Hodgkin Lymphoma: Diagnosis, Investigation, Findings & Treatment

Overview

Classification

Classic HL Subtypes

Pathogenesis

• RS cells derive from germinal center B cells (confirmed by identical immunoglobulin gene rearrangements in microdissected RS cells).
• EBV is present in RS cells in up to 70% of mixed-cellularity cases; EBV integration precedes clonal expansion.
• RS cells secrete cytokines (IL-5, TGF-β, IL-13) driving the reactive inflammatory infiltrate.
• RS cells evade immunity by overexpressing PD-L1/PD-L2 (chromosome 9p amplification) and losing MHC class I expression — the basis for anti-PD-1 immunotherapy efficacy.

Clinical Presentation & Symptoms

• Asymptomatic peripheral adenopathy is the most common presentation — typically cervical or supraclavicular lymphadenopathy.
• B symptoms (in ~25% of patients):
  • Fever >38°C (persistent)
  • Drenching night sweats
  • Unexplained weight loss >10% body weight over 6 months
• Pruritus — severe, generalized; often precedes diagnosis by months (rare in NHL).
• Mediastinal mass — especially in NS subtype (may cause SVC syndrome, cough, dyspnea).
• HL spreads in a contiguous, stepwise pattern through anatomically adjacent nodal groups (unlike NHL which spreads non-contiguously).

Diagnosis: The Reed-Sternberg Cell

• Large cell (15–45 μm diameter)
• Enormous multilobed nucleus
• Exceptionally prominent nucleoli
• "Owl-eye" appearance — two mirror-image nuclei each with a large acidophilic nucleolus surrounded by a clear halo

• ✅ CD15+, CD30+
• ❌ CD45− (leukocyte common antigen negative)
• ❌ B-cell and T-cell markers negative

• "Popcorn" (LP) cells — CD20+, CD45+, CD15−, variably CD30+

Flow cytometry is often non-diagnostic in HL — tissue biopsy is mandatory.

Histology — Mixed-Cellularity HL

Fig. 10.26 — Classic binucleate Reed-Sternberg cell surrounded by eosinophils, lymphocytes, and histiocytes. (Robbins & Kumar Basic Pathology)

Investigation & Workup

1. Tissue Diagnosis

• Excisional lymph node biopsy — required; provides tissue for histology, IHC, and molecular studies.
• IHC panel: CD15, CD30, CD45, CD20, CD3, PAX5.

2. Laboratory Studies

• Full blood count, ESR, LDH, β2-microglobulin, albumin, liver/renal function.
• HIV serology.

3. Imaging — Staging Investigations

• 18F-FDG PET/CT — investigation of choice for staging (sensitivity 97%, specificity 100% for HL). Changes management in ~30% of HL cases vs CT alone. Provides baseline for treatment response monitoring.
• CT chest/abdomen/pelvis — acceptable if PET/CT unavailable.
• CT neck — optional; may assist in radiotherapy planning.
• Chest X-ray — not required for staging.

4. Bone Marrow Biopsy

• No longer required for routine staging if PET/CT has been performed.

5. Additional

• Whole-body MRI — only if PET/CT and CT are both unavailable.
• Echocardiography and pulmonary function tests — baseline before anthracycline/bleomycin therapy.
• Fertility counselling and sperm/egg banking before chemotherapy.

Staging — Ann Arbor System with Cotswolds Modification

• A — No B symptoms
• B — B symptoms present
• E — Contiguous extranodal involvement
• X — Bulky disease (MMR >0.33 on CXR or >0.35 on CT; or nodal mass >10 cm)

Treatment — When to Start & What to Use

Favorable Early-Stage (Stage I–II, No Bulky Disease, No B Symptoms)

• Combined modality: 2–4 cycles ABVD + involved-field/involved-site radiotherapy (ISRT 20–30 Gy)
• If PET-negative after 2 cycles → can omit radiotherapy in selected patients (to reduce long-term toxicity)
• Durable remission rate: 90–95%

Unfavorable Early-Stage (Stage I–II with Bulky Disease or B Symptoms)

• 4–6 cycles ABVD + consolidation radiotherapy
• Durable remission: ~80%

Advanced Stage (Stage III–IV)

• 6–8 cycles ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) — the backbone regimen
• Alternative: BEACOPPescalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) — higher CR rate but greater toxicity; used in high-risk/young fit patients
• PET-adapted therapy — interim PET (after cycle 2) guides de-escalation (switch to ABVD if PET-negative) or escalation
• Durable remission: ~70%

ABVD Regimen

Relapsed/Refractory Disease

• Salvage chemotherapy (DHAP, ICE, GDP) → high-dose chemotherapy + autologous stem cell transplant (ASCT)
• Brentuximab vedotin (anti-CD30 antibody-drug conjugate) — effective in relapsed/refractory CHL
• Checkpoint inhibitors — nivolumab (anti-PD-1) and pembrolizumab — highly active even in multiply relapsed HL; most tumors respond even after resistance to other therapies (due to PD-L1 amplification on RS cells)

Prognosis Summary

• Robbins & Kumar Basic Pathology, pp. 417–421
• Cummings Otolaryngology Head and Neck Surgery, pp. 2246–2248
• Grainger & Allison's Diagnostic Radiology, Ch. 64