A 32-year-old man presents with painless cervical lymphadenopathy and constitutional symptoms (fever, night sweats, weight loss). Physical examination reveals firm, rubbery, non-tender lymph nodes. A chest X-ray shows mediastinal widening. Which investigation is most appropriate to establish a definitive diagnosis of Hodgkin lymphoma?

Explanation

## Diagnostic Approach to Suspected Hodgkin Lymphoma ### Why Excisional Biopsy is the Gold Standard **Key Point:** Excisional (open) lymph node biopsy with histopathology is the investigation of choice for definitive diagnosis of Hodgkin lymphoma. It provides adequate tissue for: - Morphologic assessment of nodal architecture - Identification of diagnostic Reed-Sternberg (RS) cells and Hodgkin cells - Immunohistochemical confirmation (CD30+, CD15+, CD45−, CD20−) - Determination of histologic subtype (nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte-depleted) ### Tissue Requirements **High-Yield:** The entire lymph node architecture must be preserved to: 1. Assess capsular fibrosis and sclerosis 2. Identify nodular vs. diffuse involvement 3. Recognize background cellular composition (T cells, eosinophils, plasma cells) 4. Confirm diagnostic criteria (presence of RS cells in appropriate background) ### Histopathologic Hallmarks | Finding | Significance | |---------|-------------| | Reed-Sternberg cells | Large, multinucleated cells with "mirror-image" nuclei and prominent nucleoli ("owl's eye") | | Hodgkin cells | Mononuclear variants of RS cells | | Background | Small lymphocytes, eosinophils, histiocytes, plasma cells (sparse neoplastic cells) | | CD30, CD15 positivity | Confirms neoplastic cells | | CD45, CD20 negativity | Excludes B-cell lymphoma | **Clinical Pearl:** The background cellular composition is crucial — HL is characterized by a paucity of neoplastic cells in a rich inflammatory milieu, unlike NHL where neoplastic cells are abundant. ### Why Other Investigations Are Insufficient **Warning:** FNAC cannot reliably diagnose HL because: - Insufficient tissue architecture preservation - Difficulty in identifying RS cells in isolation - High false-negative rate (sensitivity ~30–50%) - Cannot assess nodal architecture or background composition LDH and ESR are prognostic markers, not diagnostic. CT is for staging, not diagnosis.