## Diagnostic Cells in Classical Hodgkin Lymphoma **Key Point:** **Reed-Sternberg (RS) cells** are the pathognomonic and most characteristic diagnostic cells in classical Hodgkin lymphoma. They are large, multinucleated cells with prominent eosinophilic nucleoli ("owl's eye" appearance). ### Morphology and Diagnostic Criteria | Cell Type | Origin | Morphology | Diagnostic Role | Frequency | |-----------|--------|-----------|-----------------|----------| | **Reed-Sternberg (RS) cells** | Clonal B cells | Large, multinucleated, "owl's eye" nucleoli, abundant cytoplasm | **Pathognomonic** for cHL | Required for diagnosis | | **Hodgkin cells** | Clonal B cells | Mononuclear variants of RS cells; similar morphology | Diagnostic equivalent | Present in all cases | | **Lacunar cells** | RS cells in formalin-fixed tissue | RS cells in clear spaces (lacunae) in nodular sclerosis | Subtype-specific | Nodular sclerosis only | | **Immunoblasts** | Non-neoplastic T cells | Large activated lymphocytes | Background inflammatory cells | Non-diagnostic | **High-Yield:** RS cells are **required for the diagnosis of classical Hodgkin lymphoma**. The WHO diagnostic criteria mandate the presence of RS cells or Hodgkin cells in a background of small lymphocytes, histiocytes, and eosinophils. ### Morphological Features of Reed-Sternberg Cells **Mnemonic:** **"OWL'S EYE"** = Obvious, Widely-separated, Large nucleoli; Eosinophilic, Abundant cytoplasm; Multinucleated, Enlarged cell. **Clinical Pearl:** The classic RS cell has: - **Multiple nuclei** (usually 2–4, but can be more) - **Prominent, eosinophilic nucleoli** that resemble owl eyes - **Abundant, basophilic cytoplasm** - **Thick nuclear membranes** - **Frequent mitotic figures** ### Immunophenotype RS and Hodgkin cells characteristically express: - **CD30** (strong, membrane/Golgi pattern) — most sensitive marker - **CD15** (75–85% of cases) - **CD45 negative** (loss of pan-B-cell antigen) - **CD20 negative or weak** (loss of B-cell marker) - **CD3 negative** (not T cells) - **EBV positive** (in many cases, detected by EBER in situ hybridization) **Warning:** Do not confuse RS cells with: - ~~Immunoblasts~~ (which are non-neoplastic activated T cells in the background) - ~~Atypical lymphocytes~~ (which are smaller and have different morphology) - ~~Carcinoma cells~~ (which are epithelial and have different immunophenotype) ### Why Lacunar Cells Are NOT the Answer Lacunar cells are **RS cell variants** seen specifically in **nodular sclerosis Hodgkin lymphoma** when tissue is fixed in formalin. They are the same neoplastic cell as RS cells but appear in clear spaces (lacunae) due to tissue retraction. They are **subtype-specific**, not universally present in all HL cases.
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