What is the differential diagnosis and management for multiple inguinal lymph nodes measuring 2.5 x 0.5 cm?

Differential Diagnosis of Multiple Inguinal Lymph Nodes Measuring 2.5 x 0.5 cm

For multiple inguinal lymph nodes measuring 2.5 x 0.5 cm, the differential diagnosis includes malignant causes (penile cancer, vulvar cancer, melanoma, lymphoma, metastatic disease from genitourinary or lower extremity primaries) and benign causes (reactive lymphadenopathy from lower extremity infections, sexually transmitted infections, or inflammatory conditions), with fine-needle aspiration being the mandatory first diagnostic step. 1, 2

Primary Malignant Etiologies

Genitourinary Malignancies

• Penile squamous cell carcinoma is a critical consideration, as 20-25% of clinically node-negative patients harbor occult metastases, and lymph node status is the strongest predictor of survival 1, 3
• Vulvar cancer commonly presents with inguinal lymphadenopathy, with nodal involvement being the strongest independent predictor of relapse 1
• Multiple bilateral inguinal nodes suggest more advanced disease (cN2 staging) in penile cancer, requiring aggressive evaluation 1

Cutaneous Malignancies

• Melanoma of the lower extremity can present with inguinal lymphadenopathy, with 30-44% of patients with clinically involved superficial inguinal nodes having pelvic node involvement 1
• Even microscopic inguinal disease can be associated with pelvic lymphadenopathy in melanoma 4

Hematologic Malignancies

• Lymphoma (Hodgkin and non-Hodgkin) can present with inguinal lymphadenopathy that may fluctuate in size 5

Benign/Reactive Etiologies

Infectious Causes

• Reactive lymphadenopathy accounts for 30-50% of palpable inguinal lymph nodes, making this a common benign etiology 2, 6
• Lower extremity infections, including cellulitis, fungal infections, or chronic wounds, commonly cause inguinal lymphadenopathy 2
• Sexually transmitted infections can cause bilateral inguinal lymphadenopathy 6
• Periprosthetic joint infection in patients with hip or knee arthroplasty can cause inguinal lymphadenopathy (median size 26mm in infected cases) 7

Inflammatory Causes

• Autoimmune conditions and chronic inflammatory diseases can cause generalized lymphadenopathy including inguinal nodes 5

Diagnostic Algorithm

Initial Assessment

1. Perform careful physical examination evaluating for palpability, number of masses, unilateral versus bilateral presentation, dimensions, mobility versus fixation, and relationship to surrounding structures 2, 6
2. Examine for primary lesions: inspect penis, vulva, lower extremities, and skin for suspicious lesions 1
3. Assess for constitutional symptoms: fatigue, weight loss, night sweats suggesting systemic disease 1

First-Line Diagnostic Test

Fine-needle aspiration (FNA) is the mandatory initial diagnostic approach for palpable inguinal lymph nodes <4 cm 1, 2, 6

• FNA should be performed with ultrasound guidance for improved accuracy 3
• If FNA is negative, confirmation with excisional biopsy or careful surveillance is required, as false negatives occur 2, 6
• If FNA is positive for malignancy, proceed immediately to appropriate oncologic management 6

Imaging Studies

CT abdomen and pelvis with IV contrast is the preferred imaging modality to assess extent, location, and relationship to surrounding structures, and to evaluate for pelvic lymphadenopathy 2, 6

• Lymph nodes >8mm in short-axis diameter in the pelvis are considered pathologically enlarged 2
• CT has 58-60% sensitivity and 75-90% specificity for detecting metastatic lymph nodes 2
• PET/CT can be valuable for functional assessment but has limitations for deposits <10mm 2

Management Based on FNA Results

If FNA is Positive for Malignancy:

• For penile cancer with nodes 2-4 cm: consider neoadjuvant chemotherapy (TIP regimen: paclitaxel, ifosfamide, cisplatin) prior to inguinal lymph node dissection 1
• For multiple or bilateral inguinal nodes in penile cancer: bilateral inguinal lymph node dissection is recommended 1, 3
• For melanoma with multiple palpable nodes: pelvic lymph node dissection should be considered given 30-44% risk of pelvic involvement 1

If FNA is Negative:

• Excisional biopsy is required for definitive diagnosis, particularly if lymphoma is suspected 2, 6
• Surveillance with repeat clinical examination is acceptable only if patient is compliant and nodes remain stable 6

Critical Pitfalls to Avoid

• Do not assume all palpable lymphadenopathy is malignant, as 30-50% represents inflammatory changes 2, 6
• Do not proceed to immediate surgical excision without prior FNA, as this leads to unnecessary morbidity 6
• Do not delay referral for chronic lymphadenopathy (>4 weeks), as early diagnosis of malignancy significantly improves outcomes 2
• Do not rely solely on imaging for diagnosis in patients with non-palpable disease, as CT and MRI have significant limitations in detecting micrometastatic disease 1, 6
• Do not use antibiotic treatment for 3-6 weeks before lymph node dissection in patients with palpable nodes, as this is not recommended 3

Specialist Referral

Immediate referral to hematologist-oncologist is warranted for coordination of diagnostic workup, as lymph node status is the most important determinant of survival in malignancies presenting with inguinal lymphadenopathy 2

• Subsequent referral to urologic oncologist if penile cancer is confirmed 2
• Referral to gynecologic oncologist if vulvar cancer is suspected 2
• Referral to surgical oncologist if melanoma is confirmed 1