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The diverse pathology of post‐transplant lymphoproliferative disorders: the importance of a standardized approach

Abstract: Post‐transplant lymphoproliferative disorders (PTLD) are a diverse group of abnormal lymphoid growths that include both hyperplasias and neoplasias. They have been divided into several general pathologic categories that have prognostic significance. These include early or hyperplastic PTLD, polymorphic PTLD, and lymphomatous or monomorphic PTLD. The majority of PTLDs are of B‐cell origin and contain Epstein–Barr virus (EBV). However, PTLDs of T‐ or NK‐cell origin have been described, and late‐arising EBV‐negative lymphoid tumors are becoming more frequently reported in this population. Other lymphoid neoplasms, such as those arising from mucosal‐associated lymphoid tissue (MALTomas), have recently been recognized in transplant patients, and their relationship to PTLD is uncertain. Multicentric PTLD may represent either advanced‐stage disease or multiple independent primary tumors. Likewise, recurrent PTLD may represent true recurrence or the emergence of a second primary tumor. Transplant patients are also at risk for other opportunistic neoplasms, including EBV‐associated leiomyosarcomas that may be seen alone or in conjunction with PTLD. This underscores the necessity for pathologic diagnosis of mass lesions in this patient population. The pathologist should strive to categorize the form of post‐transplant lymphoproliferation in accordance with currently accepted criteria. The diagnosis should incorporate the histopathologic appearance, cell phenotype, clonal status, and EB viral status. The pathologist may play a special role in guiding therapy by ascertaining the presence of such markers as CD20 on tumor cells. Specialized techniques, such as molecular analysis of oncogenes/tumor suppressor genes and evaluation of host:donor status of PTLD, may play important roles in diagnostic evaluation in the future.