A 35-year-old woman from Mumbai presents with a 6-week history of mediastinal chest discomfort, dry cough, and night sweats. Chest X-ray shows a large anterior mediastinal mass with bilateral hilar lymphadenopathy. CT chest confirms a 12 cm mass. A mediastinal lymph node biopsy reveals diffuse fibrosis with scattered large atypical cells in a background of small lymphocytes and eosinophils. Flow cytometry shows CD30+, CD15+, CD45−, CD20−, and CD3− cells. Which histological subtype of Hodgkin lymphoma is most likely?

Explanation

## Diagnosis: Nodular Sclerosis Hodgkin Lymphoma (Mediastinal Variant) ### Clinical Presentation **Key Point:** This patient presents with classic B symptoms (night sweats, fever implied by history) and a **large anterior mediastinal mass** — a hallmark of nodular sclerosis HL, particularly in young women. **High-Yield:** Mediastinal involvement occurs in ~60–70% of nodular sclerosis cases and is rare in other HL subtypes. This patient's age (35, female) and mediastinal presentation are typical. ### Histopathology **Clinical Pearl:** The description "diffuse fibrosis with scattered large atypical cells" indicates **collagen bands and fibrosis** characteristic of nodular sclerosis. The presence of: - Large atypical cells (Reed-Sternberg and Hodgkin cells) - Inflammatory background (small lymphocytes, eosinophils) - Fibrous bands (nodular architecture) All point to nodular sclerosis. ### Immunophenotype **Key Point:** The immunophenotype (CD30+, CD15+, CD45−, CD20−, CD3−) is consistent with classical Hodgkin lymphoma (cHL) and does NOT distinguish between cHL subtypes. However, the **histology and clinical context** (mediastinal mass, young woman, fibrosis) define nodular sclerosis. ### Comparison of cHL Subtypes | Subtype | Frequency | Sites | Age | Histology | Prognosis | |---------|-----------|-------|-----|-----------|----------| | **Nodular Sclerosis** | ~70% | Mediastinal, supraclavicular | Young adults (20–30) | Collagen bands, lacunar cells | Favorable | | Lymphocyte-rich | ~5% | Peripheral nodes | Older adults | Sparse RS cells, rich lymphocytes | Favorable | | Lymphocyte-depleted | ~1% | Abdominal, advanced stage | Older adults | Abundant RS cells, few lymphocytes | Poor | | Nodular LP | ~5% | Peripheral nodes | Older adults | LP cells (CD20+, CD45+) | Excellent | **Mnemonic:** **"Nodular Sclerosis = Mediastinal Mass"** — the most common HL subtype with a predilection for the anterior mediastinum and young women. ### Staging & Treatment **High-Yield:** This patient likely has stage III–IV disease (bilateral hilar involvement, mediastinal mass). Standard treatment is ABVD ± radiation. Nodular sclerosis HL has excellent prognosis with modern therapy (>85% 5-year survival).