CD4 positive/CD8 negative/CD56 positive T cell large granular lymphocyte proliferations; clonal disorders of uncertain significance

Abstract

Clonal expansions of CD4 positive T large granular lymphocytes with or without co-expression of CD8 are extremely uncommon. These typically display an indolent clinical course and are said to be associated with other solid malignancies. We present the clinicopathologic features and immunophenotypic analyses of two rare cases of CD4 positive T large granular lymphocyte proliferation with expression of natural killer cell associated antigen CD56. Both had high positive anti cytomegalovirus (CMV) IgG titres and persistent lymphocytosis with a relatively benign course at 15 and 13 months of follow up, respectively. Case 1 A 58 year old Indian man presented with fever and cough of one week duration. On examination, he was febrile with crackles in the right lower zone. Hematological investigations revealed mild neutropenia and a monotypic CD3 positive/CD4 positive/CD8 negative/CD56 positive/T cell receptor alpha-beta positive large granular lymphocyte population representing 50% of blood and bone marrow lymphocytes. Clonality was demonstrated using a T cell receptor gamma polymerase chain reaction. A chest roentgenogram showed features suggestive of bronchopneumonia. Patient was treated with broad spectrum antibiotics and antipyretics with improvement. At follow up of 15 months, he continued to have persistent large granular lymphocytosis. Case 2 A 38 year old Indian woman presented with generalized weakness and malaise of two months duration. On examination, she was afebrile with no lympadenopathy or hepatosplenomegaly. A routine hemogram showed absolute lymphocytosis. Flow cytometric evaluation was performed on peripheral blood affirmed the cells to be CD4 positive T large granular lymphocytes, with similar findings to the first case. At follow up of 13 months, patient was otherwise asymptomatic but continued to have persistent CD4 positive large granular lymphocytosis. Flow cytometric immunophenotyping remains an essential tool for the diagnosis of T cell proliferations and helped to clinch the diagnosis in these cases. The aim of this case series is to present clinical and immunophenotypic features of these rare CD4 positive T large granular lymphocyte proliferations that fulfil the WHO defining criteria, however are better regarded as clonal expansions rather than as leukemias in view of their indolent and non progressive nature.