Skin is more than just a protective bodily covering. It is the largest and most sophisticated sensory organ of human body, and plays a crucial role in vitamin D synthesis.1Soft tissue refers to the non-epithelial extra-skeletal tissues of the body, excluding organ support tissue and hematopoietic/lymphoid tissue.2 The incidence of skin cancer is relatively low in India compared to Western countries, accounting for roughly 1 to 2% of all cancers.3 Skin and soft tissue tumors represent a broad and diverse collection of cutaneous and mesenchymal extra-skeletal tumors in humans. Skin and soft tissue tumors can develop anywhere on the body, including the extremities, trunk, retroperitoneum, head and neck.4,5 Skin tumors can affect persons across all age groups and can be benign or malignant. Skin cancers are caused by a mixture of genetic, chemical, hormonal, dietary, viral and environmental variables that act together synergistically in susceptible individuals.6 Skin tumors are generally classified as surface epidermal tumors, melanocytic tumors and tumors of epidermal appendages. Clinically they may present as papules & nodules.7,8Coloured or inflamed tumor-like lesions can be misdiagnosed as malignancy, necessitating histopathological evaluation of biopsy specimens to confirm the diagnosis.9 Clinical diagnosis alone is often not conclusive; therefore, histological confirmation is required for a definitive diagnosis and remains the gold standard despite challenges posed by wide morphological diversity, complexity of histologic nature, complex nomenclature, varying classification systems, and disagreements over histogenesis.7,8 Hence, the present study was undertaken to assess the frequency and histomorphological spectrum of skin and soft tissue tumors in relation to demographic profile and site of occurence. AIM & OBJECTIVES • To study the frequency and histomorphological patterns of skin and soft tissue tumors experienced at our centre. • To study their demographic profile and site of occurrence.

A prospective observational single-centric study was conducted between the period of July 2021 to June 2024. Prior to the start of the study, approval was obtained from the Institutional Ethical Committee. The following inclusion & exclusion criteria stated below, were used INCLUSION CRITERIA  All excisional and incisional biopsies and resected specimens of skin and soft tissue tumors belonging to all age groups and both sexes.  Tumors of epidermis, melanocytes and tumors of skin appendages and subcutaneous tissue EXCLUSION CRITERIA  Specimens with inadequate patient’s information  Skin secondaries  Haemato-lymphoid tumors METHODOLOGY All specimens were received in 10% formalin and were routinely processed. Sections of 3-5micrometre thickness were cut and stained with H&E. Immunohistochemistry was deployed in selected cases wherever necessary. Clinical and demographic data was obtained from requisition forms. All tumors were classified into benign, intermediate and malignant categories and typing was done according to WHO classification. STATISTICAL ANALYSIS All the collected data was compiled and entered in Microsoft excel sheet and statistical analysis was carried out using SPSS (version 22). Frequencies and percentages were calculated for categorical variables. Results were presented in the form of tables and charts.

Among all 11,100 specimens received during study period, 218 cases (1.96%) were diagnosed as skin and soft tissue tumors. We found that the age range of the patients was between 2 to 87 years with a mean of 45.78 ± 13.31 years. We also noted a higher preponderance of these tumors during the 5th and 6th decade of life, together accounting for 59.2% of cases. With respect to gender distribution, 113 (51.8%) were males and 105 (48.2%) were females with an M:F ratio of 1.1:1 (Table 1). Table 1: Age and Gender distribution of skin and soft tissue tumors Irrespective of the gender, the most commonly affected site was the head and neck region with 70 cases (32.1%), followed by upper limb (25.2%) and trunk (19.72%). The head and neck region was the most common site of involvement observed in 32.7% of males and 26.6% of females. In contrast, the upper limb was more frequently affected in females (27.6%) compared to males (23%) (Fig:1). Fig 1: The distribution of skin and soft tissue tumors according to anatomical site and gender Benign tumors (63.3%) outnumbered the malignant ones (36.7%) with soft tissue tumors forming majority (52.75%) followed by epidermal tumors (22.48%), adnexal tumors (18.80%) and melanocytic tumors(5.96%). Among 138 benign tumors, soft tissue tumors were most common (89/138, 40.8%) followed by adnexal tumors (36/138). Among 80 malignant tumors, epidermal carcinomas (38/80, %) were more common followed by soft tisue sarcomas(26/80). (Table:2). Table 2: Pattern of distribution of benign and malignant skin and soft tissue tumors Almost equal numbers of males (25) and females(24) were affected by benign skin tumors and were spread across with no single subtype extremely common in either gender. Among 36 benign adnexal tumor category, sweat gland tumors (23/36) were most frequent, followed by hair follicle and sebaceous tumors. (Table 3) Table 3: Distribution of benign skin tumors according to histological subtype Table 4: Frequency distribution of benign soft tissue tumors of skin Among benign soft tissue tumors of skin (89 cases), lipoma and its variants were most common subtype (57.3%), followed by nerve sheath tumors (17.9%) and fibroblastic tumors (11/89) and vascular tumors (10/89) (Table:4) Table 5: Frequency distribution of malignant tumors of skin Among 54 malignant skin tumors, epidermal tumors particularly basal cell carcinomas and squamous cell carcinomas were more common (47.5%) followed by malignant melanoma (11/54). (Table 5) Amongst 26 soft tissue sarcomas, dermatofibrosarcoma protuberans (73.1%), were predominant (Table 6). Table 6: Frequency distribution of intermediate and malignant soft tissue sarcomas of skin Fig 2 : Benign tumors of skin and soft tissue. (H&E) a) Seborrhoeic keratosis: showing numerous horn cysts. (H&E, 4x) , b) Cylindroma: showing jigsaw pattern with in the dermis. (H&E, 10x) , c) Hidradenoma : showing clear cells and polyhedral cells (H&E, 40x) , d)Neurofibroma: showing benign spindle cells proliferation. (H&E, 4x) , e)Proliferating trichilemmal tumour: showing copious trichilemmal type of keratinization. (H&E, 10x) , f)Glomus tumor: Showing sheets of glomus cells surrounding branching, capillary sized vessels. (H&E, 40x) , g)Granular cell tumor: Showing round to polygonal cells with abundant eosinophilic granular cytoplasm. (H&E, 4x) , h)Syringocystadenoma papilliferum : showing papillae lined by double layer of epithelium and stroma contain plasma cells. (H&E, 10x), i)Squamous cell papilloma: Showing multiple finger like projections covered by benign squamous epithelium. (H&E, 4x) , j)Intradermal nevus: showing nests and sheets of pigmented melanocytes in dermis. (H&E, 10x). Fig 3: Malignant tumors of skin and soft tissue tumors(H&E 40x) a)Basal cell carcinoma: Showing peripheral palisading arrangement of basaloid cells, b) Adenoid cystic carcinoma: composed of myoepithelial cells admixed with hyalinized globules, c) Squamous cell carcinoma: showing nuclear pleomorphism in squamous cells and many horn pearls, d)Dermatofibrosarcomaprotuberans: showing storiform pattern, e) Malignant melanoma: showing cytologic atypia, prominent nucleoli and melanin pigment, f)Malignant peripheral nerve sheath tumor: showing epitheloid cells.

Soft tissue is described as the tissue that supports numerous organs as well as non-epithelial, extra-skeletal structures that are not lymphohematopoietic. It consists of fibrous connective tissue, adipose tissue, skeletal muscle, blood/lymph vessels, along with the peripheral nervous system.2 Soft tissue tumours presents with an array of diseases that cultivate within the body's supportive soft tissues.10 Reportedly, the vast majority of soft tissue tumours are benign, with a very high cure rate following surgical resection. Nevertheless, malignant mesenchymal neoplasms account for less than 1% of the total human cancer burden, yet they are life-threatening and provide considerable diagnostic and treatment problems. The yearly clinical incidence of benign soft tissue tumors has been estimated to be up to 3000 per million population, accounting for less than 1% of all malignant tumors. 11 Apart from soft tissue neoplasms, both malignant and benign epithelial neoplasms can commonly affect the skin. It has been testified by researchers that benign epithelial neoplasms are frequent and usually harmless biologically, but they can cause severe psychological distress for the patient.6 Benign tumors of soft tissue are far more prevalent than benign tumors of bone. They can form in practically any location, including between and within muscles, ligaments, nerves, even blood vessels. These tumors vary greatly in appearance and behaviour. Certain cancers can be highly aggressive. Invasion of adjacent tissues raises the likelihood of a partial excision and the potential of the tumor recurring.12 Traditionally, cancers were classified based on histogenetic characteristics. Moreover, more than 50 histological subtypes of soft tissue tumorshave been frequently linked with distinct clinical, prognosis, and therapeutic characteristics. Immunohistochemistry is utilized to detect tumor-specific changes; however, several types of cancers still lack accurate immunohistochemical markers.13 Histologic analysis of a biopsy specimen is necessary to provide a definitive diagnosis & guide appropriate action and follow-up for pigmented or inflammatory lesions, which are frequently misdiagnosed as cancer.9 In our study, amongst 218 patients, 113 (51.8%) were males and 105 (48.2%) were females with an M:F ratio of 1.1:1, which was also agreed upon by Solanki P & Mangar U2with a ratio of 1.18:1. However, there was a slightly higher predominance noted by Myes DD et al.,14with a ratio of 1.27:1. There were contrasting results obtained by Duduyemi BM et al., 4 wherein there was a definite female predominance, accounting for a M:F ratio of 1: 1.2. Nevertheless, data reveals that most of the researchers such as Laishram SN et al.,15 Chakravarthy RC et al.,16 and Ahmed et al.,17 have reported a definite male predominance, which was also agreed upon by Solanki P & Mangar U2. In our study, the most commonly affected age range of the patients was found to be 2-87 years with a mean age of 45.78±13.31 years amongst the subjects. Also, the majority of tumors were seen in 4th decade of life, accounting to 38.1% of patients, followed by 21.1% in the 5th decade of life; totally accounting to approximately 60% of the patients. However, Duduyemi BM4 reported their mean age of subjects to be 33.52 ± 15.05 years, with peak age of occurrence being 30–39 years which was slightly less than that observed in our study with the age range of their patients being 4–85 years. On further analysis, we found that irrespective of the age, the most commonly affected site was the upper limb in 55 (25.2%) subjects, followed by the head region in 45 (20.6%) & the trunk region with 42 (19.3%) subjects. A similar study carried out by Duduyemi BM.,4 reported that the most common site for maximum no of cases, is to be the extremities (50.7%) followed by head (22.2%), whereas the least common sites were the perineal and neck areas (5.3% each). On carrying out a correlative analysis of the affected gender with the site, we noted that amongst either gender, the upper limb accounting to 55.2% cases was the most common site, trailed by the head (20.6%), and then the trunk area with 19.3% cases. Distributive, we noted the predominantly affected site amongst males to be the head (25.7%), followed by the upper limb (23.0%); whereas amongst females it was the upper limb (27.6%), followed by the lower limb (18.1%). Our results were in definite agreement with that of Duduyemi BM.,4 who found the commonest site in females to be the upper limb (32.4%) and the head and lower limb were the commonest sites in males (28.4% each). Benign epithelial neoplasms are not uncommon with an inconsequential biologic outcome, but may require intervention to relieve patient discomfort while eliminating the misunderstanding of such lesion/condition being malignancy. Characteristics such as pigmentation, inflammation, necessitates histologic examination of a biopsy specimen to render a definitive diagnosis with appropriate intervention and follow up.6 In our study, benign tumors were more common (64%) than malignant tumors, which was also agreed upon by Deychen D Myes14who found it to be61%, whereas Goel, et al.6 reported 53% benign tumors. Further, amongstbenignskin tumors; poroma accounted for14.3% of the tumors, trailed by seborrheic keratosis, sebaceoma, cylindroma in 12.2% of cases; which was also partially agreed upon by Myes DD et al.,14 who found seborrheic keratosis in 24.59%, as they found poroma and sebaceoma in only 1.6% cases, which is comparable to that of Kusumastuti et al.18 Lipomas are the most frequent mesenchymal neoplasm that can arise anywhere there is fat. The majority of soft tissue tumors are benign and have a high cure rate following surgical removal. Lipomas account for at least one-third of benign tumors, followed by fibrohistiocytic and fibrous tumors, 10% vascular, and 5% nerve sheath tumors.19Lipomas are painless, mostly occurs in fatty tissue like abdomen, thigh and back. It is rare in hands, lower legs and foot and very uncommon in children. Researchers have found that there exists a link between tumour kind, symptoms, location, and the patient's age and gender.2 Amongst benign soft tissue tumors we found lipoma accounting to 42.7% cases, followed by neurofibroma in 12.4% of the cases. In case of malignant tumors, we observed that 47.5% of the tumors were of epidermal origin; particularly basal cell carcinoma (46.3%) and squamous cell carcinoma (24.1%) were more common (47.5%); nevertheless Myes DD et al.,14 found keratinocytic malignant tumor in 66.64%, trailed by squamous cell carcinoma in 38.46% cases, and then basal cell carcinoma in 15.38% cases. Furthermore, in case of malignant soft tissue tumor; Dermatofibrosarcomaprotuberans accounted for73.1% of the tumors amongst our patients, followed by malignant peripheral nerve sheath tumor in 11.5%. Even though the incidence of malignant tumors are not as high as that of benign tumors, yet their consequential outcome are more deleterious and require early & rapid intervention. Therefore, early detection of the same is highly advocated. Even though clinical diagnosis provides us with a hypothetical provisional diagnosis, the underlying cellular changes points out towards an a more definitive diagnosis as the plethora of characteristics of the lesion/condition may lead to a more broader perspective in terms of diagnosis, Histopathology has been known for its high accuracy in determining the underlying disease whilst eliminating the other proximate diagnostic conditions, therefore it is still regarded as the gold standard test for diagnosis.

Skin and soft tissue tumors exhibited a diverse histological spectrum. In our study benign tumors outnumbered malignant ones having wide age range and slight male predominance. Head and neck region was the most common affected site. A wide histological diversity underlines the essential role of histopathology for accurate diagnosis and subtyping highlighting its indispensable role in clinical practice.

1. Pappala P, Raksha S, Vasundara G, Anusha P, Mohan KM. Histopathological study of skin tumours. Indian J Pathol Oncol. 2019 Nov 15;6(4):543-7. 2. Solanki P, Mangar U. Study of histopathological pattern of soft tissue tumours in tertiary care centre of Gandhi Nagar,Gujarat. Trop J Path Micro 2018;4(8):604-9. 3. Samanta M, Mangal N, Bhavani K, Koteeswaran G, Parmar PC. Histopathological study of skin tumours.Trop J Path Micro 2018;4(2):195-200. 4. Duduyemi BM, Omonisi AE, Titiloye NA. Skin and soft tissue lesions in a district hospital in Central Nigeria: a histopathological study. Dermatology research and practice. 2019;2019(1):8143680. 5. Masood QU, Mohammed UH, Karsan UN, Farouk K, Sharoz RM. Managing soft tissue sarcomas in a developing country: are prognostic factors similar to those of developed world? World Journal of Surgical Oncology. 2012;10(1):p. 188 6. Goel P, Kaur S, Garg A, Batra J, Garg B, Sood N. A clinicopathological study of skin tumors from a tertiary care centre in North India. Indian Dermatol Online J 2021;12:66-71. 7. Skin. Rosai and Ackerman’s Surgical Pathology. Elsevier ; 2011,. p.128–136. 8. Leboit PE, Burg G, Weedon D, Sarasin A. Pathology and genetics of skin tumours. In World health organisation classification of tumours. IARC press. Lyon ; 2006,. 9. Higginns JC, Maher MH, Douglas MS. Diagnosing common benign skin tumors. Am Fam Physician 2015;92:610‑7. 10. Agravat AH, Dhruva GA, Parmar SA. Histopathology study of Soft Tissue Tumours and Tumour like Lesions. J. cell and Tissue Research. 2010; 10(2):2287-92. 11. Fletcher CDM, Unni KK, Mertens F (Eds): WHO classification of tumors: Pathology and genetics of soft tissue and bones. IARC press, Lyon 2002;p12-6. 12. Marcus SG, Merino MJ, Glatstein E, et al. Long-term outcome in 87 patients with low-grade soft-tissue sarcoma. Arch Surg. 1993 Dec;128(12):1336-43. 13. Thway K. Pathology of soft tissue sarcomas. Clin Oncol (R Coll Radiol). 2009 Nov;21(9):695-705. 14. Myes DD, Shah T, Shah SA. Histopathological study of skin tumors: A 100 case study in a tertiary care hospital. International Journal of Clinical and Diagnostic Pathology 2022; 5(1): 39-42 15. Laishram et al., Pattern of skin malignancies in Manipur India, Journal of Pakistan association of Dermatologists. 2010;128-132 16. Chakravorty RC. Malignant neoplasms of the skin in Eastern India. Indian journal of cancer. 1968;5:13-144 17. Ahmed et al. Incidence of Squamous cell carcinoma in Karnataka, Global journal of medical research. 2014, XIV. 18. Kusumati. Cytological diagnostic accuracy in skin tumor, Folia Medica Indonesia, 49, 66-71 19. Chakrabarti PR, Chakrabarti S, Pandit A, Agrawal P, Dosi S, Jain MR. Histopathological study of soft tissue tumors: A three year experience in tertiary care centre. Ind J Pathol Oncol. 2015;2(3);141-9