A 28-year-old man from Delhi presents with a 3-month history of progressive painless swelling of cervical and mediastinal lymph nodes. He reports B symptoms (fever, night sweats, weight loss of 4 kg). Physical examination reveals firm, mobile, non-tender lymph nodes in the neck. Chest X-ray shows mediastinal widening. Lymph node biopsy reveals effacement of normal architecture with scattered large cells containing multiple nuclei and prominent eosinophilic nucleoli, surrounded by small lymphocytes, histiocytes, and eosinophils. What is the most likely diagnosis?

Explanation

## Diagnosis: Hodgkin Lymphoma, Nodular Sclerosis Subtype ### Clinical Presentation **Key Point:** The combination of painless cervical and mediastinal lymphadenopathy with B symptoms in a young adult is classic for Hodgkin lymphoma (HL). **Clinical Pearl:** Mediastinal involvement is particularly common in nodular sclerosis HL, which accounts for 60–70% of HL cases in developed countries and is the most frequent subtype in India. ### Histopathology Findings The biopsy description is pathognomonic for Hodgkin lymphoma: | Feature | Finding | Significance | |---------|---------|---------------| | Large multinucleated cells | Reed-Sternberg (RS) cells | Diagnostic hallmark | | Prominent eosinophilic nucleoli | "Owl's eye" appearance | Characteristic of RS cells | | Background infiltrate | Small lymphocytes, histiocytes, eosinophils | Reactive, non-neoplastic | | Architecture | Effaced normal nodal structure | Indicates neoplastic process | **High-Yield:** Reed-Sternberg cells are CD30^+^, CD15^+^, CD45^−^, CD20^−^ (variable), and EBV^+^ (in many cases, especially in nodular sclerosis subtype). ### Why Nodular Sclerosis? The nodular sclerosis subtype is characterized by: 1. **Fibrous bands** dividing the lymph node into nodules (not explicitly mentioned but implied by "nodular sclerosis") 2. **Lacunar cells** (RS cell variants in formalin-fixed tissue appearing in empty spaces) 3. **Mediastinal involvement** — most common in this subtype (50–80% of cases) 4. **Young adult presentation** — peak incidence 20–40 years 5. **B symptoms** — present in ~30% at diagnosis **Mnemonic:** **NSLR** = Nodular Sclerosis (most common), Lymphocyte-rich, Lymphocyte-depleted, Mixed cellularity (subtypes of classical HL, in rough order of frequency). ### Differential Considerations - **Lymphocyte-rich HL:** Abundant background lymphocytes, fewer RS cells, better prognosis — but mediastinal involvement is less common. - **DLBCL:** Would show diffuse infiltration of large atypical B cells without the characteristic RS cell morphology and reactive background. - **Reactive lymphadenopathy:** Would lack RS cells and architectural effacement. **Warning:** Do not confuse RS cells with other large cells (e.g., immunoblasts in reactive nodes or blast cells in acute leukemia) — the specific morphology and immunophenotype are diagnostic. [cite:Robbins 10e Ch 20]