Hodgkin lymphoma

Overview

• Tumor of B-cell origin with unusual pathological and clinical manifestations
• Consists of neoplastic cells (Reed-Sternberg cells) and non-neoplastic inflammatory cells
• Arises in a single lymph node or chain and spreads in stepwise (contiguous) fashion to adjacent nodes

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Reed-Sternberg (RS) Cells

• Large cells, either multinucleated or bilobed
• Prominent acidophilic (eosinophilic) nucleoli surrounded by a clear zone → “owl eye” appearance
• Immunophenotype: CD30(+), CD15(+), PAX5(+), CD45(−), CD20(−)

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Classification

1. Classical HL (4 subtypes)

Nodular sclerosis (most common overall)

• Equally frequent in both sexes; seen in teenagers and young adults
• Often in lower cervical, supraclavicular, or mediastinal lymph nodes
• RS cells + lacunar cells (single multilobate nucleus, multiple small nucleoli, pale cytoplasm → cytoplasm disappears in fixation, appearing as empty lacunae)
• Collagen bands divide lymphoid tissue into circumscribed nodules

Mixed cellularity (most common in older patients >50)

• Male predominance
• Classic RS cells within heterogenous reactive infiltrate: small lymphocytes, eosinophils, plasma cells, macrophages

Lymphocyte rich

• Few RS cells surrounded by diffuse infiltration of small lymphocytes

Lymphocyte depletion (worst prognosis)

• Sheets and clusters of RS cells → solid masses
• Lymphocyte count decreases

2. Lymphocyte-predominant HL (non-classical)

• 5% of all HL
• Contains lymphohistiocytic (L&H) variant RS cells = “popcorn cells”: delicate, multilobed, puffy nucleus
• Found in large nodules with many small resting B-cells and macrophages
• Indolent clinical course
• Immunophenotype: CD20(+), CD15(−), CD30(−)

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Pathogenesis

• Germinal center B-cell origin
• Up to 70% of HL cases associated with EBV → clonal viral genomes found in RS cells
• Non-neoplastic inflammatory infiltrate results from cytokines secreted by RS cells: IL-5, TGFβ, IL-13
• RS cells express PD ligands → inhibit T-cells → immune escape

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Staging (Ann Arbor)

Stage	Distribution of disease
I	One region of lymph node or single extra-lymphatic organ
II	More than one lymph node region, all on same side of diaphragm
III	Lymph node regions both below and above the diaphragm
IV	Disseminated disease with organ involvement

Clinical features

• Presents as painless lymph node enlargement
• Stage I/II: younger patients, favorable histology, usually no systemic symptoms
• Stage III/IV: systemic symptoms — fever, night sweats, weight loss (B symptoms)
• Treatment: radiotherapy + chemotherapy + PD1 antibody therapy
• 5-year survival ~90% (excellent response to treatment)

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HL vs. NHL comparison

Hodgkin Lymphoma	Non-Hodgkin Lymphoma
B-cell origin	B- or T-cell origin
Reed-Sternberg cells present	No Reed-Sternberg cells
Localized, single lymph node group	Multiple lymph nodes involved
Contiguous spread	Non-contiguous spread
Less common	More common

💡 High-yield: HL = RS cells (owl eye); CD30+/CD15+/CD45−/CD20−. Most common subtype: nodular sclerosis (young adults, mediastinum). LPHL = popcorn cells, CD20+. EBV in 70%. Staging I–IV; 5-yr survival ~90% with treatment.