What is the recommended approach to evaluating and managing perineal lymphadenopathy?

Approach to Perineal Lymphadenopathy

Perineal lymphadenopathy requires immediate systematic evaluation beginning with fine-needle aspiration (FNA) for any node >1 cm, while simultaneously conducting a focused search for primary lesions in the drainage basin—including the perineum, genitalia, anus, and lower extremities—because 70% of palpable inguinal nodes harbor malignancy in adults, though infectious causes predominate in children. 1, 2, 3

Initial Clinical Assessment

Determine if lymphadenopathy is localized or generalized, as this fundamentally changes your differential diagnosis and workup strategy. 2, 3

Critical History Elements

• Duration of lymphadenopathy – nodes persisting >4 weeks require imaging and laboratory workup regardless of other features 3, 4
• Constitutional symptoms – fever, night sweats, unintentional weight loss suggest malignancy or systemic disease 3, 4
• Age and sex – males >40 years with white race have higher malignancy risk 4
• Sexual history – in sexually active adolescents/adults, consider STIs including lymphogranuloma venereum, HSV, or syphilis 5
• Recent trauma or infection – examine for cuts, abrasions, insect bites, cellulitis, or fungal infections of lower extremities 5

Physical Examination Priorities

Examine the entire lymphatic drainage basin systematically: 2

• Perineum and genitalia – look for ulcers, warts, condylomata, herpes lesions, or masses 2
• Anus and rectum – perform anogenital examination for rectal cancer, anal lesions, or STDs 2
• Lower extremities bilaterally – inspect for skin lesions, melanoma, or infection sources 5
• Contralateral groin – crossover lymphatic drainage occurs, making bilateral assessment mandatory 2

Document node characteristics precisely: 2

• Size (nodes >2 cm are concerning for malignancy) 3
• Number of nodes
• Unilateral vs bilateral
• Mobility vs fixation to skin or deeper structures
• Tenderness
• Overlying skin changes (erythema, ulceration)

Diagnostic Algorithm by Clinical Scenario

For Adults with Palpable Inguinal/Perineal Nodes

Proceed directly to FNA as the mandatory first diagnostic step – sensitivity 91.7%, specificity 98.2% for malignancy detection. 1 Do not delay with empiric antibiotics unless there is clear evidence of acute bacterial infection (rapid onset, fever, erythema, tenderness). 1, 4

If FNA is negative but node characteristics are concerning (heterogeneous on imaging, hard, matted, >2 cm), confirm with excisional biopsy because FNA can miss malignancy. 1, 3

If FNA is positive for malignancy, proceed immediately to disease-specific oncologic management:

• Penile cancer → immediate inguinal lymph node dissection (ILND) 1, 2
• Melanoma → wide excision and sentinel node mapping 1
• Lymphoma → core needle or excisional biopsy for full histologic classification 1

For Children with Inguinal/Perineal Lymphadenopathy

Search systematically for infection sources before considering biopsy: 5

• Inspect ipsilateral lower extremity – cuts, abrasions, insect bites, cellulitis, tinea pedis 5
• Examine perineal/genital/perianal region – diaper dermatitis, trauma, lesions 5
• Consider STIs only if appropriate – genital ulcers or concerning social history in adolescents 5

For small, mobile, tender nodes without systemic symptoms – observe with clinical reassessment in 2-4 weeks. 5 Nodes should decrease in size within 4-6 weeks; lack of improvement mandates escalation. 5

Avoid empiric antibiotics when viral prodrome or minor local infection is identified – observation alone is appropriate. 5

If biopsy is needed in children, excisional biopsy is preferred over FNA when malignancy or granulomatous disease (including nontuberculous mycobacteria) is suspected. 5

Laboratory and Imaging Workup

Obtain when lymphadenopathy persists >4 weeks or systemic symptoms are present: 3, 4

• Complete blood count with differential 3
• C-reactive protein and erythrocyte sedimentation rate 3
• Tuberculosis testing (PPD or IGRA) 3
• HIV testing in appropriate clinical contexts 2

Imaging modalities by indication: 2

• Ultrasound – first-line for characterizing node architecture and guiding FNA 2
• CT or MRI – for palpable disease to assess size, extent, relationship to structures, and pelvic/retroperitoneal involvement 2
• PET/CT – sensitivity 88%, specificity 98%, but cannot distinguish inflammation from metastasis and has limited resolution <10 mm 2
• MRI – best single modality for evaluating primary lesion and lymph node status when physical exam is difficult 2

Critical Differential Diagnoses

Malignant Etiologies (Require Urgent Evaluation)

• Penile squamous cell carcinoma – inguinal nodes are the most frequent metastatic site; 70% of palpable nodes harbor malignancy 2
• Melanoma of lower extremity – popliteal and inguinal nodes are abnormal when palpable 4
• Vulvar/anal cancer – drain to inguinal and pelvic nodes 1
• Lymphoma – requires excisional biopsy, not FNA alone, for definitive diagnosis 1

Infectious/Inflammatory Causes

• Reactive lymphadenopathy – 30-50% of palpable inguinal nodes are inflammatory, not malignant 1, 2
• Bacterial lymphadenitis – Staphylococcus aureus or Streptococcus pyogenes with rapid onset, fever, tenderness 5
• STIs – lymphogranuloma venereum, HSV, syphilis in sexually active patients 5
• Nontuberculous mycobacteria – rare in inguinal region but consider in immunocompromised 6

Common Pitfalls to Avoid

Do not assume all palpable lymphadenopathy is malignant – 30-50% of cases are inflammatory, but do not delay FNA in adults with concerning features. 1, 2

Do not proceed to immediate surgical excision without FNA in adults – this leads to unnecessary morbidity and delays diagnosis. 1

Do not use corticosteroids empirically – they mask histologic diagnosis of lymphoma and other malignancies. 3, 4

Do not forget to examine the contralateral groin – crossover lymphatic drainage occurs through presymphyseal lymphatics. 2

In children, do not overlook minor skin infections – small cuts or fungal infections between toes commonly cause reactive inguinal nodes. 5

Follow-Up Strategy

If confirmed reactive lymphadenopathy: 1

• Address underlying cause (treat infection, remove irritant)
• Monitor node size and characteristics at 2-4 week intervals
• Consider repeat biopsy if node enlarges or develops concerning features

If malignancy is confirmed: 1

• Follow disease-specific oncologic protocols
• Repeat imaging to assess treatment response
• For penile cancer with positive nodes, consider adjuvant chemotherapy if extranodal extension is present 2