A 28-year-old man from Delhi presents with a 3-month history of progressive cervical lymphadenopathy and low-grade fever. On examination, he has firm, rubbery, non-tender lymph nodes in the neck. A chest X-ray shows mediastinal widening. A lymph node biopsy is performed and histology reveals scattered large cells with clear cytoplasm and prominent eosinophilic nucleoli, admixed with small lymphocytes, plasma cells, and eosinophils. Immunohistochemistry shows these large cells are CD30+, CD15+, and CD45−. What is the most likely diagnosis?

Explanation

## Diagnosis: Hodgkin Lymphoma, Nodular Sclerosis Subtype ### Histopathologic Features The biopsy description is classic for Hodgkin lymphoma (HL). The key diagnostic cells are: - **Large cells with clear cytoplasm and prominent eosinophilic nucleoli** = Reed-Sternberg (RS) cells or Hodgkin cells - **Mixed inflammatory background** (small lymphocytes, plasma cells, eosinophils) = characteristic of HL ### Immunophenotype **Key Point:** The immunoprofile CD30+, CD15+, CD45− is pathognomonic for Hodgkin lymphoma. - CD30+ and CD15+ = RS cells and Hodgkin cells - CD45− (CD20−, CD3−) = distinguishes HL from reactive lymphocytes and NHL ### Subtype Classification The **nodular sclerosis subtype** is the most common (60–70% of all HL cases) and is characterized by: 1. Nodular fibrosis pattern with collagen bands dividing the lymph node into nodules 2. Lacunar cells (RS cell variants in formalin-fixed tissue, appearing in empty spaces) 3. Mediastinal involvement (common in this subtype) 4. Typically affects young adults and adolescents 5. Generally has a favorable prognosis The clinical presentation (young adult, cervical and mediastinal lymphadenopathy) and histology fit nodular sclerosis perfectly. ### Why Not Other Subtypes? | Subtype | Key Features | Frequency | |---------|--------------|----------| | **Nodular Sclerosis** | Nodular fibrosis, lacunar cells, mediastinal involvement | 60–70% | | **Lymphocyte-Rich** | Abundant small lymphocytes, few RS cells, better prognosis | 5% | | **Lymphocyte-Depleted** | Numerous RS cells, few lymphocytes, worst prognosis, rare | <5% | | **Mixed Cellularity** | Numerous RS cells, mixed inflammation, no nodular pattern | 15–25% | **High-Yield:** Nodular sclerosis is the most common subtype in developed countries and typically presents with mediastinal involvement in young adults. ### Clinical Pearl The presence of mediastinal widening on chest X-ray is a strong clue toward nodular sclerosis, as this subtype has a predilection for anterior mediastinal involvement.