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. 223-224

Journal of Postgraduate Medicine, Vol. 56, No. 3, July-September, 2010, pp. 223-224

Case Snippet

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

Dadu T, Rangan A, Bhargava M

Department of Hematology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India

Correspondence Address: Dr. Tina Dadu, Department of Hematology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India, dadu.tina@gmail.com

Code Number: jp10066

PMID: 20739776

DOI: 10.4103/0022-3859.68643

The lymphoproliferative disease of granular lymphocytes is a relatively rare atypical clonal lymphocytosis that may have either a CD3 ⁺ or a CD3 ^- phenotype. ^[1] Clonal proliferations of these cells have been termed as T- and natural killer (NK)- Large Granular Lymphocytic (LGL) leukemias respectively. ^[2] The hallmark of T-LGL is the expansion of a discrete or clonal population of CD8 ⁺ cytolytic lymphocytes in the peripheral blood. Monoclonal expansions of CD4 ⁺ T-LGL have only been sporadically reported in the literature. ^[3] We present here a case of CD4 ⁺ /NKa ⁺ /CD8 ^dim+ T-cell LGL.

A 64-year-old male presented with complaints of persistent lymphocytosis for the past 17 years with the absolute lymphocyte count ranging from 10,000-13,000/ml during this period. Clinically, the patient was completely asymptomatic and on clinical examination showed no organomegaly, lymphadenopathy or any evidence of infection. Computed tomography (CT) chest and abdomen did not reveal any lymphadenopathy or organomegaly. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within normal limits. A panel of autoimmune markers (ANA, dsDNA, SSA, SSB, Sm, RNP, Scl-70 and Jo-1) were negative. On account of the persistent lymphocytosis, a clinical diagnosis of lympho-proliferative disease had been made by his attending physician.

Peripheral blood findings showed a hemoglobin of 17.2 gm/dl, platelet count of 2,30,000/ml and a leukocyte count of 19,000/ml with absolute lymphocytosis. The absolute lymphocyte count was 13,110/ml and absolute neutrophil count was 5,320/ml. Peripheral smear showed around 69% mature lymphoid cells, with most showing characteristic large granular lymphocytic morphology [Figure - 1]. A cytogenetic analysis was not performed.

Flowcytometric immunophenotypic analysis was done on an ethylenediaminetetraacetic acid (EDTA) sample on Beckman Coulter Epics - XL flow cytometer. An overtly abnormal single large lymphoid cluster of cells (~70% of all cells) was seen with bright CD45 positivity. The cells were of T-cell origin and showed CD3 and CD5, CD7, CD4 and CD8 positivity. A double positivity of CD4 and CD8 was seen on these cells. CD4 was seen to be bright positive whereas the CD8 was dim positive as compared to the normal residual T-cells. Of the NK cell markers, most of these cells expressed moderately bright CD56 marker, however CD16 was seen to be negative [Figure - 2]. The other markers which had been utilized in the lymphoma panel included CD38, CD20, FMC7, CD103 and CD11c and were seen to be negative. CD2 and CD57 were not available in our antibody panel. Double positivity for CD4 and CD8 was accepted as an evidence of clonality. However, clonality could not be proven on T- cell receptor variable beta TCRV b repertoire.

Immunophenotypically, CD4 ⁺ T-LGL is a clonal expansion of granular lymphocytes that co-express CD56 and CD57 NK-associated antigens and variable levels of CD8 (CD8 ^-/+dim ) and of CD7 (CD7 ^-/+dim ). ^[3]

CD8 ⁺ T-LGL shows a strong association with autoimmune diseases, especially rheumatoid arthritis ^[4] and is associated with a mild to moderate stable lymphocytosis, neutropenia, splenomegaly, and occasionally anemia.

CD4 ⁺ LGLs on the other hand, are marked by their association with malignant diseases and characteristically show absence of cytopenias, splenomegaly and autoimmune phenomena. ^[3] Some studies suggest that activated CD4 ⁺ /NKa ⁺ /CD8 ^-/+dim T-LGL may proliferate and expand as an effort of the immune system to control tumor growth. ^[3]

The high frequency of second malignancies, which may crop up after months to years after the initial diagnosis, makes it essential that we perform a wide cancer survey and a close follow-up of patients with peripheral blood showing clonal expansions of CD4 ⁺ /NKa ⁺ /CD8 ^-/+dim T-LGL populations, even when there is no evidence of an associated disease at diagnosis, and even if peripheral blood lymphocyte counts are stable.

References

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