## Immunophenotype of Classical Hodgkin Lymphoma **Key Point:** Reed-Sternberg and Hodgkin cells in classical Hodgkin lymphoma are CD30^+^, CD15^+^, CD45^−^, and CD20^−^ (or weakly positive). This distinctive phenotype is crucial for diagnosis and distinguishes cHL from other lymphomas. ### Immunophenotypic Profile of cHL Neoplastic Cells | Marker | Expression | Significance | | --- | --- | --- | | **CD30** | Positive (strong) | Activation marker; defining feature | | **CD15** | Positive (75–85% of cases) | Myeloid marker; highly specific for cHL | | **CD45 (LCA)** | Negative | Absent pan-leukocyte antigen | | **CD20** | Negative or weak | B-cell marker; typically absent | | **CD3** | Negative | T-cell marker; absent | | **CD79a** | Negative or weak | B-cell marker; typically absent | | **EBV (EBER)** | Variable (40–50% overall, higher in MC subtype) | In situ hybridization | | **PAX5** | Weak or absent | B-cell transcription factor; reduced | ### Why This Phenotype Matters 1. **CD30+ CD15+:** Highly specific for cHL; distinguishes from primary mediastinal B-cell lymphoma (which is CD30+ but CD15−). 2. **CD45− CD20−:** Indicates loss of B-cell lineage markers despite B-cell origin (by clonality studies). 3. **Diagnostic Algorithm:** CD30+ in a background of inflammatory cells + CD15+ + CD45− + CD20− = cHL until proven otherwise. **High-Yield:** The **CD30+ CD15+ CD45− CD20−** phenotype is the classic immunophenotype taught for cHL. Any deviation (e.g., CD20+ or CD15−) should prompt consideration of alternative diagnoses. **Clinical Pearl:** Flow cytometry may be falsely negative for CD30 if the neoplastic cells are sparse; immunohistochemistry on tissue is more reliable. Always correlate with morphology. **Mnemonic:** **"cHL = CD30 CD15 Negative for 45 and 20"** — Remember the positive markers (30, 15) and the negative ones (45, 20).
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