An Institutional Experience

Original Research Article

Skin Adnexal Tumors- An Institutional Experience

1 2* 3 4 5 6 Rekha M Haravi , Roopa K N , Priya Patil , Rujuta Datar , Meena N Jadhav , Shreekant K Kittur

1,5Associate Professor, 2Post Graduate Student, 3,4Assistant Professor, 6Professor & HOD, Department of Pathology, Belgaum Institute of Medical Sciences Dr B R Ambedkar Road, Belagavi, Karnataka – 590001, INDIA. Email: [email protected] Abstract Background: Skin adnexal tumors are a wide spectrum of benign and malignant tumors that differentiate towards one or more adnexal structures found in normal skin. The adnexal structures of skin are the hair follicles, sebaceous glands, eccrine and apocrine sweat glands. These skin adnexal tumors are often difficult to diagnose clinically. This retrospective study was undertaken to know the various histomorphological patterns of skin adnexal tumors at our institution and to determine the incidence among the genders and age groups along with the site distribution. Materials and methods: A total of 40 specimens received and diagnosed as skin adnexal tumors in the department of Pathology at Belgaum Institute of Medical Sciences, Belagavi for a period of 6 years from January 2014 to December 2019 were taken for the study. Histopathological slides prepared from tissue blocks retrieved from departmental archives were reviewed and classified according to the WHO classification 2017. Results: Out of the total 40 samples, benign tumors were 36 (90%) and malignant were 4 (10%). Largest group was the benign tumors of apocrine and eccrine differentiation (47.5%) followed by benign tumors of hair follicle differentiation (40%). Malignant tumors of sebaceous differentiation were 5%, malignant tumors of eccrine and apocrine differentiation were 2.5% and malignant hair follicle differentiation tumors were 2.5% of the total. Conclusions: Benign skin adnexal tumors were more compared to malignant tumors with most common being tumors of eccrine and apocrine origin. Keywords: Benign, histopathology, malignant, skin adnexal tumors

*Address for Correspondence: Dr Roopa K N , W/O Dr Sukumara S, # 4233, Jayapriya Heights, Pipeline road, Bagalagunte, Near Mallasandra Government Hospital, Jalahalli West, Bengaluru- 560057, Karnataka, INDIA. Email: [email protected] Received Date: 23/09/2020 Revised Date: 14/10/2020 Accepted Date: 19/11/2020 DOI: https://doi.org/10.26611/1051723 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

diagnostic confirmation.2 Certain specific types of tumors Access this article online may be associated with some complex genetic syndromes Quick Response Code: like Cowden’s syndrome, Muir Torre syndrome, Myotonic dystrophy, Skull dysostosis, and Trisomy 9.3 Website: www.medpulse.in In Indian population, the overall incidence of skin adnexal tumors is very low.4 These tumors have variable histomorphological patterns, due to which the histological diagnosis can be challenging, yet histopathological Accessed Date: diagnosis plays the main role in the diagnosis of skin 22 February 2021 adnexal tumors. Fewer studies have been conducted on the histomorphological patterns of various skin adnexal tumors. Literature review has shown tumors of different INTRODUCTION adnexal structures predominating at different institutions. Skin adnexal tumors are a wide spectrum of benign and This study is undertaken to know the various malignant tumors that differentiate towards one or more histomorphological patterns of skin adnexal tumors at our adnexal structures found in normal skin.1 The adnexal institution and to determine the variation in incidence structures of skin are the hair follicles, sebaceous glands, among the genders and age groups along with the site eccrine and apocrine sweat glands. These skin adnexal distribution. tumors are often difficult to diagnose clinically. Histopathology and immunohistochemistry provide MATERIALS AND METHODS

How to cite this article: Rekha M Haravi, Roopa K N, Priya Patil, Rujuta Datar, Meena N Jadhav, Shreekant K Kittur. Skin Adnexal Tumors- An Institutional Experience. MedPulse International Journal of Pathology. February 2021; 17(2): 31-35. https://www.medpulse.in/Pathology/ MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 17, Issue 2, February 2021 pp 31-35

Source of data: All specimens received and diagnosed as and histopathology requisition forms. Tissue blocks of skin adnexal tumors in the department of Pathology at these cases were retrieved from the departmental Belgaum Institute of Medical Sciences, Belagavi for a archives. Histopathological slides were prepared from period of 6 years from January 2014 to December 2019. these blocks and stained with hematoxylin and eosin stain Method of collection of data: The total number of and reviewed. Special stains like Periodic acid Schiff, etc. specimens received from the Departments of was done wherever required. The tumors were analyzed Dermatology and venereology, General Surgery and considering their clinical features and histomorphological various other clinical departments to the Department of patterns and classified according to the WHO Pathology and diagnosed on histopathology as skin classification 2017. The collected data was presented in adnexal tumors were taken for this study. All clinical the form of percentage or proportions and graphs. details of the cases were noted down from the case files

OBSERVATION AND RESULTS

Figure 1

A C

Figure 2 Figure3 Figure 4 Figure 5 Figure 6 Figure 7

Figure 1: Case distribution based on appendageal differentiation; Figure 2: Microphotograph showing Pilomatrixoma with osseous metaplasia (H&E100x) ; Figure 3: Microphotograph showing Clear cell Hidradenoma (H&E 100x); Figure 4: Microphotograph showing Syringocystadenoma papilliferum (H&E 100x). Inset sowing plasma cells (H&E 400x); Figure 5: Microphotograph showing Primary Cutaneous Mucinous Carcinoma (H&E 100x). Inset (PAS 100x; Figure 6: Microphotograph showing PCMC – IHC- A: ER positive (400x), B: PR positive (400x), C: CK 7 positive (400x); Figure 7: Microphotograph showing Sebaceous Carcinoma (H&E 400x)

During the study period, 40 adnexal tumors of skin were 3 (7.5%) cases were diagnosed as tumors of sebaceous diagnosed on histopathological examination. Out of these, differentiation. Out of these 3 cases, 1 case was 37 cases (92.5%) were benign and 3 (7.5%) cases were Sebaceoma (2.5%) and the other 2 cases were sebaceous malignant. There were 19 (47.5%) benign sweat gland carcinoma (5%). (Table 1, Figure 1). tumors and 1 (2.5%) malignant sweat gland tumor. On the basis of their line of differentiation, the most Benign tumors included Clear cell hidradenoma (n=7, common group of tumors was of eccrine/ apocrine 17.5%), Poroma (n=1, 2.5%), Syringocystadenoma differentiation. (Table 1, Figure 1). papilliferum [SCAP] (n=5, 12.5%), papillary eccrine Most common age group affected ranged from 21-40 adenoma (n=2, 5%), Cylindroma (n=2, 5%) and apocrine years (35%) followed by 41-60 years of age (30%). Male: hydrocystoma (n=2, 5%). Malignant tumor was primary Female ratio was found to be 1.5: 1 with slight male cutaneous mucinous carcinoma [PCMC] (n=1, 2.5%). preponderance. Head and neck was the most common site (Table 1). affected (57%) with predominance in the facial region There were 17 (42.5%) benign tumors of hair follicle followed by trunk (17%), Upper limb (13%), Lower limb differentiation, out of which Pilomatrixoma constituted (10%) and Genitalia (3%). the majority (n=16, 40%) followed by proliferating trichilemmal tumor (n=1, 2.5%). (Table 1, Figure 1)

MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 17, Issue 2, February 2021 Page 32 Rekha M Haravi, Roopa K N, Priya Patil, Rujuta Datar, Meena N Jadhav, Shreekant K Kittur

DISCUSSION Table 1: Comparison of incidence of skin adnexal tumors in various published studies with the present study 1 2 3 7 Studies Kaur et al Radhika et al Sahu et al Garima et al Present study Commonest age 20-39 20-30 21-30 41-60 21-40 group(in years) Male: Female 1.03:1 0.7:1 1.7:1 1:1.3 1.5:1 Commonest site Head & Neck Head & Neck Scalp Head & Neck Head & Neck Benign tumors 82.72 % 77.14 % 78.33 % 96.5 % 92.5 % Malignant tumors 17.28 % 29.63 % 21.66 % 3.5 % 7.5 % Commonest line of Hair follicle Sweat gland Sweat gland Sweat gland Sweat gland differentiation (39.09 %) (48.57 %) (45 %) (49.12 %) (50 %) Commonest Pilomatrixoma (28.2%) Nodular hidradenoma, Poroma Pilomatrixoma Pilomatrixoma benign tumor Sebaceous nevus (14.2%each) (16.66 %) (26.2 %) (40 %) Commonest Sebaceous carcinoma Sweat gland Sebaceous Sebaceous Sebaceous malignant tumor (11.8%) carcinoma(11.4%) carcinoma(13.33%) carcinoma(3.5%) carcinoma (5 %) Differentiation Benign eccrine Clear cell hidradenoma 15.45 % 14.28 % 5 % 22.8 % Poroma 3.63 % - 16.66 % 3.5 % Syringoma 5.45 % 2.8 % 11.66 % - Spiradenoma 1.8 % 8.5 % 3.33 % 17.54 % Chondroidsyringoma 3.63 % - - - Malignant eccrine Primary mucinous - - - - carcinoma Porocarcinoma 0.9 % - 3.33 % - Hidradenocarcinoma - - 3.33 % - Adenoid cystic 2.72 % - 1.66 % - carcinoma Benign apocrine Syringocystadenoma 0.9 % - - - papilliferum Papillary eccrine - - - - adenoma Cylindroma 1.8 % 2.85 % - 1.75 % Apocrine - - - - hydrocystoma Hidradenoma - 8.5 % - 3.5 % papilliferum Malignant Adenocarcinoma 0.9 % - - - apocrine Hair follicle Pilomatrixoma 28.2 % 5.7 % 11.66 % 26.31 % Proliferating 2.72 % - 3.33 % 1.75 % (Benign) trichilemmal tumor Trichofolliculoma 1.81 % 2.8 % - 1.75 % Trichoblastoma - - 3.33 % -

Hair follicle Pilomatrix carcinoma 0.9 % - - - (Malignant) Tricholemmal - 5.7 % - - carcinoma Benign sebaceous Sebaceoma - - 3.33 % 1.75 % Sebaceous adenoma 0.9 % - 15 % 1.75 % Malignant sebaceous Sebaceous carcinoma 11.8 % 5.7 % 13.33 % 3.5 %

Skin adnexal tumors are thought to originate from multi are found to be important contributing factors in tumors potent undifferentiated stem cells. These cells have the having genetic basis. (9) Incidence and location of tumors capability to differentiate along particular or multiple vary in different regions and institutions as documented pathways. (3, 8) Mendelian inheritance and p53 mutations by several studies.

Copyright © 2021, Medpulse Publishing Corporation, MedPulse International Journal of Pathology, Volume 17, Issue 2 February 2021 MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 17, Issue 2, February 2021 pp 31-35

Clinically, tumors of hair follicle differentiation are hidradenoma (14.28%) as the most common tumor predominantly seen in the scalp region and less followed by Spiradenoma and hidradenoma papilliferum commonly over the trunk. Tumors of sebaceous gland (8.5% each) whereas Sahu et al (3) observed Poroma differentiation arise most commonly over the face with (16.66%) as the most common tumor overall followed by predilection to area around the eyelids. Among the sebaceous carcinoma (13.33%) (Table 1). eccrine/ apocrine tumors, Poroma is usually seen over There are very few studies in the literature from India that palms/ soles, hidradenomas over the scalp/ axilla, SCAP describe in detail about the skin adnexal tumors. (2) Most and papillary eccrine adenoma over the scalp/ face, of the Pilomatrixoma cases that we encountered showed Cylindroma over the scalp and apocrine hydrocystoma the characteristic microscopic features like encapsulation, over the face, especially around the eyelids. (5) basaloid cells and ghost cells. Similar observations were In the present study, the site of predilection was head and made by Kaur et al (1), Radhika et al (2) and Sahu et al (3). neck region similar to observation made by Kaur et al (1), Few of the cases in our study showed foreign body giant Radhika et al (2) and Garima et al (7)(Table 1). cell reaction and calcification and one case showed We observed predominance of cases of Pilomatrixoma in ossification (Figure 2). Out of the 7 clear cell the head and neck region (43.75%), clear cell hidradenoma cases reported in the present study, all of hidradenoma in the lower limbs (57.14%), SCAP in the them showed dual population of cells on microscopy and head and neck region (80%), all cases of Cylindroma, 5 cases showed ductal differentiation and cystic change as Poroma and Proliferating trichilemmal tumor over the seen by other studies (1, 3) (Figure 3). There was one case scalp, all cases of Papillary eccrine adenoma, PCMC, of clear cell hidradenoma with mucinous metaplasia. Sebaceoma and Sebaceous carcinoma over the face and 1 .Radhika et al (2) encountered one case of papillary case each of apocrine hydrocystoma over back and labia hidradenoma. Out of the 5 cases of SCAP, 4 cases were minora. isolated lesions whereas 1 case was associated with The present study showed 21-40 years age group desmoplastic nevus. 3 cases showed verrucous to be the most commonly affected. This was similar to the presentation. The lesions on microscopy showed studies done by Kaur et al (1), Radhika et al (2) and Sahu et bilayered epithelial lining with cystic invaginations and al (3). The male: female ratio was found to be 1.5: 1 which dense plasma cell infiltration (Figure 4). These histologic was comparable to that of Sahu et al (3)and Kaur et al. (1) features were comparable to cases studied by Kaur et al. However, Garima et al(7) and Radhika et al (2) found (1) One case of PCMC was diagnosed with the help of female preponderance in their study (Table 1). Majority histochemical stains like Periodic acid Schiff, Alcian blue of the cases were benign (n=37, 92.5%) as seen by other at pH 2.5 and immunohistochemistry to rule out studies. (1,2,3,7) Sweat gland tumors constituted the largest metastatic mucinous carcinoma from other organs like group of tumors in the present study followed by tumors breast, lungs, colon, prostate and salivary glands. The of hair follicle differentiation. Similar observations were present case showed ER, PR and CK 7 positivity and reported by Radhika et al (2), Sahu et al (3) and Garima et TTF-1, Napsin, CDX2, CK 20 and PSA negativity al(7) in their studies. Pilomatrixoma (40%) was the most (Figure 5). Cases of Cylindroma showed the pathognomic common benign tumor encountered in our study which features of jigsaw pattern of arrangement of cells, also was also seen in studies done by Kaur et al (1)and Garima observed by Kaur et al (1). Irregularly shaped tubular et al (7). Radhika et al (2) reported Nodular hidradenoma structures with bilayered epithelium and papillary and sebaceous nevus as the commonest benign tumor infoldings were seen in cases of papillary eccrine (14.2% each). Poroma was reported as the most common adenoma. Broad fronds of anastomosing bands of benign tumor by Sahu et al (3)in their study. Sebaceous epithelial cells with connection to the epidermis were carcinoma was the most common malignant tumor seen in case of Poroma. Cystic space with columnar observed in our study which was comparable to most of lining and decapitation secretion were seen in cases of the other studies. (1, 3, 7) However, Radhika et al (2) found apocrine hydrocystoma. The case of proliferating sweat gland carcinoma as the most common malignant trichilemmal tumor showed multiple squamous epithelial tumor. (Table 1) lined cysts with amorphous keratin filled lumens similar In the present study, the overall predominance to the case diagnosed by Sahu et al (3). Proliferating was seen by Pilomatrixoma (40%) followed by clear cell trichilemmal tumors may mimic squamous cell carcinoma hidradenoma (17.5%). Kaur et al (1) and Garima et al (7) grossly and hence, histopathological examination helps in also found similar observation in their studies with accurate diagnosis. Majority of basaloid cells with few Pilomatrixoma being 28.2% (1) and 26.31% (7), and clear islands of sebaceous cells were seen in the case of cell hidradenoma being 15.45% (1) and 22.8% Sebaceoma diagnosed in the present study. Sebaceous (7)respectively. Radhika et al (2) reported clear cell carcinoma was the most common malignant tumor and

MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 17, Issue 2, February 2021 Page 34 Rekha M Haravi, Roopa K N, Priya Patil, Rujuta Datar, Meena N Jadhav, Shreekant K Kittur showed sheets and irregular lobules of atypical cells with 2. Radhika K, Phaneendra BV, Rukmangadha N, Reddy bubbly cytoplasm (Figure 6). It is important to MK. A study of biopsy confirmed skin adnexal tumors: differentiate them from basal cell carcinoma with experience at a tertiary care teaching hospital. J Clin Sci Res 2013;2:132-8. sebaceous differentiation and squamous cell carcinoma 3. Alka Sahu, Dilip KS, Salil KN, Kailash CA. Skin adnexal with hydropic change and IHC plays a role in diagnosis. tumors: A histopathological study of 60 cases at a tertiary Various other skin adnexal tumors of benign and care centre. Annals of Pathology and Laboratory malignant nature were encountered by other studies (1, 2, 3, Medicine 2018;5(3):A-215-20. 7) (Table 1). 4. V Srinivas Kumar, V Geeta, Nikhil Kumar Voruganti, O Shravan Kumar, Tamilarasi. Histopathological study of skin adnexal tumors-A ten years study. IAIM CONCLUSION 2018;5(10):95-100. Incidence of skin adnexal tumors is low and are 5. Campbell LS, Roberto AN, John TS. Tumors of challenging to diagnose due to many overlapping epidermal appendages. In: David E Elder editor. Lever’s histopathological features. Benign skin adnexal tumors histopathology of the skin. 11th edn. Philadelphia:Wolters Kluver;2015 are more common than malignant tumors with a 6. Elder DE, Massi D, Scolyer RA, Willemze R, editors. predilection to male gender. Occur most commonly in the WHO Classification of skin tumors. 4th edn. head and neck region, most commonly in the 20-40 years France:IARC;2018 age group followed by 41-60 years. Clinical history and 7. Garima, Neelu Gupta, Sunita Kulhari. A prospective histopathological examination supported by study of histomorphological spectrum of biopsy histochemical stain and immunohistochemistry plays a confirmed skin adnexal tumors in a tertiary care centre at Bikaner region. International Journal of Contemporary major role in diagnosing the skin adnexal tumors. Medical Research 2019;6(4):D4-D7. 8. Santa Cruz DJ. Tumors of the skin. In: Fletcher CD, REFERENCES editor. Diagnostic histopathology of tumors. 3rd ed. Vol 1. Kaur K, Gupta K, Hemrajani D, Yadav A, Mangal K. 2. Philadelphia: Churchill Livingstone Elsevier; 2007. p Histopathological analysis of skin adnexal tumors: A 1423-526. three year study of 110 cases at a tertiary care center. 9. Perez MI, Robins P, Biria S, Roco J, Siegel E, Pellicer Indian J Dermatol 2017;62:400-6. A. P53 oncoprotein expression and gene mutations in some keratoacanthomas. Arch Dermatol 1997; 133: p 189-93.

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