25. Novel translocation t(5;19)(q35;p13.3) in a patient with T-Cell large granular lymphocytic leukemia: report of a rare case

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare malignant neoplasm of mature cytotoxic T cells that accounts for 2-3% of mature small lymphocytic leukemias. Lymphocytosis and neutropenia are common in patients with T-LGLL. Characteristically, T cell receptor (TCR) gene rearrangement is present most cases of T-LGLL. Typically, the neoplastic cells express CD2, CD3, CD8, CD57, and ab TCR. Most T-LGLL cases have a normal karyotype and no specific recurrent cytogenetic abnormality has been established thus far. There is a small number of case reports and series describing abnormal cytogenetic findings including translocations and deletions in T-LGLL. To our knowledge, no translocation between chromosomes 5 and 19 in T-LGLL has been reported. We present a 56-year-old woman with a past medical history of hepatitis C, who underwent bone marrow biopsy for persistent lymphocytosis and neutropenia. Molecular studies demonstrated TCR gene rearrangement. Peripheral blood flow cytometry revealed a significantly increased CD4:CD8 (11.3) and CD2+, CD3+, CD4+, CD57+, and ab TCR-positive atypical T cells comprising approximately 85% of the lymphocytes. Bone marrow flow cytometry showed involvement of the bone marrow with the same population of the cells. Histology demonstrated CD3+, Granzyme B+, and TIA1+ large lymphocytes with cytoplasmic granules. Chromosome analysis revealed clonal abnormalities of a reciprocal translocation between 5q35 and 19p13.3 and loss of the X chromosome, 45,X,-X,t(5;19)(q35;p13.3)[9]/46,XX[12]. Furthermore, Fluorescence in-situ hybridization (FISH) confirmed this translocation. This translocation is predicted to yield fusion of NPM1 and TYK2, a novel fusion that has been reported only in cutaneous CD30-positive lymphoproliferative disorders in a single study thus far. Our case report illustrates the first T-LGLL with t(5;19)(q35;p13) with possible NPM1/TYK2 fusion protein. To precisely map the breakpoints and characterize the fusion protein, additional FISH and molecular studies are being performed. Our results raise the possibility for a novel therapeutic target in T-LGLL.