100 PAX-5-negative Hodgkin lymphoma may be associated with aggressive histopathological features

Introduction/Objective Classical Hodgkin lymphoma (CHL) is a neoplasm originating from germinal center B cells, and PAX-5 positivity is one of the desirable diagnostic criteria. A small subset of CHL cases exhibits PAX-5 negativity, posing diagnostic challenges that often require additional immunostaining, review by multiple pathologists, and expert consultation. Herein, we evaluated the histopathological features of PAX-5-negative CHL. Methods/Case Report We retrospectively reviewed CHL cases diagnosed at our institution over the past seven years. A total of 25 cases were identified; five were excluded due to the absence of PAX-5 immunohistochemistry (IHC) results. The remaining 20 cases were categorized into PAX-5-positive (n = 13) and PAX-5-negative (n = 7) groups based on immunoreactivity. Results PAX-5-negative CHL exhibited a similar age distribution to the PAX-5-positive group (40 vs. 37 years) and showed a male predominance in both groups (71% vs. 77%). The nodular sclerosis subtype predominated in both PAX-5-positive (n = 8, 62%) and PAX-5-negative CHL cases (n = 6, 86%), followed by the mixed cellularity subtype (n = 3 [23%] in PAX-5-positive, and n = 1 [14%] in PAX-5-negative cases). Subtype information was unavailable for two PAX-5-positive CHL cases. All PAX-5-positive CHL cases demonstrated CD30 and CD15 immunoreactivity in Hodgkin and Reed–Sternberg cells. In contrast, while CD30 was uniformly expressed in PAX-5-negative cases, CD15 was negative in two of them. Notably, two PAX-5-negative CHL cases (29%) presented at extranodal sites (chest wall and epidural space), whereas all PAX-5-positive cases involved lymph nodes. Syncytial growth, a feature associated with aggressive histology, was observed in 3 (43%) of the PAX-5-negative cases, compared to only 1 (8%) in the PAX-5-positive group. Conclusion PAX-5-negative CHL presents diagnostic challenges. A comprehensive immunophenotypic panel including PAX-5, CD15, CD30, FASCIN, and MUM1, along with careful assessment of the classic cytomorphological features of Hodgkin lymphoma, can aid in diagnosis. Although this is a small observational study, several atypical or aggressive features—such as CD15 negativity, extranodal involvement, and syncytial growth patterns—were more frequent in PAX-5-negative CHL. The prognostic and therapeutic implications of these findings remain unclear and warrant further investigation.