Adnexal Skin Tumors; A Histopathological Review of 64 Cases

Academic Journal of Medical Sciences ISSN: 2708-2725 ORIGINAL ARTICLE AJMS | 35 Adnexal Skin Tumors; A Histopathological Review of 64 Cases Taif Ali Mohammed Ali1*, Prof. Dr. Asaad Abdul Hamza Hasani Al-Janabi 2, Aseel Abd Al-Zahra Alqzweni3, Liqaa Mohammed Muslim4 ABSTRACT Author’s Information 1.M.B.Ch. B, Resident physician, Candidate of the Arab Board of Health Specialization in Pathology, Al-Sader Medical City, Najaf-Iraq 2.M.B.Ch. B, M.Sc., PhD, Professor in Pathology (Histopathology), Department of Pathology, Faculty of medicine, University of Kufa 3.M.B.CH.B, F.I.C.M.S (path), Specialist pathologist, Department of Histopathology, Al-Sader Medical City, Al-Najaf, Iraq 4. M.B.CH.B, F.I.B.M.S (path), Specialist pathologist, Department of Histopathology, Al-Sader Medical City, Al-Najaf, Iraq Corresponding author: Taif Ali Mohammed Ali [email protected] Background: Most adnexal tumors are benign and do not carry a risk of recurrence, however, according to the histological origin, these tumors show histological overlapping, therefore, are usually misdiagnosed clinically and often further workup for conformation is required. Objective: To highlight the spectrum of histopathological features of adnexal skin tumors and to categorize these tumors histologically according to World Health Organization (WHO) classification. Materials and Methods: This was a retrospective cross-sectional study, carried out in AlNajaf center of histopathology, Najaf, Iraq. It included sixty-four registered cases of adnexal skin tumors diagnosed between January 2020 and August 2024 at our center. Histopathological examination was performed using tissue sections that fixed with formalin and embedded by paraffin , the hematoxylin and eosin used in staining of these sections. Clinical data and provisional diagnoses were reported from the archive of pathology unit. Histopathological reexamination of these tumors concerning on cell differentiation was carried out for all cases. Results: A total of 64 biopsies of skin tumors were diagnosed as adnexal tumors. The studied group composed of 25 males and 39 females (Male: Female ratio was 1:1.56). Among cases, (23.4%) at the 6th age group. Head and neck are the most affected sites (64%), followed by extremities (18.8%) and then trunk (17.2%). Benign and malignant tumors contributed for (71.9%) and (28.1%), respectively. Sweat gland differentiation contributed for (57.8%), hair follicle differentiation (39.1%) and sebaceous differentiation accounted for (3.1%). Hidradenoma was most common benign adnexal tumor followed by pilomatrixoma. Conclusion: we find through the histopathological review of adnexal skin tumors emphasized that these tumors are rare and have a wide spectrum of morphology and workup including IHC study is essential for confirmation of the diagnosis. Funding information Self-funded Conflict of interest None declared by author DOI: 10.5281/zenodo.16736841 Keywords: Adnexal Skin Tumors, Morphology Histopathological evaluation This article is open access published under CC BY-NC Creative Commons Attribution Non-Commercial License: This License permits users to use, reproduce, disseminate or display the article provided that the author is attributed as the original creator and that the reuse is restricted to noncommercial purposes, (research or educational use). Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS | 36 1. INTRODUCTION The adnexa are epidermal apparatus of the skin and consisting of hair follicles, sebaceous and sweat glands. Rather than the mature cells located in within the epidermis or appendageal structures, tumors of these adnexa arise from multipotent stem cells (1-3). It has been evident that neoplastic transformation of these elements may give rise to one or more differentiation lines of appendageal apparatus with different histological type (4-5). According to their origin, they may differentiate to a wide variety of tumors with evident of histological overlapping. So, they are usually misdiagnosed clinically and often further workup for conformation is required (6-7). The histological classification of these tumors is notably complex due to their shared origin, which results in overlapping histological features both within this group and with surface epidermal-type tumors (8-11). Accurate identification of their origin is crucial for determining the optimal management approach (12-13). Most of benign tumors do not carry a risk of recurrence, however, they may serve as markers for clinical syndromes linked to internal cancers, such as Cowden syndrome (14). The counterpart malignant adnexal tumors are rare and heterogeneous in their histological presentation. These are aggressive neoplasms with a propensity for nodal involvement and distant metastases, resulting in poor clinical outcomes (15-19). Consequently, diagnosing malignancy in adnexal tumors is crucial for treatment and prognosis considerations (20). Bernard Ackerman was the first to underscore the significance of architectural characteristics in differentiating between benign and malignant tumors. He has elucidated that benign tumors exhibit well-defined orientation and histological symmetry with homogeneous epithelial cells, dense fibrotic stroma devoid of atypia, necrosis, and mitotic activity, whereas malignant tumors display heterogeneous histological characteristics with asymmetry and all aforementioned traits (21). Depending on histological differentiation bases, adnexal tumors can be divided into 3 major groups with their characteristic features (15). Sebaceous glands tumors are characterized by vacuolated sebocytes. Sweat glands tumors are more frequent and composed of two types (eccrine and/or apocrine), characterized by ducts formation ranging from small to large dilated cystic spaces. The last entity are the hair follicles tumors. They are usually difficult to be recognized in histopathological evaluation as they represent a diverse histological group with Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 37 wide morphological overlapping (22). As a role in histological examination of adnexal tumors, ruling out sebaceous proliferations is of priority, followed by sweat glands. The last step in histopathology is to consider the possibility of hair follicle tumors. The prevalence of adnexal skin tumors is 1-2% worldwide. In Iraq, according to cancer registry of 2023, malignant skin tumors in general have formed 3.5% and 3.5/100,000 population, skin appendage carcinoma had formed 2.3% of all malignant skin tumors. Therefore, in this context, the objective of our study was to highlight the pathological variety and spectrum of adnexal tumors of the skin in respect to age, sex, location and histopathological pattern in our setting. 2. METHODOLOGY This was a cross-sectional retrospective observational study carried in AlNajaf center of histopathology, Najaf, Iraq. It included sixty-four cases of adnexal skin tumors diagnosed between January 2020 and August 2024 at our center. Histopathological examination was performed using tissue sections that fixed with formalin and embedded by paraffin, the hematoxylin and eosin used in staining of these sections. Clinical data included the age, sex and site of tumor were extracted from the archive of pathology in this center. Also, clinical provisional diagnoses were reported. Histopathological reexamination of these tumors concerning on cell differentiation was carried out for all these cases. The data analysis plan included using the SPSS software. Parametric and non-parametric statistical tests were applied according to the type of variables to assess the relationship between histopathological results and clinical at a level of significance of 0.05. 3. RESULTS During the studied period, a total of 64 biopsies of skin tumors were diagnosed as adnexal tumors during three years. Twenty-five patients (39.0%) were males and 39 patients (61.0%) were females. Male to female ratio was 1:1.56, with a significant difference between both gender in regard to the frequency of tumor, (P. value<0.05). Patients’ age ranged between 6 and 77 years and majority of patients at the age between the third and sixth decade, however, most of these tumors ( 23.4%) were reported in patients at the age group 51-60 years, followed by age group 41-50 (20.3% ), while less frequently presented tumors were seen in Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 38 other age groups as follow; 9 cases (14.1%) in age group 21-30, 7 cases (10.9%) in each age group 11-20 and 61-70 years, 6 cases (9.4%) in age group31-40 years, 4 cases (6.3%) in age group 71-80 years and lastly 3 cases (4.7%) in age group 1-10 years. Nonetheless, no significant difference in the frequency of tumors across all age groups, (P. value >0.05). The distribution of the tumors according to the site of their location showed that head and neck were the most affected sites (41 out of 64 cases) forming 64.1%, followed by extremities (12 cases) forming 18.8% and then trunk (11 cases) forming 17.2%. The origin of differentiation, was categorized into the following; sweat gland tumors which contributed for 57.8% of all tumor, hair follicle tumors (39.1%) and sebaceous glands tumors (3.1%). All aforementioned findings are summarized in (Table 1). In regard to the gender distribution of adnexal tumor in general, it has been found that sweat gland tumors were more frequently reported in females than males; (56.8%) vs. 43.2%, respectively. Hair follicle tumors were also reported in both genders; they formed 72.0% in females and 28.0% in males, however, no significant differences were found in the distribution of these two tumors across both genders. In contrast to both sweat glands tumors and hair follicles tumors, sebaceous glands tumors were less frequently reported in this study and interestingly found in male gender only. They formed 3.1% of the total adnexal tumors. A part from sebaceous glands tumors, there was no significant difference among these adnexal tumors in regard to their frequency and gender distribution (p value>0.05), (Table 2). Histopathological evaluation of all submitted cases in this study revealed that benign tumors were significantly the most frequent histological type, accounted for (46 out of 64 cases), and represented (71.9%), while the malignant tumors were less frequent, contributed for 28.1% (18/64) cases, (P. value <0.05) (Figure 1). From other point of view, benign adnexal skin tumors were significantly, (P. value<0.05), more frequently diagnosed in females (32 vs 14 cases), while malignant tumors were more frequently diagnosed in males (11 vs. 7 cases). Distribution of adnexal skin tumors according to age showed that these tumors were more frequently diagnosed in patients at earlier age groups (50 years and younger), (38/64), , (Table 3). Additionally, benign tumors were the more frequently diagnosed among cases aged 50 years and below, they formed 86.8% of patients in this age group, while 13.2% of cases in this age Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 39 group had malignant tumors. Malignant tumors were more frequently diagnosed in patients older than 50 years, compared to those younger than 50 years; 50% vs. 13.2%, respectively. The difference in the proportional distribution of benign and malignant tumors across the age groups was statistically significant, (P. value<0.05), (Table 3). Regarding the distribution of the site of adnexal skin tumors, head and neck sites were the more frequent in benign than malignant tumors, 75.6% vs. 24.4%, respectively, with significant difference (P. value <0.05). Trunk site was more frequently associated with benign tumors (63.6%) in contrast to malignant tumors (36.4%), furthermore, extremities sites were also found to be more frequently reported in benign tumors rather than malignant (66.7%) vs. 33.3%, respectively, (P. value<0.05), (Table 3). In regard to histopathological types of skin tumors, the results revealed that hidradenoma was the most frequent type of benign tumos17(37%), followed by pilomatricoma 11(23.9%). While sweat gland carcinoma was the most frequent type of malignant adnexial tumors 8(44.4%). By comparing the tumor types across gender, hidradenoma was more frequent among females; 11 (28.2%) cases, compared to 6 (24%) cases among males. Pilomatricoma tumors were also more frequent among females compared to males; where they reported in 8(20.5%) and 3 (12%), respectively. The trichoblastoma was found in 3 (7.7%) females and 1(4.0%) male. While other types showed variable frequency between both genders. In contrast, malignant adnexal tumors Sweat gland carcinoma, was more frequent in males with 5(20.0%) compared 3(7.7%) to in females. While other tumors showed variable frequency between both genders. The findings are shown in (Table 4 & Table 5) and (Figures 2, 3, 4 & 5). Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 40 Table 1. Demographic features of the studied 64 cases of adnexal skin tumors Characteristic feature No. % P. value Gender Male 25 39.1 <0.05 Female 39 60.9 Male: female ratio 1:1.56 Age(year) 1 - 10 3 4.7 11 - 20 7 10.9 21 - 30 9 14.1 31 - 40 6 9.4 >0.05 41 - 50 13 20.3 51 - 60 15 23.4 61 - 70 7 10.9 71 - 80 4 6.3 Site Head and neck 41 64.1 <0.05 Extremities 12 18.8 Trunk 11 17.2 Histopathology Benign 46 71.9 <0.05 Malignant 18 28.1 Origin of differentiation Sweat gland 37 57.8 <0.05 Hair follicles 25 39.1 Sebaceous gland 2 3.1 Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 41 Figure 1. Distribution of adnexal skin tumors according to the type Table 2. Distribution frequency of adnexal skin tumors according to gender. Gender Sweat glands Sebaceous glands Hair follicles P. value No. % No. % No. % Male (n=25) 16 43.2 2 8.0 7 28.0 <.0.05 Female (n=39) 21 56.8 0 0.0 18 72.0 > 0.05 Total 37 57.8 2 3.1 25 39.1 > 0.05 Male: female ratio 1.0: 1.3 2.0: 0.0 1.0: 2.6 > 0.05 Table 3. Distribution of benign and malignant adnexal skin tumors according to gender, age and site of tumor Variable Type of tumor Total P. value Benign Malignant No. % No. % Gender Male 14 56.0 11 44.0 25 <0.05 Female 32 82.1 7 17.9 39 Age (years) ≤ 50 33 86.8 5 13.2 38 <0.05 > 50 13 50.0 13 50.0 26 Site of tumor Head & neck 31 75.6 10 24.4 41 <0.05 Trunk 7 63.6 4 36.4 11 Extremities 8 66.7 4 33.3 12 46 71.9% 18 28.1% Benign Malignant Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 42 Table 4. Cross-tabulation for the relationship between gender and histopathological types of Benign adnexial skin tumors Gender Total (n=64) Benign tumors (n=46) Male (n=25) Female (n=39) No. % No. % No. % Hidradenoma 6 24 11 28.2 17 37 Pilomatricoma 3 12 8 20.5 11 23.9 Trichoblastoma 1 4 3 7.7 4 8.7 Proliferative pilar cyst 1 4 2 5.1 3 6.5 Chondroid syringma 0 0 3 7.7 3 6.5 Trichofolliculoma 0 0 2 5.1 2 4.3 Sebaceoma 1 4 0 0 1 2.2 Syringocystadenoma Papilliferum 1 4 0 0 1 2.2 Spiradenoma 0 0 1 2.6 1 2.2 Syringoma 0 0 1 2.6 1 2.2 Sebaceous adenoma 1 4 0 0 1 2.2 Trichelmmoma 0 0 1 2.6 1 2.2 P. value <0.05 significant Table 5. Cross-tabulation for the relationship between gender and histopathological types of Malignant adnexial skin tumors Gender Total (n=64) Malignant tumors (n=18) Male (n=25) Female (n=39) No. % No. % No. % Sweat gland carcinoma 5 20 3 7.7 8 44.4 Porocarcinoma 2 8 1 2.6 3 16.7 Malignant adnexal 2 8 0 0 2 11.1 Malignant pilar tumor 0 0 2 5.1 2 11.1 Trichilemmal carcinoma 1 4 0 0 1 5.6 Digital papillary ad. 0 0 1 2.6 1 5.6 Pilomatrix carcinoma 1 4 0 0 1 5.6 P. value <0.05 significant Mohammed Ali et al., AJMS 2025; 11 (3): 35-48 AJMS| 43 Figure 2: Hidradenoma is well circumscribes dermal mass showing both cystic & solid components. The cells polyhedral basophilic cells with hyalinized stroma. There are foci of glycogen containing clear cells with eccentric nucleus (as pointed by the arrow). At 4x H&E magnification. Figure 3: pilomatricomas showing lobulated dermal mass with eosinophilic shadow cells with central pallor indicating ghost nucleus as pointed by the arrow). At 4x H&E magnification.