Utility of immunohistochemistry in bone marrow evaluation of T-lineage large granular lymphocyte leukemia

Abstract

Although T-lineage large granular lymphocyte (LGL) leukemia has been described for over 20 years, many patients with this neoplasm go unrecognized. Chief among the difficulties in diagnosing this entity is that the morphologic features are nonspecific and that it is difficult to distinguish it from reactive processes. The purpose of this study was to examine the histologic and immunophenotypic appearance of T-LGL leukemia in the peripheral blood and bone marrow, and to determine what features may suggest that ancillary studies such as flow cytometric and molecular analysis should be pursued to make a definitive diagnosis. We took a multidisciplinary approach by using morphology, immunoperoxidase staining, flow cytometric analysis, and molecular studies on 9 cases of T-lineage LGL leukemia. Our findings indicate that T-lineage LGL leukemia typically infiltrates the marrow diffusely. Most cases show a hypercellular marrow with an increase in myeloid precursors relative to the mature cells (ie, an inversion of the myeloid maturation pyramid) and a decreased myeloid:erythroid ratio. Neutropenia without a left shift is usually seen in the peripheral blood. The tumor cells are usually CD3+, CD8+, CD57+, and TIA-1+. Most notably, the number of CD3+ T cells per high-power field is markedly elevated in T-LGL leukemia compared with normal, reactive, and pathologic marrows with neutropenia (mean values, 559 cells/mm 2 v 7/mm 2, 11/mm 2, and 263/mm 2, respectively, P < .01). Moreover, CD57 staining also shows an increase in positive cells in T-LGL cases in comparison with normal, reactive, and pathologic marrows with neutropenia. Taken together, these findings indicate immunoperoxidase findings may be a useful tool to identify cases that should proceed to molecular or flow cytometric analysis. H UM P ATHOL 31:1266-1273.