Phys · general-medicine

Undifferentiated Lymphadenopathy — A Systematic Diagnostic Approach

Also known as lymphadenopathy · enlarged lymph nodes · swollen glands · lymph node enlargement · cervical lymphadenopathy · supraclavicular lymphadenopathy · axillary lymphadenopathy · inguinal lymphadenopathy · generalised lymphadenopathy · Virchow node · Troisier sign · infectious mononucleosis · B symptoms · excisional biopsy · International Prognostic Index · R-IPI · Lugano classification · Kikuchi-Fujimoto disease · cat-scratch disease · pseudolymphoma

Consultant-physician-depth guide to the diagnostic approach to the patient with lymph node enlargement of unknown cause. Covers the localised-versus-generalised framework and its regional differentials (cervical, supraclavicular Virchow, axillary, inguinal, epitrochlear), the generalised causes (infection — EBV infectious mononucleosis, CMV, HIV, TB, toxoplasmosis, syphilis; haematological — Hodgkin and non-Hodgkin lymphoma, CLL, ALL; autoimmune — SLE, RA, sarcoid; drug — phenytoin pseudolymphoma; metastatic malignancy), the focused history and examination discriminators (node size, consistency, mobility, tenderness, matting; the B symptoms of lymphoma; the exposure history), the red-flag features that mandate biopsy (supraclavicular node, hard fixed node, node above 2 cm, persistence beyond 6 weeks, B symptoms, hepatosplenomegaly), the first-tier investigations (FBC, film, LDH, EBV serology, HIV, toxoplasma, syphilis, chest X-ray, ultrasound), the biopsy decision (excisional biopsy as the gold standard for lymphoma, FNA for metastatic or infective, core biopsy when excision is not feasible), the Lugano classification and the revised International Prognostic Index, and lymphadenopathy in the immunocompromised host. Structured for FRACP DWE and DCE preparation.

high5 referencesUpdated 26 July 202645 min readVerification in progress

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Red flags

A supraclavicular node of any size in an adult is a red flag — it drains the abdominal cavity via the thoracic duct (left, Virchow node) or the mediastinum and right lung (right) and classically indicates gastric, pancreatic, hepatic, renal, lung or oesophageal malignancy or lymphoma; biopsy rather than observeA hard, fixed or matted node is a red flag — soft mobile nodes are reactive, rubbery nodes suggest lymphoma, hard fixed nodes suggest metastatic carcinoma or advanced lymphomaA node above 2 cm without an obvious infective cause is a red flag — the larger the node, the higher the probability of malignancy; nodes above 3 cm in the cervical chain are highly concerningA node persisting beyond 4 to 6 weeks is a red flag — reactive nodes from a viral illness resolve within 2 to 4 weeks; a node that does not regress mandates investigationThe B symptoms — drenching night sweats (soaking the sheets), unintentional weight loss (more than 10 per cent body weight over 6 months) and unexplained fever — are the B-symptom triad of lymphoma; any lymphadenopathy with B symptoms mandates investigationLymphadenopathy with hepatosplenomegaly indicates a systemic process — EBV, CMV, lymphoma, leukaemia, sarcoidosis — and mandates investigationNever give corticosteroids before a tissue diagnosis in unexplained lymphadenopathy — steroids can mask the histology of lymphoma by inducing apoptosis in the lymphoma cells and distorting the nodal architecture

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Red flags

Undifferentiated Lymphadenopathy — A Systematic Diagnostic Approach

The answer first

Lymphadenopathy of unknown cause is diagnostically loaded — the registrar's job is to separate the node that is biopsied from the node that is observed, and the discriminator is the red-flag screen. Use the localised-versus-generalised distinction as the organising axis, discriminate by the node characteristics, and let the red flags decide.[1]

The reproducible sequence for any lymph node:[1]

Characterise the node — size (with a ruler), consistency (soft, rubbery, hard), mobility, tenderness, matting, overlying skin. Examine all node groups, not just the one the patient noticed.
Classify as localised or generalised — localised points to the drainage territory or a regional malignancy; generalised indicates a systemic process.
Apply the red-flag screen — supraclavicular location, hard or fixed, above 2 cm, persisting beyond 4 to 6 weeks, B symptoms, hepatosplenomegaly. Any red flag mandates biopsy.
If no red flags and a plausible reactive cause is present, observe for 3 to 4 weeks and reassess. A node that persists or grows at 4 weeks is biopsied.
Make the biopsy decision correctly — excisional biopsy is the gold standard for suspected lymphoma because it preserves architecture and provides tissue for immunohistochemistry and flow cytometry. FNA is acceptable for suspected metastatic carcinoma or an infective node, but FNA alone is never adequate for the primary diagnosis of lymphoma.[1]

The mantra: supraclavicular is biopsied, not observed — and never give steroids before a tissue diagnosis.[1]

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References5Show ledger

[1]Gaddey HL, Riegel AM Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis Am Fam Physician, 2016.PMID 27929264
[2]Bazemore AW, Smucker DR Lymphadenopathy and malignancy Am Fam Physician, 2002.PMID 12484692
[3]Hoagland RJ Infectious mononucleosis Am J Med, 1952.PMID 12976417
[4]Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP Blood, 2007.PMID 17105812
[5]Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification J Clin Oncol, 2014.PMID 25113753

Undifferentiated Lymphadenopathy — A Systematic Diagnostic Approach

high5 referencesUpdated 26 July 202645 min readVerification in progress

The answer first

The reproducible sequence for any lymph node:[1]

Characterise the node — size (with a ruler), consistency (soft, rubbery, hard), mobility, tenderness, matting, overlying skin. Examine all node groups, not just the one the patient noticed.

Classify as localised or generalised — localised points to the drainage territory or a regional malignancy; generalised indicates a systemic process.

Apply the red-flag screen — supraclavicular location, hard or fixed, above 2 cm, persisting beyond 4 to 6 weeks, B symptoms, hepatosplenomegaly. Any red flag mandates biopsy.

If no red flags and a plausible reactive cause is present, observe for 3 to 4 weeks and reassess. A node that persists or grows at 4 weeks is biopsied.

Make the biopsy decision correctly — excisional biopsy is the gold standard for suspected lymphoma because it preserves architecture and provides tissue for immunohistochemistry and flow cytometry. FNA is acceptable for suspected metastatic carcinoma or an infective node, but FNA alone is never adequate for the primary diagnosis of lymphoma.[1]

The mantra: supraclavicular is biopsied, not observed — and never give steroids before a tissue diagnosis.[1]

Physician Medicine Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Physician Medicine fellowship atlas.

References5Show ledger

[1]Gaddey HL, Riegel AM Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis Am Fam Physician, 2016.PMID 27929264
[2]Bazemore AW, Smucker DR Lymphadenopathy and malignancy Am Fam Physician, 2002.PMID 12484692
[3]Hoagland RJ Infectious mononucleosis Am J Med, 1952.PMID 12976417
[4]Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP Blood, 2007.PMID 17105812
[5]Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification J Clin Oncol, 2014.PMID 25113753