Search

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 of BRAFwas observed in all cases of tubular adenoma (n=4). YAP1:MAML2and YAP1::NUTM1fusions were observed in poroid tumors (n=15/25). ETV6::NTRK3and TRPS1::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 revealed BRD3::NUTM1or NSD3::NUTM1fusions in 2 cases of NUT adnexal carcinoma and NCOA4::RETand CCDC6::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.

Digital papillary adenocarcinoma (DPA) is a rare sweat gland neoplasm that has exceptionally been reported outside acral locations. Recently, human papillomavirus 42 was identified as the main oncogenic driver of DPA. Herein, we report 5 tumors arising in extra-acral locations predominantly in the female anogenital skin. Four patients were female and 1 patient was male. The mean age at the diagnosis time was 65 years (range: 55 to 82 y). Tumors were located on the vulva (n=3), perianal area (n=1), and forearm (n=1). Histologically, all tumors were lobular and mainly solid and composed of sheets of cells with rare focal papillae and frequent glandular structures in a “back-to-back” pattern and lined by atypical basophilic cells. Immunohistochemistry showed diffuse positivity for SOX10. Epithelial membrane antigen and carcinoembryonic antigen highlighted the luminal cells and staining for p63 and p40 revealed a consistent and continuous myoepithelial component around glandular structures. Follow-up was available in 3 cases (mean duration: 12 mo [range: 8 to 16 mo]). One patient developed local recurrence and 1 experienced regional lymph node metastases. HPV Capture Next-generation sequencing revealed the presence of the HPV42 genome in all samples. Viral reads distributions were compatible in the 5 cases with an episomal nature of the viral genome, with a recurrent deletion in the E1and/or E2open reading frames. In conclusion, this study demonstrates that digital DPA may rarely present in nonacral locations mainly in the female anogenital area, usually with a more solid pattern as compared with those cases presenting on the digits and it is also associated with HPV42.

L’adénocarcinome papillaire digital (APD) est une tumeur annexielle agressive survenant exclusivement en peau acrale. Le diagnostic de cette entité est souvent difficile avec de nombreux diagnostics différentiels (hidradénome, adénome tubuleux, cystadénome…). Alors que des anomalies génétiques récurrentes ont été identifiées dans plusieurs de ces entités (transcrits de fusion CRTC1-MAML2dans les hidradénomes, mutation de BRAFdans les adénomes tubuleux), les déterminants génétiques conduisant au développement des APD étaient jusqu’à récemment inconnus. En 2019, Thomas Wiesner et al. ont rapporté la détection d’intégrations génomiques du papillomavirus humain de type 42 (HPV42) au sein d’une petite cohorte d’APD. L’objectif principal de la présente étude était d’évaluer les performances diagnostiques d’un panel d’outils moléculaires intégrant la détection de l’HPV42 pour distinguer les APD d’autres tumeurs sudorales survenant dans les mêmes sites anatomiques.