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Keratoacanthoma: A Narrative Review  \nMariafrancesca Hyeraci 1, *,†, Dario Didona 2,†, Damiano Abeni 2, Francesca Magri 2, Francesco Ricci 2, Chiara Bertagnin 1, Arianna Loregian 1,3, Giovanni Di Lella 2, Antonio Di Guardo 2, Annarita Panebianco 2, Camilla Chello 2, Claudio Conforti 2,4, Elena Dellambra 2,‡ and Luca Fania 2,4,‡  \nAcademic Editor: Terrence Piva  \nReceived: 20 August 2025  \nRevised: 8 October 2025  \nAccepted: 10 October 2025  \nPublished: 15 October 2025  \nCitation: Hyeraci, M.; Didona, D.; Abeni, D.; Magri, F.; Ricci, F.; Bertagnin, C.; Loregian, A.; Di Lella, G.; Di Guardo, A.; Panebianco, A.; et al. New Insights into Pathogenesis and Management ofKeratoacanthoma: A Narrative Review. Int. J. Mol. Sci. 2025, 26, 10040. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms262010040  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Molecular Medicine, University of Padua, 35122 Padua, Italy; [chiara.bertagnin@unipd.it](chiara.bertagnin@unipd.it) (C.B.); [arianna.loregian@unipd.it](arianna.loregian@unipd.it) (A.L.)  \n2 IRCCS Istituto Dermopatico dell’Immacolata (IDI-IRCCS), Dermatological Research Hospital, 00167 Rome, Italy; [d.didona@idi.it](d.didona@idi.it) (D.D.); [d.abeni@idi.it](d.abeni@idi.it) (D.A.); [f.magri@idi.it](f.magri@idi.it) (F.M.); [f.ricci@idi.it](f.ricci@idi.it) (F.R.);  \n[g.dilella@idi.it](g.dilella@idi.it) (G.D.L.); [a.diguardo@idi.it](a.diguardo@idi.it) (A.D.G.); [a.panebianco@idi.it](a.panebianco@idi.it) (A.P.); [c.chello@idi.it](c.chello@idi.it) (C.C.);  \n[c.conforti@idi.it](c.conforti@idi.it) (C.C.); [e.dellambra@idi.it](e.dellambra@idi.it) (E.D.); [l.fania@idi.it](l.fania@idi.it) (L.F.)  \n3 Microbiology and Virology Unit, Padua University Hospital, 35128 Padua, Italy  \n4 Department of Life Science, Health and Health Professions, Link University of Rome, 00165 Rome, Italy  \n* [Correspondence: mariafrancesca.hyeraci@unipd.it](Correspondence: mariafrancesca.hyeraci@unipd.it)[ ](Correspondence: mariafrancesca.hyeraci@unipd.it)† These authors contributed equally to this work.  \n‡ These authors aslo contributed equally to this work.  \nAbstract  \nKeratoacanthoma (KA) is a rapidly growing epithelial neoplasm characterized by clinical and histopathological features that often overlap with well-differentiated squamous cell carcinoma (SCC), posing diagnostic challenges. This review provides a comprehensive overview of KA, emphasizing advances in non-invasive diagnostic techniques such as dermoscopy, reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT), which improve lesion characterization and differentiation from SCC. We discuss the histopathological phases of KA and highlight key features aiding in diagnosis. Furthermore, we explore the emerging role of human papillomavirus (HPV), particularly β-genus types, as a cofactor in KA carcinogenesis through modulation of apoptosis and DNA damage response pathways, especially under ultraviolet (UV) radiation exposure. Therapeutic strategies remain centered on complete surgical excision; however, alternative treatments, including radiotherapy, cryotherapy, topical agents, and systemic retinoids, are discussed with their respective benefits and limitations. Finally, we review current HPV vaccines and novel vaccine candidates targeting a broad spectrum of mucosal and cutaneous HPV types. This review underscores the importance of integrated diagnostic and therapeutic approaches to optimize KA management and highlights future directions in understanding its pathogenesis and treatment.  \nKeywords: keratoacanthoma; human papil","cbCaifcZPWla5cMm","https://ap.wps.com/l/cbCaifcZPWla5cMm","pdf",3853517,"English","# Abstract\n# Keywords\n# Introduction\n## Clinical features and epidemiology\n## Clinical phases and signaling pathways","[{\"question\":\"Why is keratoacanthoma difficult to diagnose?\",\"answer\":\"Keratoacanthoma can show clinical and histopathological features that overlap with well-differentiated squamous cell carcinoma, creating diagnostic challenges.\"},{\"question\":\"Which non-invasive diagnostic techniques are highlighted for KA?\",\"answer\":\"The review emphasizes dermoscopy, reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT) to improve lesion characterization and differentiation from squamous cell carcinoma.\"},{\"question\":\"What role does human papillomavirus (HPV) play in KA?\",\"answer\":\"The review discusses an emerging role for HPV, particularly β-genus types, as a cofactor in KA carcinogenesis by modulating apoptosis and DNA damage response pathways, especially under ultraviolet radiation exposure.\"}]","New Insights into Pathogenesis and Management of Keratoacanthoma: A Narrative Review | PDF",1790195346,48]