Indian Journal of Medical and Paediatric Oncology

: 2019  |  Volume : 40  |  Issue : 3  |  Page : 453--455

CD4+/CD8- T cell large granular lymphocytic leukemia: A rare entity

Ashish Gupta1, Anurag Bansal2, Alok Kumar2,  
1 Department of Hematology and Molecular Biology, Quest Diagnostics India Limited, Gurgaon, Haryana, India
2 Department of Hematology, Quest Diagnostics India Limited, Gurgaon, Haryana, India

Correspondence Address:
Ashish Gupta
Flat No. 101, Tower 14, CHD Avenue, Sector 71, Gurgaon - 122 001, Haryana

How to cite this article:
Gupta A, Bansal A, Kumar A. CD4+/CD8- T cell large granular lymphocytic leukemia: A rare entity.Indian J Med Paediatr Oncol 2019;40:453-455

How to cite this URL:
Gupta A, Bansal A, Kumar A. CD4+/CD8- T cell large granular lymphocytic leukemia: A rare entity. Indian J Med Paediatr Oncol [serial online] 2019 [cited 2020 Sep 22 ];40:453-455
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Large granular lymphocytic leukemia (LGL) is a well-recognized disorder of mature T-cells or NK cells. T-cell LGL leukemia (T-LGL) is characteristically a disorder of mature CD3+/CD8+ cytotoxic T-cells. Rare variants include CD 3+/CD4+/CD8-cases. To the best of our knowledge, 11 such cases (4 cases by Lima et al.[1] in 2003, 4 cases by Olteanu et al. in 2010,[2] 2 cases by Mutreja et al.[3] in 2014, and 1 case by Rabade et al.[4] in 2014) of T-LGL showing CD3+/CD4+/CD8-immunophenotype has been published in literature so far. There is a paucity of literature explaining the monoclonal expansion of CD3+/CD4+ T-LGL.[1] Unlike CD8+ T-LGL, CD4+ T-LGL does not show cytopenia, autoimmune phenotypes,[1],[5] or splenomegaly. However, CD4+ T-LGL is frequently associated with nonhematological malignancies.[1] Here, we report a case presenting with CD3+/CD4+/CD8-immunophenotype. Such immunophenotypic variant form of T-LGL cases should have a close clinical follow-up as they are prone to develop either simultaneously or months and years after, secondary hematological or nonhematological malignancies.[1]

We received a peripheral blood sample for immunophenotyping from a 51-year-old female with a 4-month history of persistent lymphocytosis. Clinical examination revealed a single cervical lymphadenopathy with no hepatosplenomegaly. The complete blood count showed mild anemia (hemoglobin - 11.9 g/dL), a normal platelet count (platelets 150,000/μL), and absolute lymphocytosis (total leukocyte count 13.0 × 103/μL with 79.5% lymphocytes). Peripheral smear examination revealed a large number of large granular lymphocytes. Cytogenetic analysis was not performed.

Immunophenotyping of peripheral blood was carried out using the lyse wash method and a four-color flow cytometry panel [Table 1]. The antibody clones used are shown in [Table 2]. The sample was run on a BDFACS Calibur instrument (Becton/Dickinson Biosciences), and the immunophenotyping data were analyzed with BD Cell Quest software. The percentage of positive cells above a threshold set against a processed isotype control tube was used to express the florescence measurement. Flow cytometry analysis of a heparin peripheral blood sample showed a large lymphoid cell cluster (62% of total cells) with bright CD45 positivity. The cells showed positivity for CD3 (96%), CD4 (94%), CD5 (96%), CD2 (97%), CD16 (41%), CD56 (90%), and-CD57 (91%), indicating a T-cell origin [Figure 1]. There was an aberrant loss of CD7 expression, and CD8 expression was negative [Figure 1]. Other B lymphoid cells markers were negative including CD10, CD19, CD23, CD20, CD38, and surface kappa/lambda light chain expression. In accordance with morphology [Figure 2] and immunophenotypic findings, a laboratory diagnosis of CD3+/CD4+/CD8-T-LGL was established. The patient was monitored, and no chemotherapy was administered. On follow-up at 6 months, the patient was asymptomatic with persistent cervical lymphadenopathy.{Table 1}{Table 2}{Figure 1}{Figure 2}

T-LGL was first described by McKenna et al.[6] in 1977. According to the WHO 2008 classification,[7] the diagnostic criterion for T-LGL is an LGL count exceeding 2 × 109/L for a period of more than 6 months. Immunophenotypically, CD4+ T-LGL is a clonal expansion of large granular lymphocytes that shows co-expression of NK cell-associated antigens – CD56 and CD57 – with variable expression of CD8 (CD8-/+dim) and CD7 (CD7-/+dim).[1] The index case fulfills the criteria for CD4+ T-LGL, both immunophenotypically and according to the WHO diagnostic criteria. Some studies have shown that CD4+/CD8-T-LGL proliferates and expands as a result of tumor growth control by the immune system.[1] The leukemic clone blocks the normal Fas-mediated apoptosis of activated T-cells, thus leading to the etiopathogenesis of T-LGL.[8] Clinically, CD4+ T-LGL usually follows an indolent course with the absence of neutropenia, anemia, and splenomegaly. In contrast, CD8+ T-LGL presents with neutropenia, splenomegaly, and occasionally anemia. In view of indolent and nonprogressive nature of CD4+/CD8-T-LGL, these should be regarded as clonal expansions rather than leukemia.[3] Association of CD4+ T-LGL with other malignancies has been well described in the literature. Lima et al.[1] described a study of 33 patients with CD4+ and variable expression of CD8 (CD8-/+dim) T-LGL, of whom 6 (18%) had a concomitant B-cell lymphoproliferative disorder (SMZL, lymphoplasmacytic lymphoma, typical B-chronic lymphocytic leukemia [B CLL], and atypical B CLL), and 3 (9%) had a nonhematological malignancy (thyroid carcinoma, gastric adenocarcinoma, and leiomyosarcoma). The patients presented with these malignancies either 2–4 years before,[1] 1–4 years after,[1] or at the same time they developed CD4+ T-LGL. Our patient, however, did not present with any secondary malignancies and has not developed any malignancies during the 6 months of follow-up after the diagnosis of CD4+ T-LGL. The subsequent monitoring will be continued at 3 monthly intervals till 4 years as described by Lima et al.,[1] who found secondary malignancies manifesting up to a time frame of 4 years after developing CD4+/CD8-T-LGL.

To conclude, CD4+/CD8-T-LGL is a T lymphoproliferative disorder that is distinct, both immunophenotypically and clinically, from CD8+/CD4-T-LGL. Patients should be closely monitored, as 18% and 9% of cases[1] are prone to develop secondary hematological and nonhematological malignancies, respectively. It will be too early to reach to ascertain this association in our case as she had a short clinical follow-up of 6 months and further needs a long follow-up (approximately 4 years).

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

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