Male genital dermatoses encompass a wide range of conditions with overlapping clinical manifestations, including infectious, inflammatory, and neoplastic disorders, which often lead to diagnostic challenges. These dermatoses may be localized to the genital area or represent a manifestation of a more widespread dermatologic condition. Misdiagnosis or delayed diagnosis can result in inappropriate management and significant psychological distress for patients. Patients often delay seeking medical attention owing to the sensitive location of lesions, increasing risks of delayed or incorrect diagnoses and subsequent therapeutic delays. Meanwhile, patients frequently worry that genital lesions may indicate sexually transmitted infections (STIs), a concern that can lead to significant psychological distress and social stigma. This highlights the crucial need for accurate differentiation between STI-related and non-STI-related dermatoses during clinical evaluations (1). Although histopathological examination remains the gold standard for diagnosis, biopsies of the external genitalia carry risks, including potential impacts on function, appearance, psychological well-being, and overall quality of life. To better understand the clinical characteristics of these conditions, we conducted a retrospective analysis of demographic data, disease profiles, lesion morphology, and clinical-dermatocopic-pathological diagnostic discrepancies in male external genitalia biopsies performed at our center over the past decade. This study aims to enhance the recognition of these conditions among dermatologists and urologists while reducing the likelihood of misdiagnosis.

In this retrospective study, we analyzed 572 cases of histopathologically confirmed skin lesions of the male external genitalia (defined as involving the penis and/or scrotum) at Peking Union Medical College Hospital from March 2015 to March 2025. Only cases with clinical photographs, histopathological images, and comprehensive medical records were included. Data were extracted from electronic medical records, including demographics, disease duration, disease distribution, clinical presentation, symptoms, pathological diagnosis, and clinical diagnosis. All patients scheduled for skin biopsy will be screened for hepatitis B, hepatitis C, syphilis, and human immunodeficiency virus, as well as whole blood routine and coagulation tests. Additionally, for cases with available dermoscopy data, those findings were also incorporated into the analysis. All dermoscopic interpretations and histopathological evaluations were independently assessed and confirmed by two experienced dermatologists. The final histopathological results will refer to laboratory results, especially in the case of infectious diseases, for accurate diagnosis. The study was approved by the ethics committee of Peking Union Medical College Hospital (K 8437).

Our retrospective study evaluated 572 histopathologically confirmed cases from Peking Union Medical College Hospital, encompassing a comprehensive assessment of demographic data, disease duration, clinical manifestations, and diagnostic concordance between initial clinical impressions and definitive histological findings. STIs, including syphilis, herpes simplex virus (HSV) infection, and gonorrhea, represent the most prevalent conditions affecting the male external genitalia. In contrast, non-STI dermatoses of the male external genitalia encompass a wide spectrum of disease with varied etiologies. There are only a few comprehensive studies on the pattern of nonvenereal dermatoses in males (2, 3). To the best of our knowledge, our study is the largest single-center study of male external genitalia skin diseases in China to date. Our cohort demonstrated remarkable etiological diversity, incorporating infectious pathogens, immune-mediated conditions, chronic inflammatory disorders, and metabolic deposition diseases, thereby providing a representative cross-section of genital dermatopathology in male patients.

In our study, we observed significant differences in the disease spectrum among various age groups. Adolescents predominantly affected by inflammatory and autoimmune conditions, while sexually active adults showed a higher prevalence of human papillomavirus (HPV)-associated diseases. Notably, elderly patients had a significantly elevated risk of developing cutaneous tumors, emphasizing age as a critical oncogenic risk factor. These findings highlight the importance of age-stratified diagnostic approaches. In particular, for elderly populations, proactive tumor screening for genital lesions is strongly recommended to facilitate early detection and optimize clinical outcomes.

In our study, the most common biopsied skin disease was EMPD. EMPD is a rare cutaneous malignancy with metastatic potential, predominantly affecting elderly individuals in apocrine-rich regions such as the genital, perianal, and axillary areas. This dermatologic entity may either precede or coexist with underlying visceral malignancies (4). Clinically, EMPD can mimic common inflammatory and infectious dermatoses, leading to delays in diagnosis and potentially resulting in metastasis and a poor prognosis. In our study, EMPD was characterized by late onset, long disease duration, and a predilection for the scrotum. A panel of immunohistochemical staining, including AE1/AE3, CK7, CEA, EMA, S100, and periodic acid-Schiff staining, is useful for diagnosing EMPD (5). Additionally, other skin tumors can also occur in the male genitalia area. Mazzoni et al. reviewed a cohort of 1525 patients with genital premalignant and malignant diseases in Australia, providing further context to the range of conditions that can affect this region (6). In our study, premalignant or malignant lesions were identified in 5% of cases (74 cases), with penile intraepithelial neoplasia (57%), SCC (15%), and BP (12%) being the most common. These lesions exhibited distinct anatomical distributions: penile intraepithelial neoplasia and BP were found on the penile shaft, SCC on the glans, and BCC on the scrotum. The benign tumors in our cohort included seborrheic keratosis, angiokeratoma, dermatofibroma, acrochordon (soft fibroma), epidermolytic acanthoma, solitary reticular histiocytoma, keloid, and melanocytic nevus. Malignant neoplasms identified included Bowen’s disease, SCC, BCC, verrucous carcinoma, and cutaneous B-cell lymphoma. Histopathological examination is the golden standard for distinguishing these diseases. Our findings suggested that cutaneous neoplasms in the external genital region may develop either as primary lesions or as secondary manifestations of systemic malignancies.

In our research, the relatively low incidence of classic STIs can be attributed to two key factors. Firstly, these infections are typically diagnosed through serological tests, viral cultures, or nucleic acid amplification tests rather than histopathological examination. Secondly, biopsy is generally unnecessary for their clinical confirmation unless atypical presentations warrant histological evaluation. Therefore, our current study design cannot fully capture the true epidemiological profile of STIs diagnosed by standard laboratory methods. Some atypical manifestations of syphilis, such as Follmann balanitis, phagedenic chancres or multiple chancres, may be misdiagnosed or missed in the study if they were not clinically suspected and therefore not biopsied (7, 8). Among infectious etiologies in our cohort, the most prevalent diagnoses were BP, warts, syphilis, HSV infection, scabies and molluscum contagiosum. BP, a genital dysplasia induced by HPV infection, is characterized by multiple asymptomatic, well-demarcated, red-brown to violaceous papules with a flat, smooth, or verrucous surface. These lesions typically arise on the glans penis and foreskin in male patients and may coalesce into larger plaques (9). In our research, BP was found to have the highest incidence rate among adults aged 18–60 years. Despite its prevalence, we observed a 42% discordance rate between initial clinical impressions and final histopathological diagnoses, primarily due to its morphological similarity to other conditions such as condyloma acuminatum, viral warts, lichen planus, and seborrheic keratosis. Pathologically, BP needs to be differentiated from Bowen disease and erythroplasia of Queyrat. Although the transformation of BP into invasive SCC is rare, occurring in less than 1% of patients, it is still recommended to perform HPV subtyping tests to screen for potential carcinogenic HPV infections. Additionally, concurrent physical examinations and cytologic screening for sexual partners are recommended to ensure comprehensive management and prevention of disease progression (10).

In our study, inflammatory dermatoses were the most common disease category, accounting for 191 out of 572 cases. Therefore, these conditions require particular clinical attention due to their potential for chronicity, functional impairment, and significant impact on quality of life. The predominant entities in our cohort included LS, LP, balanitis, and psoriasis. LS, also referred to balanitis xerotica obliterans, is a chronic inflammatory disorder that affects both genital and extragenital mucocutaneous tissues. In our research, it primarily affected the glans penis and prepuce. LS can present with hypopigmented lesions, erosions, or atrophy, and is characterized by debilitating symptoms such as pruritus, pain, dysuria, urinary stream obstruction, dyspareunia, and sexual dysfunction (11). Importantly, LS is associated with an increased risk of developing squamous cell carcinoma of penis, highlighting the need for vigilant monitoring and management of this condition (12). Early identification of LS is crucial for alleviating symptoms, preventing disease progression, and reducing the risk of malignant transformation. In contrast, psoriasis often presents as well-demarcated, erythematous plaques, with genital involvement affecting up to 63% of patients (13). However, in 2%–5% of patients, genital involvement may be the only manifestation of cutaneous psoriasis (14). This isolated presentation, particularly when it affects the glans penis and coronal sulcus, frequently exhibit atypical clinical features that complicate diagnosis. We observed a 53% discordance rate between initial clinical impressions of genital psoriasis and histopathological diagnoses. In such challenging cases, the presence of extragenital psoriatic features, such as nail pitting, arthropathy or classic skin lesions, often provides valuable diagnostic clues.

In addition, our study observed several rare conditions, including epidermolytic acanthoma, solitary reticular histiocytoma, verruciform xanthoma, and porokeratosis. However, the limited sample size of these cases presents certain limitations in our research findings. Despite these constraints, the identification of these rare conditions contributes to a broader understanding of dermatological disease spectrum.

In our study, 198 patients (34.6%) showed discrepancies between clinical and histological diagnoses. This inconsistency may be due to the clinical similarities among various male genital dermatoses. To address this challenge, dermoscopy and reflectance confocal microscopy (RCM), as non-invasive diagnostic tools, can be used to evaluate both melanocytic and non-melanocytic skin lesions, as well as a range of inflammatory and infectious skin diseases. Our analysis revealed a 57.5% diagnostic concordance rate (42/73) between dermoscopic features and histopathological confirmation, underscoring the clinical utility of dermoscopy in characterizing prototypical genital lesions such as LS, SCC, LP and melanocytic nevus. However, diagnostic discrepancies persisted in cases with atypical presentations or non-specific dermoscopic patterns (e.g., inflammatory dermatoses and early malignant transformations), necessitating multimodal integration of clinical-pathological correlation. Notably, the limited adoption of concurrent dermoscopic-histopathological evaluation (16.9%, 73/433 cases) highlights systemic gaps in real-world diagnostic workflows. By identifying characteristic patterns, dermoscopy and RCM significantly improve diagnostic accuracy and help to minimize the need for unnecessary invasive procedures. Extensive literature has documented the dermoscopic and RCM features of common genital diseases, providing valuable references for their diagnosis and differential diagnosis, thereby enhancing the precision of dermatological assessments (9, 15). We have reviewed and summarized the most common male external genital skin disorders in our study in the Table 5 (16–23). Given the unique nature of the anatomical area, some scholars have suggested using polarized, non-contact dermoscopy to prevent the spread of infectious diseases. Additionally, videodermatoscope can be used to avoid close contact between the examiner’s head and the patient’s genitals (16).

In conclusion, our research presents a comprehensive single-center retrospective study encompassing 572 histopathologically confirmed cases of male external genital skin lesions. The primary objective of this study was to enhance diagnostic accuracy and minimize misdiagnosis by thoroughly examining the demographic, clinical, and histopathological features of these conditions.