What questions should be asked when evaluating a patient with lymphadenopathy?

Essential Questions When Evaluating Lymphadenopathy

When evaluating a patient with lymphadenopathy, systematically obtain information about duration, location, associated symptoms, exposures, and node characteristics to distinguish benign from malignant or serious infectious causes. 1, 2

Critical Historical Elements

Temporal Characteristics

• Duration of lymphadenopathy ≥2 weeks is concerning for malignancy and requires heightened vigilance, particularly if nodes persist beyond 4-6 weeks without diagnosis 1, 2
• Rapid onset with fever and tenderness suggests acute bacterial infection, while gradual progression over weeks to months raises concern for malignancy or chronic infection 1, 3

Constitutional Symptoms (Red Flags)

• Fever, night sweats, and unintentional weight loss ("B symptoms") strongly suggest lymphoma or other malignancy 2, 3
• Persistent unexplained fever, particularly in children, may indicate Kawasaki disease if accompanied by cervical lymphadenopathy ≥1.5 cm 4
• Malaise and systemic symptoms suggest bacteremia or disseminated infection requiring urgent evaluation 5

Localized vs. Regional Symptoms

• Pain and tenderness typically indicate benign reactive or infectious causes 1, 2
• Recent upper respiratory infection, dental problems, or pharyngitis suggest reactive lymphadenopathy 1, 2
• Skin lesions, rashes, or insect bites in the drainage area point toward localized infection 1, 2

Exposure History

• Travel history is essential: tuberculosis endemic areas, regions with endemic fungi (histoplasmosis, coccidioidomycosis), or areas with leishmaniasis 6, 1, 2
• Animal exposures: cats (cat-scratch disease/Bartonella), unpasteurized dairy products (brucellosis), wild game (tularemia) 1, 2
• For children aged 1-5 years, ask about soil and water contact as this age group has peak incidence of nontuberculous mycobacterial (NTM) cervical adenitis 4

Medical and Social History

• HIV status and risk factors must be assessed, as HIV-positive patients have increased risk of opportunistic infections, Kaposi sarcoma, and lymphoma 6, 5
• Immunosuppression from medications (corticosteroids, chemotherapy), transplantation, or diabetes increases risk for atypical organisms 6, 5
• Medication history: certain drugs cause lymphadenopathy (phenytoin, allopurinol, atenolol) 2, 3
• Recent vaccination history may explain transient lymphadenopathy 2
• Sexual history and intravenous drug use assess risk for HIV, syphilis, and hepatitis 2, 3
• Tobacco and alcohol use increase risk of head and neck malignancies 6
• Family history of malignancy or autoimmune disease 2

Occupational Exposures

• Healthcare workers, veterinarians, farmers, and meat processors have specific infection risks 2

Physical Examination Findings to Document

Node Characteristics (Critical for Risk Stratification)

• Size >1.5-2 cm is suspicious, particularly if persistent 1, 2, 3
• Firm, hard, or "rock-hard" consistency suggests malignancy 1, 2, 7
• Fixed or matted nodes (immobile, fused to surrounding structures) are highly concerning for malignancy 1, 2, 7
• Ulceration of overlying skin is a suspicious feature 1, 4
• Tenderness typically indicates benign/infectious cause, though absence doesn't exclude malignancy 2, 3

Location-Specific Risk Assessment

• Supraclavicular nodes are abnormal and highly suspicious for malignancy (>90% risk in adults >40 years) 2, 3, 8, 7
• Epitrochlear nodes >5 mm are abnormal and warrant investigation 3
• Popliteal and iliac nodes are abnormal when palpable 3
• Unilateral cervical adenopathy in children aged 1-5 years suggests NTM infection in 95% of cases 4

Pattern Recognition

• Localized (75% of cases) vs. generalized lymphadenopathy (≥2 non-contiguous regions, 25% of cases): generalized pattern suggests systemic disease 2, 3, 8
• Examine the drainage area for localized lymphadenopathy to identify primary source 2, 3

Associated Physical Findings

• Complete head and neck examination including oropharyngeal inspection for masses, tonsillar asymmetry, or mucosal lesions 6, 1
• Skin examination for rashes, lesions, or signs of infection 1
• Hepatosplenomegaly suggests lymphoproliferative disorder or systemic infection 2, 9
• Edema may indicate lymphatic obstruction 6

Age-Specific Considerations

Children

• In children, lymph nodes ≥1.5 cm persisting ≥2 weeks without fluctuation increase risk for malignancy or chronic infection 4
• Nodes >2 cm that are hard or matted are particularly concerning in pediatric patients 2
• Peak age 1-5 years for NTM cervical adenitis; ask about soil/water exposure 4

Adults

• Age >40 years is a significant risk factor for malignancy 3, 7
• Male sex and white race also increase malignancy risk 3

Common Diagnostic Pitfalls to Avoid

• Never dismiss persistent cervical lymphadenopathy (>2 months) without proper evaluation, especially in adolescents and adults 1
• Do not give empiric antibiotics without evidence of acute bacterial infection (rapid onset, fever, tenderness, erythema), as this delays diagnosis of malignancy 1, 4
• Avoid corticosteroids before establishing diagnosis, as they mask histologic findings in lymphoma 2, 3
• Partial resolution after antibiotics may represent infection in underlying malignancy—complete resolution must be documented 4
• Supraclavicular and infraclavicular nodes always require immediate investigation; observation is not appropriate 8

When to Proceed Beyond History and Physical

• Duration >4-6 weeks without diagnosis warrants imaging and/or biopsy 1, 2
• Presence of any red flag features (constitutional symptoms, suspicious node characteristics, high-risk location) 1, 2, 3
• Failure to improve or progression despite appropriate treatment 1, 4
• If infectious etiology suspected and single course of antibiotics given, re-evaluate within 2 weeks 1