{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:21:26Z","timestamp":1778498486509,"version":"3.51.4"},"reference-count":16,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:sec id=\"ab-dbr240016-4\"><jats:title>Importance<\/jats:title><jats:p>Germline <jats:italic>SUFU<\/jats:italic> pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with <jats:italic>SUFU<\/jats:italic> PVs has not been well delineated.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240016-5\"><jats:title>Objective<\/jats:title><jats:p>To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline <jats:italic>SUFU<\/jats:italic> PVs.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240016-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline <jats:italic>SUFU<\/jats:italic> PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240016-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240016-8\"><jats:title>Results<\/jats:title><jats:p>All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240016-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Patients with germline <jats:italic>SUFU<\/jats:italic> PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with <jats:italic>SUFU<\/jats:italic> PVs from <jats:italic>PTCH1<\/jats:italic> BCNS. Awareness of the clinicopathologic spectrum of <jats:italic>SUFU<\/jats:italic>-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2024.3315","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T15:02:22Z","timestamp":1726671742000},"page":"1220","source":"Crossref","is-referenced-by-count":6,"title":["Inherited Basaloid Neoplasms Associated With <i>SUFU<\/i> Pathogenic Variants"],"prefix":"10.1001","volume":"160","author":[{"given":"James J.","family":"Abbott","sequence":"first","affiliation":[{"name":"Department of Dermatology, Billings Clinic, Billings, Montana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela J.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Oregon Health and Sciences University, Portland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rama","family":"Godse","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St Luke\u2019s University Health Network, Easton, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.","family":"Senft","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St Luke\u2019s University Health Network, Easton, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, St Luke\u2019s University Health Network, Easton, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justine V.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara C.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Temitayo A.","family":"Ogunleye","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"H. 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Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore F.","family":"Priore","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Castelo-Soccio","sequence":"additional","affiliation":[{"name":"Cutaneous Microbiome and Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalie","family":"Elenitsas","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Seykora","sequence":"additional","affiliation":[{"name":"Department of 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