A 28-year-old man presents with painless cervical lymphadenopathy and constitutional symptoms. Lymph node biopsy reveals diagnostic Reed-Sternberg cells. What is the most common histological subtype of Hodgkin lymphoma in this patient?

Question

Accepted Answer

C. Nodular sclerosis. ## Histological Subtypes of Hodgkin Lymphoma

**Key Point:** Nodular sclerosis is the most common histological subtype of classical Hodgkin lymphoma (cHL), accounting for approximately 60–70% of cases in developed countries.

### Frequency Distribution

| Subtype | Frequency | Key Features | Prognosis |
|---------|-----------|--------------|----------|
| **Nodular sclerosis** | 60–70% | Lacunar cells, collagen bands, mediastinal involvement | Favorable |
| Mixed cellularity | 15–25% | Numerous RS cells, diffuse infiltrate, no nodules | Intermediate |
| Lymphocyte-rich | 5% | Abundant small lymphocytes, few RS cells | Favorable |
| Lymphocyte-depleted | 1–5% | Numerous RS cells, sparse lymphocytes | Poor |

**High-Yield:** Nodular sclerosis typically presents in young adults (teens to 40s) with **mediastinal involvement** — a hallmark feature that helps distinguish it from other subtypes.

### Clinical Correlations

**Clinical Pearl:** Nodular sclerosis frequently involves the **anterior mediastinum**, which may present as a mediastinal mass on chest X-ray even before lymphadenopathy is clinically apparent. This is why a chest imaging study is part of the initial workup.

**Mnemonic:** **NSMCLD** = Nodular Sclerosis, Mixed Cellularity, Lymphocyte-Rich, Lymphocyte-Depleted (in order of frequency).

### Why Nodular Sclerosis is Most Common

The nodular sclerosis subtype:
- Arises from germinal center B cells
- Shows characteristic fibrous bands dividing the lymph node into nodules
- Contains lacunar cells (RS cell variants in formalin-fixed tissue)
- Has the best prognosis among classical HL subtypes when treated appropriately

**Warning:** Do not confuse nodular sclerosis with nodular lymphocyte-predominant HL (NLPHL), which is a separate entity with a different cell of origin (T-cell rich background) and better prognosis.

Answer

A. Lymphocyte-depleted

Answer

B. Mixed cellularity

Answer

D. Lymphocyte-rich

A 28-year-old man presents with painless cervical lymphadenopathy and constitutional symptoms. Lymph node biopsy reveals diagnostic Reed-Sternberg cells. What is the most common histological subtype of Hodgkin lymphoma in this patient?

Explanation

Histological Subtypes of Hodgkin Lymphoma

Frequency Distribution

Clinical Correlations

Why Nodular Sclerosis is Most Common

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Subtype	Frequency	Key Features	Prognosis
Nodular sclerosis	60–70%	Lacunar cells, collagen bands, mediastinal involvement	Favorable
Mixed cellularity	15–25%	Numerous RS cells, diffuse infiltrate, no nodules	Intermediate
Lymphocyte-rich	5%	Abundant small lymphocytes, few RS cells	Favorable
Lymphocyte-depleted	1–5%	Numerous RS cells, sparse lymphocytes	Poor