Related Experiment Video
Updated: Dec 4, 2025
High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model
Published on: October 11, 2022
Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome
L A Jonker1, C A Lebbink1,2, M C J Jongmans2,3
1Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Children with PTEN hamartoma tumor syndrome (PHTS) have a higher risk of differentiated thyroid carcinoma (DTC). Early surveillance starting at age 10 with physical exams and ultrasounds is recommended to reduce morbidity.
Area of Science:
- Pediatric Endocrinology
- Oncology
- Genetics
Background:
- PTEN hamartoma tumor syndrome (PHTS) is caused by PTEN gene mutations.
- Children with PHTS have an increased risk of differentiated thyroid carcinoma (DTC).
- Evidence supporting current thyroid surveillance guidelines for these children is limited.
Purpose of the Study:
- To provide evidence for a thyroid carcinoma surveillance program in children with PHTS.
- To establish recommendations for DTC surveillance in pediatric PHTS patients.
Main Methods:
- Extensive literature search for studies on DTC in pediatric PHTS.
- Analysis of 5 cohort studies and presentation of 2 pediatric cases.
- Consensus reached by balancing DTC incidence, behavior, and surveillance pros/cons.
Main Results:
- DTC incidence in childhood PHTS ranged from 4-12% across studies.
- 27 out of 57 identified cases were confirmed DTC, with a median age of 12.
- Follicular thyroid carcinoma (FTC) comprised 52% of pediatric DTC cases; no difference in aggressiveness compared to sporadic DTC.
Conclusions:
- Children with PHTS face an elevated risk of DTC, with FTC being common.
- Surveillance is justified for early diagnosis and reduced morbidity.
- Recommendations include surveillance from age 10, yearly palpation, triennial ultrasound, and specialized centers.
Background:
PTEN hamartoma tumor syndrome (PHTS) represents a group of syndromes caused by a mutation in the PTEN gene. Children with a germline PTEN mutation have an increased risk of developing differentiated thyroid carcinoma (DTC). Several guidelines have focused on thyroid surveillance in these children, but studies substantiating these recommendations are lacking.
Objective:
The present study intends to provide the available evidence for a thyroid carcinoma surveillance program in children with PHTS.
Methods:
An extensive literature search was performed to identify all studies on DTC in pediatric PHTS patients. Two pediatric cases are presented to illustrate the pros and cons of thyroid carcinoma surveillance. Recommendations for other patient groups at risk for DTC were evaluated. Consensus within the study team on recommendations for children with PHTS was reached by balancing the incidence and behavior of DTC with the pros and cons of thyroid surveillance, and the different surveillance methods.
Results:
In 5 cohort studies the incidence of DTC in childhood ranged from 4 to 12%. In total 57 cases of DTC and/or benign nodular disease in pediatric PHTS patients were identified, of which 27 had proven DTC, with a median age of 12 years (range 4-17). Follicular thyroid carcinoma (FTC) was diagnosed in 52% of the pediatric DTC patients. No evidence was found for a different clinical behavior of DTC in PHTS patients compared to sporadic DTC.
Conclusions:
Children with PHTS are at increased risk for developing DTC, with 4 years being the youngest age reported at presentation and FTC being overrepresented. DTC in pediatric PHTS patients does not seem to be more aggressive than sporadic DTC.
Recommendations:
Surveillance for DTC in pediatric PHTS patients seems justified, as early diagnosis may decrease morbidity. Consensus within the study team was reached to recommend surveillance from the age of 10 years onwards, since at that age the incidence of DTC seems to reach 5%. Surveillance for DTC should consist of yearly neck palpation and triennial thyroid ultrasound. Surveillance in children with PHTS should be performed in a center of excellence for pediatric thyroid disease or PHTS.
