Deep Phenotyping of Pathology-Confirmed Benign Lesions in PTEN Hamartoma Tumor Syndrome Patients

PTEN Hamartoma Tumor Syndrome (PHTS) is a rare hereditary syndrome. PHTS has a variable phenotype characterized by benign lesions and increased cancer risks. Clarifying the extent of the benign phenotype could facilitate early recognition of PHTS patients before cancer development. Therefore, we assessed the spectrum, frequency, and age of excerpt of pathology-confirmed benign lesions in PHTS patients. Pathology reports were collected for 379 patients with a pathogenic PTEN variant from the Dutch nationwide pathology databank (Palga). Benign lesions were classified as PHTS-related based on current clinical diagnostic guidelines and non-PHTS-related lesions by ICD-10 codes. Age of last follow-up was year of pathology request minus birth year. Analyses were stratified by sex and index status. Patients presented mainly with gastrointestinal (54%), skin (47%), thyroid (31%) and vascular lesions (26%). Males developed lipomas at an early age (9 years (5-34)). Females developed endometrial hyperplasia (16%) at an earlier age (41 years (35-49)) and uterine polyps (13%) more often than the general population. No significant differences were observed between sexes or index and non-index patients. The results are reflective of current diagnostic guidelines. Early-onset lipomas may be useful for early detection of PHTS patients. Additionally, uterine polyps should be considered for inclusion as a PHTS-related lesion.