Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study

Abstract

Background: Dermatologic phenotypes in PTEN hamartoma tumor syndrome (PHTS) are heterogeneous and poorly documented.

Objective: To characterize dermatologic findings among PHTS and conduct an analysis of genotype-dermatologic phenotype associations.

Methods: Mucocutaneous findings were reviewed in a multicenter cohort study of PHTS. Genotype-dermatologic phenotype associations were tested using multivariable regression.

Results: A total of 201 patients were included. Children were significantly less likely than adults to have oral papillomas, vascular malformations, benign follicular neoplasms, and acral keratoses. There were no cases of skin cancer among children. Basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma developed in 5%, 2%, and 1% of White adults, respectively. After adjusting for age, missense mutations were associated with 60% lower odds of developing cutaneous papillomatous papules (odds ratio: 0.4; 95% confidence interval [0.2, 0.7]), oral papillomas (0.4; 95% confidence interval [0.2, 0.9]), and vascular malformations (0.4; 95% confidence interval [0.2, 0.8]).

Limitations: Partly retrospective data.

Conclusion: Children are less likely than adults to have certain dermatologic findings, likely due to age-related penetrance. The risk of pediatric melanoma and the lifetime risk of nonmelanoma skin cancer in PHTS may not be elevated. Missense variants may be associated with the development of fewer dermatologic findings but future validation is required.

Keywords: PTEN; PTEN hamartoma tumor syndrome; genotype; melanoma; nonmelanoma.