Department of Dermatology, Billings Clinic, Billings, Montana.
Department of Dermatology, Oregon Health and Sciences University, Portland.
JAMA Dermatol. 2024 Nov 1;160(11):1220-1224. doi: 10.1001/jamadermatol.2024.3315.
Germline 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.
To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs.
DESIGN, SETTING, AND PARTICIPANTS: 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 SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.
Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.
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.
Patients 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.
种系 SUFU 致病性变异（PVs）先前与基底细胞痣综合征（BCNS）和多发性漏斗部囊状基底细胞癌综合征相关；然而，种系 SUFU PV 患者的更广泛的皮肤表现尚未得到很好的描述。
定义种系 SUFU PV 患者的皮肤表现的临床和组织病理学谱。
设计、地点和参与者：这项病例系列研究在美国多个学术皮肤科、医学遗传学和肿瘤学诊所进行，时间为 2014 年 7 月至 2022 年 7 月。研究纳入了经皮肤科医生评估后确诊为种系 SUFU PV 的患者。分析于 2023 年 3 月至 9 月进行。
皮肤活检的组织病理学评估，伴有或不伴有免疫组织化学染色，以及肿瘤标本的靶向下一代测序（NGS）。
所有 5 名患者均为女性。发病时的平均（范围）年龄为 50.2（31-68）岁，皮肤表现最初出现在第四至第六个十年。均无角化囊肿性牙源性肿瘤。对 5 名患者的 29 份皮肤病理学标本进行了回顾性分析；其中 3 份（10.3%）被诊断为基底细胞滤泡错构瘤（BFHs），10 份（34.5%）归类为漏斗部囊状基底细胞癌（iBCCs），6 份（20.7%）归类为结节性基底细胞癌（nBCCs），1 份（3.4%）归类为浸润性基底细胞癌（BCC）。肿瘤标本的靶向 NGS 研究表明，与更惰性的基底细胞滤泡错构瘤相比，紫外线特征变异的数量增加与基底细胞癌相关。
种系 SUFU PV 患者除了常见的基底细胞癌外，还可能表现出多种惰性的基底样肿瘤，通常出现在第四至第六个十年。尽管有重叠的临床表现，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。皮肤科医生和皮肤科病理学家了解 SUFU 相关基底样肿瘤的临床病理谱非常重要，因为这些病变中的许多（尽管不是全部）是惰性的，不需要激进的手术治疗。重要的是，由于 SUFU 位于蛋白 smoothened 的下游，因此 vismodegib 和其他 smoothened 抑制剂不太可能成为这部分患者的有效治疗药物。
