Lymphadenopathy: Approach and Management for MCCQE1

Introduction

Lymphadenopathy refers to lymph nodes that are abnormal in size (usually >1 cm), consistency, or number. It is a common clinical presentation encountered in both primary care and internal medicine. For MCCQE1 preparation, it is crucial to distinguish between benign, self-limiting causes (reactive hyperplasia) and serious pathologies (malignancy, chronic infection).

Candidates must demonstrate the CanMEDS Medical Expert role by applying a structured clinical approach to identify the underlying etiology and the Communicator role when explaining the need for investigations (or lack thereof) to patients.

Etiology and Classification

Lymphadenopathy is broadly classified into localized and generalized. This distinction narrows the differential diagnosis significantly.

Localized

Localized Lymphadenopathy involves one specific chain or region.

Cervical: Upper respiratory infection (URI), Mononucleosis, Strep pharyngitis, Dental abscess, Kawasaki disease, Malignancy (Head & Neck SCC, Lymphoma).
Supraclavicular: ALWAYS PATHOLOGICAL.
- Left (Virchow’s Node): Abdominal malignancy (Gastric, Pancreatic).
- Right: Mediastinal/Thoracic malignancy (Lung, Esophageal).
Axillary: Skin infection of arm, Cat-scratch disease, Breast cancer, Brucellosis.
Inguinal: Lower extremity infection, STIs (Syphilis, LGV, Chancroid), Pelvic malignancy.

The “MIAMI” Mnemonic

A useful mnemonic for the differential diagnosis of lymphadenopathy for MCCQE1:


M - Malignancies (Metastatic, Lymphoma, Leukemia)
I - Infections (Viral, Bacterial, Fungal, Parasitic)
A - Autoimmune disorders (SLE, RA, Sarcoidosis)
M - Miscellaneous (Amyloidosis, Lipid storage diseases)
I - Iatrogenic (Medications, Serum sickness)

Clinical Approach

The MCCQE1 tests your ability to gather relevant data to stratify risk.

Step 1: Focused History

Age: Malignancy risk increases with age. (Risk is <1% in primary care, but higher in older adults).
Duration:
- <2 weeks: Likely infectious.
- >1 year (stable): Likely benign.
- Persistent/Progressive: Concerning for malignancy.
Constitutional Symptoms (B-Symptoms): Fever, night sweats, unexplained weight loss (>10% in 6 months).
Exposures:
- Canadian context: Travel history, TB exposure (Indigenous communities, foreign-born), pets (cats), sexual history, occupational exposure.
- Medications: Antiepileptics, antibiotics.

Step 2: Physical Examination

Characterize the nodes based on the following features:

Feature	Benign / Reactive	Malignant / Pathologic
Size	Usually <1-2 cm	Often >2 cm
Consistency	Soft, rubbery	Hard, stony, or firm
Tenderness	Tender (suggests rapid expansion/inflammation)	Non-tender (usually)
Mobility	Mobile	Fixed, matted, or adhered to underlying tissue
Overlying Skin	Erythematous, warm	Normal, or ulcerated (late stage)

Step 3: Associated Findings

Splenomegaly: Suggests EBV, Leukemia, Lymphoma.
Rash: Viral exanthem, SLE, Drug reaction.
ENT Exam: Look for primary sources (tonsils, teeth, scalp).

Step 4: Initial Investigations

If the history and physical suggest a benign cause (e.g., URI), observation for 3-4 weeks is appropriate. If nodes persist or red flags are present:

CBC + Differential: Assess for leukemia, infection.
Peripheral Smear: Blast cells, atypical lymphocytes.
Serology: EBV, CMV, HIV, Toxoplasmosis, Syphilis (if indicated).
Chest X-ray: If supraclavicular nodes, pulmonary symptoms, or suspicion of TB/Sarcoidosis.

Red Flags and Malignancy Risk

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CRITICAL MCCQE1 CONCEPT: Supraclavicular lymphadenopathy is considered malignant until proven otherwise.

Virchow’s Node: Left supraclavicular node enlargement $\rightarrow$ suggestive of abdominal metastasis (e.g., Gastric cancer).

Referral for Biopsy is indicated if:

Node >2 cm and persistent >4-6 weeks.
Supraclavicular location.
Abnormal Chest X-ray (mediastinal adenopathy).
Associated B-symptoms.
Fixed, hard, or matted texture.

Diagnostic Imaging and Biopsy

Imaging

Ultrasound: Useful for differentiating cystic vs. solid masses and characterizing architecture (hilum presence).
CT Scan: Staging for lymphoma or searching for a primary tumor (Head/Neck, Chest, Abdomen).

Biopsy Techniques

This is a frequent testing point on the MCCQE1 regarding the appropriateness of the procedure.

Excisional Biopsy:
- Gold Standard for suspected lymphoma.
- Preserves nodal architecture required for sub-typing lymphomas.
Core Needle Biopsy:
- Alternative if excisional is not feasible (e.g., retroperitoneal nodes).
Fine Needle Aspiration (FNA):
- Useful for: Carcinoma metastasis (e.g., SCC, Thyroid) or recurrence.
- NOT recommended for initial diagnosis of lymphoma (cannot determine architecture).

Canadian Guidelines & Context

🇨🇦 Canadian Context for MCCQE1

Tuberculosis (TB): While overall incidence is low, maintain a high index of suspicion for lymphadenitis (Scrofula) in patients from endemic areas or specific Indigenous populations.
Choosing Wisely Canada: Do not order neck ultrasounds for pediatric patients with simple cervical lymphadenopathy typical of a viral infection. Clinical monitoring is preferred.
Lyme Disease: Consider in patients with regional adenopathy and Erythema Migrans, specifically in endemic areas (Southern Ontario, Nova Scotia, Southern Manitoba/Quebec).
Wait Times: In the Canadian system, urgent referral pathways exist for “Suspicion of Cancer.” Understanding triage is part of the Management role.

Specific Scenarios

1. Infectious Mononucleosis (EBV)

Classic Triad: Fever, Pharyngitis, Lymphadenopathy (typically Posterior Cervical).
Dx: Monospot (Heterophile antibody) test.
Tx: Supportive. Avoid contact sports (splenic rupture risk).

2. Cat-Scratch Disease (Bartonella henselae)

Hx: Scratch/bite from a cat (kitten).
Presentation: Regional adenopathy (axillary/epitrochlear) proximal to the scratch.
Tx: Usually self-limiting; Azithromycin in severe cases.

Key Points to Remember for MCCQE1

High-Yield Summary

Generalized adenopathy usually implies a systemic viral infection or hematologic malignancy.
Supraclavicular nodes are the highest risk for malignancy.
Posterior cervical nodes strongly suggest EBV (Mononucleosis).
Painful nodes usually indicate acute infection/inflammation (rapid capsule stretching).
Painless, hard, fixed nodes are classic for malignancy.
Excisional biopsy is preferred over FNA for suspected lymphoma.
In a young patient with an unexplained node, observation for 3-4 weeks is a valid initial management step if no red flags are present.

Sample Question

Case Presentation

A 24-year-old male presents to his family physician with a 3-week history of fatigue, low-grade fever, and a sore throat. He has no significant past medical history. On examination, his temperature is 37.8°C. There is pharyngeal erythema without exudate. Palpation reveals bilateral, tender, mobile posterior cervical lymphadenopathy and mild splenomegaly. There are no supraclavicular or axillary nodes. A skin exam reveals no rashes.

Question

Which one of the following is the most appropriate initial diagnostic test?

A. CT scan of the neck
B. Excisional lymph node biopsy
C. Heterophile antibody test (Monospot)
D. Fine needle aspiration (FNA) of the lymph node
E. Throat culture for Group A Streptococcus

Explanation

The correct answer is:

C. Heterophile antibody test (Monospot)

Detailed Explanation: The clinical presentation is classic for Infectious Mononucleosis, caused by the Epstein-Barr Virus (EBV). Key features include the young age, triad of fever, pharyngitis, and lymphadenopathy (specifically posterior cervical), along with fatigue and splenomegaly.

Option C: The Monospot test is the standard initial screening test for EBV mononucleosis in immunocompetent adults. It has good sensitivity and specificity in this clinical context.
Option A: A CT scan is unnecessary for a clinically suspected viral infection and involves radiation exposure. It is reserved for staging malignancy or deep neck space infections.
Option B & D: Biopsy (Excisional or FNA) is invasive and not indicated for acute/subacute lymphadenopathy with a clear infectious differential. Biopsy is reserved for persistent nodes (>4-6 weeks), red flags (supraclavicular, fixed/hard), or when the diagnosis remains unclear after initial workup.
Option E: While Group A Strep can cause adenopathy (usually anterior cervical) and sore throat, the presence of posterior cervical nodes, significant fatigue, and splenomegaly points much more strongly toward Mononucleosis. Additionally, the pharyngitis in Mono is often non-exudative (though can be exudative), whereas Strep is typically exudative.

References

Medical Council of Canada. MCCQE Part I Clinical Decision-Making and Multiple-Choice Questions Objectives.
Toronto Notes 2024. Infectious Diseases & Hematology Sections.
Choosing Wisely Canada. Pediatrics: Don’t order neck ultrasounds for routine lymphadenopathy. Link
Public Health Agency of Canada. Canadian Tuberculosis Standards, 8th Edition. Link
Ferrer, R. (2021). Lymphadenopathy: Differential Diagnosis and Evaluation. American Family Physician.