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A 32-year-old woman presented with cervical lymphadenopathy. Excision biopsy specimen demonstrated partially altered architecture by atypical lymphoid infiltrate with patchy, predominantly interfollicular distribution (panel A, hematoxylin and eosin [H&E], 4× objective), comprising large, atypical cells with prominent nucleoli admixed with histiocytes, eosinophils, and neutrophils (panel B, H&E, 40× objective). CD30 highlighted interfollicular pattern (panel C, 4× objective) with strong expression in atypical cells (panel D, 40× objective) that were positive for CD15 (panel E, 40× objective), weak PAX5 (panel F, 40× objective), MUM1 (panel G, 40× objective), and negative for CD20, CD19, CD79a, EBER, ALK, TIA-1, granzyme B, CD3, CD2, and CD45. D2-40 highlighted lymphatic sinuses with intrasinusoidal localization of atypical cells (panel H, 40× objective). Differential diagnosis included anaplastic large cell lymphoma (ALCL; typically exhibiting a sinusoidal pattern and rarely expressing weak PAX5) and classic Hodgkin lymphoma (CHL). Immunoglobulin heavy chain and T-cell receptor γ gene rearrangement studies showed no clonal rearrangements, and gene sequencing revealed no pathogenic alterations. Diagnosis was CHL with interfollicular and focal intrasinusoidal involvement.

Interfollicular involvement by CHL is rare, and sinusoidal involvement is exceedingly uncommon. Interfollicular mixed cellularity CHL may be Epstein-Barr virus-associated, although this was EBER-negative. CHL with this unusual pattern may be overlooked because of subtle morphologic features and may mimic ALCL. Awareness of this diagnostic pitfall is important, particularly in CD30⁺/ALK⁻ T-cell lymphomas with JAK2 rearrangements, often demonstrating CD15 expression and CHL-like morphology.

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