Does CD30 loss preclude the diagnosis of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma? Insights from a rare case.

CD30 positivity serves as a critical diagnostic hallmark for anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK+ ALCL); however, rare cases with partial or complete loss of CD30 expression present diagnostic challenges. We report a unique case with two morphologically and immunophenotypically distinct subpopulations within the same tumor: A typical CD30-positive component and a CD30-negative counterpart. Comparative genetic analysis revealed overlapping but divergent molecular features, including nucleophosmin 1-ALK (NPM1-ALK) fusion, notch receptor 1 mutations, and differential gene amplifications involving MYC proto-oncogene and BCL2-like 1. These findings offer insights into the regulatory mechanisms of CD30 and highlight that loss of CD30 expression alone should not preclude the diagnosis of ALK-positive ALCL, underscoring the importance of integrated histopathological and molecular evaluation in diagnostically challenging cases. Meanwhile, it provides a basis for optimizing the diagnostic process of clinically suspected cases.