An evidence-based approach to familial nonmedullary thyroid cancer: Screening, clinical management, and follow-up

Approximately 5% of nonmedullary thyroid cancers are of familial origin. When two or more family members are diagnosed with nonmedullary thyroid cancer in the absence of other known associated syndromes it is termed familial nonmedullary thyroid cancer (FNMTC). The genetic inheritance of FNMTC remains unknown, but it is believed to be an autosomal dominant mode of inheritance with incomplete penetrance and variable expressivity. FNMTC has been shown to be more aggressive and to have a worse prognosis than sporadic nonmedullary thyroid cancer. For example, studies have demonstrated that individuals with FNMTC have an increased risk of multifocal disease, local invasion, and lymph node metastases. These aggressive features appear to contribute to the higher recurrence rate and decreased disease-free survival seen in FNMTC patients compared to those with sporadic differentiated thyroid cancer. This article is an overview of the literature available in the English language discussing FNMTC. Critical questions regarding the screening, management, and follow-up of these patients are addressed with answers proposed based on the available literature. The quality of the evidence is ranked according to Sackett's criteria. Overall, the literature quality is somewhat limited, based on the low prevalence of FNMTC, the difficulty in identifying familial cases, the variable study designs, and limited long-term follow-up. Conclusions: To date, the optimal clinical approach is yet to be established, but improved awareness and screening will permit earlier detection, more timely intervention, and hopefully improved outcomes for patients and their families.