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Background: Non-neoplastic skin lesions are a wide array of benign, inflammatory, cys tic, vascular, and reactive processes. Non-neoplastic skin lesions often mimic neoplastic diseases clinically. The clinical overlap with neoplastic entities makes histopathological examination the gold standard for a definitive diagnosis. Objective: The present retrospective study aims to delineate the histopathological chara teristic spectrum, the demographic characteristics, and the anatomical site distribution met rics of non-neoplastic skin lesions in biopsies received at Government Medical College, Anantnag, a tertiary care referral center. Methods: This present study was carried out over a one year period, wherein 109 consec utive non-neoplastic skin biopsy specimens sampled from Government Medical College, Anantnag, were reviewed. The demographic and clinical data were exerted from the re spective medical records. Histopathological evaluations were performed on formalin-fixed, paraffin-embedded hematoxylin and Eosin (H &E) stained slides. The descriptive statistics and data analysis were performed using Python 3.9 and associated directories. Significance tests like χ2 test and Fischer’s tests were used. Results: Patient ages ranged from 3 year old to 85 years with a mean age of 37.5 ± 18.0 years, and a male predominance (65 M : 44 F). Epidermal inclusion cysts (31%) were the most frequent lesions, followed by pilomatrixomas (11%) and keratinous cysts (8.0 %). Overall, the cystic lesions comprised 57% of the total cohort. We also documented a squamous cell carcinoma arising in an epidermal cyst (0.9%). Pediatric patients (<18years; n=7) showed a higher proportion of pilomatrixomas and keratinous cysts. The most common biopsy sites were the scalp (14%), chest (11%), and the neck (9%). Males were characterized by a significantly larger frequency of cystic lesions (75.4% vs. 51.3%, χ2 = 5.42, p = 0.02). Conclusion: Non-neoplastic cutaneous lesions were most common in middle-aged males, with cystic lesions predominating. Epidermal inclusion cysts were the most frequent, and pilomatrixomas were more common in children. Scalp was the leading biopsy site. One rare case of malignant transformation was noted.
As the largest organ of the human body, the skin is susceptible to a wide spectrum of pathological conditions, ranging from benign cystic lesions to aggressive malignant neoplasms. Among these, non-neoplastic skin lesions encompass a wide variety of entities including benign proliferative, cystic, inflammatory, reactive, and vascular conditions. These lesions often present with overlapping clinical features, which poses significant challenges in making an accurate clinical diagnosis. Given the nonspecific and sometimes misleading clinical appearances, histopathological examination remains the gold standard for definitive diagnosis and classification of such lesions [1,2]. The global distribution and prevalence of non-neoplastic cutaneous lesions are influenced by various climatic, genetic, social, and environmental factors [3,4]. These determinants may result in significant regional and ethnic variability in both the incidence and presentation of skin lesions. Among the commonly encountered cystic lesions, epidermal inclusion cysts (EICs)—also referred to as infundibular cysts—are particularly noteworthy. In Western populations, EICs have been reported to comprise approximately 47.8% of all cutaneous cysts [5], whereas in South Asian cohorts, they account for around 34.2% [6].
Another important lesion in the spectrum is pilomatrixoma, a benign tumor originating from hair matrix cells. These lesions exhibit a bimodal age distribution, most commonly occurring in children aged ≤10 years and again in middle-aged adults between 50 and 65 years [7]. The incidence of pilomatrixomas varies geographically, comprising approximately 2–5% of all benign skin tumors in Western populations [8], while higher rates—ranging from 8–12%—have been observed in East Asian countries, particularly in Japan and Korea [7]. Although epidermal inclusion cysts are generally benign, rare cases of malignant transformation have been documented, most frequently into squamous cell carcinoma (SCC). The incidence of such malignant change remains low, estimated between 0.011% and 0.045% [9,10]. Factors associated with increased risk of transformation include cysts with a prolonged clinical duration exceeding five years and those with a larger diameter (>5 cm). Alarmingly, such malignant transformations are often asymptomatic and remain clinically occult until advanced stages, underscoring the critical need for histopathological analysis of long-standing or atypical cystic lesions.
Despite the extensive global literature detailing the histopathological profile and potential for malignant transformation in benign cutaneous lesions, there remains a notable paucity of data from South Asian tertiary care centers [11]. This gap is particularly evident in geographically and socially distinct regions such as South Kashmir, where access to specialist dermatopathology services has historically been limited. The present study is therefore undertaken to characterize the clinicopathological spectrum of non-neoplastic skin lesions in a referral population from South Kashmir, India. We aim to elucidate the demographic distribution, anatomical site prevalence, and rare instances of malignant transformation over a one-year period. Through comprehensive histopathological analysis, this study endeavors to contribute valuable regional data, bridging the existing knowledge gap and potentially informing clinical decision-making in similar healthcare settings. In the forthcoming sections, we outline the study methodology, present the analytical findings, and discuss the patterns of diagnostic frequency, site-specific correlations, and demographic influences observed within our cohort.
This study was conducted as a retrospective, cross-sectional, observational analysis at the tertiary care referral center of Government Medical College, Anantnag, spanning the period from January 1 to December 31, 2024. All skin biopsy specimens received during this period and diagnosed histopathologically as definitive non-neoplastic lesions at the time of presentation were included. Strict exclusion criteria were applied to ensure the quality and relevance of the data. Specimens were excluded if they demonstrated inadequate tissue sampling, were diagnosed with dysplastic, neoplastic, or infectious pathologies, or if the tissue was poorly preserved or yielded inconclusive diagnostic results.
Clinical and demographic data, including patient age, sex, and lesion location, were retrieved from the institutional electronic pathology archive system. All skin lesions were grouped into diagnostic categories based on histopathological findings. The primary diagnostic categories included cystic lesions, inflammatory or reactive conditions, vascular lesions, and other benign entities. All biopsy specimens were processed using standard histopathological protocols. The tissue samples were formalin-fixed, paraffin-embedded, sectioned at a thickness of 4 micrometers, and stained using routine hematoxylin and eosin (H&E). Two board-certified dermatopathologists independently reviewed each histological slide to ensure diagnostic accuracy and consistency. The lesions were further subclassified as follows:
Statistical Analysis
Descriptive statistical methods were used to summarize demographic characteristics and lesion distribution. Both quantitative and categorical variables were analyzed using Python version 3.9, incorporating libraries such as pandas for data manipulation, matplotlib and seaborn for data visualization, and SciPy for statistical computation. Additionally, SPSS version 25 was utilized for further statistical validation. Associations between categorical variables, such as sex and lesion type, were evaluated using the Chi-square test or Fisher’s exact test where appropriate. A p-value of less than 0.05 was considered indicative of statistical significance throughout the analysis
The present study analyzed a total of 109 patients who underwent histopathological evaluation of non-neoplastic skin lesions during the defined study period. The age of patients ranged from 3 to 85 years, with a mean age of 37.5 ± 18.0 years, indicating a broad age spectrum affected by these lesions. Males constituted the majority of the cohort, with 65 cases (59.6%), compared to 44 females (40.4%), yielding a male-to-female ratio of approximately 1.5:1. Age distribution analysis revealed bimodal peaks, with the highest concentration of cases occurring in the 18–30-year and 51–60-year age brackets, suggesting increased clinical presentation or biopsy referral during early adulthood and middle age.
Histopathological examination of the 109 skin biopsy specimens revealed a diverse spectrum of non-neoplastic lesions, with cystic and benign proliferative lesions constituting the majority. When categorized according to frequency, epidermal inclusion cysts emerged as the most common histopathological diagnosis, observed in 31 cases (31.0%). These were followed by pilomatrixomas, benign tumors originating from hair matrix cells, which accounted for 11 cases (11.0%).
Pilomatrixomas showed a clear predilection for younger individuals, consistent with their known age distribution patterns. Keratinous cysts were identified in 8 cases (8.0%), while seborrheic keratosis, a common benign epidermal proliferation, was diagnosed in 7 cases (7.0%). Trichilemmal cysts, typically originating from the outer root sheath of hair follicles, were noted in 6 cases (6.0%). Inflammatory/reactive lesions numbered 24/109 (22.0%), including granulomatous der matitis (n=10) and lichen planus (n=8). Vascular lesions (n=5, 4.6%) and other benign growths (n=6, 5.5%) completed the distribution. Anatomical site analysis revealed that the scalp was the most frequently biopsied location, accounting for 14% of all cases. This was followed by the chest, which contributed 11%, and the neck, representing 9% of the total biopsy sites as shown in fig 3. These findings suggest a predilection for lesion development in areas rich in pilosebaceous units, particularly the scalp, which is commonly associated with cystic lesions such as epidermal inclusion and trichilemmal cysts.
In the pediatric subgroup, which included seven patients aged 18 years or younger, the most frequently diagnosed lesions were keratinous cysts and pilomatrixomas, each comprising 2 out of 7 cases (28.6%). Notably, the scalp was the most common anatomical site in this age group, involved in 42.9% of pediatric cases. This distribution aligns with the known clinical behavior of pilomatrixomas, which often arise in the head and neck region of children and adolescents. A rare but clinically significant finding in this study was the malignant transformation of an epidermal inclusion cyst into squamous cell carcinoma (SCC), observed in one case (0.9%). Histopathological examination under low-power magnification revealed preserved cystic architecture with overlying areas of cellular atypia. High-power views confirmed the presence of invasive squamous cell carcinoma arising in direct continuity with the epithelial lining of the cyst. This case underscores the potential, albeit rare, for malignant transformation in long-standing or atypical cystic lesions, emphasizing the importance of thorough histopathological evaluation, especially in lesions with unusual clinical features, size, or duration.
This study reinforces the observation that benign cystic lesions, particularly epidermal inclusion cysts (EICs), constitute the predominant category among non-neoplastic cutaneous biopsies, consistent with findings reported in both global and regional studies [12,13]. The observed 31% prevalence of EICs in our cohort closely aligns with earlier reports from Asian populations, which document frequencies ranging between 25–35% [9,14]. This consistency across studies highlights the high diagnostic yield of these lesions in routine dermatopathology, especially in populations with similar demographic and environmental exposures.A noticeable male predominance (male-to-female ratio of 1.5:1) was evident in our series. This finding mirrors several prior studies that attribute such sex distribution to androgen-mediated follicular occlusion, thereby supporting the theory of androgen-dependent cystogenesis in the pathogenesis of EICs [15-17]. These hormonal
influences may play a role in both lesion development and progression, and their recognition can be valuable in clinical assessment.
The frequency of pilomatrixomas (11%) in our study is significantly higher than that typically reported in Western literature, where figures generally range from 2–5%. However, this finding is consistent with increased rates documented in Asian cohorts [8,18]. This elevated frequency may reflect greater clinical awareness and diagnostic suspicion, or alternatively, may indicate underlying genetic or sociocultural factors unique to regional populations. Given the strong association of pilomatrixomas with the pediatric age group, these
results emphasize the importance of early dermatologic referral in children presenting with firm, mobile subcutaneous nodules, to ensure timely recognition and intervention [19].
A rare but clinically important finding in this series was the malignant transformation of an epidermal inclusion cyst into squamous cell carcinoma (SCC), observed in one case (0.9%). This falls within the range reported in the literature, where such transformations occur at a rate of approximately 0.011–0.045% [10,20]. The identification of this rare event underscores the importance of maintaining a high index of suspicion for atypical or long-standing cystic lesions, particularly those demonstrating rapid growth, pain, or changes in surface morphology, and reinforces the critical role of histopathological evaluation. Inflammatory and reactive dermatoses constituted a significant portion of the lesions, accounting for 24% of the cohort. Their relatively high frequency highlights the diagnostic challenges these entities pose clinically, often necessitating histological confirmation in the context of chronic or treatment-resistant cutaneous presentations [21]. In contrast, vascular lesions and other benign entities such as seborrheic keratosis and verruca vulgaris were encountered less frequently, though they remain clinically significant for differential diagnosis, particularly in lesions with ambiguous or overlapping features. The pediatric subgroup, although limited in size, demonstrated a distinct lesion distribution compared to adults, with pilomatrixomas and keratinous cysts being predominant. This suggests the presence of age-related variation in lesion types, and reinforces the need for age-specific diagnostic considerations when evaluating skin biopsies in children.
Several limitations must be acknowledged. The study's retrospective design, single-center scope, and modest pediatric sample size may introduce referral and selection biases. Moreover, the lack of molecular or immunohistochemical analyses, such as β-catenin staining for pilomatrixomas, limited the potential for in-depth diagnostic subclassification and pathogenetic insight [36]. These constraints highlight avenues for future research, particularly involving multi-institutional collaboration, prospective enrollment, and integration of molecular diagnostics. Despite these limitations, the current study provides valuable regional data on the histopathological patterns of non-neoplastic skin lesions. The demographic and anatomical trends documented herein offer practical insights for both clinicians and pathologists, facilitating improved diagnostic accuracy, clinical correlation, and management strategies in dermatopathology practice.
This study highlighted the predominance of benign cystic lesions, particularly epidermal inclusion cysts, among non-neoplastic cutaneous biopsies in a South Kashmiri population. The observed male predominance and age-related lesion distribution are consistent with existing literature and may reflect underlying hormonal, genetic, or environmental factors. The relatively high frequency of pilomatrixomas, especially in the pediatric group, underscores the need for early clinical recognition and referral in younger patients presenting with subcutaneous nodules. Although rare, the identification of malignant transformation in an epidermal cyst reinforces the importance of histopathological evaluation, even in seemingly benign lesions. Inflammatory and reactive dermatoses formed a notable subset, emphasizing the diagnostic value of skin biopsies in clinically ambiguous cases. While the study’s retrospective, single-center design and limited pediatric sample present inherent limitations, it nonetheless provides meaningful regional insights into the histopathological spectrum of non-neoplastic skin lesions. These findings contribute to better diagnostic stratification and clinical decision-making, and they lay the groundwork for future research involving molecular profiling and broader population-based analyses.
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