Carcinoma of the penis must be differentiated from condyloma acuminata, penile intraepithelial neoplasia (PeIN), balanitis xerotica obliterans, buschke-Lowenstein tumour, bowenoid papulosis, and leukoplakia.

Carcinoma of the penis must be differentiated from:^[1][2]

• Noncancerous conditions

• Condyloma acuminata
  • A common sexually transmitted disease caused by a virus belonging to the human papilloma virus (HPV) group
  • Lesions normally grow as a papilloma and are usually found on the glans, prepuce, or shaft of the penis
  • Lesions are benign, caused by low-risk HPV 6/11
  • Mixed infections with high-risk HPV types are relatively common
  • Progression to malignancy is rare.

• Precancerous conditions ^[3]

• Penile intraepithelial neoplasia (PeIN)
  • most common precancerous condition of the penis
  • General term used to describe precancerous conditions of the penis that may develop into invasive squamous cell carcinoma (SCC) if they are not treated
  • Refers to abnormal cell changes, called carcinoma in situ, that occur on the skin surface of the penis
  • PeIN on the glans (head) or foreskin of the penis is also called erythroplasia of Queyrat
  • PeIN on the shaft of the penis is also called Bowen’s disease
• Balanitis xerotica obliterans (BXO) also known as lichen sclerosis
  • A precancerous skin condition localized to the glans and the prepuce
  • Presents as white atrophic patches
  • The secondary development of phimosis inhibits washing and prevents early diagnostics of possible malignancy development on the glans or inside of the prepuce
  • A radical circumcision should therefore be performed for this disease
• Buschke-Lowenstein tumour
  • A slow–growing, locally destructive verrucous plaque
  • Cauliflower-like mass
  • A regional variant of verrucous carcinoma, also known as giant condyloma acuminate
  • Can involve the penis, vulva, scrotum, bladder, and perianal or anorectal regions
  • Rare
• Bowen’s Disease
  • Undifferentiated PeIN
  • Manifests as a solitary, pigmented, scaly or scab-covered area
  • Affects the penis shaft, scrotum, perineum, and the suprapubic area
• Bowenoid papulosis
  • Multiple, slightly elevated, red to violet or brownish papules, on the penis shaft and scrotum
  • Very rare, is preferably seen young men
  • May regress without treatment
  • Caused by high-risk HPV, most commonly HPV 16
  • Histologically cannot be separated from undifferentiated PeIN
• Leukoplakia
  • Rare
  • Appear as a white hypertrophic or atrophic patch and usually occur secondary to chronic irritation
  • Develops in the meatus
  • Biopsy is necessary to exclude cancer and intraepithelial neoplasia (PeIN)
• Erythroplasia of Queyrat
  • Grows on the glans and the prepuce
  • Presents as a well-defined, red patch
  • Undifferentiated PeIN