{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:07:56Z","timestamp":1784178476498,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanofi and BMS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as \u22659 BCCs within 3 years. Objective: To analyse demographic, clinical, and histopathological features of non-syndromic HF-BCC in a Belgian cohort, compared with low-burden BCC patients and healthy controls. Methods: A retrospective cohort study was conducted at Erasme Hospital (Brussels) using data from the EUSCAP platform. Clinical, behavioural, and histopathological data were collected and statistically analysed. Results: Of 783 patients, 16 with HF-BCC were identified. For comparison, 32 patients with 1\u20132 BCCs and 117 patients without BCC were selected. HF-BCC patients showed distinct characteristics, including a higher proportion of superficial BCCs (68.3% vs. 50%, p = 0.01) and fewer nodular subtypes (43.2% vs. 63.5%, p = 0.01). Their tumours were less frequently located on the nose and ears compared with patients having 1\u20132 BCCs. HF-BCC was associated with a personal history of squamous cell carcinoma (SCC) and actinic keratosis (AK). Conclusions: HF-BCC patients display distinct anatomical, histopathological and clinical characteristics, with a predominance of superficial BCC and an association with a personal history of SCC and AK. They show a lower frequency of tumours on the nose and ears, with a stronger tendency for localisation on the trunk and extremities. Identifying risk factors and genetic markers may contribute to improved early detection strategies, preventive measures, and the development of targeted therapies.<\/jats:p>","DOI":"10.3390\/jcm14134678","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:11:04Z","timestamp":1751429464000},"page":"4678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High-Frequency Basal Cell Carcinoma: Demographic, Clinical, and Histopathological Features in a Belgian Cohort"],"prefix":"10.3390","volume":"14","author":[{"given":"Katharina Charlotte","family":"Wunderlich","sequence":"first","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1570-7856","authenticated-orcid":false,"given":"Carmen","family":"Orte Cano","sequence":"additional","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9266-0342","authenticated-orcid":false,"given":"Mariano","family":"Suppa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Gaide","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, CHUV, University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7460-522X","authenticated-orcid":false,"given":"Hassane","family":"Njimi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Euromelanoma Working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4359-0667","authenticated-orcid":false,"given":"V\u00e9ronique Del","family":"Marmol","sequence":"additional","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/35041694","article-title":"The age of cancer","volume":"408","author":"DePinho","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ci\u0105\u017cy\u0144ska, M., Kami\u0144ska-Winciorek, G., Lange, D., Lewandowski, B., Reich, A., S\u0142awi\u0144ska, M., Pabianek, M., Szczepaniak, K., Hankiewicz, A., and U\u0142a\u0144ska, M. (2021). The incidence and clinical analysis of non-melanoma skin cancer. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-94435-7"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1002\/cam4.4046","article-title":"Global, regional and national incidence, mortality and disability-adjusted life-years of skin cancers and trend analysis from 1990 to 2019: An analysis of the Global Burden of Disease Study 2019","volume":"10","author":"Zhang","year":"2021","journal-title":"Cancer Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pellegrini, C., Maturo, M.G., Di Nardo, L., Ciciarelli, V., Guti\u00e9rrez Garc\u00eda-Rodrigo, C., and Fargnoli, M.C. (2017). Understanding the Molecular Genetics of Basal Cell Carcinoma. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112485"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wunderlich, K., Suppa, M., Gandini, S., Lipski, J., White, J.M., and Del Marmol, V. (2024). Risk Factors and Innovations in Risk Assessment for Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma. Cancers, 16.","DOI":"10.3390\/cancers16051016"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e646","DOI":"10.1111\/jdv.16512","article-title":"High-Frequency Basal Cell Carcinoma in Danish patients: Prevalence and consistency","volume":"34","author":"Saldanha","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.jaad.2020.07.088","article-title":"Prevalence and risk factors for high-frequency basal cell carcinoma in the United States","volume":"84","author":"Chiang","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1136\/jmg.2010.083022","article-title":"Cancer and neurologic degeneration in xeroderma pigmentosum: Long term follow-up characterises the role of DNA repair","volume":"48","author":"Bradford","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/0140-6736(92)90868-4","article-title":"Location of gene for Gorlin syndrome","volume":"339","author":"Farndon","year":"1992","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jaad.2017.02.047","article-title":"Correlates of multiple basal cell carcinoma in a retrospective cohort study: Sex, histologic subtypes, and anatomic distribution","volume":"77","author":"Kuo","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e122744","DOI":"10.1172\/jci.insight.122744","article-title":"Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility","volume":"3","author":"Cho","year":"2018","journal-title":"JCI Insight"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e515","DOI":"10.1111\/jdv.19710","article-title":"EUSCAP: A Euromelanoma project to investigate skin cancer risk factors in Europe","volume":"38","author":"Wunderlich","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jdv.18195","article-title":"Prevention and screening of melanoma in Europe: 20 years of the Euromelanoma campaign","volume":"36","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1001\/archderm.136.12.1524","article-title":"Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: A critical review of the literature and meta-analysis","volume":"136","author":"Marcil","year":"2000","journal-title":"Arch. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/0190-9622(90)70343-G","article-title":"The risk of developing subsequent nonmelanoma skin cancers","volume":"23","author":"Schreiber","year":"1990","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/bjd.12420","article-title":"The natural history of actinic keratosis: A systematic review","volume":"169","author":"Werner","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.jaad.2020.03.126","article-title":"Field cancerization: Definition, epidemiology, risk factors, and outcomes","volume":"83","author":"Willenbrink","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/cncr.24284","article-title":"Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial","volume":"115","author":"Criscione","year":"2009","journal-title":"Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Choquet, H., Jiang, C., Yin, J., Kim, Y., Hoffmann, T.J., Jorgenson, E., and Asgari, M.M. (2024). Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma. Commun. Biol., 7.","DOI":"10.1038\/s42003-023-05753-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1365-2133.2006.07234.x","article-title":"Basal cell carcinoma: Histological classification and body-site distribution","volume":"155","author":"Raasch","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Di Nardo, L., Pellegrini, C., Di Stefani, A., Ricci, F., Fossati, B., Del Regno, L., Carbone, C., Piro, G., Corbo, V., and Delfino, P. (2021). Molecular alterations in basal cell carcinoma subtypes. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-92592-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/s41586-023-06740-y","article-title":"The extracellular matrix dictates regional competence for tumour initiation","volume":"623","author":"Bansaccal","year":"2023","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000444792","article-title":"Nevoid Basal Cell Carcinoma Syndrome: Report from the Zurich Nevoid Basal Cell Carcinoma Syndrome Cohort","volume":"232","author":"Winterton","year":"2016","journal-title":"Dermatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1046\/j.1365-2133.2002.04804.x","article-title":"Variations of basal cell carcinomas according to gender, age, location and histopathological subtype","volume":"147","author":"Scrivener","year":"2002","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0190-9622(96)90114-0","article-title":"Increased proportion of aggressive-growth basal cell carcinoma in the Veterans Affairs population of Palo Alto, California","volume":"35","author":"Wrone","year":"1996","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/cup.14753","article-title":"Frequent Occurrence of High-Risk Basal Cell Carcinoma in Xeroderma Pigmentosum: A Histopathological Insight From an Indian Cohort","volume":"52","author":"Imran","year":"2025","journal-title":"J. Cutan. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00403-021-02316-w","article-title":"Clinical and pathological features associated with high-risk, multiple, and recurrent basal cell carcinomas: A retrospective cohort analysis from the Levantine coast of the Mediterranean Sea","volume":"315","author":"Soutou","year":"2023","journal-title":"Arch. Dermatol. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:50Z","timestamp":1760032970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":27,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134678"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134678","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]}}}