About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- NHL encompasses all lymphomas that are NOT Hodgkin lymphoma — >60 subtypes classified by WHO. 85-90% are B-cell origin
- Diffuse large B-cell lymphoma (DLBCL) is the commonest NHL (~35%) — aggressive but curable with R-CHOP. Follicular lymphoma is the commonest low-grade NHL (~25%)
- Excisional lymph node biopsy is essential for diagnosis — core biopsy is second-line. Fine needle aspiration (FNA) is INADEQUATE
- Staging: Ann Arbor + PET-CT (for aggressive subtypes). IPI (International Prognostic Index) guides prognosis for DLBCL
- Indolent NHL (follicular): watch and wait if asymptomatic. Aggressive NHL (DLBCL): treat urgently with R-CHOP (rituximab + CHOP). Burkitt lymphoma is a medical emergency
Overview
Non-Hodgkin lymphoma (NHL) is a diverse group of lymphoid malignancies. The key clinical distinction is between indolent (low-grade) and aggressive (high-grade) subtypes. Indolent lymphomas (e.g. follicular) grow slowly, may not need immediate treatment, but are generally incurable with conventional therapy. Aggressive lymphomas (e.g. DLBCL, Burkitt) progress rapidly and are fatal without treatment, but are potentially curable with immunochemotherapy. NHL spreads NON-CONTIGUOUSLY (unlike Hodgkin lymphoma) and frequently presents with advanced-stage disease.
Epidemiology
NHL is the sixth most common cancer in the UK, with approximately 14,000 new cases per year. Incidence rises with age, with a median age of ~65 years at diagnosis. DLBCL accounts for ~35% and follicular lymphoma ~25% of cases. Risk factors include immunosuppression (HIV — associated with primary CNS lymphoma and Burkitt lymphoma), autoimmune disease, prior chemotherapy/radiotherapy, H. pylori infection (gastric MALT lymphoma), EBV (Burkitt lymphoma), and hepatitis C.
Clinical Features
Symptoms
Painless lymphadenopathy — often peripheral, may be widespread at presentation
B symptoms (fever, night sweats, >10% weight loss) — more common in aggressive subtypes
Fatigue and malaise
Abdominal discomfort or early satiety (mesenteric nodes, splenomegaly)
Extranodal symptoms: GI (abdominal pain, obstruction), skin lesions, CNS symptoms
Rapidly enlarging mass (aggressive NHL)
Signs
Peripheral lymphadenopathy — may be localised or generalised
Hepatosplenomegaly
Skin lesions (cutaneous T-cell lymphoma — mycosis fungoides)
Waldeyer ring involvement (tonsillar enlargement)
Extranodal masses (GI, testicular, orbital)
Investigations
First-line
Excisional lymph node biopsyGOLD STANDARD for diagnosis — required for accurate subtyping. FNA is INADEQUATE (cannot assess architecture). Core biopsy is acceptable if excision not feasible
FBC, LDH, beta-2-microglobulinLDH is a key prognostic marker (part of IPI). Raised B2M indicates higher tumour burden
Immunohistochemistry and flow cytometryEssential for subtyping: DLBCL (CD20+, CD10±, BCL2/6±), Follicular (CD10+, BCL2+, BCL6+), Mantle cell (CD5+, cyclin D1+, SOX11+)
Second-line
PET-CTStaging for FDG-avid subtypes (DLBCL, follicular, mantle cell). CT alone for non-avid subtypes
CT chest/abdomen/pelvisIf PET-CT not indicated or not available
HIV, Hepatitis B/CScreen before immunochemotherapy — Hep B reactivation risk with rituximab
Specialist
Bone marrow biopsyStaging in many subtypes. Not routinely needed if PET-CT negative in marrow for DLBCL
FISH/cytogeneticsMYC, BCL2, BCL6 rearrangements in DLBCL — "double-hit" or "triple-hit" lymphoma = very poor prognosis
H. pylori testingFor gastric MALT lymphoma — H. pylori eradication can induce complete remission
Management
NICE NG52 (Non-Hodgkin Lymphoma), 20161
DLBCL (aggressive)
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) — standard first-line
- 6-8 cycles R-CHOP for advanced disease. 3 cycles R-CHOP + radiotherapy for localised disease
- CNS prophylaxis (intrathecal or high-dose IV methotrexate) for high-risk sites (testicular, breast, renal, adrenal, CNS)
- Overall cure rate ~60-65% with R-CHOP
2
Follicular lymphoma (indolent)
- Watch and wait if asymptomatic, low tumour burden — treatment does NOT improve survival in early asymptomatic disease
- Treatment indications: symptomatic disease, organ compromise, B symptoms, progressive disease
- First-line: rituximab + bendamustine or R-CVP or R-CHOP
- Rituximab maintenance for 2 years after response — prolongs progression-free survival
3
Burkitt lymphoma (very aggressive)
- Medical EMERGENCY — doubling time of 24-48 hours
- High-intensity chemotherapy with CNS prophylaxis: R-CODOX-M/IVAC or similar
- Aggressive tumour lysis syndrome prophylaxis — rasburicase, intensive hydration
- Cure rate >80% in children/young adults with intensive therapy
4
Gastric MALT lymphoma
- If H. pylori positive: triple therapy eradication — may achieve complete remission
- If H. pylori negative or persists after eradication: radiotherapy or rituximab
Complications
- Transformation: Indolent NHL (follicular) can transform to aggressive DLBCL in 2-3% per year — suspect if sudden clinical deterioration
- Tumour lysis syndrome: Especially Burkitt lymphoma — hyperuricaemia, hyperkalaemia, hyperphosphataemia, AKI
- SVC obstruction: Mediastinal lymphadenopathy — emergency
- Spinal cord compression: Epidural disease — emergency MRI and steroids
- Immunosuppression: From disease and treatment — opportunistic infections, Hepatitis B reactivation with rituximab
UKMLA Exam Tips
- 1Excisional biopsy is REQUIRED — FNA is inadequate for lymphoma diagnosis (cannot assess architecture)
- 2DLBCL = aggressive but curable (R-CHOP). Follicular = indolent, watch and wait if asymptomatic
- 3Burkitt lymphoma: "starry-sky" histology, t(8;14) MYC-IGH, doubling time 24-48h — emergency treatment
- 4Gastric MALT lymphoma + H. pylori → eradicate H. pylori first (may be curative)
- 5NHL spreads NON-CONTIGUOUSLY (vs Hodgkin which spreads contiguously between adjacent node groups)
- 6CD20 positivity (B-cell) → rituximab can be added. This is the basis of R-CHOP
- 7IPI score for DLBCL: age >60, LDH raised, ECOG ≥2, stage III/IV, >1 extranodal site
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