A Case Report Of Classic Hodgkin Lymphoma With Unusually Abundant Tumor Cell Expression Of B-Cell Markers: A Diagnostic Dilemma And Treatment Challenge

Context The diagnosis of classic Hodgkin Lymphoma (cHL) appears quite straightforward, as it is built upon extended histological and immunophenotypic assessment. Hodgkin and Reed-Sternberg cells reflect monoclonal cell proliferation, presumably originating from germinal center B-cells. In general, these cells lose the B-cell phenotype, yet one-third of cHL cases express at least one B-cell marker, which in some instances leads to diagnostic difficulties in distinguishing cHL from B-Cell Lymphomas (BCL). Objective We present a diagnostically complex case of cHL CD30+/CD15+ in a 21-year-old male. Immunohistochemistry demonstrated unusual, strong expression of markers of B-cell differentiation and positivity for Epstein-Barr Virus (EBV), which brought out serious constraints in the differential diagnosis of an EBV-positive Diffuse Large BCL. Patient Case Report A previously healthy 21-year-old male presented at our institution with neck lymphadenopathy. He experienced no B-symptoms. Except for a slightly elevated sedimentation rate, blood analyses were within normal ranges. Initial PET-CT scan identified stage II disease involving supradiaphragmatic lymph nodes. Fine needle aspiration of the lymph node was suggestive of HL. However, histological examination of the surgically extirpated lymph node was puzzling. The atypical lymphoid cells expressed classical Hodgkin phenotype CD30+/CD15+, but they showed strong CD20+ co-expression. The tumor cells were strongly positive for EBV, and a diagnosis of EBV-associated BCL was assumed. In addition, high EBV loads in blood were confirmed. PCR studies for B- and T-cell gene rearrangements were negative. The tumor tissue was sent for consultative opinion in three centers independently. Immunostains were consistent; lymphoma cells were strongly positive for CD30, CD15, EBV, and EBV receptor CD21, as well as the B-cell markers CD20, Bcl-6, and MUM1. Finally, next-generation sequencing for B-cell rearrangement was negative. In absence of sufficient diagnostic criteria for EBV-positive BCL and all things considered, the diagnosis of classic HL was concluded. Conclusions In consensus with reported literature, treatment was initiated with R-ABVD regimen. Complete regression of tumor masses became evident after the first cycle. An interim PET scan is planned for further evaluation.