A 28-year-old male from Delhi presents with a 3-month history of progressive cervical lymphadenopathy, fever, and night sweats. On examination, he has firm, non-tender, rubbery lymph nodes in the neck. A lymph node biopsy shows effacement of normal architecture with scattered large cells containing multiple nuclei and prominent nucleoli, surrounded by a rich inflammatory infiltrate of small lymphocytes, eosinophils, and histiocytes. Immunohistochemistry reveals CD30+ and CD15+ large cells that are CD45−, CD20−, and CD3−. What is the most likely diagnosis?

Explanation

## Diagnosis: Classical Hodgkin Lymphoma (cHL), Nodular Sclerosis Subtype ### Clinical Presentation **Key Point:** The vignette describes a young adult with B symptoms (fever, night sweats) and cervical lymphadenopathy—the classic presentation of Hodgkin lymphoma. Nodular sclerosis is the most common subtype (60–70% of cHL cases). ### Histopathology & Immunophenotype **High-Yield:** The diagnostic cells are **Hodgkin cells** (multinucleated giant cells with "mirror-image" nuclei and prominent eosinophilic nucleoli, described as "owl's eye" appearance) and **Reed-Sternberg (RS) cells** (larger variants with multiple nuclei). These are embedded in a rich inflammatory background—a hallmark feature that distinguishes cHL from other lymphomas. **Key Point:** The immunophenotype is pathognomonic: - **CD30+, CD15+** (large cells) — markers of Hodgkin/RS cells - **CD45−, CD20−, CD3−** — absence of pan-B and pan-T markers - The neoplastic cells are typically **CD19−, CD79a−** (B-cell markers lost) ### Nodular Sclerosis Subtype **Clinical Pearl:** Nodular sclerosis is characterized by: - Nodular fibrosis dividing the lymph node into nodules - Lacunar cells (RS cell variants in formalin-fixed tissue appearing to sit in lacunae) - Frequent mediastinal involvement (though this case presents with cervical nodes) - Most common in young adults and adolescents ### Why NOT the Other Subtypes of cHL? - **Lymphocyte-rich:** Predominantly small lymphocytes, few RS cells; CD30+ cells present but sparse - **Mixed cellularity:** Numerous RS cells without nodular fibrosis; more common in older adults and advanced stage - **Lymphocyte-depleted:** Numerous RS cells, few small lymphocytes; rare and associated with poor prognosis ### Differential Diagnosis Table | Feature | cHL (Nodular Sclerosis) | NLPHL | PMBL | DLBCL | | --- | --- | --- | --- | --- | | **CD30** | + (large cells) | − | + (variable) | − | | **CD15** | + (large cells) | − | − | − | | **CD20** | − (large cells) | + (LP cells) | + | + | | **CD45** | − (large cells) | + (LP cells) | − | + | | **Background** | Rich inflammatory | Small lymphs only | Sclerosis, mediastinal | Monomorphic B cells | | **Age** | Young adults | Young males | Young females, mediastinal | Any age | **Mnemonic: CHOP** — **C**lassical HL is **CD30+, CD15+**; **H**odgkin/RS cells; **O**wl's eye nucleoli; **P**rominent inflammatory background. ### Staging & Prognosis **Clinical Pearl:** Once diagnosed, the patient requires: - CT chest/abdomen/pelvis for staging (Ann Arbor classification) - PET-CT to assess metabolic activity - Prognostic factors: International Prognostic Score (IPS) based on age, stage, hemoglobin, albumin, lymphocyte count, and WBC [cite:Robbins 10e Ch 13]