How should a markedly enlarged inguinal lymph node be evaluated and managed?

Evaluation and Management of a Large Groin Lymph Node

Fine-needle aspiration (FNA) is the mandatory first diagnostic step for a markedly enlarged inguinal lymph node, with a sensitivity of 91.7% and specificity of 98.2% for detecting malignancy. 1, 2

Initial Clinical Assessment

Before proceeding with FNA, perform a focused physical examination documenting:

• Node characteristics: Size (measure in centimeters), number, mobility versus fixation, consistency, relationship to surrounding structures (skin, Cooper's ligament), and presence of ulceration or skin involvement 3
• Laterality: Unilateral versus bilateral presentation, as crossover lymphatic drainage can occur 3
• Primary lesion search: Examine the genitalia (penis, vulva), perineum, perianal region, and entire ipsilateral lower extremity for primary malignancy, skin lesions, ulcers, or infection sources 3, 1
• Constitutional symptoms: Fever, night sweats, weight loss, or lower extremity edema 3

Critical point: 30-50% of palpable inguinal lymphadenopathy at initial presentation is inflammatory rather than metastatic, but nodes that enlarge during follow-up are malignant in nearly 100% of cases. 3, 2

Diagnostic Algorithm Based on Node Size

For nodes <4 cm:

• Proceed directly with ultrasound-guided FNA as the first-line diagnostic test 3, 1
• Ultrasound features suggesting malignancy include: longitudinal/transverse ratio <2 (81% sensitivity), absent echogenic hilum (68% sensitivity, 95% specificity), and eccentric cortex (96% specificity) 4

For nodes ≥4 cm:

• Obtain CT abdomen/pelvis with IV contrast before FNA to assess extent, location, relationship to surrounding structures, and evaluate for pelvic or retroperitoneal involvement 1
• Perform FNA regardless of node mobility, as size ≥4 cm significantly increases malignancy risk 1

Management Based on FNA Results

If FNA is positive for malignancy:

• Initiate immediate oncologic management based on the primary malignancy identified 1, 2
• For penile squamous cell carcinoma: Proceed with immediate inguinal lymph node dissection (ILND), as early treatment of lymph node involvement positively impacts survival 3, 1
• For nodes ≥4 cm with confirmed penile cancer: Consider neoadjuvant chemotherapy before surgical resection 1
• For vulvar cancer with positive nodes: Perform complete inguinofemoral lymphadenectomy and/or administer adjuvant radiation to affected groin(s) 3

If FNA is negative:

• Do not assume the node is benign—confirm with excisional biopsy, especially if the node has heterogeneous appearance on imaging or remains clinically suspicious 3, 1, 2
• If excisional biopsy is deferred, implement careful surveillance every 3 months with repeat FNA or excisional biopsy if nodes enlarge or new systemic symptoms develop 1, 2

Common pitfall: A negative FNA has a false-negative rate of 20-30% in the setting of palpable lymphadenopathy, so clinical suspicion should guide the decision for excisional biopsy. 3

Differential Diagnosis to Consider

Malignant etiologies (require urgent evaluation):

• Penile squamous cell carcinoma: Most common cause of metastatic inguinal lymphadenopathy in males; inguinal node involvement is the single most important prognostic indicator 3, 2
• Vulvar cancer: In females, evaluate for primary vulvar lesions 3, 2
• Melanoma of lower extremity: Examine entire leg and foot for pigmented lesions 1, 2
• Lymphoma: Consider if B symptoms (fever, night sweats, weight loss) are present 1, 2
• Anal or lower extremity sarcoma: Less common but important to exclude 1

Infectious/inflammatory causes:

• Reactive lymphadenopathy: From skin/soft tissue infection, cellulitis, or fungal infection of lower extremity or perineum 2, 5
• Lymphogranuloma venereum (LGV): Consider in sexually active patients with tender unilateral inguinal lymphadenopathy; treat with doxycycline 100 mg orally twice daily for 21 days 1
• Other STIs: HSV or syphilis can present with painful inguinal nodes 5

Role of Advanced Imaging

• CT scan: Primary modality for assessing pelvic and retroperitoneal nodes, though sensitivity for inguinal nodes is only 36% 3, 1
• MRI: Best choice for evaluating primary lesion and lymph node status when physical examination is difficult (e.g., obesity, prior surgery/radiation) 3
• PET/CT: Shows 88% sensitivity and 98% specificity for lymph node metastases; useful for detecting distant metastases in node-positive disease, but cannot distinguish inflammation from metastasis or resolve lesions <10 mm 3

Critical Pitfalls to Avoid

• Do not proceed to immediate surgical excision without FNA, as this leads to unnecessary morbidity and delays diagnosis 2
• Do not rely solely on imaging (CT/MRI) to exclude malignancy in clinically suspicious nodes, as sensitivity is inadequate 3
• Do not delay lymphadenectomy with prolonged antibiotic trials in the absence of clear infection, as delayed intervention adversely impacts survival in metastatic disease 3
• Be aware that granular cell tumors can mimic reactive lymph nodes on FNA, leading to false-negative results 6