{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:29:06Z","timestamp":1781191746179,"version":"3.54.1"},"reference-count":120,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Squamous cell carcinoma of the nail unit (SCCNU) is a rare yet often underrecognized malignancy that can lead to delayed diagnosis and significant functional morbidity. This review aims to comprehensively summarize the current understanding of SCCNU, focusing on its clinical, dermoscopic, and molecular features, diagnostic approaches, and evolving management strategies, including the role of emerging technologies and immunotherapy. Methods: A detailed literature review was conducted using peer-reviewed publications, case series, and institutional guidelines related to SCCNU. Emphasis was placed on studies addressing clinical presentation, dermoscopic patterns, molecular pathology, histologic subtypes, imaging, biopsy techniques, staging systems, and both conventional and novel therapeutic approaches. Comparative analyses of histopathological variants and diagnostic algorithms were included. Results: SCCNU presents in patients with diverse clinical manifestations, often mimicking benign nail disorders, leading to diagnostic delays. Dermoscopy improves lesion visualization, revealing features such as vascular changes and onycholysis. Histologically, SCCNU exhibits two main subtypes: basaloid (HPV-related) and keratinizing (HPV-negative) types. Molecular analyses have identified TP53 as the most frequently mutated gene, with additional alterations in HRAS, BRAF, and TERT. Imaging modalities such as MRI and LC-OCT aid in staging and surgical planning. Management is centered on complete excision\u2014often via Mohs micrographic surgery\u2014while topical, intralesional, and HPV-directed therapies are under investigation. Immunohistochemical markers (p16, Ki-67, AE1\/AE3) and neoadjuvant immunotherapy represent promising adjuncts. Conclusions: Early diagnosis through non-invasive imaging, improved molecular characterization, and personalized treatment strategies are essential to advancing care in SCCNU. Future directions include clinical trials evaluating immunotherapy, vaccine strategies, and precision-guided surgical approaches to preserve function and minimize recurrence.<\/jats:p>","DOI":"10.3390\/diagnostics15182378","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T14:45:46Z","timestamp":1758206746000},"page":"2378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Squamous Cell Carcinoma of the Nail Unit: A Comprehensive Review of Clinical Features, Diagnostic Workflow, Management Strategies and Therapeutic Options"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5053-4172","authenticated-orcid":false,"given":"Federico","family":"Venturi","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy"},{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3263-4353","authenticated-orcid":false,"given":"Elisabetta","family":"Magnaterra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy"},{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biagio","family":"Scotti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy"},{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Alessandrini","sequence":"additional","affiliation":[{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Veneziano","sequence":"additional","affiliation":[{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Vaccari","sequence":"additional","affiliation":[{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Baraldi","sequence":"additional","affiliation":[{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3186-2861","authenticated-orcid":false,"given":"Emi","family":"Dika","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy"},{"name":"Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.5826\/dpc.0803a017","article-title":"Squamous cell carcinoma of the nail unit","volume":"8","author":"Starace","year":"2018","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000537760","article-title":"Update on Squamous Cell Carcinoma of the Nail Unit: An Human Papillomavirus-Associated Condition","volume":"10","author":"Bray","year":"2024","journal-title":"Skin Appendage Disord."},{"key":"ref_4","first-page":"509","article-title":"The Diagnosis and Treatment of Nail Disorders","volume":"113","author":"Wollina","year":"2016","journal-title":"Dtsch. \u00c4rztebl. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1111\/jdv.20078","article-title":"Intra-operative dermoscopy (onychoscopy) of the nail unit-A systematic review","volume":"38","author":"Sobjanek","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol. (JEADV)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/ced.14345","article-title":"Intraoperative dermoscopy features of subungual squamous cell carcinoma: A study of 53 cases","volume":"46","author":"Carlioz","year":"2021","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.abd.2024.01.005","article-title":"Differential diagnosis of pigmented nail lesions","volume":"99","author":"Bertanha","year":"2024","journal-title":"An. Bras. Dermatol."},{"key":"ref_8","first-page":"7","article-title":"Oral and nail pigmentations: A useful parallelism for the clinician","volume":"18","author":"Dika","year":"2020","journal-title":"J. Dtsch. Dermatol. Ges. (JDDG)"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e70051","DOI":"10.1111\/srt.70051","article-title":"Amelanotic melanoma of the nail unit: Clinical and dermoscopic features of the nail plate changes","volume":"30","author":"Dika","year":"2024","journal-title":"Skin Res. Technol."},{"key":"ref_10","first-page":"e413","article-title":"Line-field confocal optical coherence tomography (LC-OCT) for the in vivo examination of nails: Analysis of typical features for the differentiation of nail disorders","volume":"38","author":"Eijkenboom","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol. (JEADV)"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.25122\/jml-2019-0129","article-title":"Dermoscopy and Reflectance Confocal Microscopy in the Diagnosis and Management of Nail Fold Squamous Cell Carcinoma","volume":"13","author":"Mazzilli","year":"2020","journal-title":"J. Med. Life"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/DSS.0000000000001805","article-title":"Squamous Cell Carcinoma of the Nail Unit: A Clinical Histopathologic Study and a Proposal for Classification","volume":"45","author":"Dika","year":"2019","journal-title":"Dermatol. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Iorizzo, M., Vollono, L., and Richert, B. (2024). Diagnosis and Management of Malignant Epithelial Nail Unit Tumors. Diagnostics, 14.","DOI":"10.3390\/diagnostics14212379"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/DSS.0000000000002144","article-title":"Mohs Micrographic Surgery as the Standard of Care for Nail Unit Squamous Cell Carcinoma","volume":"46","author":"Gou","year":"2020","journal-title":"Dermatol. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/12034754221134226","article-title":"Squamous Cell Carcinoma in Situ of the Nail Unit: Current Evidence and Recommendations for Patient Centered Treatment","volume":"27","author":"Barone","year":"2023","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.clindermatol.2013.06.006","article-title":"Nail anatomy","volume":"31","year":"2013","journal-title":"Clin. Dermatol."},{"key":"ref_17","unstructured":"(2025, July 19). Disorders of the Hair and Nail: Diagnosis and Treatment\u2014Antonella Tosti\u2014Bianca Maria Piraccini\u2014Libro in Lingua Inglese\u2014McGraw-Hill Education\u2014|Feltrinelli n.d. Available online: https:\/\/www.lafeltrinelli.it\/disorders-of-hair-nail-diagnosis-libro-inglese-antonella-tosti-bianca-maria-piraccini\/e\/9781260462470?gad_source=1&gad_campaignid=17182894279&gbraid=0AAAAAC8kHMS0k402JdSexdZZCK2eQ59JT&gclid=Cj0KCQjwhO3DBhDkARIsANxrhTpGi_nl8DRNbZeAuRNEOsv5d8Ih0Zc9JGQuQcOk77Jd3-Yxh5NWHYcaAlbVEALw_wcB."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101644","DOI":"10.1016\/j.hansur.2024.101644","article-title":"Surgical anatomy of the nail","volume":"43","author":"Cammas","year":"2024","journal-title":"Hand Surg. Rehabil."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5826\/dpc.0702a01","article-title":"Epidemiological trends in skin cancer","volume":"7","author":"Apalla","year":"2017","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/exd.14518","article-title":"Mutational landscape in squamous cell carcinoma of the nail unit","volume":"31","author":"Dika","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1111\/j.1365-2133.2012.11107.x","article-title":"The risk of squamous cell carcinoma in women from exposure to UVA lamps used in cosmetic nail treatment","volume":"167","author":"Diffey","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pagnotta, A., Patan\u00e8, L., Zoccali, C., Kaciulyte, J., Lo Torto, F., and Ribuffo, D. (2025). Squamous Cell Carcinoma of the Thumb: Misdiagnosis and Consequences. J. Clin. Med., 14.","DOI":"10.3390\/jcm14134640"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/ced.14202","article-title":"Trauma and foreign bodies may favour the onset of melanoma metastases","volume":"45","author":"Maida","year":"2020","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1111\/odi.14049","article-title":"Chronic mechanical trauma\/irritation and oral carcinoma: A systematic review showing low evidence to support an association","volume":"28","author":"Pentenero","year":"2022","journal-title":"Oral Dis."},{"key":"ref_25","first-page":"e14703","article-title":"Genital piercing: A warning for the risk of vulvar lichen sclerosus","volume":"34","author":"Silvestri","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.jaad.2019.03.070","article-title":"Nail squamous cell carcinoma: A hidden high-risk human papillomavirus reservoir for sexually transmitted infections","volume":"81","author":"Shimizu","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1186\/s12967-025-06470-x","article-title":"Human papilloma virus (HPV) mediated cancers: An insightful update","volume":"23","author":"Baba","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1097\/01.MP.0000077417.08371.CE","article-title":"Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA","volume":"16","author":"Lu","year":"2003","journal-title":"Mod. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4161\/21645515.2014.983858","article-title":"HPV vaccination for prevention of skin cancer","volume":"11","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1158\/1078-0432.CCR-08-3099","article-title":"Can routine posttransplant HPV vaccination prevent commonly occurring epithelial cancers after allogeneic stem cell transplantation?","volume":"15","author":"Savani","year":"2009","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104562","DOI":"10.1016\/j.oraloncology.2019.104562","article-title":"Cutaneous Squamous Cell Carcinoma in the Organ Transplant Recipient","volume":"103","author":"Bibee","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Khaddour, K., Murakami, N., Ruiz, E.S., and Silk, A.W. (2024). Cutaneous Squamous Cell Carcinoma in Patients with Solid-Organ-Transplant-Associated Immunosuppression. Cancers, 16.","DOI":"10.3390\/cancers16173083"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1365-2133.2012.11090.x","article-title":"Occupational skin cancer induced by ultraviolet radiation and its prevention","volume":"167","author":"Diepgen","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_34","first-page":"5","article-title":"Occupational nonsolar risk factors of squamous cell carcinoma of the skin: A population-based case-controlled study","volume":"11","author":"Mitropoulos","year":"2005","journal-title":"Dermatol. Online J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e316","DOI":"10.3346\/jkms.2024.39.e316","article-title":"Occupational Risk Factors for Skin Cancer: A Comprehensive Review","volume":"39","author":"Lee","year":"2024","journal-title":"J. Korean Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1470-2045(09)70358-4","article-title":"A review of human carcinogens\u2014Part D: Radiation","volume":"10","author":"Baan","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8886","DOI":"10.3390\/curroncol29110699","article-title":"An Epidemiological Update on Indoor Tanning and the Risk of Skin Cancers","volume":"29","author":"Dessinioti","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1111\/jdv.13654","article-title":"Bowen disease of the nail unit: A retrospective study of 12 cases and their association with human papillomaviruses","volume":"30","author":"Perruchoud","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2340\/00015555-0966","article-title":"Delay in diagnosis and treatment of squamous cell carcinoma of the skin","volume":"90","author":"Renzi","year":"2010","journal-title":"Acta Derm. Venereol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1080\/07853890.2022.2044511","article-title":"Optimal diagnosis and management of common nail disorders","volume":"54","author":"Lee","year":"2022","journal-title":"Ann. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1111\/jdv.15108","article-title":"Imaging technique for the diagnosis of onychomatricoma","volume":"32","author":"Cinotti","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1590\/abd1806-4841.20165084","article-title":"Subungual squamous cell carcinoma","volume":"91","author":"Padilha","year":"2016","journal-title":"An. Bras. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4103\/JCAS.JCAS_35_16","article-title":"Squamous Cell Carcinoma of the Nail Bed: The Great Mimicker","volume":"10","author":"Tambe","year":"2017","journal-title":"J. Cutan. Aesthetic Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.det.2018.05.010","article-title":"Onychoscopy: Dermoscopy of the Nails","volume":"36","author":"Piraccini","year":"2018","journal-title":"Dermatol. Clin."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"536","DOI":"10.4103\/ijdvl.IJDVL_242_16","article-title":"Onychoscopy: A practical guide","volume":"83","author":"Grover","year":"2017","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.det.2012.06.012","article-title":"New directions in dermatopathology: In vivo confocal microscopy in clinical practice","volume":"30","author":"Longo","year":"2012","journal-title":"Dermatol. Clin."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.det.2016.05.010","article-title":"Confocal Microscopy for Special Sites and Special Uses","volume":"34","author":"Cinotti","year":"2016","journal-title":"Dermatol. Clin."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1111\/bjd.13384","article-title":"Intraoperative diagnosis of nonpigmented nail tumours with ex vivo fluorescence confocal microscopy: 10 cases","volume":"172","author":"Debarbieux","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e13592","DOI":"10.1111\/srt.13592","article-title":"Onychopapilloma: Does free edge confocal microscopy of the nail improve the diagnosis?","volume":"30","author":"Veronesi","year":"2024","journal-title":"Skin Res. Technol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejca.2020.01.007","article-title":"European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention","volume":"128","author":"Stratigos","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.jaad.2008.05.027","article-title":"Biopsy of the pigmented lesion\u2014When and how","volume":"59","author":"Tran","year":"2008","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"121","DOI":"10.5152\/balkanmedj.2016.16442","article-title":"The Role of p16, p21, p27, p53 and Ki-67 Expression in the Differential Diagnosis of Cutaneous Squamous Cell Carcinomas and Keratoacanthomas: An Immunohistochemical Study","volume":"33","author":"Bedir","year":"2016","journal-title":"Balk. Med. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/cup.14666","article-title":"Squamous cell carcinoma of the nail apparatus: Histopathology and immunohistochemistry correlation study","volume":"51","author":"Moulart","year":"2024","journal-title":"J. Cutan. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00403-016-1700-5","article-title":"Cytokeratin AE1\/AE3 immunostaining and 3D-histology: Improvement of diagnosis in desmoplastic squamous cell carcinoma of the skin","volume":"309","author":"Schweinzer","year":"2017","journal-title":"Arch. Dermatol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jid.2016.10.032","article-title":"p63 in Squamous Cell Carcinoma of the Skin: More Than a Stem Cell\/Progenitor Marker","volume":"137","author":"Missero","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1046\/j.1365-2559.2000.00999.x","article-title":"Ber EP4 and epithelial membrane antigen aid distinction of basal cell, squamous cell and basosquamous carcinomas of the skin","volume":"37","author":"Beer","year":"2000","journal-title":"Histopathology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.jaad.2010.02.057","article-title":"Ungual and periungual human papillomavirus-associated squamous cell carcinoma: A review","volume":"64","author":"Riddel","year":"2011","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1111\/exd.14344","article-title":"Podoplanin is required for tumor cell invasion in cutaneous squamous cell carcinoma","volume":"30","author":"Schwab","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12601","DOI":"10.1038\/ncomms12601","article-title":"Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates","volume":"7","author":"Chitsazzadeh","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1126\/science.aaa6806","article-title":"Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin","volume":"348","author":"Martincorena","year":"2015","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1001\/archdermatol.2010.375","article-title":"UV-A and UV-B penetration of normal human cadaveric fingernail plate","volume":"147","author":"Stern","year":"2011","journal-title":"Arch. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1038\/s41467-018-06027-1","article-title":"The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature","volume":"9","author":"Inman","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Am\u00f4r, N.G., Santos, P.S.D.S., and Campanelli, A.P. (2021). The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.636544"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11864-019-0697-3","article-title":"Epidermal Growth Factor Receptor\u2019s Function in Cutaneous Squamous Cell Carcinoma and Its Role as a Therapeutic Target in the Age of Immunotherapies","volume":"21","author":"Joseph","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.det.2020.12.010","article-title":"Concepts, Role, and Advances on Nail Imaging","volume":"39","author":"Wortsman","year":"2021","journal-title":"Dermatol. Clin."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1097\/DSS.0000000000002352","article-title":"Evaluating the Utility of Routine Imaging in Squamous Cell Carcinoma of the Nail Unit","volume":"46","author":"Clark","year":"2020","journal-title":"Dermatol. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00256-022-04164-9","article-title":"MRI of squamous cell carcinoma of the nail apparatus: Report of 6 cases","volume":"52","author":"Ammar","year":"2023","journal-title":"Skeletal Radiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000511740","article-title":"Subungual Invasive Squamous Cell Carcinoma with Doubtful Underlying Bone Invasion: A Treatment Proposal","volume":"7","year":"2021","journal-title":"Skin Appendage Disord."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ejrad.2019.01.004","article-title":"High resolution MRI of nail tumors and tumor-like conditions","volume":"112","author":"Mundada","year":"2019","journal-title":"Eur. J. Radiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/jum.16000","article-title":"Top Advances in Dermatologic Ultrasound","volume":"42","author":"Wortsman","year":"2023","journal-title":"J. Ultrasound Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00403-024-03179-7","article-title":"Diagnostic accuracy of high-frequency ultrasound for cutaneous neoplasms: A narrative review of the literature","volume":"316","author":"Hobayan","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/srt.12888","article-title":"Ultrasound features of the subungual glomus tumor and squamous cell carcinomas","volume":"26","author":"Sechi","year":"2020","journal-title":"Skin Res. Technol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Pola\u0144ska, A., Mikiel, D., Szymoniak-Lipska, M., Olszewska, B., and Da\u0144czak-Pazdrowska, A. (2025). High-Frequency Ultrasonography in Hair and Nail Disorders-How It May Be Helpful. Diagnostics, 15.","DOI":"10.3390\/diagnostics15030332"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.1007\/s12070-021-02495-y","article-title":"Evaluation of Metastatic Lymph Nodes in Oral Squamous Cell Carcinoma: A Comparative Study of Clinical, FNAC, Ultra Sonography and Computed Tomography with Post Operative Histopathology","volume":"74","author":"Hallur","year":"2022","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.ejrad.2010.10.020","article-title":"Ultrasound guided Core Biopsy, Fine Needle Aspiration Cytology and Surgical Excision Biopsy in the diagnosis of metastatic squamous cell carcinoma in the head and neck: An eleven year experience","volume":"80","author":"Saha","year":"2011","journal-title":"Eur. J. Radiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"42","DOI":"10.12788\/j.sder.2016.011","article-title":"Radiographic imaging for skin cancer","volume":"35","author":"Belkin","year":"2016","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1097\/DSS.0000000000004191","article-title":"Use of Imaging in Cutaneous Squamous Cell Carcinoma to Detect High-Risk Tumor Features, Nodal Metastasis, and Distant Metastasis: A Systematic Review","volume":"50","author":"Libson","year":"2024","journal-title":"Dermatol. Surg."},{"key":"ref_78","first-page":"1422","article-title":"S3 guideline \u201cactinic keratosis and cutaneous squamous cell carcinoma\u201d\u2014Update 2023, part 2: Epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention","volume":"21","author":"Leiter","year":"2023","journal-title":"J. Dtsch. Dermatol. Ges. (JDDG)"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1177\/0194599817731735","article-title":"Preoperative Positron Emission Tomography for Node-Positive Head and Neck Cutaneous Squamous Cell Carcinoma","volume":"158","author":"Hirshoren","year":"2018","journal-title":"Otolaryngol.-Head Neck Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e15832","DOI":"10.1111\/dth.15832","article-title":"Noninvasive diagnostic techniques in the preoperative setting of Mohs micrographic surgery: A review of the literature","volume":"35","author":"Venturi","year":"2022","journal-title":"Dermatol. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1524-4725.1992.tb02000.x","article-title":"Nail biopsy: Indications and methods","volume":"18","author":"Rich","year":"1992","journal-title":"Dermatol. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e2023092","DOI":"10.5826\/dpc.1302a92","article-title":"The Histopathologic Evaluation of Diagnostic Procedures in Nail Melanoma","volume":"13","author":"Dika","year":"2023","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/idoj.IDOJ_268_17","article-title":"Nail Biopsy: A User\u2019s Manual","volume":"9","author":"Grover","year":"2018","journal-title":"Indian Dermatol. Online J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1200\/JCO.2012.48.5326","article-title":"Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women\u2019s Hospital tumor staging for cutaneous squamous cell carcinoma","volume":"32","author":"Karia","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_85","unstructured":"Sobin, L.H., Gospodarowicz, M.K., and Wittekind, C. (2025). TNM Classification of Malignant Tumours, Wiley. [9th ed.]. Available online: https:\/\/www.wiley.com\/en-us\/TNM+Classification+of+Malignant+Tumours%2C+9th+Edition-p-9781394216871."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"113251","DOI":"10.1016\/j.ejca.2023.113251","article-title":"European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention-Update 2023","volume":"193","author":"Stratigos","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_87","first-page":"579","article-title":"Comparison and evaluation of the current staging of cutaneous carcinomas","volume":"10","author":"Breuninger","year":"2012","journal-title":"J. Dtsch. Dermatol. Ges. (JDDG)"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.jhsa.2018.01.010","article-title":"Squamous Cell Carcinoma of the Nail Unit: Review of the Literature","volume":"43","author":"Dijksterhuis","year":"2018","journal-title":"J. Hand Surg."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1111\/jdv.15036","article-title":"Mohs micrographic surgery for nail unit tumours: An update and a critical review of the literature","volume":"32","author":"Lambertini","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol. (JEADV)"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1097\/DSS.0000000000001075","article-title":"Mohs Micrographic Surgery for Management of Nail Unit Squamous Cell Carcinomas","volume":"43","author":"Taylor","year":"2017","journal-title":"Dermatol. Surg."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1097\/DSS.0000000000000452","article-title":"Mohs Surgery for Squamous Cell Carcinoma of the Nail Unit: 10 Years of Experience","volume":"41","author":"Dika","year":"2015","journal-title":"Dermatol. Surg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1001\/jamadermatol.2017.0014","article-title":"Surgical Treatment of Subungual Squamous Cell Carcinoma by Wide Excision of the Nail Unit and Skin Graft Reconstruction: An Evaluation of Treatment Efficiency and Outcomes","volume":"153","author":"Surinach","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/DSS.0000000000003319","article-title":"Treatment Options and Outcomes for Squamous Cell Carcinoma of the Nail Unit: A Systematic Review","volume":"48","author":"Ning","year":"2022","journal-title":"Dermatol. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.ad.2018.05.002","article-title":"Functional Surgery for Malignant Subungual Tumors: A Case Series and Literature Review","volume":"109","author":"Mendoza","year":"2018","journal-title":"Actas Dermosifiliogr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"31","DOI":"10.25259\/IJDVL_912_2023","article-title":"Recurrence rates after functional surgery versus amputation for nail squamous cell carcinoma not involving the bone: A systematic review","volume":"91","author":"Wong","year":"2025","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_96","first-page":"e14165","article-title":"The role of topical imiquimod in melanoma cutaneous metastases: A critical review of the literature","volume":"33","author":"Patrizi","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/bjd.18945","article-title":"Bowen disease of the nail apparatus with HPV16 positivity and resolution with human papillomavirus vaccination","volume":"183","author":"Jeon","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/ced.12149","article-title":"Multiple-digit periungual Bowen\u2019s disease: A novel treatment approach with radiotherapy","volume":"38","author":"Hunt","year":"2013","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s41571-022-00603-7","article-title":"HPV-associated oropharyngeal cancer: Epidemiology, molecular biology and clinical management","volume":"19","author":"Lechner","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"113252","DOI":"10.1016\/j.ejca.2023.113252","article-title":"European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment-Update 2023","volume":"193","author":"Stratigos","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1056\/NEJMoa1805131","article-title":"PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma","volume":"379","author":"Migden","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejca.2020.01.008","article-title":"European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2","volume":"128","author":"Stratigos","year":"2020","journal-title":"Treatment. Eur. J. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Bertino, G., Groselj, A., Campana, L.G., Kunte, C., Schepler, H., Gehl, J., Muir, T., Clover, J.A.P., Quaglino, P., and Kis, E. (2022). Electrochemotherapy for the treatment of cutaneous squamous cell carcinoma: The INSPECT experience (2008\u20132020). Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.951662"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1001\/jamaoto.2024.0259","article-title":"Neoadjuvant-Intent Immunotherapy in Advanced, Resectable Cutaneous Squamous Cell Carcinoma","volume":"150","author":"Kim","year":"2024","journal-title":"JAMA Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJMoa2209813","article-title":"Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma","volume":"387","author":"Gross","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Spadafora, M., Paganelli, A., Raucci, M., Kaleci, S., Peris, K., Guida, S., Pellacani, G., and Longo, C. (2025). Neoadjuvant Immunotherapy in Cutaneous Squamous Cell Carcinoma: Systematic Literature Review and State of the Art. Cancers, 17.","DOI":"10.3390\/cancers17040637"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Yaniv, D., Naara, S., Netto, F.O.G., Stafford, H., Buell, J., Chiang, E., Shahrukh, A., Li, S., Nagarajan, P., and Hanna, E.Y. (2025). Response-Adapted Oncologic Surgery in Cutaneous Squamous Cell Carcinoma: A Paradigm Shift Following Neoadjuvant Immunotherapy. Ann. Surg. Oncol.","DOI":"10.1245\/s10434-025-18035-9"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1111\/ced.14804","article-title":"Lasting response after discontinuation of cemiplimab in a patient with locally advanced basal cell carcinoma","volume":"46","author":"Trane","year":"2021","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_109","first-page":"e32","article-title":"Cytoreductive approach with hedgehog inhibitors followed by reflectance confocal microscopy assisted Mohs surgery for morpheiform basal cell carcinoma","volume":"39","author":"Venturi","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol. (JEADV)"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1111\/exd.14882","article-title":"Neoadjuvant treatment of basosquamous carcinomas with Sonidegib: An innovative approach","volume":"32","author":"Dika","year":"2023","journal-title":"Exp. Dermatol."},{"key":"ref_111","unstructured":"Davar, D. (2025, July 06). Phase II Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04808999?term=NCT02252042%20NCT02883556%20NCT03284424%20NCT03833167%20NCT04150900%20NCT04808999%20NCT04929041%20NCT05027633&rank=3."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/jdv.12330","article-title":"Confocal microscopy for healthy and pathological nail","volume":"28","author":"Cinotti","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol. (JEADV)"},{"key":"ref_113","first-page":"e398","article-title":"Short-term teledermoscopic monitoring of atypical melanocytic lesions in the early diagnosis of melanoma: Utility more apparent than real","volume":"34","author":"Gori","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol. (JEADV)"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Quadri, M., Iuliano, M., Rosa, P., Mangino, G., and Palazzo, E. (2025). Exploring the Complexity of Cutaneous Squamous CellCarcinoma Microenvironment: Focus on Immune Cell Roles by Novel 3D In Vitro Models. Life, 15.","DOI":"10.3390\/life15081170"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Venturi, F., Magnaterra, E., Scotti, B., Ferracin, M., and Dika, E. (2025). Predictive Factors for Sentinel Lymph Node Positivity in Melanoma Patients-The Role of Liquid Biopsy, MicroRNA and Gene Expression Profile Panels. Cancers, 17.","DOI":"10.3390\/cancers17081281"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Naddeo, M., Broseghini, E., Venturi, F., Vaccari, S., Corti, B., Lambertini, M., Ricci, C., Fontana, B., Durante, G., and Pariali, M. (2024). Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas. Cancers, 16.","DOI":"10.3390\/cancers16091688"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1042\/EBC20200048","article-title":"Non-coding RNA dysregulation in skin cancers","volume":"65","author":"Durante","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/14737159.2022.2049243","article-title":"Circulating microRNA biomarkers in melanoma and non-melanoma skin cancer","volume":"22","author":"Durante","year":"2022","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00403-020-02125-7","article-title":"Squamous cell carcinoma in situ upstaging is not frequent in the nail unit: A tertiary cancer center experience","volume":"314","author":"Aleissa","year":"2022","journal-title":"Arch. Dermatol. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/s00403-025-03933-5","article-title":"The evolving treatment landscape for CSCC","volume":"317","author":"Miller","year":"2025","journal-title":"Arch. Dermatol. Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/18\/2378\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:37Z","timestamp":1760035717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/18\/2378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":120,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15182378"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15182378","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]}}}