BACKGROUND: Differentiated thyroid cancer (DTC) is seen in 3%-10% of individuals 
carrying a germline PTEN mutation. Patients with PTEN mutations are at risk for 
additional neoplasms as are their affected offspring. However, the frequency of 
PTEN mutations among DTC cases has not been systematically analyzed. The 
objective of this study was to determine the frequency of PTEN mutations in an 
unselected group of patients with DTC and to identify whether additional 
clinical features might indicate the need for referral for genetic counseling 
and possible testing.
METHODS: We collected personal medical and family history information, head 
circumference data, and blood from 259 consecutively identified clinic-based 
patients with DTC, unselected for personal or family history. Individuals were 
categorized for diagnostic criteria for Cowden syndrome (CS) using the 2009 
National Comprehensive Cancer Network (NCCN) guidelines and underwent germline 
PTEN mutation analysis.
RESULTS: Two of the 259 patients (0.8%), with both follicular thyroid carcinoma 
and macrocephaly, were found to carry a germline mutation in the PTEN gene. The 
PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 
4.8%.
CONCLUSION: The frequency of germline pathogenic PTEN mutations in an unselected 
series of patients with DTC is relatively low, but it is enriched by considering 
follicular histology and macrocephaly. These results suggest that by adding head 
circumference to the clinical assessment, thyroid cancer specialists can more 
effectively identify patients needing referral for cancer genetic services.