Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(4):e2022222 1 Clinicopathological and Demographic Characteristics of Paget’s Disease: a 4-year Study Showing a Male Predominance in Extra-mammary Paget Kamran Balighi1,2, Yasamin Kalantari1,2, Kambiz Kamyab Hesari3, Vahide Lajevardi2, Hamidreza Kheiri2, Zeinab Aryanian1,4 1 Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Dermatopathology, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran 4 Department of Dermatology, Babol University of Medical Sciences, Babol, Iran Key words: paget, extramammary paget, mammary paget, Paget cells Citation: Balighi K, Kalantari Y, Kamyab Hesari K, Lajevardi V, Kheiri H, Aryanian Z. Clinicopathological and demographic characteristics of Paget’s disease: A 4-year study showing a male predominance in extra-mammary paget. Dermatol Pract Concept. 2022;12(4):e2022222. DOI: https://doi.org/10.5826/dpc.1204a222 Accepted: March 31, 2022; Published: October 2022 Copyright: ©2022 Balighi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Zeinab Aryanian, Assistant Professor of Dermatology, Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran; Department of Dermatology, Babol University of Medical Sciences, Babol, Iran, 1445613131, Iran. tel. 021-55630223. E-mail: z_aryanian@yahoo.com Introduction Paget disease is a rare skin neoplasm and is categorized into mammary (MPD) and extra-mammary (EMPD) [1,2]. To date, its detailed histopathological features along with patients de- mographic characteristics have not been investigated in Iran. In this study, we performed a clinic-pathological analysis of Paget cases in a single tertiary center between 2016 and 2020. Cases Presentation A total of 32 cases including 26 (81.25%) females and 6 (18.75%) males with the mean age of 53 ±9 .96 years (range 34-78) were included in our study. All patients gave informed consent for participating in our study. The ma- jority of our patients 26/32 (81.25%) had MPD, and 6/32 (8.75%) had EMPD. All cases had a history of scaly and erythematous prolonged lesions. Out of the 26 MPD cases, 25/26 (96.1%) were female and 1/26 (3.9%) were male. The mean age of the MPD cases was 51.03 ± 8.80 (range 34-78). Out of the 6 EMPD cases, 5/6 (83.3%) were male and 1/6 (16.7%) were female. The mean age of the EMPD cases was 61.5 ± 10.98 (range 42-74). Of note, all EMPD pa- tients had ano-genital involvement. 2/6 (33.33%) cases had scrotum EMPD, 1/6 (16.66%) patient had penis and scro- tum EMPD, 2/6 (33.3%) had peri-anal involvements, and 2 Research Letter | Dermatol Pract Concept. 2022;12(4):e2022222 1/6 (16.66%) patient had labia major EMPD. Histopatho- logical examination revealed the presence of cells with pale cytoplasm in addition to prominent nuclei along with a high nuclei cytoplasm ratio (N/C) in all 32 cases. Moreover, 10/32 (31.25%) had lymphocyte infiltration. IHC was performed for 6 EMPD patients and all of them were positive for CK7 and (CK AE3/AE1) (Table 1). Conclusions It is believed that Paget disease is more prevalent among older female patients [1-5]. The peak incidence of MPD is reported after the age of 60, while the mean age of the MPD patients in our study was 51 years [1]. Asian studies have shown a significant EMPD predom- inance in males and likewise, in our study, we found that the majority of EMPD patients were men, although, other studies have reported a higher prevalence of EMPD in fe- male patients [1]. The most common location for EMPD is the vulva in 65% of cases, perianal area, scrotum, penis, and axilla [1]. In this regard, the only female EMPD patient in our study had labia major involvement. Based on the Ghazawi et al study, the most common sites for EMPD in males are the scrotum and penis, which is consistent with the findings of our study [4]. The histologic hallmark of Paget disease is the presence of Paget’s cells [1]. In our study, the pathologic examina- tion revealed the presence of Paget cells in all cases along with lymphocytic infiltrations in one-third of patients. In a study done by Elbendary et al the histopathologic evaluation showed no significant differences between MPD and EMPD which is consistent with our study [5]. Our study confirms that MPD is more prevalent than EMPD. Based on our study, there is a female predominance in MPD cases at younger ages in comparison to other re- ports, and penis and scrotal involvements of EMPD are highly probable locations. Acknowledgment: The authors would like to thank the Au- toimmune Bullous Diseases Research Center, Tehran Univer- sity of Medical Sciences, Tehran, Iran for its technical and editorial assists References 1. Lopes Filho LL, Lopes IM, Lopes LR, Enokihara MM, Micha- lany AO, Matsunaga N. Mammary and extramammary Paget’s disease. An Bras Dermatol. 2015;90(2):225-231. DOI:10.1590/ abd1806-4841.20153189. PMID: 25830993. PMCID: PMC4371672. 2. Yasir M, Khan M, Lotfollahzadeh S. Mammary Paget Disease. 2021 Jun 2. In: StatPearls [Internet]. Treasure Island (FL): Stat- Pearls Publishing; 2021 Jan–. PMID: 33085375. 3. Shu B, Shen XX, Chen P, Fang XZ, Guo YL, Kong YY. Primary invasive extramammary Paget disease on penoscrotum: a clinico- pathological analysis of 41 cases. Hum Pathol. 2016;47(1):70-77. DOI: 10.1016/j.humpath.2015.09.005.. PMID: 26508372. 4. Ghazawi FM, Iga N, Tanaka R, et al. Demographic and clin- ical characteristics of extramammary Paget’s disease patients in Japan from 2000 to 2019. J. Eur. Acad. Dermatol. Vene- reol. 2021;35(2):e133-e135. DOI: 10.1111/jdv.16868. PMID: 32780877. 5. Elbendary A, Xue R, Valdebran M, et al. Diagnostic Crite- ria in Intraepithelial Pagetoid Neoplasms: A Histopathologic Study and Evaluation of Select Features in Paget Disease, Bowen Disease, and Melanoma In Situ. Am J Dermatopathol. 2017;39(6):419-427. DOI: 10.1097/DAD.0000000000000704. PMID: 28525420. Table 1. The results of immunohistochemistry staining. Number of patients that were assessed for the presence of this antigen Number of patients that were positive N (%) CK7 6 6 (100%) CK AE1/AE3 6 6 (100%) S100 3 2 (66.66%) CEA 6 5 (83.4%) Melan A 4 3 (75%) Ki-67 2 2 (100%) HMB-45 2 1 (50%)