Context: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a complex disorder caused by germline-inactivating mutations of the PTEN tumor suppressor gene. Carriers develop benign and malignant tumors of multiple tissues, including the breast, thyroid, intestine, and skin. Surveillance to facilitate the early detection and treatment of malignancies is recommended but, because thyroid cancers have been reported almost exclusively in adults, childhood risk is considered to be low, and consensus guidelines recommend that surveillance imaging begin at 18 yr of age.
Objective/patients: Seven children with PHTS referred to two thyroidologists form the basis of this report. Medical records, operative histology, and PTEN mutational analysis were reviewed to evaluate the pediatric presentation of PHTS-associated thyroid neoplasia.
Results: Five of the seven children presented with thyroid nodules or thyroid cancer between the ages of 6 and 12 yr, often as the initially identified component of their PHTS. Two others were diagnosed with PHTS on the basis of extrathyroidal features but had markedly abnormal screening ultrasounds with solid thyroid nodule(s) of at least 2 cm, despite the documentation of normal physical examinations. Five of the seven children in this cohort developed thyroid cancer.
Conclusions: Patients with PHTS can develop thyroid nodules and thyroid cancer in early childhood. This argues both for a high index of suspicion for PHTS in children diagnosed with multiple thyroid nodules and for careful thyroid surveillance in children diagnosed with PHTS. Because early detection improves the outcome of thyroid cancer, we recommend ultrasound surveillance for all patients upon the confirmation of a germline PTEN mutation, regardless of their age.