与 SUFU 致病变体有关的遗传性基底细胞瘤

IF 11.5 1区 医学 Q1 DERMATOLOGY JAMA dermatology Pub Date : 2024-09-18 DOI:10.1001/jamadermatol.2024.3315
James J. Abbott, Angela J. Jiang, Rama Godse, Sarah Ahmed, Stephen C. Senft, Melissa A. Wilson, Justine V. Cohen, Tara C. Mitchell, Temitayo A. Ogunleye, H. William Higgins, Thuzar M. Shin, Christopher J. Miller, Jacquelyn J. Roth, Salvatore F. Priore, Leslie Castelo-Soccio, Rosalie Elenitsas, John T. Seykora, Katherine L. Nathanson, Emily Y. Chu
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Chu","doi":"10.1001/jamadermatol.2024.3315","DOIUrl":null,"url":null,"abstract":"ImportanceGermline <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.ObjectiveTo define the clinical and histopathologic spectrum of cutaneous findings in patients with germline <jats:italic>SUFU</jats:italic> PVs.Design, Setting, and ParticipantsThis 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.Main Outcomes and MeasuresHistopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.ResultsAll 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.Conclusions and RelevancePatients 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. 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引用次数: 0

摘要

重要性种系 SUFU 致病变异体 (PV) 以前曾与基底细胞痣综合征 (BCNS) 和多发性基底细胞癌综合征相关;但是,SUFU PV 患者更广泛的皮肤发现尚未得到很好的界定。设计、设置和参与者这项病例系列研究于 2014 年 7 月至 2022 年 7 月期间在美国多家皮肤病学、医学遗传学和肿瘤内科学诊所进行。研究对象包括经皮肤科医生评估确诊的种系 SUFU PV 患者。主要结果和测量方法对皮肤活检进行组织病理学评估,进行或不进行免疫组化染色,并对肿瘤标本进行有针对性的新一代测序(NGS)。发病时的平均年龄(范围)为 50.2(31-68)岁,皮肤表现最初出现在生命的第四至第六个十年。没有人患有角化囊性牙源性肿瘤。研究人员对 5 名患者的 29 份皮肤病理标本进行了复查,其中 3 份(10.3%)被诊断为基底型滤泡状癌 (BFH),10 份(34.5%)被归类为基底细胞内囊癌 (iBCC),6 份(20.7%)被归类为结节型基底细胞癌 (nBCC),1 份(3.4%)被归类为浸润型基底细胞癌 (BCC)。对肿瘤标本进行的靶向 NGS 研究表明,与较不活跃的基底细胞性腺泡状突变相比,基底细胞癌与 UV 信号变体数量的增加有关。虽然临床表现存在重叠,但这些发现有助于将与 SUFU PV 相关的临床综合征与 PTCH1 BCNS 区分开来。了解与 SUFU 相关的基底细胞瘤的临床病理范围对皮肤科医生和皮肤病理学家来说非常重要,因为这些病变中的许多(尽管不是全部)都是隐匿性的,不需要积极的手术治疗。重要的是,由于 SUFU 位于平滑肌蛋白的下游,vismodegib 和其他平滑肌蛋白抑制剂不太可能成为这类患者的有效疗法。
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Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants
ImportanceGermline SUFU 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 SUFU PVs has not been well delineated.ObjectiveTo define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs.Design, Setting, and ParticipantsThis 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 SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.Main Outcomes and MeasuresHistopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.ResultsAll 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.Conclusions and RelevancePatients with germline SUFU 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 SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-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.
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来源期刊
JAMA dermatology
JAMA dermatology DERMATOLOGY-
CiteScore
14.10
自引率
5.50%
发文量
300
期刊介绍: JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery. JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care. The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists. JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.
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