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Primary cutaneous SMARCB1 ‐deficient carcinoma
Author(s) -
Hui Yiang,
Cotzia Paolo,
Rana Satshil,
Kezlarian Brie E.,
Lin Oscar,
Hollmann Travis J.,
Dogan Snjezana
Publication year - 2021
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.13996
Subject(s) - smarcb1 , loss of heterozygosity , basal cell carcinoma , merkel cell , mutation , cancer research , exome sequencing , pathology , biology , carcinoma , medicine , merkel cell carcinoma , basal cell , gene , genetics , allele , transcription factor , chromatin remodeling
Background 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). Methods 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. Results 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. Conclusions 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.