Tumor predisposition: what's the skin got to do with it?

Abstract

Purpose of reviewRecognition of skin findings associated with tumor predisposition syndromes can prompt early evaluation and surveillance and improve management. Additionally, knowing when to test and when to defer performing genetic testing can streamline management. This article reviews tumor predisposition syndromes with recently characterized skin findings and disorders for which early recognition and counseling can impact the course of disease.Recent findingsCafé au lait macules (CALMs) are important in many tumor predisposition syndromes, and ‘atypical’ CALMs are associated with constitutional mismatch repair deficiency and Fanconi anemia. Melanoma predisposition syndromes caused by pathogenic variants in POT1 and BAP1 are more recently described, and both are associated with Spitzoid tumors. Somatic pathogenic variants can cause segmental nevoid basal cell carcinoma syndrome and a mosaic form of Peutz–Jeghers syndrome. Patients with PTEN hamartoma syndrome have increased risk for melanoma but this might not occur until adulthood.SummaryThe cutaneous manifestations of tumor predisposition syndromes can aid diagnosis. Early photoprotection is key to modifying a main risk factor for skin cancer in many of these syndromes. Implementing surveillance guidelines facilitates early detection of tumors.

Approach of Multiple Endocrine Neoplasia Type 1 (MEN1) Syndrome–Related Skin Tumors

“…We still do not know enough with respect to particular endocrine configuration concerning the subgroup of MEN1 individuals with skin findings and whether the relationship is in terms of skin issues influencing the endocrine evolution or quite the other way around. From a dermatologic perspective, differential diagnosis of angiofibromas, collagenomas, and lipomas should include other genetic syndromes (mostly genodermatoses like Birt-Hogg-Dubé, tuberous sclerosis, and Cowden Syndrome since skin is a strong player) in addition to different clinical endocrine and non-endocrine entities due to multiple gene anomalies [ 115 , 116 , 117 , 118 , 119 , 120 ]. It is also worth mentioning that sometimes, even though a number of cutaneous tumors typically associated with genodermatosis are present in the same patient, the occurrence might be coincidental according to current knowledge.…”