Sweat Gland Tumors Arising on Acral Sites

Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet. Cases of acral sweat gland tumors were identified from the database of the French network CARADERM. After histologic review, the presence of previously identified genetic alterations was investigated in the entire cohort (n=79) using a combination of immunohistochemistry and targeted DNA and RNA sequencing. Tumor entities with no recurrent genetic alterations were submitted to whole-transcriptome sequencing.CRTC1::MAML2fusion was identified in cases of hidradenoma and hidradenocarcinoma (n=9/12 and n=9/12). A p.V600E mutation ofBRAFwas observed in all cases of tubular adenoma (n=4).YAP1:MAML2andYAP1::NUTM1fusions were observed in poroid tumors (n=15/25).ETV6::NTRK3andTRPS1::PLAG1fusion transcripts were identified in secretory carcinoma (n=1/1) and cutaneous mixed tumors (n=3/4), respectively. The HPV42 genome was detected in most cases of DPA (n=10/11) and in 1 adnexal adenocarcinoma not otherwise specified. Finally, whole-transcriptome analysis revealedBRD3::NUTM1orNSD3::NUTM1fusions in 2 cases of NUT adnexal carcinoma andNCOA4::RETandCCDC6::RETfusion transcripts in 2 cystadenoma/hidrocystoma-like tumors. Our study confirms distinctive cytogenetic abnormalities in a wide number of acral adnexal neoplasms and supports the use of molecular analysis as a valuable aid in the diagnosis of these rare and often difficult to diagnose group of neoplasms.