Abstract

Merkel cell polyomavirus (MCPyV) is an oncogenic alphapolyomavirus that infects most humans in early childhood and is considered etiologic in approximately 80% of Merkel cell carcinomas. Recently, three cases of CD4-positive T cell lymphomas (two compatible with mycosis fungoides and one compatible with peripheral T cell lymphoma) were reported to harbor MCPyV within lymphoma cells. We report the identification of two additional cases of MCPyV-positive T cell lymphoproliferative disorders (T-LPDs). The first is a 7-year-old girl who underwent heart transplantation at age 1 for dilated cardiomyopathy and presented at age 6 with failure to thrive, diffuse lymphadenopathy, and eczema. Skin biopsies showed lymphocyte exocytosis and a superficial perivascular lymphocytic infiltrate comprised almost entirely of CD4+ T cells, with shared clonal sequences in TCR beta by next-generation sequencing. A subset of the T cells showed strong nuclear positivity for MCPyV by in situ hybridization. Concurrent lymph node and peripheral blood sampling demonstrated involvement by the same population of atypical CD4-positive TRBC1-restricted MCPyV-positive T cells. The patient’s disease responded to alemtuzumab and high-dose cytarabine. Upon archival review, we identified one additional MCPyV-positive T-LPD: an angioimmunoblastic T cell lymphoma in an 8-year-old boy with history of heart transplantation who presented with diffuse lymphadenopathy and a waxing/waning papular rash. These exceptionally rare cases expand the emerging spectrum of T-LPDs associated with MCPyV. As 4/5 MCPyV-positive T-LPDs reported to date occurred in heart transplant patients, we speculate that alterations to the T cell compartment secondary to thymectomy may predispose to MCPyV-mediated lymphomagenesis.