Sweat Gland Tumors Arising on Acral Sites

Abstract

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.

Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: An update

“…Interestingly, the evaluation of NUT expression in skin tumours in several independent studies [15][16][17]47 confirmed the high specificity of NUT expression for the diagnosis of poroma and porocarcinoma, but also allowed identification of a new tumour entity, i.e. NUT adnexal carcinoma, [19][20][21]99 an extremely rare tumour that will be mentioned as a provisional tumour entity in the 5th WHO classification of cutaneous tumours.…”

“…So far, only four cases with either BRD3:: NUTM1 or NSD3::NUTM1 fusions have been published. 19,20,99 One case with BRD3::NUTM2B may belong to the same spectrum. 21 So far no primary cutaneous tumour with BRD4::NUTM1 fusion has been identified.…”

“…In this setting, recognition of a distinctive architecture with formation of thin strands and isolated tumour cells, a characteristic cytology with fine/clear chromatin and prominent nucleoli, as well as detection of abrupt keratinisation foci, would allow NUT adnexal carcinoma to be distinguished from NUT-rearranged porocarcinoma. [19][20][21]99…”

Primary cutaneous NUT carcinoma with BRD4::NUTM1 fusion

“…Recently, five cases of primary cutaneous NUT carcinomas have been reported with BRD3::NUTM1 , BRD3::NUTM2B , and NSD3::NUTM1 rearrangements 4–7 . Interestingly, these tumors morphologically show an eccrine ductal and follicular infundibular phenotype in contrast to the typical poorly differentiated phenotype of extracutaneous NUT carcinomas 4–6 .…”

NUT Expression Is of Diagnostic Utility in the Distinction of Digital Papillary Carcinoma From Poroid Hidradenoma

“…These results are consistent with results indicating that 13/14 of poroid hidradenomas showed NUT-1 expression. 4 Recently, Kervarrec et al 7 reported YAP-1-NUTM1 fusion in 3 of 3 cases of poroid hidradenoma at acral sites. The limited data available suggest that DPAC does not show NUT-1 staining.…”