A 24-year-old male presents with painless cervical lymphadenopathy and B symptoms (fever, night sweats, weight loss). Lymph node biopsy shows scattered large cells with multiple nuclei and prominent nucleoli in a background of small lymphocytes, eosinophils, and plasma cells. The diagnostic cell marked **A** in the diagram is immunophenotyped and found to be CD15+, CD30+, and CD45 negative. Which of the following is the most likely diagnosis?

Explanation

## Why Classical Hodgkin Lymphoma is right The structure marked **A** is the Reed-Sternberg cell, the pathognomonic diagnostic cell of classical Hodgkin lymphoma. The immunophenotype CD15+, CD30+, and CD45 negative is the defining immunophenotypic signature of Reed-Sternberg cells in classical Hodgkin lymphoma. These cells are derived from germinal center B-cells but have lost pan-B-cell markers (CD45, CD20). The clinical presentation of painless cervical lymphadenopathy with B symptoms in a young adult, combined with the characteristic histology and immunophenotype, confirms classical Hodgkin lymphoma. According to Robbins 10e and Harrison 21e, this is among the most curable malignancies with ABVD chemotherapy achieving >80% cure rates even in advanced stages. ## Why each distractor is wrong - **Diffuse Large B-Cell Lymphoma (DLBCL)**: DLBCL is a non-Hodgkin lymphoma composed of large neoplastic B-cells that are CD20+ and CD45+. The CD45 negativity and CD15 positivity of the cells in this case are inconsistent with DLBCL, which would show CD20+ and CD45+ phenotype. - **Nodular Sclerosis Lymphoma**: While nodular sclerosis is a subtype of classical Hodgkin lymphoma (not a separate diagnosis), the question asks for the most likely diagnosis. The immunophenotype and clinical presentation point to classical Hodgkin lymphoma as the overarching diagnosis. Nodular sclerosis is defined by collagen bands and lacunar cells, not by immunophenotype alone. - **Peripheral T-Cell Lymphoma, NOS**: This is a T-cell lymphoma with CD4+ or CD8+ phenotype. The CD30+ and CD15+ immunophenotype with CD45 negativity is not characteristic of peripheral T-cell lymphomas, which would typically show CD45+ and lack CD15 expression. **High-Yield:** Reed-Sternberg cells are CD15+, CD30+, CD45−, CD20− (loss of B-cell markers despite B-cell origin); this immunophenotype distinguishes classical Hodgkin lymphoma from non-Hodgkin B-cell lymphomas which are CD20+, CD45+. [cite: Robbins 10e Ch 13; Harrison 21e Ch 105]