Haematology & Oncology

Lymphoma

A heterogeneous group of clonal lymphoid malignancies that may present with persistent lymphadenopathy, splenomegaly, extranodal disease or systemic symptoms; tissue classification and subtype-specific staging determine urgency and treatment.

Definition

Lymphoma is a malignant clonal lymphoid neoplasm, broadly divided into Hodgkin lymphoma and non-Hodgkin lymphoma, with behaviour and treatment determined by the exact pathological subtype, stage, biology and patient factors.

Epidemiology

Non-Hodgkin lymphoma is more common than Hodgkin lymphoma and is predominantly diagnosed in older adults. Classical Hodgkin lymphoma has a younger-adult and later-life distribution. Risk is increased by some immune deficiencies, HIV, autoimmune disease and selected infections, but most cases have no single identifiable cause.

Pathophysiology

Genetic and epigenetic changes at different stages of lymphoid development create clonal B-cell, T-cell or Hodgkin-lineage malignancies. Cells accumulate in nodes, spleen, marrow or extranodal tissues; cytokine and host immune responses contribute to fever, night sweats, pruritus and weight loss. The clinical course ranges from indolent to highly aggressive, and molecular classification increasingly influences treatment.

First principles

Lymphoma is heterogeneous, so the label alone is not a treatment plan

Lymphoma includes Hodgkin lymphoma and many B-cell, T-cell and other non-Hodgkin subtypes. Some are indolent and may be monitored for years, while others are rapidly progressive and potentially curable if treatment starts promptly. Disease may be nodal, extranodal, splenic, marrow-involving or occasionally present in blood, so the old contrast of lymphoma as node disease versus leukaemia as blood disease is an oversimplification.^1,2,3

Diagnosis requires adequate tissue and expert classification

The diagnosis depends on lymph-node architecture, immunophenotyping, flow cytometry and, for selected high-grade B-cell lymphomas, molecular or FISH testing. NICE recommends excision biopsy first for suspected non-Hodgkin lymphoma when feasible, with a sufficiently large core biopsy when surgical risk outweighs benefit; if a core is non-diagnostic, proceed to excision rather than simply repeating a small core. Fine-needle aspiration alone cannot reliably provide the required architecture.¹

B symptoms are a defined systemic burden, not a vague constitutional complaint

The formal B symptoms are unexplained fever, drenching night sweats and unintentional weight loss of more than 10% of body weight over 6 months. They reflect systemic inflammatory activity and are recorded in staging and risk assessment, but absence of B symptoms does not exclude lymphoma. Pruritus, fatigue, breathlessness and alcohol-associated node pain may support suspicion but are not diagnostic alone.^4,5,6

Staging and biology guide treatment more than anatomy alone

After tissue diagnosis, PET-CT or contrast CT, blood tests and selected marrow or organ assessments define the distribution, metabolic activity, prognostic factors and treatment fitness. Classical Hodgkin lymphoma is generally staged with PET-CT, which usually makes marrow biopsy unnecessary for staging; non-Hodgkin lymphoma requires a subtype-specific combination of imaging, pathology and risk scoring. Treatment must therefore be agreed by a specialist lymphoma multidisciplinary team.^1,5,7

Presentation

Persistent, usually painless lymphadenopathy or splenomegaly with or without B symptoms, extranodal symptoms or cytopenias. Rapid growth, airway or mediastinal compromise, neurological deficit, sepsis or tumour lysis features require urgent specialist or emergency care.^4,6,8

Cardinal features

Persistent, unexplained, usually painless lymphadenopathy in the neck, axilla, groin or elsewhere
Splenomegaly or abdominal fullness, with or without hepatomegaly
Unexplained fever, drenching night sweats or unintentional weight loss over 10% in 6 months
Fatigue, pruritus, recurrent infections or symptoms from extranodal disease
Breathlessness, cough, chest pressure or facial and upper-limb swelling from mediastinal or thoracic disease
Cytopenias or abnormal LDH in advanced, marrow-involving or high-grade disease

Red flags

Stridor, airway compromise, rapidly worsening breathlessness or superior vena cava obstruction
Back pain with weakness, sensory change, gait disturbance or bladder or bowel dysfunction suggesting spinal cord compression
Rapidly enlarging mass, severe systemic upset or suspected high-grade lymphoma requiring urgent haematology assessment
Acute kidney injury, arrhythmia, seizures or marked electrolyte disturbance suggesting spontaneous or treatment-related tumour lysis syndrome
Fever or sepsis in a person receiving immunochemotherapy, or severe anaemia, neutropenia or thrombocytopenia

Investigations

History, examination and baseline blood tests

Map all nodal stations and extranodal symptoms, document B symptoms and performance status, and assess for splenomegaly, liver disease, infection and treatment fitness. Baseline FBC, film, LDH, ESR, renal function, liver function, bone profile and viral serology help identify complications and prepare for treatment.

Expected finding: May be normal early; anaemia, cytopenias, raised LDH, inflammatory markers or organ dysfunction may indicate marrow involvement, tumour burden or another diagnosis.

^4,5,6

Excision or adequately planned core biopsy with lymphoma pathology

Obtain enough viable tissue for architecture, histology, immunohistochemistry, flow cytometry and molecular tests. For suspected non-Hodgkin lymphoma, prefer excision when feasible; use the largest calibre and maximum number of cores when surgery is unsuitable, and proceed to excision if the core is non-diagnostic.

Expected finding: A defined Hodgkin or non-Hodgkin subtype with immunophenotype and, when needed, cytogenetic or molecular classification; a report of lymphoma without subtype is not enough to choose treatment.

Immunophenotyping and molecular risk testing

Use immunohistochemistry and flow cytometry to classify the lymphoid neoplasm. In newly diagnosed histologically high-grade B-cell lymphoma, NICE recommends considering FISH for MYC rearrangement and, if present, testing for the immunoglobulin partner and BCL2 and BCL6 rearrangements.

Expected finding: A lineage and subtype-defining immunophenotype with molecular results that may identify high-grade biology and alter the specialist treatment protocol.

^1,7

PET-CT and or contrast CT for staging

Use FDG-PET-CT for FDG-avid Hodgkin lymphoma and appropriate non-Hodgkin subtypes, alongside contrast CT where needed for anatomy and radiotherapy planning. Record stage using the lymphoma-specific Ann Arbor or Lugano framework and use interim or end-of-treatment PET response criteria where relevant.

Expected finding: Nodal, splenic or extranodal sites mapped with metabolic and anatomical extent; stage and response assessment depend on subtype and imaging protocol.

^1,5,2

Selected marrow, organ and treatment-fitness investigations

Bone marrow biopsy is selected by subtype and staging plan rather than performed routinely for every lymphoma; PET-CT usually makes it unnecessary for classical Hodgkin staging. Assess cardiac or pulmonary fitness for planned agents, fertility and pregnancy where relevant, and CNS, testicular or other extranodal sites when the subtype and risk indicate.

Expected finding: Results refine stage, prognostic scoring and safe protocol selection; a normal selected test does not exclude lymphoma elsewhere.

^5,7,1

Management

Step	Detail	Source
Refer suspected lymphoma urgently and triage immediate threats	Use the current NICE suspected-cancer pathway for unexplained lymphadenopathy or splenomegaly, taking account of fever, night sweats, breathlessness, pruritus and weight loss. Same-day emergency assessment is needed for airway or mediastinal compromise, spinal cord compression, sepsis, severe cytopenia or suspected tumour lysis syndrome.^4,6	NICE NG12 and NHS lymphoma information
Obtain diagnostic tissue before treatment whenever safely possible	Arrange an excision or adequately planned core biopsy with lymphoma pathology and multidisciplinary review. Avoid empiric corticosteroids before biopsy when clinically safe because they can reduce lymphoma tissue and impair diagnosis; if there is life-threatening airway, spinal or other compressive disease, discuss immediate treatment with the relevant specialist team rather than delaying rescue therapy.^1,9	NICE NG52 and NICE NG234 specialist corticosteroid advice
Stage, risk-stratify and agree treatment in the lymphoma MDT	Complete subtype-specific staging with PET-CT or contrast CT, baseline blood and viral tests, risk scoring, and selected marrow or organ investigations. Record performance status, comorbidity, fertility and patient priorities before choosing curative, disease-control or palliative intent.^1,5,7	NICE NG52, BSH classical Hodgkin lymphoma guideline and BSH large B-cell lymphoma guideline
Use subtype- and response-adapted treatment	Classical Hodgkin lymphoma is treated with PET-adapted specialist combination therapy, with radiotherapy for selected early-stage or bulky disease. Aggressive B-cell non-Hodgkin lymphoma is generally treated with curative-intent immunochemotherapy selected by subtype and risk, such as an R-CHOP or current approved R-CHP-based protocol for appropriate large B-cell lymphoma. Indolent follicular or other low-grade lymphoma may be observed when asymptomatic, with treatment for symptoms, progressive, bulky or organ-threatening disease. Do not prescribe a generic lymphoma regimen; use the current specialist protocol and BNF or oncology formulary.^5,7,1,2,3,10	BSH classical Hodgkin lymphoma guideline, BSH large B-cell lymphoma guideline, NICE NG52 and current NHS treatment information
Prevent and treat tumour lysis syndrome and treatment complications	Risk-assess before systemic anticancer therapy, particularly for Burkitt or lymphoblastic lymphoma, bulky or high-grade disease, high LDH or renal impairment. Use protocol-led hydration, urate-lowering prophylaxis and monitoring of potassium, phosphate, calcium, urate, creatinine and fluid balance; use rasburicase promptly when indicated and check G6PD status before it. Escalate laboratory or clinical tumour lysis syndrome to acute oncology, renal and critical-care teams.^11,12,10	BSH 2025 tumour lysis syndrome guideline and NHS England patient-safety alert
Manage relapse, late effects and survivorship with specialist follow-up	At follow-up assess new symptoms, relapse, infection, cardiovascular and pulmonary late effects, second malignancy, fertility, endocrine health, neuropathy, psychosocial wellbeing and treatment-related fatigue. Relapsed disease may require salvage therapy, targeted or cellular treatment and autologous or allogeneic transplantation depending on subtype, response and fitness; involve the specialist team early rather than repeating first-line therapy automatically.^5,7,2,3	BSH lymphoma guidance and NHS Hodgkin and non-Hodgkin lymphoma treatment information

Illustrations

Reed-Sternberg cellPhotomicrograph of a lymph node biopsy showing binucleate Reed-Sternberg cells in a reactive background.Unknown authorUnknown author, Wikimedia Commons · Public domain

Ann Arbor stagingDiagram of Ann Arbor staging showing nodal regions above and below the diaphragm and extranodal extension.PassFinals · original

Differentials

Reactive or viral lymphadenopathy

Tender or fluctuant nodes with a recent infective syndrome that improve over time; persistent unexplained nodes need reassessment rather than repeated empirical antibiotics.

Metastatic carcinoma

Hard, fixed or anatomically draining nodes with a possible solid-tumour primary; tissue is required for distinction.

Chronic lymphocytic leukaemia or other leukaemia

Lymphocytosis, cytopenias or a characteristic blood and flow-cytometry pattern may permit a blood or marrow diagnosis.

Tuberculosis or other chronic infection

Exposure, fever, matted nodes or organ-specific features with microbiological or histological evidence.

Sarcoidosis or other inflammatory disease

Bilateral hilar or multisystem involvement with compatible imaging and non-caseating granulomas after infection and malignancy are assessed.

Complications

Marrow infiltration with anaemia, neutropenia or thrombocytopenia
Airway or superior vena cava obstruction from mediastinal or thoracic disease
Spinal cord or nerve compression from vertebral or epidural disease
Spontaneous or treatment-related tumour lysis syndrome, acute kidney injury and electrolyte disturbance
Sepsis, treatment-related immunosuppression, infertility, organ toxicity and second malignancy

Prognosis

Prognosis varies widely. Classical Hodgkin lymphoma and several aggressive B-cell lymphomas can be cured in many patients with modern treatment, while indolent lymphomas are often controllable but relapse over time. Stage, subtype, performance status, LDH, extranodal disease, treatment response and molecular features guide prognosis and treatment intensity.

Guidelines

Suspected cancer: recognition and referral (NG12) (NICE, 2015)
Non-Hodgkin lymphoma: diagnosis and management (NG52) (NICE, 2016)
Guideline for the first-line management of Classical Hodgkin Lymphoma (British Society for Haematology, 2022)

References

Evidence checked: 2026-08-03

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.