Attack of the clones: a T-cell population resembling adult T-cell leukemia/lymphoma, and large granular lymphocytosis, in an HTLV-2-infected patient

The HTLV-1 and HTLV-2 viruses, though closely genetically related, have divergent clinical impact: HTLV-1 has been causally linked with adult T-cell leukemia/lymphoma as well as neurologic disorders, whereas HTLV-2 shows no clear association with lymphoproliferative disorders. We report a patient who presented with two concomitant clonal T-cell lymphoproliferative disorders, who was found to have an HTLV-2, but not HTLV-1 infection. The patient’s clonal T-cell proliferations were characterized and compared using multiparameter flow cytometry, fluorescence in situ hybridization, and TCR gene rearrangement analysis on flow-sorted cell samples from blood, bone marrow, and skin biopsy specimens. The patient had a CD4 + /CD25 + T-cell population, resembling adult T-cell leukemia/lymphoma both by clinical presentation and immunophenotype, as well as a separate clonal CD8 + population of large granular lymphocytes. Interestingly, she also had a STAT3 mutation; large granular lymphocytic leukemia has been reported in association with HTLV-2 infection. This patient has had an indolent clinical course to date and is being managed expectantly. The unexpected finding of HTLV-2 infection is of uncertain significance with an unusual CD4 + /CD25 + clonal T-cell population resembling adult T-cell leukemia/lymphoma, but fits a reported association with clonal LGL-expansion and STAT3 mutation.