A 28-year-old man from Delhi presents with a 3-month history of progressive cervical lymphadenopathy and intermittent fever. On examination, he has firm, non-tender, rubbery lymph nodes in the neck and mediastinal involvement on chest X-ray. A lymph node biopsy shows effacement of normal architecture with scattered large multinucleated cells (20–50 μm) surrounded by a rich inflammatory infiltrate of small lymphocytes, eosinophils, and plasma cells. The multinucleated cells are CD30+, CD15+, and CD45−. What is the most likely diagnosis?

Explanation

## Diagnosis: Nodular Sclerosis Hodgkin Lymphoma ### Histopathological Features **Key Point:** Hodgkin lymphoma (HL) is characterized by the presence of **Hodgkin cells** (large multinucleated or multilobated cells, 20–50 μm) and **Reed–Sternberg (RS) cells** (true multinucleated giant cells with "mirror-image" or "owl-eye" nuclei) within a rich inflammatory background. **High-Yield:** The diagnostic hallmark is the **immunophenotype**: - CD30+ (strong, membrane and Golgi pattern) - CD15+ (75–85% of cases) - CD45− (negative — rules out reactive lymphocytes) - CD20− or weakly positive - EBV+ (varies by subtype) ### Nodular Sclerosis Subtype **Clinical Pearl:** Nodular sclerosis is the **most common subtype** (60–70% of HL cases in developed countries), typically presenting with: - **Mediastinal involvement** (as seen in this case) - Cervical/supraclavicular lymphadenopathy - Young adults (peak 20–40 years) - Better prognosis than other subtypes ### Diagnostic Algorithm ```mermaid flowchart TD A[Lymphadenopathy + fever]:::outcome --> B{Biopsy findings}:::decision B -->|Large multinucleated cells| C{CD30+ CD15+ CD45−?}:::decision C -->|Yes| D[Hodgkin Lymphoma]:::outcome D --> E{Nodules + sclerosis?}:::decision E -->|Yes| F[Nodular Sclerosis HL]:::action E -->|No| G[Other HL subtype]:::outcome B -->|Small lymphocytes only| H[Reactive/Viral]:::outcome ``` ### HL Subtypes Comparison | Subtype | Frequency | Mediastinal | EBV | Prognosis | |---------|-----------|-------------|-----|----------| | Nodular Sclerosis | 60–70% | Common (60%) | 20–40% | Favorable | | Mixed Cellularity | 15–25% | Rare | 75–95% | Intermediate | | Lymphocyte-Rich | 5% | Rare | 20–40% | Favorable | | Lymphocyte-Depleted | <5% | Rare | 75–95% | Poor | **Key Point:** The presence of **mediastinal involvement** in a young adult with cervical lymphadenopathy strongly favors nodular sclerosis HL. ### Why This Is Not Other Entities - ~~Diffuse large B-cell lymphoma~~ — Would be CD20+, not CD30+/CD15+; different morphology - ~~Peripheral T-cell lymphoma~~ — Would be CD4+ or CD8+, not CD30+/CD15+ - ~~Reactive lymphadenopathy~~ — Would lack RS/Hodgkin cells and show polyclonal B/T cells