## Immunophenotype of Reed-Sternberg Cells **Key Point:** Reed-Sternberg (RS) cells in classical Hodgkin lymphoma are **CD30+, CD15+, CD45−, CD20−**. This immunophenotype is essential for diagnosis and distinguishes cHL from other lymphomas. ### Immunophenotypic Profile of RS Cells | Marker | Expression in RS Cells | Significance | |--------|------------------------|---------------| | **CD30** | **+** (strong) | Activation antigen; hallmark of RS cells | | **CD15** | **+** (75–85%) | Myeloid-associated antigen; highly specific | | **CD45** | **−** | Absent; excludes lymphoid lineage | | **CD20** | **−** | Absent; B-cell marker lost in cHL | | **CD3** | **−** | T-cell marker; absent | | **EBV** | **+** (variable) | Present in ~40% of cases; detected by EBER ISH | | **PAX5** | **Weak/−** | Weakly expressed or absent | **High-Yield:** The **CD30+ CD15+ CD45− CD20−** phenotype is pathognomonic for RS cells and is used in flow cytometry and immunohistochemistry to confirm the diagnosis of classical Hodgkin lymphoma. **Clinical Pearl:** CD30 is also expressed in primary cutaneous lymphomas (cutaneous ALCL, lymphomatoid papulosis) and systemic ALCL, but the combination of CD30 + CD15 + CD45− is highly specific for cHL. ### Diagnostic Algorithm ```mermaid flowchart TD A[Suspected Hodgkin Lymphoma]:::outcome --> B{CD30+?}:::decision B -->|Yes| C{CD15+?}:::decision B -->|No| D[Not cHL; consider other diagnoses]:::action C -->|Yes| E{CD45−, CD20−?}:::decision C -->|No| F[Consider ALCL or other CD30+ lymphoma]:::action E -->|Yes| G[Classical Hodgkin Lymphoma confirmed]:::outcome E -->|No| H[Atypical; review morphology]:::action ``` **Mnemonic:** **CD30-CD15 Rule** — Remember "30-15" as the signature markers of RS cells. CD30 is the activation antigen, CD15 is the myeloid marker. Both must be present; CD45 and CD20 must be absent. 
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