Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
J Cutan Pathol. 2021 Aug;48(8):1051-1060. doi: 10.1111/cup.13996. Epub 2021 Mar 14.
SMARCB1-deficient malignancies can arise in various sites. We describe a novel primary SMARCB1-deficient carcinoma of skin (SDCS) and characterize SMARCB1 mutations in non-melanoma skin cancers (NMSC).
Cases underwent immunophenotyping and targeted exome sequencing (MSK-IMPACT) assay interrogating somatic mutations in 468 cancer-related genes. The MSK-IMPACT database from 2014 to 2020 encompassing 55, 000 cases was searched for NMSC with SMARCB1 mutations.
SDCS arose on the scalp of an 18-year-old woman showing homozygous SMARCB1 deletion with a LATS2 G963E variant. Another case arose on the temple of a 76-year-old man harboring a SMARCB1 W206* mutation associated with loss of heterozygosity (LOH), 59 concurrent mutations, and a UV mutation signature (UV-MS). Both tumors exhibited INI1 loss, positive CK5/6, p40, p63, and claudin-4 with negative CD34. Of 378 NMSC cases, including 370 carcinomas, 7 SMARCB1-mutated tumors were identified: 3 squamous cell, 3 Merkel cell, and one basal cell carcinoma. Six showed UV-MS. Five INI1-interrogated cases retained protein expression suggesting they were SMARCB1-proficient.
SDCS can be clinically aggressive, harbor SMARCB1 homozygous deletions or truncating SMARCB1 mutations associated with LOH, and can occur with or without UV-MS. Overall, SMARCB1 mutations in NMSC are rare with most being of undetermined significance and associated with retained INI1 and UV-MS.
SMARCB1 缺陷型恶性肿瘤可发生于多个部位。我们描述了一种新的原发性 SMARCB1 缺陷型皮肤癌（SDCS），并对非黑色素瘤皮肤癌（NMSC）中的 SMARCB1 突变进行了特征分析。
对病例进行免疫表型分析和靶向外显子组测序（MSK-IMPACT）检测，以检测 468 个与癌症相关基因中的体细胞突变。对 2014 年至 2020 年包含 55000 例病例的 MSK-IMPACT 数据库进行搜索，以寻找具有 SMARCB1 突变的 NMSC。
SDCS 发生于 18 岁女性患者的头皮，该患者存在 SMARCB1 纯合性缺失，同时伴有 LATS2 G963E 变异。另一个病例发生于 76 岁男性的颞部，携带 SMARCB1 W206*突变，伴有杂合性丢失（LOH）、59 个共突变和 UV 突变特征（UV-MS）。两个肿瘤均表现出 INI1 缺失、CK5/6、p40、p63 和 claudin-4 阳性，CD34 阴性。在 378 例 NMSC 病例中，包括 370 例癌，有 7 例发现 SMARCB1 突变肿瘤：3 例为鳞状细胞癌，3 例为 Merkel 细胞癌，1 例为基底细胞癌。其中 6 例有 UV-MS。5 例进行 INI1 检测的病例保留了蛋白表达，提示它们为 SMARCB1 功能获得型。
SDCS 可能具有临床侵袭性，存在 SMARCB1 纯合缺失或截断 SMARCB1 突变，伴有或不伴有 UV-MS。总体而言，NMSC 中的 SMARCB1 突变较为罕见，大多数为意义未明，同时伴有 INI1 保留和 UV-MS。
