What is the appropriate diagnostic workup and treatment for a patient presenting with unilateral inguinal lymphadenopathy?

Unilateral Inguinal Lymphadenopathy: Diagnostic Workup and Management

Initial Diagnostic Approach

Fine-needle aspiration (FNA) is the mandatory first diagnostic step for unilateral inguinal lymphadenopathy, particularly for nodes <4 cm, as 30-50% of palpable inguinal nodes are inflammatory rather than malignant. 1, 2

Critical Clinical Assessment

Before proceeding with FNA, perform a focused examination documenting:

• Node characteristics: Size (diameter in cm), number, mobility versus fixation, consistency (hard/matted nodes suggest malignancy), and relationship to surrounding structures (skin, Cooper ligament) 3, 4
• Laterality: Unilateral versus bilateral presentation (note that crossover lymphatic drainage occurs, so bilateral examination is essential even when mass appears unilateral) 3, 4
• Associated findings: Edema of penis, scrotum, or legs; presence of skin ulcers or lesions in the drainage area 3, 4
• Primary lesion search: Examine genitalia, perineum, lower extremities, and perianal region for potential primary malignancy 4, 2

Size-Based Diagnostic Algorithm

For nodes <4 cm:

• Perform FNA as initial diagnostic test (sensitivity 91.7%, specificity 98.2% for malignancy) 2
• If FNA is negative, confirm with excisional biopsy or careful surveillance over 3-4 weeks 1, 2
• Do not proceed to immediate surgical excision without FNA, as this leads to unnecessary morbidity 2

For nodes ≥4 cm (fixed or mobile):

• Obtain imaging (CT or MRI of abdomen/pelvis with IV contrast) before biopsy to assess extent, location, and relationship to surrounding structures 3, 1
• Consider these as potentially bulky disease requiring more aggressive evaluation 1
• Perform FNA regardless of mobility status 3

Imaging Considerations

CT abdomen and pelvis with IV contrast is the preferred imaging modality when:

• Nodes are borderline enlarged or difficult to assess clinically 1
• Concern exists for deeper pelvic or retroperitoneal involvement 1
• Metastatic disease is suspected 4

Note that CT/MRI have limited utility in nonpalpable disease but are valuable for palpable nodes (sensitivity 58-60% for detecting metastases in normal-sized nodes) 3, 1

Critical Differential Diagnoses

Malignant Etiologies (Require Urgent Evaluation)

• Penile squamous cell carcinoma: Most common cause of malignant inguinal lymphadenopathy; assess for penile lesions, HPV infection, HIV status, poor hygiene, tobacco use 4, 2
• Vulvar cancer: In women, perform vaginal examination 4
• Melanoma of lower extremity: Examine entire lower extremity and perineum 2
• Lymphoma: Consider with systemic symptoms (fever, night sweats, weight loss) 5, 6

Infectious/Inflammatory Causes

• Lymphogranuloma venereum (LGV): Tender unilateral inguinal lymphadenopathy in sexually active patients; treat with doxycycline 100 mg orally twice daily for 21 days 3, 7
• Reactive lymphadenopathy: From skin/soft tissue infection of lower extremity or perineum 2
• Tuberculosis: Rare in developed countries but consider in endemic areas (usually bilateral, but unilateral cases reported) 8, 9

Management Based on FNA Results

If FNA is positive for malignancy:

• Proceed immediately with appropriate oncologic management based on primary malignancy identified 2
• For penile cancer: Immediate inguinal lymph node dissection (ILND) through separate incisions from primary tumor 3
• Early treatment of lymph node involvement improves survival except in bulky nodal spread or distant metastases 3

If FNA is negative:

• Confirm with excisional biopsy (gold standard providing most tissue for pathologic evaluation), especially if node has heterogeneous appearance on imaging 1, 2, 9
• Alternative: Careful surveillance with clinical examination every 3 months 1, 2
• Re-biopsy if nodes enlarge or new systemic symptoms develop 1

Common Pitfalls to Avoid

• Do not assume all palpable lymphadenopathy is malignant: 30-50% of cases are inflammatory, but conversely, 20-25% of clinically node-negative patients harbor occult metastases 3, 4, 2
• Do not delay lymphadenectomy with antibiotics in high-risk primary lesions: Omit FNA for patients with high-risk primary malignancies to avoid delay 3
• Do not use corticosteroids: They mask histologic diagnosis of lymphoma or other malignancy 5, 6
• Do not overlook sexually transmitted infections: In sexually active patients with tender unilateral inguinal lymphadenopathy, consider LGV and examine for genital ulcers 3, 7

Follow-Up Strategy

For confirmed reactive lymphadenopathy:

• Address underlying cause (antibiotics for bacterial infection, antituberculous therapy if TB confirmed) 5, 9
• Monitor node size and characteristics clinically every 3 months 1, 2
• Consider repeat biopsy if nodes persist beyond 4 weeks, enlarge, or develop concerning features 2, 5

For malignancy:

• Follow disease-specific oncologic protocols 2
• Repeat imaging to assess treatment response 2