What are the differential diagnoses, work‑up, and management for a painful inguinal lymph node?

Painful Groin Lymph Node: Differential Diagnosis, Work-Up, and Management

A painful inguinal lymph node most commonly represents reactive lymphadenopathy from infection (70% of palpable nodes), but requires systematic evaluation to exclude sexually transmitted infections (particularly lymphogranuloma venereum in sexually active patients) and malignancy (30% of palpable nodes in penile cancer patients). 1, 2

Differential Diagnosis

Most Common Causes of Painful Inguinal Lymphadenopathy

• Reactive lymphadenopathy from local infection accounts for 30-50% of palpable inguinal nodes and typically presents with tender, mobile nodes 1, 3
• Lymphogranuloma venereum (LGV) presents as unilateral tender inguinal/femoral lymphadenopathy, particularly in sexually active men who have sex with men 2, 4
• Metastatic penile cancer accounts for approximately 70% of palpable nodes in patients with known penile lesions, though nodes may be painful when there is rapid enlargement or secondary infection 1
• Granuloma inguinale typically presents with painless nodes, but can cause discomfort with progressive ulcerative lesions showing a "beefy red appearance" 2

Key Clinical Distinctions

• Tender, mobile nodes suggest inflammatory or infectious etiology (LGV, reactive lymphadenopathy) 2
• Fixed or matted lymph nodes indicate advanced malignancy and require urgent evaluation 2, 3
• Unilateral presentation in sexually active patients strongly suggests LGV 2
• Bilateral involvement increases likelihood of metastatic disease 2

Clinical Assessment

Essential Physical Examination Elements

• Evaluate node characteristics: palpability, number, dimensions, mobility versus fixation, unilateral versus bilateral distribution 1, 3
• Assess relationship to surrounding structures: skin involvement, Cooper ligament infiltration, presence of edema in penis, scrotum, or legs 1
• Examine potential infection sources: inspect ipsilateral lower extremity for cuts, abrasions, insect bites, cellulitis, or fungal infections; examine perineal/genital/perianal region for lesions 5
• Look for primary lesions: penile ulcers, masses, or erythematous lesions that may indicate underlying malignancy 1

Important caveat: Physical examination has only 82% sensitivity and 79% specificity for staging lymph node disease, with incorrect staging in 26% of cases 1

Diagnostic Work-Up

First-Line Investigations

• Fine-needle aspiration (FNA) is the standard initial diagnostic approach for palpable inguinal lymph nodes, with 91.7% sensitivity and 98.2% specificity for detecting malignancy 3
• For suspected LGV: Diagnosis is primarily serological and by exclusion of other causes; collect throat, urethral, and rectal swabs for Chlamydia trachomatis testing using real-time PCR 2, 4
• For suspected granuloma inguinale: Diagnosis requires visualization of Donovan bodies on tissue crush preparation or biopsy using Wright or Giemsa stain 2

Imaging Considerations

• CT or MRI may be used to assess size, extent, location, and proximity to other structures in patients with palpable disease 1
• Ultrasound-guided FNA increases diagnostic yield for metastases greater than 2 mm in diameter 1
• PET/CT has limited utility with 88% sensitivity and 98% specificity, but cannot distinguish inflammation from metastasis and has difficulty resolving lesions less than 10 mm 1

Critical limitation: CT and MRI have poor diagnostic accuracy in patients with nonpalpable disease; ultrasound-guided FNA in clinically negative groins has only 39% sensitivity 1

Management Algorithm

For Suspected Infectious/Inflammatory Etiology

• If LGV suspected: Treat immediately with doxycycline 100 mg orally twice daily for 21 days without waiting for confirmatory testing 2
• If granuloma inguinale suspected: Treat with trimethoprim-sulfamethoxazole one double-strength tablet orally twice daily for minimum 3 weeks 2
• For reactive lymphadenopathy: Address underlying cause (treat local infection or inflammation) and schedule clinical follow-up 3
• Follow-up for treated STIs: Continue clinical monitoring until complete resolution, typically 6-7 weeks 2, 4

For Suspected or Confirmed Malignancy

• If FNA is positive for malignancy: Proceed with immediate inguinal lymph node dissection (ILND) for penile cancer with positive nodes 3
• For N2-N3 disease: Perform bilateral inguinal lymphadenectomy 2
• Consider neoadjuvant cisplatin-based chemotherapy for bulky nodes before surgical intervention 2
• Pelvic lymph node dissection is indicated if ≥2 inguinal nodes are positive on frozen section 2

Critical point: Historical practice of treating all palpable lymphadenopathy with prophylactic antibiotics before intervention is no longer recommended due to concerns about delayed treatment adversely impacting survival 1

If FNA is Negative but Clinical Suspicion Remains High

• Proceed with excisional biopsy for definitive diagnosis rather than observation alone 3

Red Flags Requiring Urgent Evaluation

• Fixed or matted lymph nodes indicate advanced malignancy requiring immediate oncologic consultation 2, 3
• Painless progressive ulceration requires biopsy to exclude granuloma inguinale or malignancy 2
• Bilateral involvement substantially increases likelihood of metastatic disease 2
• Rapid enlargement with systemic symptoms warrants expedited work-up 5

Follow-Up Strategy

For Benign/Infectious Causes

• Reactive lymphadenopathy: Regular clinical examinations to monitor node size and characteristics; nodes should decrease within 4-6 weeks 3, 5
• Treated STIs: Clinical follow-up until complete resolution 2

For Malignancy

• Intensive surveillance protocol: Clinical examination every 3 months for years 1-2, then every 6 months for years 3-5 2
• Post-surgical monitoring: Watch for wound complications, lymphedema, and lymphocele formation 2
• Repeat imaging to assess treatment response according to primary cancer management protocols 3

Common Pitfalls to Avoid

• Do not delay definitive diagnosis with prolonged antibiotic trials in patients with concerning features for malignancy, as this adversely impacts survival 1
• Do not rely solely on physical examination for staging, as it incorrectly stages disease in 26% of cases 1
• Do not assume all tender nodes are benign; 70% of palpable nodes in penile cancer patients represent metastatic disease despite potential tenderness 1
• Do not overlook STI screening in sexually active patients, particularly men who have sex with men presenting with unilateral tender lymphadenopathy 2, 4