Mixed-phenotype large granular lymphocytic leukemia: a rare subtype in the large granular lymphocytic leukemia spectrum

Large granular lymphocytic leukemia (LGLL) is a chronic proliferation of cytotoxic lymphocytes in which more than 70% of patients develop cytopenia(s) requiring therapy. LGLL includes T-cell LGLL and chronic lymphoproliferative disorder of natural killer (NK) cells. The neoplastic cells in LGLL usually exhibit a single immunophenotype in a patient, with CD8-positive/alpha beta T-cell type being the most common, followed by NK-cell, gamma delta T-cell, and CD4-positive/alpha beta T-cell types. We investigated a total of 220 LGLL cases and identified 12 mixed-phenotype LGLLs (5%): 7 cases with coexistent alpha beta, T-cell and NK-cell clones and 5 with coexistent alpha beta and gamma delta T-cell clones. With a median follow-up of 48 months, the clinicopathological characteristics of these patients seemed similar to those of typical LGLL patients. Treatment was instituted in 9 patients, and 5 patients (55%) attained complete hematologic response or partial response. The therapeutic response rate of this cohort is comparable to the reported overall response rate of 40% to 60% in typical LGLL patients. Three patients who did not receive any treatment had progressive or persistent cytopenias. Interestingly, inverted proportions of 2 clones at disease recurrence were identified in 4 patients (36%) and stable clonal proportions in 7 patients (64%). Mixed-phenotype LGLL is rare, and this study underscores the importance of recognizing this rare type of LGLL in patients who may benefit from LGLL treatment. (C) 2018 Elsevier Inc. All rights reserved.