01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Lymph nodes enlarge when immune cells proliferate, inflammatory cells accumulate, malignant cells replace tissue or drainage is obstructed. The first clinical task is anatomical: localised nodes direct examination to their drainage territory, whereas nodes in two or more non-contiguous regions suggest a systemic process. Tempo matters. Acute painful enlargement with a nearby infection differs from a steadily growing painless node over weeks. Children and young adults commonly have reactive nodes, but age does not neutralise red flags and a persistent unexplained mass still requires a documented review point.
Splenomegaly shares some causes but adds haemodynamic and sequestration mechanisms. Portal hypertension congests the spleen; haemolytic disorders increase reticuloendothelial work; infection and immune disease activate splenic tissue; lymphoma, leukaemia and myeloproliferative neoplasms infiltrate it. Very large enlargement particularly suggests selected myeloid, lymphoid, parasitic or storage diseases rather than uncomplicated viral infection. Examination records the distance below the costal margin, tenderness and signs of liver disease, but ultrasound or CT provides objective size and associated anatomy.
Investigation is directed and tissue aware. FBC, film, LDH, liver profile and targeted infection testing are common initial studies, but broad low-probability serology creates false positives. Ultrasound can distinguish node, cyst and vascular structure and guide core sampling; contrast CT maps deep nodal stations and organ involvement. When lymphoma is plausible, discuss biopsy with the receiving team before giving corticosteroids or choosing a low-yield sampling method. The endpoint is a diagnosis with stage and fitness information, not repeated scans of unexplained enlargement.
Key points
- Confirm that a lump is a lymph node and map every region. Size alone is insufficient; site, consistency, tenderness, fixation, matting, skin change, duration and progression all alter probability.
- Localised tender nodes usually follow drainage from infection or inflammation, while generalised lymphadenopathy broadens the differential to viral infection, HIV, tuberculosis, medicines, autoimmune disease and haematological malignancy.
- Supraclavicular, persistent hard or fixed nodes, progressive enlargement, unexplained splenomegaly, cytopenias and systemic symptoms justify urgent cancer-pathway or haematology assessment under current NICE criteria.
- Ask specifically about measured fever, drenching night sweats, unintentional weight loss, pruritus, recurrent infection, bruising, alcohol, travel, animal exposure, sexual health, tuberculosis risk and new medicines.
- Examine liver, spleen, skin, joints, throat, breasts, testes and likely drainage territories. A palpable spleen generally implies enlargement, but ultrasound distinguishes spleen from a renal or other abdominal mass.
- Use blood and imaging to choose tissue, not to avoid it. Excision preserves architecture and is often preferred for suspected lymphoma; core biopsy is an alternative when excision is impractical and adequate tissue can be obtained.
- Fine-needle aspiration may answer selected metastatic-carcinoma questions but often cannot classify lymphoma because architecture, flow and molecular material are needed.
- Give people with splenomegaly safety advice about contact trauma and urgent pain or collapse; after splenectomy, fever is an emergency requiring the established infection-prevention plan.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Infective immune stimulation
Viral, bacterial, mycobacterial and parasitic infections enlarge nodes through antigen-driven lymphoid proliferation and can enlarge the spleen through reticuloendothelial activation or sequestration.
Haematological malignancy
Lymphoma, leukaemia and myeloproliferative neoplasms infiltrate nodes, spleen, blood or marrow, often producing constitutional symptoms, cytopenias or a clonal circulating population.
Metastatic solid cancer
Malignant cells drain to regional nodes or spread systemically; node territory, primary-site symptoms and tissue architecture guide origin and staging.
Inflammatory and congestive disease
Autoimmune disease, sarcoidosis, medicines, portal hypertension, haemolysis and storage disorders enlarge lymphoid or splenic tissue through inflammation, congestion, sequestration or infiltration.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Antigen-driven expansion
Infection or inflammation activates lymphocytes and macrophages within organised nodal compartments, producing tender or generalised reactive enlargement.
- 2Clonal tissue replacement
A malignant lymphoid or myeloid clone expands within nodes, spleen and marrow, disrupting architecture and normal blood-cell production.
- 3Reticuloendothelial sequestration
An enlarged congested or hyperactive spleen pools and removes red cells, white cells and platelets, sometimes producing multilineage cytopenia.
- 4Capsular and local effects
Rapid splenic or nodal expansion stretches capsules and compresses adjacent airway, vessels, nerves or abdominal organs, creating pain and emergency syndromes.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Tender mobile enlargement in the drainage field of tonsillar, dental, skin or limb infection supports reactive lymphadenopathy and should regress with the underlying process.
Persistent painless rubbery or firm nodes, splenomegaly, drenching sweats, weight loss, fever or pruritus raises lymphoma, while normal blood counts do not exclude it.
Hard fixed nodes, particularly supraclavicular or in a territory linked to a primary-site symptom, suggest metastatic carcinoma and require cancer-pathway evaluation.
Stridor, dysphagia, facial swelling, venous distension or neurological deficit with cervical or mediastinal adenopathy indicates airway, vascular or neural compression.
Sudden left-upper-quadrant or shoulder-tip pain, guarding, syncope or shock in a patient with splenomegaly suggests rupture and concealed haemorrhage.
Splenomegaly with anaemia, leucopenia or thrombocytopenia and a compensatory marrow response supports sequestration after marrow failure and immune destruction are considered.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
FBC, film and reticulocytesFirst step - Why
- Identify cytopenia, lymphocytosis, blasts, myeloid proliferation, haemolysis and hypersplenic response.
- Interpretation and limitations
- A normal count does not exclude lymphoma. Clonal-looking lymphocytes or immature myeloid cells direct flow or molecular testing, while multilineage cytopenia may require marrow assessment.
- 02
Liver profile, LDH, renal, calcium and inflammatory markers - Why
- Assess organ involvement and identify congestive, proliferative or inflammatory context.
- Interpretation and limitations
- LDH is non-specific and should not diagnose lymphoma alone. Liver synthetic or portal features support congestive splenomegaly; calcium or renal abnormalities may alter urgency and differential.
- 03
Targeted infection testing - Why
- Confirm clinically plausible EBV, CMV, HIV, tuberculosis or other infections.
- Interpretation and limitations
- Select tests from exposure, sexual health, travel and immune status. Heterophile tests vary with timing and age; positive tuberculosis immune tests do not by themselves prove nodal active disease.
- 04
Ultrasound of node or spleen - Why
- Confirm anatomy, measure spleen and guide a safe tissue approach.
- Interpretation and limitations
- Morphological features can stratify concern but cannot reliably exclude malignancy. Doppler helps avoid vascular structures and select a representative solid target.
- 05
Contrast CT of neck, chest, abdomen and pelvis - Why
- Map deep nodes, organ involvement and complications when malignancy or systemic disease is plausible.
- Interpretation and limitations
- Distribution supports staging and biopsy selection but is not a tissue diagnosis. Tailor field and contrast to the clinical question, renal function and pregnancy context.
- 06
Excision or image-guided core biopsy - Why
- Preserve architecture and obtain immunophenotypic, molecular and microbiological material.
- Interpretation and limitations
- Excision is preferred when lymphoma is strongly suspected and accessible; core is an alternative when surgery is impractical. Coordinate fresh tissue for flow and culture before fixation.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Reactive infection
Tender mobile nodes with a local infective source or compatible viral syndrome favour reactive disease, but persistence, progression or atypical features require reassessment.
Lymphoma or leukaemia
Firm persistent generalised nodes, splenomegaly, drenching sweats, weight loss, pruritus or cytopenias raise clonal disease and justify tissue-preserving referral.
Metastatic carcinoma
Hard fixed regional nodes, supraclavicular involvement or a primary-site symptom pattern suggest epithelial cancer; core or excision tissue should permit immunophenotypic classification.
Autoimmune or granulomatous disease
Rash, arthritis, uveitis, lung disease, hypercalcaemia or systemic inflammatory features support lupus, sarcoidosis or another immune process after infection and malignancy are assessed.
Portal or haematological splenomegaly
Liver disease and portal hypertension cause congestive enlargement, whereas haemolysis and myeloproliferative disease produce characteristic blood, film and constitutional patterns.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01ThreatStabilise compression or ruptureFirst stepNodes or spleen are associated with airway, vascular, neurological or haemodynamic compromise.+
- 1Use ABCDE, senior surgical, haematology, oncology and critical-care help, cross-sectional or bedside imaging chosen for stability, and blood-bank preparation when internal bleeding is possible.
- 2PreferredPreferred management preserves diagnostic tissue while stabilising the threatened organ; corticosteroid, radiotherapy, surgery or endovascular alternatives require specialist choice because each can alter later pathology.
- 3EscalationEscalate suspected splenic rupture to emergency surgical and major-haemorrhage pathways and suspected airway or SVC compromise to monitored treatment without sending an unstable patient for routine outpatient biopsy.
02LocalisedReview or biopsy a regional nodeOne nodal region is enlarged without current compression, shock or severe systemic illness.+
- 1Examine the complete drainage territory, document size and texture, review infection and cancer symptoms and use targeted blood tests only when the history supports them.
- 2First linePreferredFor a clearly reactive phenotype, the first-line option is treatment or observation of the cause with a documented short review; persistent, enlarging, hard, fixed or supraclavicular nodes instead need preferred urgent imaging and tissue referral.
- 3AlternativeEscalationChoose excision when lymphoma architecture matters; core is an alternative after specialist discussion, while repeated empirical antibiotics or corticosteroids without a supported cause should trigger escalation.
03SystemicInvestigate generalised nodes or splenomegalySeveral nodal regions, unexplained splenomegaly, constitutional symptoms or blood-count abnormalities suggest systemic disease.+
- 1Obtain FBC, film, reticulocytes, liver, renal, calcium and LDH tests plus exposure-directed infection and autoimmune testing; examine for liver disease, rash and marrow-failure signs.
- 2PreferredAlternativeThe preferred next step is contrast imaging to identify distribution and the safest highest-yield tissue target when malignancy remains plausible; blood flow or molecular testing is an alternative only for a suitable circulating clone.
- 3EscalationEscalate progressive cytopenia, very large spleen, blasts or systemic decline to haematology and arrange marrow or nodal tissue rather than extending a non-diagnostic serology panel.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Airway or vascular compression
Bulky cervical or mediastinal nodes can compromise airway, superior vena cava or major vessels, causing stridor, facial swelling, hypoxia or neurological symptoms.
Splenic rupture
An enlarged friable spleen can rupture spontaneously or after modest trauma, causing left-upper-quadrant pain, shoulder-tip pain, shock and concealed haemorrhage.
Hypersplenism
Sequestration and accelerated removal of circulating cells produces anaemia, leucopenia and thrombocytopenia while marrow may remain appropriately active.
Infection and marrow failure
Progressive haematological malignancy or its treatment impairs normal immunity and haematopoiesis, causing infection, bleeding and symptomatic anaemia.
Diagnostic distortion
Empirical corticosteroids can shrink lymphoma and alter morphology, delaying definitive classification unless a time-critical compressive emergency justifies specialist-led treatment.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- For observed nodes, record exact site, dimensions, texture, symptoms and a review date; progression or failure to regress changes the pathway.
- Trend FBC, film and organ profile when splenomegaly or systemic disease can cause sequestration, haemolysis or marrow infiltration.
- Track every imaging, flow, microbiology and biopsy result to a named clinician and confirm that urgent cancer or haematology referrals were received.
- After splenectomy or functional asplenia, verify vaccination, antibiotic-prevention and fever plans through current national and local guidance.
- During treatment of lymphoma or infection, monitor node and spleen response alongside disease-specific biochemical and marrow endpoints rather than palpation alone.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Nodes follow anatomy
A regional node is a map to the likely source. Oral, skin, breast, genital and limb examination can reveal a cause missed by indiscriminate blood testing.
Normal blood does not exclude lymphoma
Many lymphomas remain tissue based until advanced disease. Persistent high-risk nodes require biopsy reasoning even with normal FBC and LDH.
Steroids can erase evidence
Lymphoid tissue may involute rapidly after corticosteroids. Unless organ threat requires treatment, secure adequate diagnostic tissue first through the specialist team.
Spleen size is mechanistic
Massive enlargement narrows the differential towards myeloid, lymphoid, parasitic and storage causes; mild enlargement is broader and can be reactive.
Asplenic fever cannot wait
Loss of splenic function increases rapid invasive infection risk. Patients need an explicit prevention and emergency plan rather than vaccination alone.
11Common pitfallsFrequent interpretation and management errors.
- 01
Calling a persistent supraclavicular node reactive without a review or tissue plan.
- 02
Using normal FBC or LDH as a lymphoma rule-out test.
- 03
Giving repeated antibiotics when there is no bacterial focus or response.
- 04
Starting corticosteroids before lymphoma biopsy without an organ-threatening indication and specialist plan.
- 05
Using fine-needle aspiration as the default lymphoma test when architecture is required.
- 06
Failing to advise a patient with splenomegaly about trauma and rupture symptoms.
- 07
Losing ownership of a biopsy addendum or molecular result after the preliminary report.