Molecular pathology of skin adnexal tumours

Aims Tumors of the cutaneous adnexa arise from, or differentiate toward, structures in normal skin such as hair follicles, sweat ducts/glands, sebaceous glands, or a combination of these elements. This class of neoplasms includes benign tumors and highly aggressive carcinomas. Adnexal tumors often present as solitary sporadic lesions, but can herald the presence of an inherited tumor syndrome such as Muir-Torre Syndrome, Cowden Syndrome, or CYLD Cutaneous Syndrome. In contrast to squamous cell carcinoma and basal cell carcinoma, molecular changes in adnexal neoplasia have been poorly characterized, and there are few published reviews on the current state of knowledge. Methods and results We reviewed findings in peer-reviewed literature on molecular investigations of cutaneous adnexal tumors published through June 2021. Conclusions Recent discoveries have revealed diverse oncogenic drivers and tumor suppressor alterations in this class of tumors, implicating pathways including Ras/MAPK, PI3K, YAP/TAZ, beta-catenin, and NF-kappaB. These observations have identified novel markers, such as NUT for poroma and porocarcinoma, and PLAG1 for mixed tumors. Here, we provide a comprehensive overview and update of the molecular findings associated with adnexal tumors of the skin.