Lymphadenopathy (adults)

Overview

Lymphadenopathy is defined as one or more enlarged lymph nodes ≥1cm diameter. Although size alone does not determine the cause, risk of malignancy is less likely if lymph nodes are smaller than 2cm diameter and/or progressive enlargement has not been documented. There is a correlation with increasing size of lymphadenopathy with risk of malignancy/pathology. See sections below for details and referral guidelines.

Localised lymphadenopathy refers to only one region effected. Generalised lymphadenopathy is when more than one region effected.

Regions include neck, axillae, groins, mediastinal and abdominal.

Lymphadenopathy is most commonly due to infection, but can be due to inflammation (e.g. sarcoidosis), autoimmune disorders or malignancy including lymphoproliferative diseases (lymphoma).

Malignancies are identified in 14% of people presenting with lymphadenopathy which increases to 28% if patients are >65 years. A core or excision biopsy of a lymph node will be required to make a diagnosis.

Please also see the following pages:

• Head & Neck incl Thyroid - USC (2WW)- lists USC criteria for referral of neck lumps
• Neck Lumps (including Goitre)- advice on different neck lumps in adults and when and where to refer
• Axillary masses - advice on management of axillary masses in adults
• Children & Young People – USC (2WW) - contains information on lymphadenopathy and when to refer in children.
• Lymphadenopathy (Benign) in Children - advice on assessment and management of reactive lymphadenopathy in children.

Before Referral

Assessment in Primary care

• Size - ≥1cm diameter? ≥2cm diameter?
• Is it localised or generalised? 
• If localised, is there a local infective or neoplastic cause (examine area that drains nodal group)? 
• Duration of lymph node enlargement and any change in size (especially progressive enlargement)? 
• Any symptoms of infection e.g. URTI, glandular fever or bacterial infection? Any foreign travel or animal exposure (e.g. tick bites, cat scratches)?
• Any accompanying ‘B’ symptoms (poor appetite, >10% weight loss in 6 months, drenching night sweats, unexplained fevers)? 
• Any symptoms of suspected airway obstruction or superior vena cava obstruction or dysphagia?
• Any hepatosplenomegaly?
• Any abnormalities of the FBC e.g. lymphocytosis or cytopenias? 

• Repeatedly waxing and waning lymphadenopathy does not necessarily exclude a diagnosis of lymphoma. 
• Small volume inguinal lymphadenopathy is a common normal finding.
• If lump >5cm and deep to fascia then consider sarcoma (see red flag section)

Investigations in primary care

• Virology infection screen: Paul Bunnell or Monospot. If the PB test is negative then a repeated test in a few days may become positive if glandular fever is present. HIV test is also recommended (incidence of HIV is increasing). Consider EBV and CMV serology.
• If unexplained lymphadenopathy urgent FBC within 48 hours (to exclude leukaemia)
• If unexplained lymphadenopathy (>1cm) for more than 6 weeks then refer via Haematology - USC (2WW) pathway (?Lymphoma) and request FBC, UE, LFT and LDH (normal blood tests do not rule out need for assessment but it is useful to request these at time of referral or provide results if available)
• Consider urgent Chest Xray (within 2 weeks) if supraclavicular or persistent cervical lymphadenopathy, 40 and over (looking for lung malignancy and mediastinal lymphadenopathy).

If clinical assessment is that nodes are benign and if patient is well with unexplained small volume lymphadenopathy and above tests are normal, then imaging is not required -this approach is supported by NG12 (4) and local Ultrasound guidance.

BMJ Best Practice

The following has a guide to assessment and differential diagnosis of lymphadenopathy but does require a subscription to access: 

• Assessment of lymphadenopathy - Differential diagnosis of symptoms | BMJ Best Practice

Red Flags

Red flags for Haematological Malignancy 

Haematology - USC (2WW)

• Lymphadenopathy >2cm persisting for >6 weeks with no obvious infective precipitant 
• Lymphadenopathy ≥1cm for <6 weeks in association with:
• B symptoms (see above)
• Hepatic or splenic enlargement
• Rapid nodal enlargement or generalised nodal enlargement
• Abnormal FBC, raised LDH 

• Symptoms of SVCO (facial/upper limb swelling, cough, inability to lie flat), dysphagia, stridor – require immediate discussion with on call haematology SpR for emergency hospital admission
• Abnormal FBC -If FBC/ blood film suggests an acute leukaemia please arrange an immediate admission with a haematologist.
• For those age <25 years unexplained widespread lymphadenopathy or splenomegaly – seek urgent advice as may represent acute leukaemia.

Consider other malignancies depending on sight of lymphadenopathy

• Head & Neck incl Thyroid - USC (2WW)  -If an unexplained palpable lump in the neck i.e. of recent onset or a previously undiagnosed lump that has changed over a period of 3 – 6 weeks.
• Breast - USC (2WW) - if an unexplained axillary lump, without a vaccination in preceding 6 weeks (male and female)
• Other Localised Lymphadenopathy - For other localised unexplained lymphadenopathy with concern about a metastatic node refer via a USC/2WW pathway to appropriate surgical team. See Recommendations organised by symptom and findings of primary care investigations | Suspected cancer: recognition and referral | NICE

Consider Sarcoma

Features which may suggest a sarcoma rather than lymphadenopathy:

• mass greater than 5cm
• enlarging
• deep to fascia

See Bone & Soft Tissue - USC (2WW) for advice on appropriate investigation and management.

Who to Refer

If patient does not meet any of above criteria for USC/2WW referral and if still in any doubt over whether to refer urgently or observe in patients with otherwise unexplained lymphadenopathy then please consider:

• Haematology Advice & Guidance, UHBW or NBT - usual turn around times are usually 1-2 days
• Consider medical admission if acutely unwell - Medical Assessment/Admission and Weekday IUC Professional Line
• (On call haematology SpR can be contacted via switchboard but may not always be able to respond so avoid using if possible).

Referral

Referral

Refer via appropriate USC/2WW pathways as indicated in Red Flag section above.

If malignancy is not suspected and referral is still considered necessary, then please use the appropriate routine referral route via eRS according to suspected cause. There are a range of causes that will not be appropriate for assessment in a haematology clinic. 

Minimal information: the referral letter should include abnormal clinical findings (location, size, any associated features) and any abnormal full blood count results or other relevant test results, particularly if these investigations were not done in laboratories of the hospital to which the referral is made.

Advice

If unexplained lymphadenopathy but not meeting criteria for USC/2WW referral then consider Haematology advice and guidance service via eRS. Queries will be responded by a consultant haematologist within 3 working days.

Minimal information should be included as above.

Acutely Unwell Patients

Consider medical admission if acutely unwell - Medical Assessment/Admission and Weekday IUC Professional Line.

(On call haematology SpR can be contacted 9am to 5pm via hospital switchboard. ONLY for emergency advice. Out of hours and weekends – emergency advice may be obtained from the on-call haematology clinician via hospital switchboard. SpR may not always be able to respond so advice is to consider admission or use advice and guidance in preference).

Resources

SWAG guideline Lymphadenopathy (swagcanceralliance.nhs.uk)

BMJ best practice guideline: Assessment of lymphadenopathy.pdf (bmj.com)

NICE guidelines: Scenario: Lymphadenopathy | Management | Neck lump | CKS | NICE

References

(1) Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis | AAFP

(2) Assessment of lymphadenopathy - Differential diagnosis of symptoms | BMJ Best Practice

(3) Recommendations organised by symptom and findings of primary care investigations | Suspected cancer: recognition and referral | Guidance | NICE

(4) Recommendations organised by symptom and findings of primary care investigations | Suspected cancer: recognition and referral | Guidance | NICE

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