Gingival Overgrowths Revealing PTEN Hamartoma Tumor Syndrome: Report of Novel PTEN Pathogenic Variants

PTEN hamartoma tumor syndrome (PHTS), is a spectrum of disorders caused by mutations of PTEN, in which non-cancerous growths, called hamartomas, develop in different areas of the body, often including the oral mucosa. PHTS also implies a recognized increased risk of malignancies, as PTEN is a tumor suppressor gene capable of inhibiting progression of several cancers. One of the main and most common clinical manifestation of PHTS are gingival overgrowths presenting as warty lumps. The current study describes patients with gingival or mucosal enlargements leading to the diagnosis of PHTS associated to novel PTEN pathogenic variants. Patients referred to us for gingival lumps suggestive of PHTS associated overgrowths were submitted to genetic analysis in the PTEN gene. Two related and two unrelated patients were investigated. PTEN novel pathogenic variant was found in all of them. Two patients also fulfilled diagnostic criteria of Cowden syndrome (CS). Mucocutaneous lesions, and particularly diffuse gingival overgrowths, are both early and major clinical signs revealing a potential diagnosis of PHTS. Further genetic and clinical assessments are needed in order to confirm and clarify the diagnosis within the PHTS spectrum, including, among others, the CS. A correct interpretation of oral clinical features potentially associated to PHTS is mandatory for diagnosis and a surgical approach can be useful just in case of impairment of periodontal health or for aesthetic needs. The increased risk of malignancies associated to PHTS makes a correct diagnosis pivotal to set up an appropriate lifelong surveillance, aiming at secondary cancer prevention.

Automated summary

PTEN hamartoma tumor syndrome (PHTS) is a group of disorders caused by mutations of the PTEN gene, resulting in the development of non-cancerous growths called hamartomas in various parts of the body, including the oral mucosa. PHTS is also associated with an increased risk of malignancies, as PTEN is a tumor suppressor gene that inhibits the progression of several cancers. This study identifies patients with gingival or mucosal enlargements, which led to the diagnosis of PHTS associated with novel PTEN pathogenic variants.