Biomedicine and Chemical Sciences

The skin is the largest organ of the human body and serves as the primary protective barrier against physical, chemical, microbial, and environmental insults.[1] In addition to its barrier function, the skin performs several vital physiological roles, including thermoregulation, sensory perception, immune surveillance, vitamin D synthesis, and maintenance of fluid and electrolyte balance.[2] Owing to its complex structure and continuous exposure to external agents, the skin is susceptible to a wide spectrum of pathological conditions.[3] Non-neoplastic skin lesions constitute a heterogeneous group of disorders encompassing inflammatory, infectious, autoimmune, metabolic, degenerative, vascular, and hereditary diseases, many of which present with overlapping clinical manifestations.[4]

Dermatological disorders represent a major public health concern worldwide, accounting for a substantial proportion of outpatient consultations in both developed and developing countries.[5] The Global Burden of Disease Study identified skin diseases among the leading causes of non-fatal disability, emphasizing their considerable impact on quality of life and healthcare utilization.[6] Although many skin disorders can be diagnosed clinically, several diseases exhibit similar morphological features, making accurate diagnosis challenging.[7] Consequently, histopathological examination remains the gold standard for confirming the diagnosis, classifying disease entities, and guiding appropriate clinical management.[2]

Skin biopsy is an indispensable diagnostic tool in dermatopathology because it permits detailed evaluation of microscopic alterations involving the epidermis, dermis, and subcutaneous tissue.[3] Histopathological assessment not only confirms the clinical diagnosis but also differentiates disorders with similar clinical presentations, identifies disease activity, evaluates prognostic features, and facilitates the use of ancillary techniques such as special stains whenever indicated.[2] Clinicopathological correlation substantially improves diagnostic accuracy and therapeutic decision-making.[8]

The spectrum of non-neoplastic skin lesions varies considerably across different geographical regions because of differences in environmental conditions, genetic predisposition, occupational exposure, socioeconomic status, personal hygiene, nutritional status, and endemic infectious diseases.[4] In tropical countries such as India, infectious dermatoses continue to constitute a significant proportion of skin diseases, whereas inflammatory and autoimmune disorders are increasingly recognized because of improved healthcare access and diagnostic facilities.[9] Several hospital-based studies have demonstrated regional variations in the frequency and distribution of non-neoplastic skin lesions, emphasizing the importance of institution-specific epidemiological data for understanding local disease patterns.[10] Each region may exhibit distinct clinicopathological characteristics influenced by demographic and environmental factors.[11]

Histopathological studies describing the clinicopathological spectrum of non-neoplastic skin lesions remain limited in many tertiary care centres in South India.[12] Such studies provide valuable epidemiological information regarding disease distribution, age and sex predilection, anatomical site involvement, and histomorphological characteristics, thereby assisting dermatologists and pathologists in establishing accurate diagnoses and optimizing patient management.[3] Furthermore, the application of special histochemical stains, including Periodic Acid–Schiff (PAS), Modified Fite, Ziehl–Neelsen, and Van Gieson stains, enhances diagnostic precision in selected infectious and connective tissue disorders.

Therefore, the present study was undertaken to evaluate the histopathological spectrum of non-neoplastic skin lesions diagnosed at a tertiary care hospital, to analyse their demographic and clinicopathological characteristics, and to assess the role of histopathological examination and special staining techniques in establishing definitive diagnoses.

MATERIALS AND METHODS

Study Design

This cross-sectional observational study was conducted to evaluate the histopathological spectrum of non-neoplastic skin lesions in patients attending a tertiary care hospital.

Study Setting

The study was carried out in the Department of Pathology, S.V. Medical College, Tirupati, in collaboration with the Department of Dermatology, Sri Venkateswara Ramnarain Ruia Government General Hospital (SVRRGGH), Tirupati.

Study Period

The study was conducted over a period of two years, from May 2018 to April 2020.

Study Population

The study included patients presenting with clinically diagnosed non-neoplastic skin lesions who underwent skin biopsy during the study period. Clinical information, including age, sex, presenting complaints, and anatomical site of the lesion, was obtained from the case records. A total of 148 histopathologically confirmed cases of non-neoplastic skin lesions were included in the study.

Inclusion Criteria

• All biopsy specimens of non-neoplastic skin lesions received in the Department of Pathology, S.V. Medical College, Tirupati, during the study period were included.

Exclusion Criteria

The following specimens were excluded from the study:

• Autolysed specimens.
• Inadequate biopsy specimens.
• Biopsy specimens that did not demonstrate definitive histopathological evidence of a specific lesion.

Histopathological Examination

Skin biopsy specimens were fixed in 10% neutral buffered formalin immediately after receipt in the Department of Pathology. Following routine tissue processing, paraffin-embedded tissue blocks were prepared. Sections measuring 3–5 μm in thickness were cut using a rotary microtome and stained routinely with Haematoxylin and Eosin (H&E) for microscopic examination. Histopathological diagnosis was established based on characteristic morphological features.

Special Stains

Special histochemical stains were performed whenever required to confirm the diagnosis. These included Modified Fite stain for Mycobacterium leprae, Ziehl–Neelsen stain for acid-fast bacilli, Periodic Acid–Schiff (PAS) stain for fungal organisms, and Van Gieson stain for connective tissue abnormalities, depending on the suspected pathology.

Data Collection

The demographic characteristics, clinical presentation, anatomical site of involvement, and histopathological diagnosis were recorded in a predesigned proforma. The lesions were classified into various diagnostic categories based on their histopathological features for subsequent analysis.

Statistical Analysis

The collected data were compiled and analyzed using Statistical Package for the Social Sciences (SPSS) version 25.0. The results were expressed using descriptive statistics, including frequencies, percentages, tables, and graphical representations

RESULTS

During the study period from May 2018 to April 2020, a total of 188 skin biopsy specimens were received in the Histopathology Section of the Department of Pathology. Among these, 18 specimens were inadequate for processing and 22 biopsies showed inconclusive histopathological findings; therefore, these cases were excluded. The remaining 148 histopathologically confirmed non-neoplastic skin lesions constituted the study population.

The age of the patients ranged from 11 to 90 years, with a mean age of 42.4 years. The highest number of cases (26.4%) occurred in the 31–40 years age group, followed by the 41–50 years and 51–60 years age groups (15.5% each). Of the 148 patients, 78 (52.8%) were males and 70 (47.2%) were females, resulting in a male-to-female ratio of 1.1:1 (Table 1).

Table 1. Demographic Characteristics of Patients with Non-Neoplastic Skin Lesions (n = 148)

Mean age: 42.4 years

Male: Female ratio: 1.1:1.

The lower limb was the most frequently involved anatomical site (24.3%), followed by the upper limb (22.3%), while the trunk and generalized lesions each accounted for 17.6% of cases. Bilateral involvement (61.5%) was more common than unilateral involvement (38.5%) (Table 2).

Table 2. Anatomical Distribution of Non-Neoplastic Skin Lesions

Based on histopathological diagnosis, infectious diseases constituted the largest category of non-neoplastic skin lesions (55 cases; 37.2%). The second most common group comprised non-infectious erythematous and papulosquamous diseases (32 cases; 21.6%), followed by non-infectious vesiculobullous and vesiculopustular diseases (22 cases; 14.9%). Connective tissue diseases accounted for 12 cases (8.1%), metabolic diseases for 10 cases (6.8%), congenital disorders for 5 cases (3.4%), vascular diseases for 4 cases (2.7%), non-infectious granulomas for 3 cases (2.0%), inflammatory diseases of the subcutaneous fat for 3 cases (2.0%), and degenerative disorders as well as inflammatory diseases of the skin adnexa each accounted for one case (0.7%) (Table 3).

Table 3. Histopathological Spectrum of Non-Neoplastic Skin Lesions

Analysis of age distribution demonstrated that infectious skin diseases were most frequently observed during the fourth decade of life, whereas non-infectious erythematous and papulosquamous disorders occurred predominantly between 21 and 70 years. Non-infectious vesiculobullous and vesiculopustular diseases were mainly encountered between 31 and 60 years of age.

Among the 32 cases of non-infectious erythematous and papulosquamous diseases, lichen planus was the predominant diagnosis, accounting for 20 cases (62.5%), followed by psoriasis (4 cases; 12.5%) and prurigo nodularis (3 cases; 9.4%). The remaining cases included lichen nitidus, urticaria, erythema annulare centrifugum, and pityriasis rosea. Lichen planus was more frequently observed in males and occurred predominantly during the third and fourth decades of life (Table 4).

Table 4. Distribution of Non-Infectious Erythematous and Papulosquamous Diseases (n = 32)

Among the 22 non-infectious vesiculobullous and vesiculopustular disorders, pemphigus was the most common lesion (12 cases; 54.5%), followed by bullous pemphigoid (8 cases; 36.4%). Lichen simplex chronicus and erythema multiforme accounted for one case each. These disorders showed a slight male predominance and were most frequently diagnosed during the fourth decade of life (Table 5).

Table 5. Distribution of Non-Infectious Vesiculobullous and Vesiculopustular Diseases (n = 22)

Among the 55 infectious skin lesions, leprosy was the predominant diagnosis, accounting for 48 cases (87.3%). Tuberculosis and molluscum contagiosum each accounted for 3 cases (5.5%), while tinea corporis constituted 1 case (1.8%). Infectious lesions were more common in males and were predominantly observed during the third and fourth decades of life (Table 6).

Table 6. Distribution of Infectious Skin Lesions (n = 55)

Among the 48 cases of leprosy, borderline tuberculoid (BT) leprosy was the commonest subtype (22 cases; 45.8%), followed by lepromatous leprosy (7 cases; 14.6%), tuberculoid leprosy (6 cases; 12.5%), borderline lepromatous leprosy (4 cases; 8.3%), and indeterminate, mid-borderline, and histoid leprosy, each accounting for 3 cases (6.3%). Borderline tuberculoid leprosy predominantly affected males and was most frequently encountered during the third decade of life (Table 7).

Table 7. Histopathological Types of Leprosy (n = 48)

DISCUSSION

The present study analysed the clinicopathological spectrum of 148 biopsy-proven non-neoplastic skin lesions over a two-year period at a tertiary care centre. The highest incidence was observed in the fourth decade of life, which is in agreement with the studies by Adhikari et al.[14] and Rajput et al.,[15] whereas Veldurthy et al.[16] and Ogun and Okoro[13] reported a peak incidence in the third decade.The predominance of middle-aged adults may be attributed to increased occupational and environmental exposure, leading to a higher likelihood of developing inflammatory and infectious dermatoses.

A slight male predominance (male:female ratio 1.1:1) was observed in the present study, comparable to the findings of Adhikari et al. [14]and Kumar et al. [17]. In contrast, Ogun and Okoro [13] and Veldurthy et al. [16] reported female predominance. Gender differences in the occurrence of skin diseases have also been described by Chen et al., suggesting that biological, hormonal, behavioural, and healthcare-seeking factors may contribute to variations in disease distribution between males and females. [18] These differences may reflect variations in healthcare-seeking behaviour, occupational exposure, and the prevalence of infectious dermatoses among different study populations. The lower extremity was the most frequently affected site, unlike the study by Adhikari et al., in which the upper extremity was the predominant site.[14]

Infectious dermatoses constituted the largest group (37.2%) in the present study, with Hansen's disease accounting for the majority of cases. Similar observations were reported by Adhikari et al., [14] whereas Ogun and Okoro [13] identified viral infections as the most frequent infectious lesions.Borderline tuberculoid leprosy was the predominant histological subtype, reflecting the disease pattern commonly encountered in endemic regions. These findings highlight the continuing public health importance of leprosy and the pivotal role of histopathological examination in disease classification, particularly in clinically equivocal cases.

Non-infectious erythematous, papular, and squamous disorders represented the second most common category (21.6%), with lichen planus being the predominant lesion. This observation is comparable to the findings of D'Costa et al., whereas Hosamane et al. reported psoriasis as the most frequent papulosquamous disorder.[20,21] Differences in disease distribution may be related to regional and demographic variations. Histopathological examination remains indispensable in distinguishing papulosquamous disorders with overlapping clinical features and in establishing a definitive diagnosis.

Non-infectious vesiculobullous and vesiculopustular disorders accounted for 14.9% of all lesions. Pemphigus vulgaris was the most common lesion, consistent with the observations of Garg et al.[22] Bullous pemphigoid was the second most frequent disorder. Histopathological examination provided a reliable diagnosis in most cases, while immunopathological investigations may be reserved for diagnostically challenging lesions.

Connective tissue disorders constituted 8.1% of all cases, with morphea being the predominant lesion, similar to the findings reported by Karumbaiah et al.[23] Although females predominated in their study, a slight male predominance was observed in the present series. Genodermatoses were relatively uncommon (3.4%), with porokeratosis representing the most frequent lesion, consistent with Adhikari et al. In contrast, Dalave et al. reported ichthyosis as the predominant congenital dermatosis in a paediatric population.[14,19] These differences are likely attributable to variation in the age groups included in the respective studies.

Vascular disorders, non-infectious granulomas, degenerative and perforating disorders, inflammatory diseases of the skin adnexa, metabolic disorders, and inflammatory diseases of the subcutaneous fat constituted only a small proportion of cases. Although individually uncommon, accurate histopathological diagnosis was essential because these entities frequently mimic other inflammatory dermatoses clinically and require distinct therapeutic approaches.[25–28]

CONCLUSION

The present study demonstrated that infectious dermatoses were the most common category of non-neoplastic skin lesions, with leprosy being the predominant infectious disease and borderline tuberculoid leprosy the most frequent histopathological subtype. Among the non-infectious lesions, lichen planus was the commonest papulosquamous disorder, while pemphigus was the predominant vesiculobullous disease. A slight male predominance was observed, with the highest incidence occurring during the fourth decade of life.

Histopathological examination remains an indispensable tool for the accurate diagnosis and classification of non-neoplastic skin lesions, particularly in cases with overlapping clinical features. Careful clinicopathological correlation enhances diagnostic accuracy, facilitates appropriate patient management, and provides valuable epidemiological information on the spectrum of non-neoplastic skin lesions encountered in a tertiary care hospital.

DECLARATIONS

Funding: None.

Conflict of Interest: The authors declare no conflict of interest.

Ethical Approval: The study was conducted in accordance with applicable ethical standards and approved by the appropriate ethics committee where required.

Informed Consent: Informed consent was obtained from all participants involved in the study where applicable.

Author Contributions: All authors contributed to the study conception, design, data collection, analysis, manuscript preparation, and approved the final version of the manuscript.

Data Availability: Data supporting the findings of this study are available from the corresponding author upon reasonable request.

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