OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance

Abstract Context: PTEN Hamartoma Tumor Syndrome (PHTS) comprises a collection of rare clinical disorders characterized by germline mutations in the tumor suppressor gene PTEN. Current guidelines recommend screening for thyroid tumors beginning in pediatric age at the time of PHTS diagnosis; however, the benefit of early surveillance has not been well defined. Patients/Objective: We conducted a retrospective, single-site cohort investigation of patients followed at the Children’s Hospital of Philadelphia with diagnosis of PHTS between January 2003 - June 2019. In total, 81 patients under 18 years of age were identified. Clinical features, PTEN mutation codon, thyroid and gastrointestinal (GI) features were extracted from the electronic health record. The aim of the study is to assess genotype-phenotype, the incidence of thyroid and gastrointestinal disease, and to determine whether current recommendations for thyroid surveillance are improving outcomes. Results: The most common clinical feature at presentation was macrocephaly (85%) followed by impaired development (42%), skin/oral lesions (31%), and autistic spectrum disorder (27%). GI polyps were the presenting feature in 5 patients, with 14 of 81 patients ultimately diagnosed secondary to constipation (71%), rectal bleeding (64%), and/or abdominal pain (50%). All polyps were benign. A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (52%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 31% (5/16) diagnosed with thyroid cancer. All thyroid cancer patients were greater than 10 years of age at diagnosis and all displayed low-invasive behavior (ATA low-risk). Of the patients < 10 years at the time of thyroid ultrasound (US) surveillance, 74% (14/19) had a normal US. The remaining five patients who underwent thyroid surgery all had benign histology. No genotype-phenotype relations were found; however, patients with identical mutations were found to have similar clinical features. Conclusions: Patients with macrocephaly associated with impaired development, skin/oral lesions, thyroid nodules and/or early onset GI polyps should undergo germline testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance prior to 10 years of age. Early detection may not improve outcome of thyroid cancer as the majority of thyroid cancers display low-invasive behavior. In PHTS patients with a normal physical exam, thyroid ultrasound surveillance can be delayed until after 10 years of age. Early onset GI polyps may be the presenting diagnosis of PHTS.