Original StudyTwenty-Eight Cases of Extraocular Sebaceous Carcinoma: A Correlative Clinicopathological and Immunohistochemical Analysis of Extraocular Sebaceous Carcinomas and Benign Sebaceous Gland TumorsBoecker, Werner MD, PhD*,†,‡; Reusch, Michael MD†; Mielke, Volker MD†; Reusch, Ursula MD†; Hallermann, Christian MD, PhD†; Loening, Thomas MD, PhD‡; Tiemann, Markus MD§; Buchwalow, Igor PhD*,§Author Information *Gerhard-Domagk-Institute of Pathology, University of Muenster, Münster, Germany; †Dermatopathology Laboratory, Hamburg, Germany; ‡Gerhard-Seifert Referenzzentrum, Hamburg, Germany; and §Institute for Hematopathology, Hamburg, Germany. Correspondence: Igor Buchwalow, PhD, Institute for Hematopathology, Immunohistopathology, Fangdieckstreet 75a, 22547 Hamburg, Germany (e-mail: [email protected]). This study was funded by the Institute of Hematopathology, Hamburg, Germany. W. Boecker contributed to study design and study protocol development; W. Boecker, M. Reusch, V. Mielke, U. Reusch contributed to data acquisition; W. Boecker, M. Reusch, V. Mielke, Th Löning, M. Tiemann, Ch Hallermann, I. Buchwalow were involved in data analysis; W. Boecker, M. Reusch, V. Mielke, Ch Hallermann, Th Löning, M. Tiemann were involved in data interpretation; W. Boecker and I. Buchwalow were responsible for figure development; The initial manuscript was drafted by W. Boecker. All authors contributed to the final version of the manuscript and had final approval of the submitted and published version. The authors declare no conflicts of interest. The study was performed in accordance with the principles of the World Medical Association Declaration of Helsinki “Ethical Principles for Medical Research Involving Human Subjects”. Informed consent was obtained from all subjects. All experimental protocols were approved by the Institutional Review Board of the Institute for Hematopathology, Hamburg, Germany. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.amjdermatopathology.com). The American Journal of Dermatopathology: February 2021 - Volume 43 - Issue 2 - p 93-102 doi: 10.1097/DAD.0000000000001667 Buy SDC Metrics Abstract Extraocular sebaceous carcinoma (ESC) is a rare appendiceal skin tumor. In contrast to ocular sebaceous carcinoma, information about the exact cellular architecture of these lesions is scarce and the histogenesis of ESC is unknown. Here, we extend our previous study and investigate 28 extraocular carcinomas in comparison to 54 benign sebaceous tumors and 8 cases of normal sebaceous glands using a broad spectrum of antibodies against p63, several keratins, adipophilin, EMA, Ki67, androgen receptor, and mismatch repair proteins. This observational study demonstrates that p63- and K5/14-positive basaloid cells are key cells in normal sebaceous gland and in all sebaceous tumors and that these basaloid cells give rise to EMA+, adipophilin+ sebocytes, and K5/14+, K7±, K10± ductal structures. Finally, about half of ESC is associated with superficial in situ neoplasia, which provides evidence that at least part of these carcinomas arises from flat superficial in situ carcinoma. In contrast to the normal sebaceous gland, about half of all sebaceous tumors lack keratin K7. MMR protein IHC-profiles role will be discussed. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.