In an adult male with a foreskin ulcer that has rolled edges and a sloughing centre, what is the recommended diagnostic and treatment approach?

Foreskin Ulcer with Rolled Edges and Sloughy Centre

This presentation is highly suspicious for penile squamous cell carcinoma and requires urgent biopsy for histological confirmation before any treatment is initiated. 1

Immediate Diagnostic Approach

Physical Examination - Document Specifically:

• Exact dimensions and anatomic location of the ulcer
• Depth of invasion and relationship to adjacent structures (glans, corpus spongiosum, corpus cavernosum)
• Presence of phimosis that may be obscuring the full extent of disease
• Bilateral inguinal examination for lymphadenopathy (number, size, laterality, characteristics of any palpable nodes) 1

Mandatory Biopsy

Obtain a pretreatment biopsy immediately - this is a strong recommendation when malignancy is not clinically obvious or when planning any treatment 1. The rolled edges and sloughy centre are classic features of invasive penile cancer, which presents as ulcerated lesions in most cases 2.

Use punch, excisional, or incisional biopsy to establish:

• Histological type and grade
• Depth of invasion
• Presence of lymphovascular or perineural invasion
• p16 immunohistochemistry status (HPV-related vs non-HPV-related) 1

Critical Differential Diagnoses to Exclude

While penile cancer is the primary concern, also test for:

1. Syphilis - Can present as indurated ulcers in atypical locations; perform darkfield microscopy or direct fluorescent antibody testing for Treponema pallidum, plus serologic tests 3, 4

2. Other STIs - Culture or PCR for herpes simplex virus, culture for Haemophilus ducreyi if chancroid is endemic 3

3. Pyoderma gangrenosum - Rare but important; consider if infection workup is negative and patient has inflammatory bowel disease or other systemic conditions 5, 6

Staging if Malignancy Confirmed

Imaging:

• MRI of penis if there is uncertainty about corporal invasion or to assess organ-sparing surgery feasibility (ultrasound if MRI unavailable) 1
• Do not delay biopsy for imaging

Lymph Node Staging:

• If cN0 (no palpable nodes) and pathology shows ≥T1b disease: offer dynamic sentinel node biopsy (DSNB) or inguinal lymph node dissection 1
• If cN+ (palpable nodes): obtain image-guided biopsy to confirm nodal metastasis, then stage with PET-CT or CT chest/abdomen before treatment 1

Treatment Algorithm Based on Pathology

If Tis or Ta (Noninvasive):

• Circumcision with wide local excision
• Alternative: topical imiquimod 5% or 5-FU cream
• Laser ablation (CO2 or Nd:YAG) is an option but provides no tissue for staging 1, 2

If T1 G1-2 (Low-grade invasive):

• Wide local excision with 5-10mm margins (not the historical 2cm)
• Mohs surgery as option
• Close follow-up mandatory (recurrence rates up to 50% at 2 years) 2

If T1 G3-4 or ≥T2 (High-grade or deeply invasive):

• Partial or total penectomy required
• Organ preservation is secondary to oncological control 1, 2

Critical Pitfalls to Avoid

1. Never treat empirically without biopsy - Up to 20% of presumed noninvasive lesions harbour invasive disease 1

2. Do not assume infection - While STIs can cause genital ulcers, rolled edges with sloughy centre is a red flag for malignancy 2

3. Do not delay referral - If you cannot perform adequate biopsy and staging, refer immediately to urology or penile cancer specialist 7

4. Inadequate margins - Historical 2cm margins are no longer required; 5-10mm provides adequate control, but ensure clear margins histologically 2

The absence of randomized trials in penile cancer management means these recommendations are based on cohort studies and expert consensus, but the diagnostic approach is unequivocal: biopsy first, treat based on histology 1.