Familial nonmedullary thyroid carcinoma: a meta-review of case series

Familial occurrence of nonmedullary thyroid carcinoma is extremely rare but this has been increasingly recognized over the recent years. Earlier reports of such occurrence were primarily confined to individuals with previous radiation exposure, history of familial adenomatous polyposis (Gardner's syndrome) or multiple hamartomas (Cowden's syndrome), or monozygotic twins. The author reviews 15 case reports/series of familial nonmedullary thyroid carcinoma available in the literature involving kindreds with no obvious associated pathogenetic factors as mentioned above. There were a total of 87 kindreds with 178 affected individuals available for analysis, with a male to female ratio of 1:2.2. The modal age group at diagnosis was 30-39 years in both gender groups. Papillary thyroid carcinoma constituted 91% of the cases, followed by follicular (6%) and anaplastic (2%) varieties. There was one case (0.5%) each of combined papillary and medullary thyroid carcinoma and Hurthle cell carcinoma, respectively. Six of the 15 series observed that patients with familial history generally have more aggressive tumour characteristics compared to the sporadic counterparts. The incidences of multifocality, local invasion, and distant metastases at diagnosis were 49, 32, and 5%, respectively. The incidences of locoregional recurrence, distant metastases, and deaths were 29, 10, and 5.4%, respectively, at a mean follow-up period of 11 years. The actual prognostic outcome of familial nonmedullary thyroid carcinoma is still unclear in view of the limited clinical data. Although several authors have advocated an aggressive approach in managing these patients, no conclusion can be reached on the basis of this review to support this position. The author recommends that patients with familial disease should be treated according to the disease stage and other risk factors, similar to those with spontaneously occurring well-differentiated papillary or follicular thyroid carcinomas. In addition, one might consider and perform follow-up of first-degree relatives with similar degree of caution as patients who have undergone head and neck irradiation in childhood.