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?

Question

Accepted Answer

C. Nodular sclerosis Hodgkin lymphoma. ## 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

![Lymphomas — Hodgkin diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2644.webp)

Answer

A. Reactive lymphadenopathy with viral infection

Answer

B. Diffuse large B-cell lymphoma

Answer

D. Peripheral T-cell lymphoma, not otherwise specified

Explanation

Diagnosis: Nodular Sclerosis Hodgkin Lymphoma

Histopathological Features

Nodular Sclerosis Subtype

Diagnostic Algorithm

HL Subtypes Comparison

Why This Is Not Other Entities

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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