Pathologists’ overview of prior biopsies of women with germline PTEN mutations may expedite the identification of this rare cancer predisposition syndrome

Abstract

PTEN hamartoma tumour syndrome (PHTS) is a rare cancer predisposition syndrome, caused chiefly by pathogenic and likely pathogenic (P/LP) variants in the PTEN gene. The rarity of this disease, involvement of multiple sites and the absence of pathognomonic features hamper early diagnosis, limiting opportunities for cancer screening. We wondered whether PHTS patients’ prior biopsies may provide clues to this syndrome. With ethics approval, through a collaboration with our state-wide Adult Genetics Unit, we undertook a 28-year survey (1990–2018) of prior biopsies of 12 women known to have P/LP PTEN variants. One woman had a family history of PHTS. The earliest biopsy was at age 19. Multiple benign mucocutanous lesions affected 10 women, including benign vascular lesions: eight patients, fibromatous skin and mucosal lesions: six patients, one ganglioneuroma and one juvenile polyp. Ten women developed breast cancer, four under 40 years. Five women developed a second breast cancer, two synchronously and three at interval of 3–11 years. Other neoplasms included endometrial carcinoma two patients and dysplastic cerebellar gangliocytoma three patients. Overview of the biopsy histories of PTEN P/LP variant carriers may be a clue to the diagnosis, so clinical and genetic counselling and evaluation may be considered.