A 28-year-old male presents with a 3-month history of progressive painless cervical lymphadenopathy and low-grade fever. On examination, he has firm, rubbery, non-tender lymph nodes in the neck. A lymph node biopsy shows effacement of normal architecture with scattered large multinucleated cells (20–50 μm) surrounded by small lymphocytes, histiocytes, and eosinophils. Immunohistochemistry reveals CD30+ and CD15+ cells that are CD45− and CD20−. What is the most likely diagnosis?

Explanation

## Diagnosis: Nodular Sclerosis Hodgkin Lymphoma ### Clinical Presentation **Key Point:** The patient presents with classic features of Hodgkin lymphoma (HL): painless cervical lymphadenopathy, B symptoms (low-grade fever), and firm, rubbery nodes in a young adult male. ### Histopathology & Immunophenotype **High-Yield:** The diagnostic hallmark is the presence of **Reed-Sternberg (RS) cells** and **Hodgkin cells** — large multinucleated or multilobated cells (20–50 μm) surrounded by a rich inflammatory background of small lymphocytes, histiocytes, and eosinophils. **Key Point:** The immunophenotypic profile is pathognomonic: - **CD30+** and **CD15+** (present on RS/Hodgkin cells) - **CD45− (LCA−)** and **CD20−** (absent on neoplastic cells) - CD3− (T-cell marker absent) This profile distinguishes HL from B-cell lymphomas (which are CD20+) and T-cell lymphomas (which are CD3+). ### Why Nodular Sclerosis? **Clinical Pearl:** Nodular sclerosis is the most common histological subtype of HL (~70% of cases) and typically presents with: - Mediastinal and/or supraclavicular/cervical involvement - Young adults (peak 20–30 years) - Lacunar cells (RS cell variants in fibrotic background) - Collagen bands dividing lymph node into nodules ### Staging & Prognosis **High-Yield:** HL uses the Ann Arbor staging system (I–IV). Nodular sclerosis HL has a favorable prognosis with modern chemotherapy (ABVD) and radiation, with 5-year survival >90% in early stages. | Feature | Nodular Sclerosis HL | Other HL Subtypes | |---------|----------------------|-------------------| | Frequency | ~70% | 30% | | Age | Young adults (20–30) | Variable | | Sites | Mediastinal, supraclavicular | Varied | | Prognosis | Favorable | Variable | **Mnemonic:** **RS cells = Reed-Sternberg** — the diagnostic cell in HL; CD30+/CD15+ is the immunophenotypic signature.