?

Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia is undertaken in the following situations:

  • To assist (and in some cases, confirm) the initial diagnosis of indolent T-cell LGL leukemia
  • To distinguish other conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the condition

How is the Specimen Collected for Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia?

Following is the specimen collection process for Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Peripheral blood
    • Bone marrow biopsy specimen
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Note:

  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results

Cost ofMolecular Testing forIndolent T-Cell Large Granular Lymphocyte Leukemia:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia Result?

The significance of Molecular Testing for Indolent T-Cell Large Granular Lymphocyte Leukemia is explained:

  • Presence of a positive test result helps aid, and in some cases, confirm the diagnosis of indolent T-cell LGL leukemia
  • The result can help exclude other conditions/tumors with similar histological features
  • It can help determine the prognosis of the patient
  • In some cases, the test results may help in taking treatment decisions

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test
  • Additional mutations are still being discovered in many of these cases. This may further contribute towards diagnosis and treatment. Please consult with your healthcare provider for any information updates

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

Please visit our Laboratory Procedures Center for more physician-approved health information:

http://www.dovemed.com/common-procedures/procedures-laboratory/

References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 10/16/17)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 10/16/17)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 10/16/17)

https://www.leukaemiacare.org.uk/large-granular-lymphocytic-leukaemia (accessed on 10/16/17)

http://theoncologist.alphamedpress.org/content/9/3/247.full (accessed on 10/16/17)

https://rarediseases.info.nih.gov/diseases/9812/large-granular-lymphocyte-leukemia (accessed on 10/16/17)

http://www.hopkinsmedicine.org/kimmel_cancer_center/centers/bone_marrow_failure_disorders/large_granular_leukemia.html (accessed on 10/16/17)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377226/ (accessed on 10/16/17)

https://www.ncbi.nlm.nih.gov/pubmed/19394280 (accessed on 10/16/17)

https://www.ncbi.nlm.nih.gov/pubmed/22041849 (accessed on 10/16/17)

Helpful Peer-Reviewed Medical Articles:

Koskela, H. L., Eldfors, S., Ellonen, P., Van Adrichem, A. J., Kuusanmäki, H., Andersson, E. I., ... & Majumder, M. M. (2012). Somatic STAT3 mutations in large granular lymphocytic leukemia. New England Journal of Medicine366(20), 1905-1913.

Jerez, A., Clemente, M. J., Makishima, H., Koskela, H., LeBlanc, F., Ng, K. P., ... & Guinta, K. (2012). STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood120(15), 3048-3057.

Swerdlow, S. H., Campo, E., Pileri, S. A., Harris, N. L., Stein, H., Siebert, R., ... & Jaffe, E. S. (2016). The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood127(20), 2375-2390.

Lamy, T., & Loughran, T. P. (2011). How I treat LGL leukemia. Blood117(10), 2764-2774.

Gill, H., Ip, A. H. W., Leung, R., So, J. C. C., Pang, A. W. K., Tse, E., ... & Kwong, Y. L. (2012). Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis. Bone marrow transplantation47(7), 952-957.

Chen, Y. H., Chadburn, A., Evens, A. M., Winter, J. N., Gordon, L. I., Chenn, A., ... & Peterson, L. (2011). Clinical, morphologic, immunophenotypic, and molecular cytogenetic assessment of CD4–/CD8–γδ T-cell large granular lymphocytic leukemia. American journal of clinical pathology136(2), 289-299.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Oct. 22, 2017
Last updated: Oct. 22, 2017