The Clinical Spectrum of PTEN Hamartoma Tumor Syndrome: Exploring the Value of Thyroid Surveillance

Abstract

<b><i>Introduction:</i></b> Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) comprises a collection of clinical features characterized by constitutional variants in <i>PTEN</i>. Several guidelines recommend thyroid screening, beginning at the pediatric age at the time of PHTS diagnosis; however, the benefits of early surveillance has not been well defined. <b><i>Methods:</i></b> We conducted a retrospective investigation of patients followed up at the Children’s Hospital of Philadelphia with a diagnosis of PHTS between January 2003 and June 2019. In total, 81 patients younger than 19 years were identified. <b><i>Results:</i></b> The most common clinical feature at presentation was macrocephaly (85.1%), followed by impaired development (42.0%), skin/oral lesions (30.9%), and autism spectrum disorder (27.2%). A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (51.7%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 7.4% (6/81) diagnosed with thyroid cancer. All thyroid cancer patients were older than 10 years at diagnosis, and all displayed low-invasive behavior. Of the patients younger than 10 years at the time of thyroid ultrasound (US) surveillance, 71.4% (15/21) had a normal US. The remaining 6 patients had thyroid nodules, including 4 undergoing thyroid surgery with benign histology. <b><i>Discussion/Conclusion:</i></b> Patients with macrocephaly, impaired cognitive development and thyroid nodules, and/or early-onset gastrointestinal polyps should undergo constitutional testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance before 10 years of age. In PHTS patients with a normal physical examination, thyroid US surveillance can be delayed until 10 years of age.

Indeterminate Thyroid Fine-Needle Aspirations in Pediatrics: Exploring Clinicopathologic Features and Utility of Molecular Profiling

“…In our cohort, all driver alteration(s) detected in patients with benign disease were associated with low-invasive behavior and a reduced risk for metastasis [35][36][37][38][39][40]. Regarding the thyroid cancer patients with detected driver alteration(s), 52% of drivers possessed low-invasive risk, 33% possessed high-invasive risk, and 15% possessed unreported risk for invasive disease [18,41,42].…”

Benign goiters requiring thyroidectomy as the signal for PTEN hamartoma tumor syndrome diagnosis

“…Resulted from the higher rates of thyroid disease, therapeutic thyroidectomy is also much more common in these patients (Baran et al, 2020;Cameselle-Teijeiro et al, 2015;Harach et al, 1999;Laury et al, 2011;Plamper et al, 2018;Plitt et al, 2022;Smith et al, 2011;Smith et al, 2021;Tuli et al, 2021). Among all the neoplastic concerns across the entire life span of PHTS, thyroid disease appears to manifest in a younger age range.…”

“…In contrast to the general population, thyroid diseases, including nodules, hypothyroidism, and autoimmune thyroiditis, are more common in children and adolescents affected with PHTS, reported as 35.4%–68.6% in a large cohort study by Eng's group (Tan et al, 2011). Resulted from the higher rates of thyroid disease, therapeutic thyroidectomy is also much more common in these patients (Baran et al, 2020; Cameselle‐Teijeiro et al, 2015; Harach et al, 1999; Laury et al, 2011; Plamper et al, 2018; Plitt et al, 2022; Smith et al, 2011; Smith et al, 2021; Tuli et al, 2021). Among all the neoplastic concerns across the entire life span of PHTS, thyroid disease appears to manifest in a younger age range.…”