Key Facts

Non-Hodgkin lymphoma (NHL) encompasses a large, heterogeneous group of lymphoid neoplasms arising from B cells, T cells, or NK cells. They range from indolent to highly aggressive.

Epidemiology

• ~14,000 new cases/year in UK; 5th most common cancer
• Median age: 65–70 years
• Incidence increases with age
• 85% B-cell, 15% T/NK-cell

Aetiology

• Most idiopathic
• Infections: EBV (Burkitt, PTLD), H. pylori (gastric MALT), HCV (splenic marginal zone), HTLV-1 (adult T-cell leukaemia/lymphoma), HHV-8 (primary effusion lymphoma)
• Immunosuppression: HIV, post-transplant, autoimmune
• Autoimmune: Sjögren (MALT), coeliac (EATL), RA

Pathophysiology

• Malignant transformation of lymphocytes at various stages of differentiation
• Characteristic chromosomal translocations:
  • t(14;18) BCL2: follicular lymphoma (anti-apoptotic)
  • t(11;14) cyclin D1: mantle cell lymphoma
  • t(8;14) MYC: Burkitt lymphoma (proliferation)
  • t(11;18): MALT lymphoma
• Indolent NHL: accumulate slowly; incurable but long survival
• Aggressive NHL: rapid growth; curable with intensive treatment

Indolent NHL (e.g., Follicular)

• Painless lymphadenopathy (often waxing and waning)
• Often widespread at diagnosis (stage III/IV)
• Fatigue
• May be asymptomatic for years

Aggressive NHL (e.g., DLBCL)

• Rapidly enlarging lymph nodes
• B symptoms: fever, night sweats, weight loss
• Extranodal involvement: GI, CNS, bone, skin
• LDH raised

Burkitt Lymphoma

• Endemic (African): jaw/facial mass (EBV-associated)
• Sporadic: abdominal mass (ileocaecal region)
• HIV-associated: widespread
• Tumour doubling time ~24–48 hours (fastest growing human tumour)

Gastric MALT

• Dyspepsia, epigastric pain
• Often localised (stage I/II)
• H. pylori positive in ~90%

Red Flags

• Rapidly enlarging nodes
• B symptoms
• Cord compression
• SVC obstruction
• TLS (Burkitt, high-grade)

Biopsy

• Excision lymph node biopsy: ESSENTIAL for accurate subtyping (core biopsy often insufficient)
• Histopathology + immunohistochemistry: defines subtype

Bloods

• FBC, blood film: cytopenias if marrow involvement; circulating lymphoma cells in some
• LDH: raised (prognostic; reflects tumour burden)
• β2-microglobulin: prognostic
• Urate: raised in high-turnover lymphomas
• HIV, Hep B/C: screen (reactivation risk with rituximab)

Staging

• PET-CT: for FDG-avid subtypes (DLBCL, follicular, Burkitt)
• CT CAP: if PET not indicated
• Bone marrow biopsy: if relevant to treatment
• LP: CNS involvement risk (DLBCL with specific risk factors, Burkitt)
• Ann Arbor staging: I–IV (as per HL)

Prognostic Scores

• IPI (DLBCL): age >60, LDH elevated, ECOG ≥2, stage III/IV, >1 extranodal site
• FLIPI (follicular): age >60, LDH elevated, Hb <120, stage III/IV, >4 nodal areas

DLBCL (Aggressive)

• R-CHOP × 6 cycles (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone)
• ± involved-site radiotherapy
• CNS prophylaxis: intrathecal methotrexate ± high-dose IV methotrexate (if high CNS risk)
• Cure rate: ~60–65%

Follicular Lymphoma (Indolent)

• Asymptomatic, low burden: watch and wait (no survival benefit to early treatment)
• Symptomatic: R-CHOP, R-CVP, or R-bendamustine × 6 cycles
• Maintenance rituximab: every 2 months for 2 years (prolongs PFS)
• Localised (stage I/II): radiotherapy (potentially curative)

Burkitt Lymphoma

• Intensive chemotherapy: R-CODOX-M/R-IVAC or similar intensive regimen
• TLS prevention: critical (rasburicase, aggressive hydration)
• CNS prophylaxis: intrathecal chemotherapy
• Highly curable: ~80–90% in children; ~60–80% in adults

Gastric MALT

• H. pylori eradication: first-line for localised H. pylori+ gastric MALT (~60–90% respond)
• Radiotherapy: if H. pylori negative or eradication failure
• R-chlorambucil or R-CVP: advanced stage

Relapsed/Refractory

• Salvage chemotherapy + autologous SCT: DLBCL
• CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel): relapsed/refractory DLBCL (NICE TA895)
• Bispecific antibodies: glofitamab, epcoritamab (emerging)

Referral Criteria

• Haematology/oncology: all suspected lymphoma (2-week-wait referral for unexplained lymphadenopathy)

• DLBCL: ~60–65% 5-year survival with R-CHOP; IPI score predicts outcome (0–1: ~75%; 4–5: ~30%)
• Follicular: median survival >15 years; incurable but long natural history; ~3% per year transform to DLBCL
• Burkitt: ~80–90% cure in children; ~60–80% in adults with intensive chemo
• Gastric MALT: excellent prognosis; ~90% cure with H. pylori eradication (if localised)
• Mantle cell: median survival ~5–7 years (improving with BTK inhibitors)
• CAR-T: ~40% long-term remissions in relapsed/refractory DLBCL

NHL Subtypes Overview