“Thyroid nodular disease and PTEN mutation in a multicentre series of children with PTEN hamartoma tumor syndrome (PHTS)”

Abstract

Purpose To report the incidence of 4–12% of differentiated thyroid cancer (DTC) and up to 50% of benign thyroid nodular disease and to describe nodular thyroid disease in a multicentre pediatric population with PTEN mutations. Methods: Retrospective data of pediatric patients with PTEN mutations collected from tertiary Departments of Pediatric Endocrinology of Turin, Milan and Genua, Italy, in the period 2010–2020. Results Seventeen children with PTEN mutations were recruited in the study. Thyroid involvement was present in 12/17 (70.6%) subjects, showing a multinodular struma in 6/17 (35.3%), nodules with benign ultrasound features in 5/17 (29.4%) and a follicular adenoma in 1/17 (6%). No correlation was found between thyroid disease and gender, puberty, vascular manifestations, delayed development, or brain MRI abnormalities, while multiple lipomas were associated with thyroid disease (p = 0.03), as was macrocephaly. Standard Deviation (SD) score head circumference was 4.35 ± 1.35 cm in subjects with thyroid disease, 3 ± 0.43 cm (p = 0.02) in the group without thyroid disease. Thyroid involvement was present in all subjects with mutations in exon 6 (4/4) and exon 8 (3/3) of the PTEN gene (p = 0.02). Conclusion In the presented cohort, benign thyroid disorders were prevalent, with no evidence of DTC. A correlation was found between thyroid lesions and head circumference and the occurrence of multiple lipomas. Future studies in larger cohorts should assess whether risk stratification is needed when recommending surveillance strategies in children or young adolescents with PTEN hamartoma syndrome.

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.…”

Molecular testing in fine‐needle aspiration of thyroid nodules

“…72 PTEN germline mutations are associated with PTEN hamartoma tumor syndromes, such as Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, both associated with increased risk of thyroid cancer and benign thyroid nodular disease. 73,74 Loss of heterozygosity in sporadic thyroid neoplasms is more common than mutations in PTEN. 75 Loss of heterozygosity of PTEN has been identified in a quarter of follicular adenomas.…”

“…PTEN is a tumor suppressor gene that functions thought the serine–threonine kinase AKT; high levels of PTEN induce low levels of phosphorylated AKT leading to apoptosis whereas low or absent levels of PTEN induce high levels of phosphorylated AKT leading to cell survival 72 . PTEN germline mutations are associated with PTEN hamartoma tumor syndromes, such as Cowden syndrome and Bannayan‐Riley‐Ruvalcaba syndrome, both associated with increased risk of thyroid cancer and benign thyroid nodular disease 73,74 . Loss of heterozygosity in sporadic thyroid neoplasms is more common than mutations in PTEN 75 .…”

Editorial: Thyroid nodules and tumors in childhood

“…The first, produced by Vincenzi et al. , reports the occurrence of a multinodular goiter in a patient with Bannayan-Riley-Ruvalcaba syndrome associated with a PTEN variant and congenital hypothyroidism due to homozygous alterations of the TPO gene, arguing a possible synergic role of TPO and PTEN mutations, a gene known to predispose to thyroid cancer ( 5 ).…”