Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 56, Num. 3, 2010, pp. 225-225

Journal of Postgraduate Medicine, Vol. 56, No. 3, July-September, 2010, pp. 225

Commentary

Flow cytometric immunophenotyping for the diagnosis of a rare T-LGL neoplasm

Vartholomatos G, Benetatos L¹

Hematology Laboratory, ¹ Department of Hematology, University Hospital of Ioannina, Greece

Correspondence Address: Georgios Vartholomatos, Hematology Laboratory, University Hospital of Ioannina, Greece, gvarthol@cc.uoi.gr

Code Number: jp10067

Flow cytometric immunophenotyping represents an indispensable tool for the diagnosis of hematological malignancies and may assist in the diagnosis and classification of T and NK lymphoid cell neoplasms. ^[1]

T-cell large granular lymphocytic (T-LGL) leukemia is not an uncommon neoplasm and covers a heterogeneous spectrum of disorders including autoimmune diseases and hematological disorders. ^[2] T-LGL leukemia is a well-defined malignancy of CD8+ lymphocytes, is equally distributed among males and females with a median age at presentation of 60 years, and a median survival that reaches 10 years. Symptoms and signs include constitutional symptoms, fever and recurrent bacterial infections, splenomegaly, neutropenia and lymphocytosis. ^[2,3] The T-LGL malignant cell is characterized by the following immunophenotype: CD8 ⁺ , CD2 ⁺ , cytoplasmic CD3 ⁺ , CD5 ⁺ , CD7 ⁺ , CD57 ⁺ , TCRab⁺ , CD4 ^- , CD16 ^- , CD56 ^- . ^[3] To date few cases of CD4 ⁺ T-LGL leukemia have been described, ^[3],[4] while co-expression of CD56 antigen is not very frequent, ^[5] and is associated with an overall poor prognosis. ^[2]

In this issue of the journal authors of the article "CD4 ⁺ /NKa ⁺ /CD8 ^dim+ T-cell large granular lymphocytic leukemia: A rare entity" describe a rare case of a double CD4/CD8 positive patient with abberant expression of the NK cell marker CD56. ^[6] The patient had a 17-year history of asymptomatic lymphocytosis with a diagnosis of a lymphoproliferative disorder (not further categorized) based on the evaluation of circulating lymphocytes' morphology on a peripheral blood smear. Flow cytometric immunophenotyping performed later, established the diagnosis of a T-cell LGL leukemia with an aberrant phenotype. Although authors did not prove TCRab clonality they concluded that the double CD4/CD8 positivity might be accepted as evidence of clonality. More than the rarity of their case, as very few similar cases have been described, the authors highlight the power of flow cytometry, a rapid and accurate method, in establishing the correct diagnosis of T-cell neoplasms. Again, although the patient presented an aberrant CD56 ⁺ phenotype and one could aspect a more aggressive clinical course, it seems that the CD4 positivity "equilibrates" such negative predictive factor.

In conclusion, CD4 ⁺ /NKa ⁺ /CD8 ^dim+ remains a rare form of hematological neoplasm, in which the immune system seems to expand itself in order to control the tumor growth, ^[4] with the CD4 ⁺ T-LGL presenting an indolent clinical course despite the presence of CD56 antigen, and a higher incidence of an associated neoplasia. It is well known that flow cytometric studies are indispensable for the diagnosis of mature B-cell lymphoid tumors, but is less used and is a less well-established procedure for the diagnosis of T- and NK-cell lymphoid tumors, often requiring additional information from other sources such as morphologic review of fixed tissues, Fluorescence in Situ Hybridization stains and other studies. ^[1] However, the use of flow cytometry in T-cell neoplasms is expanding every day with promising results, ^[7] adding new information to the current knowledge and contributing to the classification of T-cell neoplasms.

References

1.	Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood 2008;111:3941-67.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.	Rose MG, Berliner M. T-cell large granular lymphocyte leukemia and related disorders. Oncologist 2004;9:247-58.  Back to cited text no. 2
3.	O'Malley DP. T-cell large granular leukemia and related proliferations. Am J Clin Pathol 2007;127:850-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.	Lima M, Almeida J, Dos Anjos Teixeira M, Alguero Md Mdel C, Santos AH, Balanzategui A, et al. TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. Am J Pathol 2003;163:763-71.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.	Lundell R, Hartung L, Hill S, Perkins SL, Bahler DW. T-cell large granular lymphocyte leukemias have multiple phenotypic abnormalities involving pan-t-cell antigens and receptors for MHC molecules. Am J Clin Pathol 2005;124:937-46.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.	Dadu T, Rangan A, Bhargava M. CD4 + /NKa + /CD8 dim+ T-cell large granular lymphocytic leukemia: A rare entity. J Postgrad Med 2010;56:223-4.  Back to cited text no. 6  [PUBMED]
7.	Benetatos L, Dova L, Baxevanos G, Kolaitis NI, Bourantas KL, Vartholomatos G. Peripheral blood flow cytometry based diagnosis in primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: Implications for more extensive use. thCytometry B Clin Cytom 2009;76:102-6.  Back to cited text no. 7

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