Hodgkin's Disease

Definition

Hodgkin's lymphoma (Hodgkin's disease) is a B-cell lymphoid malignancy characterised by the presence of Reed–Sternberg (RS) cells — large binucleated or multinucleated cells with prominent eosinophilic 'owl-eye' nucleoli — set against a reactive inflammatory background of lymphocytes, eosinophils, neutrophils, and plasma cells.

General / Essential Features

• Reed–Sternberg cells: large binucleated / multinucleated cells — pathognomonic
• Prominent eosinophilic 'owl-eye' nucleolus in each RS cell nucleus
• Abundant pale eosinophilic cytoplasm in RS cells
• Derived from germinal-centre B-cells (CD15+, CD30+, CD45−)
• Mixed inflammatory background: lymphocytes, eosinophils, plasma cells, neutrophils
• Nodular sclerosis subtype: broad collagen bands dividing lymph node into nodules

Sites

• Cervical and supraclavicular lymph nodes — most common presentation
• Mediastinal lymphadenopathy: nodular sclerosis type (especially young women)
• Axillary and inguinal nodes (less common)
• Spreads in contiguous nodal fashion (unlike NHL)
• Ann Arbor staging: I–IV based on nodal and extranodal involvement

Pathophysiology

RS cells are clonally derived from germinal-centre B-cells that have lost their B-cell programme (loss of PAX5, BCL6 expression but retained CD30, CD15). They secrete IL-13, IL-5, and eotaxin, recruiting eosinophils and creating a tolerogenic microenvironment. EBV latent membrane protein (LMP1) mimics CD40 signalling and is implicated in pathogenesis.

Etiology

• EBV association: LMP1 drives NFκB activation — present in ~40% of cases
• Immunosuppression: HIV-associated Hodgkin's lymphoma
• Genetic predisposition: first-degree relatives, monozygotic twins
• Bimodal age distribution: young adults (15–34) and older adults (>55)

Clinical Features

• Painless cervical lymphadenopathy — most common presentation
• B symptoms: fever, drenching night sweats, weight loss >10% over 6 months
• Mediastinal mass: cough, dyspnoea, SVC syndrome
• Alcohol-induced lymph node pain (pathognomonic)
• Pruritus — generalised

Diagnosis

• Excisional lymph node biopsy: required for subtype classification
• Histopathology + IHC: CD15+, CD30+, CD45−, PAX5 dim
• CT chest/abdomen/pelvis: staging
• PET-CT: gold standard for staging and response assessment
• Bone marrow biopsy: for stage III/IV disease

Treatment

• Early stage (I–II): ABVD chemotherapy × 2–4 cycles ± radiotherapy
• Advanced stage (III–IV): ABVD × 6 cycles or escalated BEACOPP
• PET-adapted therapy: de-escalation in PET-negative responders
• Relapsed/refractory: BV-based salvage + autologous stem cell transplant
• Brentuximab vedotin (anti-CD30): for relapsed HL