ALK-positive, EBV-positive Large B-cell lymphoma in an HIV patient: a diagnostic pitfall mimicking plasmablastic lymphoma.

ALK-positive large B-cell lymphoma (ALK + LBCL) is a rare subtype of large B-cell lymphoma characterized by plasmablastic morphology, intra-sinusoidal or sheet-like proliferation, loss of pan-B-cell markers, and expression of plasmacytic markers. According to WHO classification, CD30 expression is generally absent and Epstein-Barr virus (EBV) infection is not detected [1,2,5] . We aim to report the first case of ALK-positive, EBV-positive large B-cell lymphoma (ALK + EBV + LBCL) in an HIV-infected patient. A 60-year-old Thai male with HIV infection and severe immunosuppression (CD4 count: 93 cells/mm³) presented with generalized lymphadenopathy and an epiglottic mass. Biopsy showed a plasmablastic neoplasm proliferating in loose sheets, negative for pan-B-cell markers except OCT2, and positive for plasmacytic markers and CD30. The tumor also expressed EBER, ALK1 (paranuclear dot pattern), and ALK D5F3; HHV8 was negative. FISH confirmed ALK gene rearrangement, and targeted sequencing revealed a GORASP2::ALK fusion gene. The diagnosis of ALK + EBV + LBCL in the setting of HIV-related immunodeficiency was established. The patient developed pneumonia with septic shock and died during admission. EBV-positive plasmablastic B-cell neoplasms in HIV-infected patients are not always plasmablastic lymphoma. Immunohistochemistry for ALK and HHV8 should be included in the diagnostic panel. Importantly, CD30 and EBER positivity do not exclude ALK + LBCL.