What is the appropriate diagnostic and treatment approach for a patient presenting with a persistent penile rash characterized by non-pruritic, non-painful, ring-like pink plaques with a paler center on the shaft and base of the penis?

Diagnostic Approach for Persistent Penile Ring-Like Pink Plaques

Based on the clinical presentation of non-pruritic, non-painful, ring-like pink plaques with paler centers persisting for 6 months on the penile shaft and base, the most likely diagnosis is erythroplasia of Queyrat (penile intraepithelial neoplasia), and you must obtain a biopsy immediately to rule out carcinoma in situ before considering other inflammatory dermatoses. 1, 2

Critical History Questions

Sexual and Infectious History

• HPV exposure and sexual contacts: Erythroplasia of Queyrat and bowenoid papulosis are associated with HPV, particularly in younger sexually active men 1, 2
• History of syphilis or recent chancre: Secondary syphilis can present with annular plaques on the penis, though these are typically more widespread 1, 3
• Circumcision status: Lack of circumcision is a major risk factor for penile intraepithelial neoplasia and lichen sclerosus 1

Symptom Characterization

• Complete absence of pruritus: This argues against lichen sclerosus (which typically causes severe nocturnal itch) and lichen planus (which is usually pruritic) 1
• Absence of pain, fissuring, or dyspareunia: Lichen sclerosus commonly presents with painful fissures and erosions 1
• Duration and progression: Six-month persistence without spontaneous resolution rules out most infectious etiologies 1

Associated Conditions

• Autoimmune diseases: Lichen sclerosus has associations with other autoimmune conditions and tissue-specific antibodies 1
• Urinary symptoms or meatal stenosis: Would suggest lichen sclerosus with urethral involvement 1
• Lesions elsewhere on body: Extragenital lichen sclerosus affects upper trunk, axillae, buttocks, and lateral thighs 1

Physical Examination Findings to Document

Lesion Characteristics (Per ESMO Guidelines)

• Exact morphology: Record whether lesions are papillary, nodular, ulcerous, or flat 1
• Color and boundaries: Pink plaques with paler centers differ from the shiny erythematous plaques of erythroplasia of Queyrat or porcelain-white plaques of lichen sclerosus 1
• Number and distribution: Multiple ring-like lesions on shaft and base 1
• Relationship to anatomical structures: Document involvement of submucosa, tunica albuginea, urethra, corpus spongiosum, and corpus cavernosum 1

Specific Examination Elements

• Glans penis and inner prepuce: Erythroplasia of Queyrat presents as shiny erythematous plaques on mucosal surfaces of inner prepuce and glans 1, 2
• Coronal sulcus and prepuce: Lichen sclerosus commonly affects these areas, causing phimosis 1
• Perianal involvement: Present in 30% of women with lichen sclerosus but extremely rare in men, which helps differentiate 1
• Evidence of scarring: Lichen sclerosus causes postinflammatory scarring and may lead to meatal stenosis 1
• Follicular delling or ecchymosis: Characteristic of lichen sclerosus 1

Inguinal Lymph Node Examination

• Bilateral groin palpation: Record morphological and physical characteristics of nodes, as palpable nodes may indicate malignant transformation 1

Differential Diagnoses Ranked by Likelihood

1. Erythroplasia of Queyrat (Penile Intraepithelial Neoplasia) - HIGHEST PRIORITY

• Clinical presentation: Shiny erythematous plaque on mucosal surfaces, highest risk for progression to invasive squamous cell carcinoma among penile intraepithelial neoplasias 1, 2
• Key distinguishing features: Approximately 60% of penile SCCs occur on background of this precursor lesion 2
• Critical action: Biopsy is mandatory before any treatment to distinguish in situ from invasive disease 2

2. Bowenoid Papulosis

• Clinical presentation: Raised papules on penile shaft in young sexually active men with HPV exposure 1, 4
• Key distinguishing features: Occurs in younger age group, histologically indistinguishable from other penile intraepithelial neoplasias but has lowest risk of progression to SCC 1
• Critical pitfall: Must distinguish from pearly penile papules, which are benign anatomical variants requiring only reassurance 4

3. Bowen's Disease of the Penis

• Clinical presentation: Red scaly patches and plaques on keratinized penile shaft skin 1
• Key distinguishing features: Clinically distinct from erythroplasia of Queyrat by location on keratinized rather than mucosal surfaces 1

4. Lichen Sclerosus (Balanitis Xerotica Obliterans)

• Clinical presentation: Porcelain-white plaques with areas of ecchymosis, follicular delling, affecting prepuce, coronal sulcus, and glans 1
• Key distinguishing features: Severe nocturnal itch is the main symptom, painful fissures and erosions common, leads to phimosis 1
• Why less likely here: Absence of pruritus and pain argues strongly against this diagnosis 1

5. Lichen Planus

• Clinical presentation: Violaceous papules and plaques, typically pruritic 5
• Key distinguishing features: Vaginal and cervical involvement can occur (unlike lichen sclerosus), perianal involvement more common than in lichen sclerosus in men 1
• Why less likely here: Non-pruritic presentation makes this unlikely 5

6. Secondary Syphilis

• Clinical presentation: Can present with annular plaques, but typically part of more widespread eruption 1, 3
• Key distinguishing features: Usually accompanied by systemic symptoms, lymphadenopathy, and other mucocutaneous lesions 1
• Diagnostic approach: Serologic testing (RPR/VDRL with confirmatory treponemal testing) 1

Mandatory Diagnostic Steps

Immediate Actions

1. Biopsy is non-negotiable: Histological examination is mandatory for any persistent penile lesion to exclude neoplastic change 1, 2
2. Multiple biopsies if needed: Sample any areas with hyperkeratosis, erosion, erythema, or warty/papular features 1
3. Syphilis serology: Given the differential includes secondary syphilis 1
4. HPV testing consideration: Relevant for penile intraepithelial neoplasia risk stratification 1

Common Pitfalls to Avoid

• Never treat empirically without biopsy: The clinical appearance alone cannot distinguish benign inflammatory conditions from premalignant or malignant lesions 1, 2
• Do not confuse with pearly penile papules: These are uniform, dome-shaped papules in 1-2 rows around the corona, completely benign, and require only reassurance 4, 6
• Do not miss malignant transformation: Persistent areas despite adequate treatment require repeat biopsy 1
• Avoid misdiagnosing as STI: As illustrated by a case report, penile angiosarcoma was initially misdiagnosed as syphilis when anti-viral treatment failed to resolve the lesion 3

Follow-Up Based on Biopsy Results

• If penile intraepithelial neoplasia confirmed: Intensive surveillance every 3-6 months for first 2-3 years, then every 6-12 months, as 92% of recurrences occur within 5 years 2
• If lichen sclerosus confirmed: Long-term follow-up for squamous cell carcinoma risk, though this is predominantly described in female genital lichen sclerosus 1