In a decade-long retrospective analysis of 572 histopathologically confirmed male external genital skin lesions, researchers revealed distinct age-stratified disease patterns and clinical-pathologic diagnostic discrepancies, with inflammatory diseases and tumors each accounting for approximately one-third of cases, wrote lead study author Yue-Tong Qian, of Peking Union Medical College Hospital in Beijing, China, and colleagues.
The cohort, with a mean age of 48 years, demonstrated that patients under 18 years (1%) predominantly presented with inflammatory and autoimmune conditions, whereas patients aged 19 to 60 years (71%) most frequently developed human papillomavirus (HPV)-associated diseases such as Bowenoid papulosis and genital warts alongside inflammatory conditions such as lichen sclerosus. Older adult patients over 60 years (28%) exhibited markedly elevated malignancy rates, particularly extramammary Paget disease and squamous cell carcinoma. Because of the sensitive anatomic location, there are often in genital lesions, as patients delay seeking care over concerns that the lesions may indicate sexually transmitted infections.
Disease Distribution and Anatomic Localization
The researchers identified 47 distinct pathologic diagnoses in cases spanning March 2015 to March 2025. Inflammatory diseases accounted for 33% (n = 191) of the cases, while benign and malignant tumors comprised 42% (n = 239) of cases, infectious diseases 23% (n = 129) of cases, and autoimmune diseases with other conditions 2% (n = 13) of cases.
The 10 most prevalent diagnoses were extramammary Paget disease (68 cases, 12%), Bowenoid papulosis (57 cases, 10%), lichen sclerosus (57 cases, 10%), lichen planus (54 cases, 9%), genital warts (48 cases, 8%), squamous cell carcinoma (SCC) (44 cases, 8%), balanitis (29 cases, 5%), dermatitis or eczema (25 cases, 4%), melanocytic nevi (18 cases, 3%), and erythema hyperplasia (17 cases, 3%).
The glans penis was the most frequently biopsied site (195 cases), followed by the penile shaft (178 cases), scrotum (161 cases), and coronal sulcus (38 cases). Extramammary Paget disease demonstrated strong anatomic predilection for the scrotum (60/68 cases), while SCC most commonly affected the glans penis (22/44 cases).
Age-Stratified Disease Profiles
In the pediatric cohort, epidermoid cysts were most common (2 cases, 29%), with mean disease duration of 39 months. Adult patients showed a mean disease duration of 36 months, with Bowenoid papulosis leading at 13% (51 cases), followed by lichen sclerosus (50 cases, 12%) and lichen planus (48 cases, 12%).
The older adult cohort demonstrated a mean disease duration of 35 months and increased malignancy prevalence. Extramammary Paget disease dominated this group at 36% (58 cases), followed by SCC (25 cases, 16%) and balanitis (15 cases, 9%).
Diagnostic Concordance Analysis
Clinical-pathologic discordance occurred in 198 cases (35%). Infectious diseases demonstrated the highest discordance rate at 43%, followed by inflammatory conditions (37%), benign tumors (37%), autoimmune and other disorders (31%), and malignant or premalignant lesions (24%).
Bowenoid papulosis exhibited 42% clinical-pathologic discordance, primarily caused by morphologic similarity with condyloma acuminatum, viral warts, lichen planus, and seborrheic keratosis. Genital psoriasis showed 53% discordance rate, particularly when affecting the glans penis and coronal sulcus with atypical clinical features.
Dermoscopic Evaluation
Among 433 histopathologically evaluated patients, 73 cases (17%) had complete dermoscopic records. Dermoscopic-histopathologic concordance reached 58% (42 cases) for prototypical lesions, including lichen sclerosus, SCC, lichen planus, and melanocytic nevi.
Eighteen cases (25%) exhibited nonspecific dermoscopic patterns requiring comprehensive differential diagnosis encompassing inflammatory conditions, infectious diseases, and neoplastic lesions. Thirteen cases showed dermoscopic-pathologic discordance, notably confusion between genital warts and Bowenoid papulosis as well as between lichen sclerosus and lichen planus.
The limited availability of dermoscopic evaluation in only 17% of cases represented a significant limitation in the widespread application of this diagnostic tool in clinical practice, the researchers noted.
Malignant and Premalignant Entities
Extramammary Paget disease, characterized by persistent erythematous plaques with exudation, erosion, or ulceration, affected predominantly older adult patients (mean age = 69 years) with prolonged disease duration (51 months). Immunohistochemical panels like AE1/AE3, CK7, CEA, EMA, and S100 proved diagnostic.
SCC presented at a mean age of 59 years and disease duration 15 months, typically manifesting as nodules or indurated masses with chronic nonhealing ulcers. Verrucous carcinoma (16 cases) presented at a mean age of 53 years, while basal cell carcinoma (six cases) affected older patients (67 years).
HPV-Associated Conditions
Bowenoid papulosis affected adults with mean age 38 years and disease duration 19 months. Despite prevalence as the leading diagnosis in adults aged 19 to 60 years, the condition showed 42% clinical-pathologic discordance. Although considered a premalignant condition, transformation to invasive SCC is rare, occurring in less than 1% of patients. The researchers recommended HPV subtyping tests to screen for carcinogenic HPV infections and concurrent physical examinations with cytologic screening for sexual partners.
Genital warts presented similarly (mean age = 40 years) with 54% discordance rate and disease duration of 23 months.
Inflammatory Dermatoses
Lichen sclerosus, affecting patients with a mean age of 41 years, predominantly involved the glans penis (37 cases) and penile shaft (14 cases). Disease duration averaged 42 months, with 26% clinical-pathologic discordance. Severe cases progressed to frenular contracture and urethral stricture with associated functional impairment. Notably, lichen sclerosus is associated with an increased risk of developing SCC of the penis, highlighting the need for vigilant monitoring.
Lichen planus presented at a mean age 43 years with a relatively shorter disease duration (16 months) but the highest discordance rate at 52%. Plasma cell balanitis affected older patients (mean age = 56 years) with disease duration of 30 months and a 35% discordance rate.
The researchers declared having no competing interests.
Source: Frontiers in Medicine