Hodgkin Lymphoma
Lymphoid neoplasm characterised by Reed-Sternberg cells in a reactive inflammatory background. Highly curable with chemotherapy ± radiotherapy. Bimodal age distribution with peaks at 20–30 and >60 years.
Key Facts
Reed-Sternberg cells: large binucleated cells ('owl-eye' appearance) — pathognomonic; CD15+ and CD30+ Bimodal age distribution: peak 20–30 years and >60 years Painless cervical/supraclavicular lymphadenopathy: most common presentation (~70% cervical) B symptoms: fever >38°C, drenching night sweats, weight loss >10% in 6 months (important for staging and prognosis) Contiguous spread: spreads to adjacent lymph node groups (unlike NHL which is non-contiguous) Treatment: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) ± radiotherapy; ~85–90% cure rate overall PET-CT: essential for staging (Ann Arbor + Lugano) and response assessment (interim PET guides therapy) Alcohol-induced lymph node pain: rare but classic symptom; mechanism unclear
Overview
Key Facts
Hodgkin lymphoma (HL) is a lymphoid neoplasm characterised by the presence of Reed-Sternberg cells within a reactive inflammatory background. It is one of the most curable cancers.
Epidemiology
- ~2,000 new cases/year in the UK
- Bimodal: peak 20–30 years, second peak >60 years
- Slight male predominance
- EBV-associated in ~40% of classical HL
Aetiology
- EBV: detected in ~40% of HL (higher in mixed cellularity subtype)
- Immunosuppression: HIV, post-transplant
- Genetic: slightly increased risk in siblings
Pathophysiology
- Reed-Sternberg cells are derived from germinal centre B cells
- RS cells secrete cytokines → recruit reactive inflammatory infiltrate (T cells, eosinophils, histiocytes)
- RS cells constitute <1% of tumour mass; the rest is reactive
- Classical HL (95%): nodular sclerosis (most common), mixed cellularity, lymphocyte-rich, lymphocyte-depleted
- Nodular lymphocyte-predominant HL (5%): LP cells ('popcorn cells'), CD20+, indolent
Clinical Presentation
Typical Presentation
- Painless lymphadenopathy: cervical (~70%), mediastinal, axillary
- Nodes: rubbery, non-tender
- Mediastinal mass (bulky): especially nodular sclerosis subtype
B Symptoms (~30–40%)
- Fever >38°C (Pel-Ebstein fever: cyclical, rare but classic)
- Drenching night sweats
- Weight loss >10% in 6 months
Other
- Alcohol-induced lymph node pain (rare but specific)
- Pruritus (sometimes severe)
- Fatigue
Red Flags
- Mediastinal mass with SVC obstruction
- Progressive lymphadenopathy with B symptoms
- Young adult with unexplained lymphadenopathy >2 weeks
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| NHL | Non-contiguous spread, various subtypes, may be extranodal | Excision biopsy, flow cytometry |
| Reactive lymphadenopathy | Tender, often cervical, associated infection | Clinical, biopsy if persistent |
| TB lymphadenitis | Caseating granulomata, matted nodes, systemic features | AFB, culture, biopsy |
| Sarcoidosis | BHL, non-caseating granulomata, hypercalcaemia | ACE, biopsy |
| Metastatic carcinoma | Hard, fixed nodes, primary tumour | Biopsy, CT |
Diagnosis / Investigation
Bloods
- FBC: may be normal; eosinophilia, lymphopenia
- ESR: elevated (prognostic; >30 mm/hr is adverse)
- LDH: prognostic marker
- Albumin: low = adverse
- LFTs, U&Es: baseline
- HIV: screen
Biopsy
- Excision lymph node biopsy: ESSENTIAL (core biopsy may be inadequate)
- Reed-Sternberg cells: CD15+, CD30+, CD20-/weak, CD45-
- Nodular lymphocyte-predominant: LP cells, CD20+, CD15-, CD30-
Staging (Ann Arbor/Lugano)
- PET-CT: gold standard for staging
- Stage I: single lymph node region
- Stage II: ≥2 regions, same side of diaphragm
- Stage III: both sides of diaphragm
- Stage IV: diffuse extranodal involvement (liver, bone marrow)
- Add 'A' (no B symptoms) or 'B' (B symptoms present)
- 'X' or 'bulky' if >10cm mass
Fertility
- Semen cryopreservation / oocyte preservation BEFORE chemotherapy
Management
Early Stage (I/II) — Favourable
- ABVD × 2–4 cycles + involved-field radiotherapy (IFRT)
- ~95% cure rate
Early Stage — Unfavourable
- ABVD × 4–6 cycles ± IFRT
Advanced Stage (III/IV)
- ABVD × 6 cycles (standard)
- Escalated BEACOPP × 6: more intensive; higher response but more toxicity (used in some centres for high-risk)
- PET-adapted: interim PET after 2 cycles guides therapy (if PET-negative, may omit bleomycin — RATHL trial)
Relapsed/Refractory
- Salvage chemotherapy (DHAP, ICE, GDP) → autologous SCT (~50% cure in relapse)
- Brentuximab vedotin (anti-CD30 ADC): post-ASCT consolidation or relapsed HL (NICE TA524)
- Pembrolizumab/nivolumab (anti-PD-1): relapsed after ASCT + brentuximab (NICE TA540)
Supportive
- Fertility preservation before treatment
- Bleomycin lung toxicity monitoring (PFTs)
- Long-term follow-up: second cancers, cardiac disease, thyroid dysfunction
Referral Criteria
- Haematology/oncology: urgent for suspected lymphoma
- 2-week-wait referral: unexplained lymphadenopathy
Prognosis
- Overall cure rate: ~85–90%
- Early stage favourable: >95% cure
- Advanced stage: ~75–85% cure with ABVD
- Relapsed after ASCT: ~50% salvage with brentuximab/checkpoint inhibitors
- Late effects in survivors: secondary malignancy (breast, lung — 10–20 years), cardiac disease (anthracycline, radiotherapy), hypothyroidism, infertility
- Long-term survival: requires lifelong surveillance for late complications
Other Relevant Information
IPS-7 (International Prognostic Score for Advanced HL)
| Factor (1 point each) | Adverse |
|---|---|
| Age >45 | Adverse |
| Male sex | Adverse |
| Stage IV | Adverse |
| Hb <105 g/L | Adverse |
| Albumin <40 g/L | Adverse |
| WCC ≥15 × 10⁹/L | Adverse |
| Lymphocytes <0.6 × 10⁹/L or <8% | Adverse |
| Score 0–1: ~90% 5-year PFS; Score ≥4: ~60% 5-year PFS |