What is the next step for an adult patient with right groin lymphadenopathy, a lymph node greater than 3 cm, tender but no signs of infection, and normal laboratory results, after an ultrasound (US) measurement?

Next Step for Right Groin Lymphadenopathy >3 cm

Fine-needle aspiration (FNA) should be performed immediately as the initial diagnostic step for this >3 cm tender inguinal lymph node, and if negative, proceed directly to excisional biopsy rather than observation, given the size threshold that raises concern for malignancy. 1, 2

Immediate Diagnostic Approach

The size of this lymph node (>3 cm) places it in a critical diagnostic category that requires tissue diagnosis:

• FNA is the standard initial approach for inguinal nodes, with sensitivity of 91.7% and specificity of 98.2% for detecting malignancy 2
• Do not observe or wait - nodes >2 cm are concerning for malignancy or granulomatous disease, and this node exceeds that threshold 3
• If FNA is negative, confirm with excisional biopsy rather than surveillance, as 30-50% of palpable inguinal lymphadenopathy is inflammatory but the size here demands definitive diagnosis 1

Critical Pre-Biopsy Evaluation

Before proceeding to biopsy, obtain imaging to assess extent and guide management:

• CT abdomen and pelvis with IV contrast is mandatory to assess for deeper pelvic or retroperitoneal involvement, evaluate extent and relationship to surrounding structures, and identify potential primary malignancy sources 1, 2
• Perform focused examination of genitalia, perineum, lower extremities, and perianal region to search for primary lesions (penile cancer, melanoma, anal cancer, or lower extremity skin lesions) 2
• Document node characteristics including mobility, consistency, and relationship to surrounding structures 2

Why This Node Cannot Be Observed

Several features make observation inappropriate:

• Size >3 cm approaches the 4 cm threshold where nodes are treated as potentially bulky disease requiring aggressive evaluation 1
• Tenderness does not exclude malignancy - while tender nodes can be inflammatory, malignant nodes can also be tender, and size is the strongest predictor of pathology 4, 3
• Normal labs do not exclude malignancy - lymph node metastases or lymphoma can present with normal routine laboratory values 3, 5

Biopsy Strategy Based on Size

For this >3 cm node:

• FNA first provides rapid initial diagnosis with minimal morbidity 1, 2
• Excisional biopsy is the gold standard if FNA is negative or non-diagnostic, as it provides the most tissue for comprehensive pathologic evaluation including architecture assessment for lymphoma 1
• Do not delay excisional biopsy if FNA is non-diagnostic - the size mandates definitive tissue diagnosis 1

Common Pitfalls to Avoid

• Never give empiric antibiotics without clear signs of acute bacterial infection (erythema, warmth, fluctuance), as this delays diagnosis and can mask malignancy 6, 3
• Never use corticosteroids before obtaining tissue diagnosis, as they mask histologic features of lymphoma or other malignancy 6, 3, 5
• Do not rely on a 3-4 week observation period that might be appropriate for smaller nodes (<1-2 cm) - this node's size demands immediate action 1, 3

Differential Diagnosis to Consider

The imaging and biopsy workup should evaluate for:

• Metastatic disease: penile cancer, melanoma, anal cancer, lower extremity sarcoma, or gynecologic malignancy 4, 2
• Lymphoma: particularly if B symptoms develop (fever, night sweats, weight loss) 4, 6
• Granulomatous disease: sarcoidosis or tuberculosis can present with large inguinal nodes 7
• Infectious causes: lymphogranuloma venereum (LGV) in sexually active patients, though typically more acute and painful 2

If Malignancy is Confirmed

• Immediate oncologic management based on primary malignancy identified 2
• For penile cancer specifically: immediate inguinal lymph node dissection (ILND) is indicated 4, 2
• For nodes ≥4 cm: consider neoadjuvant chemotherapy before surgical resection in appropriate malignancies 4

Follow-Up if Biopsy Shows Benign Disease

• Clinical examination every 3 months of the affected region 1, 2
• Re-biopsy immediately if nodes enlarge further or new systemic symptoms develop 1, 2
• Maintain high index of suspicion as false-negative FNA can occur 2