Clinicopathologic and Molecular Characteristics of Merkel Cell Polyomavirus Positive T-Cell Lymphoproliferative Disorders

Previous work described 3 cases of CD4+ T-cell lymphomas harboring Merkel cell polyomavirus (MCPyV), as demonstrated by in situ hybridization (ISH), next generation sequencing, and polymerase chain reaction. Two of these cases were cutaneous T-cell lymphomas compatible with mycosis fungoides in postcardiac transplant patients, while the third was a peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), in a patient without known immunosuppression. In this study, we assess an expanded cohort of T-cell neoplasms from 4 institutions for expression of MCPyV by ISH. This cohort includes 9 T-cell lymphomas occurring in the post solid organ transplant setting, of which 5 (60%) were positive for MCPyV by ISH. Four of these cases were classified as PTCL-NOS and the remaining case as nodal T follicular helper cell lymphoma, angioimmunoblastic type. In addition, we performed MCPyV ISH on a variety of neoplastic and non-neoplastic lymphoid tissues from both transplant and nontransplant patients. No evidence of MCPyV infection was found in lymphoid tissues in the absence of T-cell lymphoma, suggesting that the presence of MCPyV is specific to this rare subset of T cell lymphomas. Furthermore, all MCPyV-positive T-cell lymphomas (8 of 8) were CD4+ and the large majority were observed in the post-transplant setting (7 of 8). Multiplex single-molecule fluorescence ISH confirmed the presence of MCPyV in CD4+ T-cells. These findings support the hypothesis that MCPyV infection is specifically associated with rare CD4+ T-cell lymphomas, particularly in transplant recipients.