Non-serous ovarian cancer in PTEN Hamartoma Tumor Syndrome: additional evidence for increased risk

• Published in: Familial cancer Vol. 24; no. 2; p. 28
• Main Authors: Schei-Andersen, Ane J., Witjes, Vera M., Vos, Janet R., Mensenkamp, Arjen R., van Altena, Anne, Schieving, Jolanda, Simons, Michiel, Schuurs-Hoeijmakers, Janneke H. M., Adank, Muriel A., van Hest, Liselotte P., van Ierland, Yvette, de Jong, Mirjam, Jongmans, Marjolijn C. J., Leter, Edward M., Nielsen, Maartje, Hoogerbrugge, Nicoline
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 18.03.2025; Springer Netherlands
• Subjects: Adenocarcinoma, Mucinous - genetics; Adenocarcinoma, Mucinous - pathology; Adult; Brief Report; Case reports; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Hamartoma Syndrome, Multiple - complications; Hamartoma Syndrome, Multiple - genetics; Humans; Middle Aged; Neoplasia; Neoplasms, Germ Cell and Embryonal - genetics; Neoplasms, Germ Cell and Embryonal - pathology; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; PTEN Phosphohydrolase - genetics; PTEN protein; Tumors; France; United States > US; Japan; PTEN; Genetics; PHTS; Phenotype; Hereditary cancer; Ovarian cancer
• ISSN: 1573-7292; 1389-9600; 1573-7292
• DOI: 10.1007/s10689-025-00453-z

Increased hereditary cancer risk is one of the hallmarks of PTEN Hamartoma Tumor Syndrome (PHTS) which is caused by a pathogenic germline variant in PTEN . Case reports and some cohort studies have described ovarian cancer (OC) in PHTS patients. Previously, we observed an enrichment of non-serous OC in PHTS compared to sporadic cases (3% vs 1%). However, ovarian cancer is currently not considered a PHTS-related cancer. The aim of this study was to describe five PHTS patients with a pathogenic germline variant in PTEN with non-serous OC. Three of the non-serous OCs were mucinous carcinomas (49, 51 and 52 years) and two were malignant germ cell tumors (8 and 15 years) and all were diagnosed before genetic testing and PHTS diagnosis. In addition to OC, the described patients developed other PHTS-related benign and malignant lesions. We provide further evidence that non-serous ovarian cancer, especially mucinous, endometrioid and malignant germ cell tumors should be further investigated as potential PHTS-related cancers.