What are the potential causes and treatment options for a nontender growth on the penis in an adult male with no significant medical history?

Nontender Growth on Penis: Diagnosis and Management

Any nontender growth on the penis requires immediate cytological or histological diagnosis through biopsy to exclude malignancy, as squamous cell carcinoma accounts for over 95% of penile cancers and can present as painless lesions. 1

Immediate Diagnostic Approach

Physical examination must document the morphological and physical characteristics of the lesion, including diameter, location, number of lesions, morphology (papillary, nodular, ulcerous, or flat), and relationship to other structures (submucosal, corpora spongiosa/cavernosa, urethra). 1

Mandatory Biopsy

• Punch, excisional, or incisional biopsy is required for any persistent penile growth to establish definitive diagnosis. 1
• Cytological diagnosis alone may be insufficient; histological confirmation is the gold standard. 1
• Do not delay biopsy based on benign appearance, as erythroplasia of Queyrat and Bowen's disease can appear clinically benign despite being squamous cell carcinoma in situ. 2

Optional Imaging

• MRI or ultrasound may be performed based on clinical suspicion to further define concerning physical exam findings, particularly to assess depth of invasion. 1
• Imaging should not replace biopsy but can complement surgical planning. 1

Differential Diagnosis Framework

Premalignant and Malignant Lesions (High Priority)

Penile intra-epithelial neoplasia (carcinoma in situ) presents in three clinical forms: 1

• Bowenoid papulosis: Raised papule on penile shaft in young males with HPV exposure history (lowest malignant potential) 1
• Bowen's disease: Red scaly patch on penile shaft 1
• Erythroplasia of Queyrat: Shiny erythematous plaque on mucosal surface of inner prepuce/glans (highest risk of developing squamous cell carcinoma) 1

Squamous cell carcinoma may present as nontender growth and includes subtypes: classic/usual, basaloid, verrucous, sarcomatoid, or adenosquamous. 1

Verrucous carcinoma presents with verrucous growth pattern and almost never invades lymph nodes but causes distinct inflammatory nodal enlargement. 1

Benign Inflammatory Conditions

Balanitis xerotica obliterans (lichen sclerosus et atrophicus) appears as atrophic white patches on glans penis and foreskin; associated with squamous cell carcinoma but no proven direct causal link. 1

Plasma cell balanitis presents as solitary, smooth, shiny, red-orange plaque on glans/prepuce in middle-aged to older men; benign but requires biopsy to exclude squamous cell carcinoma in situ. 2

Infectious Etiologies

HPV-related condyloma acuminatum (genital warts) caused by low-risk HPV 6 and 11; typically multiple papillomatous lesions. 2

Giant condyloma (Buschke-Löwenstein tumor) is potentially invasive and requires aggressive management. 3

Other Benign Lesions

Paraffinoma results from prior subcutaneous injection of paraffin, Vaseline, or mineral oils, presenting as hardened mass; confirmed by biopsy showing granulomatous inflammation. 4

Sebaceous cysts or other benign growths may occur but still require histological confirmation. 2

Treatment Algorithm Based on Histology

For Premalignant Lesions (Tis, carcinoma in situ)

• Topical therapy (imiquimod or fluorouracil cream) 1
• Laser therapy 1
• Wide local excision including circumcision 1
• Complete glansectomy (category 2B) 1

For Invasive Squamous Cell Carcinoma

T1 lesions: Penile-preserving approaches with surgical margins ≥5 mm are adequate for most tumors (recurrence rate <5%). 1

T2 or greater lesions: Partial penectomy is standard for high-grade tumors if functional penile stump can be preserved with negative margins. 1

For Benign Inflammatory Conditions

Lichen sclerosus: Highly active topical therapy, careful clinical follow-up, and surgical treatment of phimosis. 3

Plasma cell balanitis: Excision after biopsy confirmation. 2

For Infectious Lesions

Condyloma acuminatum: Imiquimod as first-line topical immunotherapeutic agent; surgical excision for refractory cases. 2

Critical Pitfalls to Avoid

• Never assume clinical benignity without histological confirmation, as squamous cell carcinoma in situ cannot be excluded clinically and may lead to lengthy periods of misdiagnosis. 2
• Do not treat empirically with topical agents before establishing diagnosis, as this delays definitive management of malignancy. 3
• Avoid dismissing nontender lesions as benign, since pain is characteristic of active-phase Peyronie's disease but not typical of penile malignancies. 1
• Do not perform only cytology without histology for definitive diagnosis, as tissue architecture assessment is essential. 1

Surveillance After Treatment

Clinical examination of the penis should occur: 1

• Year 1-2: Every 3-6 months
• Year 3-5: Every 6-12 months
• Year 5-10: Every 12 months (for certain lesions)

Imaging surveillance (chest CT/X-ray, abdominopelvic CT/MRI) is indicated for invasive cancers based on stage. 1