A 28-year-old woman presents with painless cervical lymphadenopathy and mediastinal mass on chest X-ray. Lymph node biopsy shows the structure marked **A** — large cells with abundant cytoplasm and two mirror-image nuclei, each containing a single prominent eosinophilic nucleolus surrounded by a clear halo. The neoplastic cells are surrounded by a rich inflammatory background of small lymphocytes and eosinophils. Which of the following immunophenotypic profiles is most consistent with the cells marked **A**?
A. CD3+, CD5+, CD7+, CD30−
B. CD19+, CD20+, CD79a+, CD30−
C. CD30+, CD15+, CD45−, CD20− (usually)
D. CD20+, CD45+, BCL6+, CD30−
Explanation
Why CD30+, CD15+, CD45−, CD20− (usually) is right
The structure marked A is the classic binucleated Reed-Sternberg (RS) cell, the pathognomonic neoplastic cell of Hodgkin lymphoma. Classic RS cells are CD30+ (Ki-1 antigen), CD15+, PAX5+ (weak), but characteristically CD45− and CD20− (usually). This immunophenotype reflects their origin from germinal center B cells that have lost most B-cell markers during malignant transformation. The presence of these cells in a reactive inflammatory background with mediastinal involvement in a young woman is classic for nodular sclerosis Hodgkin lymphoma (Robbins Pathology 10e; WHO 2022).
Why each distractor is wrong
CD20+, CD45+, BCL6+, CD30−: This is the immunophenotype of nodular lymphocyte-predominant HL (NLPHL) "popcorn" cells, which are biologically distinct and express B-cell markers. NLPHL cells are CD30− and CD15−, opposite to classic RS cells. This is a different entity with indolent course.
CD19+, CD20+, CD79a+, CD30−: This represents a typical B-cell lymphoma (e.g., DLBCL or follicular lymphoma) with preserved B-cell markers. Classic RS cells lose CD20 and CD19 expression, making this profile incompatible with the structure shown.
CD3+, CD5+, CD7+, CD30−: This is a T-cell phenotype (peripheral T-cell lymphoma or T-cell leukemia). RS cells are B-cell derived and do not express T-cell markers. This distractor tests confusion between lymphoid neoplasms.
High-YieldNEET PG
Classic Hodgkin lymphoma RS cells are CD30+/CD15+ but CD20−/CD45−, reflecting loss of B-cell identity; NLPHL "popcorn" cells are the opposite (CD20+/CD45+, CD30−/CD15−).
Robbins Pathology 10e; WHO Hematolymphoid Classification 2022; NCCN HL Guidelines
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