A 28-year-old male from Delhi presents with a 3-month history of painless progressive swelling of cervical and supraclavicular lymph nodes. He reports fever in the evenings, night sweats drenching his clothes, and unintentional weight loss of 8 kg over 2 months. On examination, firm, rubbery, non-tender lymphadenopathy is noted. Chest X-ray shows mediastinal widening. Lymph node biopsy reveals scattered large cells with multiple nuclei and prominent eosinophilic nucleoli ("owl's eye" appearance) admixed with small lymphocytes, histiocytes, and eosinophils. Which is the most likely diagnosis?

Explanation

## Diagnosis: Nodular Sclerosis Hodgkin Lymphoma ### Clinical Presentation **Key Point:** The constellation of B symptoms (fever, night sweats, weight loss), painless progressive lymphadenopathy, and mediastinal involvement in a young adult is classic for Hodgkin lymphoma. **High-Yield:** Nodular sclerosis is the most common subtype of classical Hodgkin lymphoma (~70% of cases), with a predilection for young adults and anterior mediastinal involvement. ### Histopathologic Features The biopsy findings are pathognomonic for Hodgkin lymphoma: | Feature | Significance | |---------|-------------| | Large multinucleated cells ("owl's eye" nuclei) | Reed-Sternberg (RS) cells — hallmark of classical HL | | Prominent eosinophilic nucleoli | "Mirror-image" or "owl's eye" appearance of RS cells | | Background of small lymphocytes, histiocytes, eosinophils | Inflammatory milieu; RS cells are sparse | | Nodular pattern with fibrosis | Nodular sclerosis subtype | **Clinical Pearl:** Reed-Sternberg cells are CD30^+^, CD15^+^, and typically CD45^−^, CD20^−^ (unlike B-cell lymphomas). Hodgkin cells (mononuclear variants) are also present. ### Nodular Sclerosis Subtype **Mnemonic:** NSHD = **N**odular **S**clerosis **H**odgkin **D**isease - Most common classical HL subtype - Mediastinal involvement frequent (60–80%) - Generally favorable prognosis with modern therapy - Age: typically 20–40 years ### Why This Is Hodgkin (Not Non-Hodgkin) **Key Point:** The sparse population of large atypical cells in a rich inflammatory background is characteristic of Hodgkin lymphoma. Non-Hodgkin lymphomas typically show diffuse infiltration of neoplastic cells. [cite:Robbins 10e Ch 13]