A 41-year-old man with a history of hepatitis C and HIV infection (CD4⁺ T-cell count, 156/mm³) receiving combination antiretroviral therapy was found to have inguinal lymphadenopathy. Positron emission tomography–computed tomography showed hypermetabolic diffuse lymphadenopathy without evidence of an effusion. An excisional lymph node biopsy showed large anaplastic-appearing cells exclusively present in the sinusoids (panels A [hematoxylin and eosin stain, original magnification ×100] and B [hematoxylin and eosin stain, original magnification ×200]). A few of the tumor cells resembled hallmark cells (panel B, inset; arrows [original magnification ×600]). There was also an exuberant reactive plasmacytosis (panels A, B, and C [immunohistochemistry (IHC), original magnification ×100]). The tumor cells were positive for MUM1 (panel C), human herpesvirus 8 (HHV8)–associated LANA (panel D [IHC, original magnification ×100]), and EBER (panel E [in situ hybridization, original magnification ×100]), as well as CD30, EMA, PRDM1/Blimp-1, and CD43. They were negative for CD45, CD20, CD79a, PAX5, CD3, CD5, ALK1, CD138, CK, melan-A, S100, HMB45, and CD68.

The morphologic and immunophenotypic findings are diagnostic of an extracavitary variant of primary effusion lymphoma, a rare large B-cell lymphoma with plasmablastic features in HIV⁺ patients associated with HHV8 and frequently Epstein-Barr virus (EBV). An intrasinusoidal pattern of the tumor cells is highly unusual in this entity and may lead to a misdiagnosis of anaplastic large-cell lymphoma, particularly when CD138 is lacking and CD30 is strongly expressed, as in this patient's case. Evaluation for HHV8 and EBV is critical to avoid this diagnostic pitfall.