FAMILIAL NONMEDULLARY THYROID CANCER

Follicular cell-derived thyroid cancer which represents 90-95% of all thyroid malignancies may occur in at least 5% of cases as familial disease. Familial nonmedullary thyroid cancer (FNMTC) is defined as the existence of two or more first degree relatives affected within a family. FNMTC may occur in two situations: pure FNMTC in which FNMTC is the predominant neoplasm although other cancers may occur with increased frequency (non syndromic NMTC) and syndromic NMTC in which other cancers or association of tumors are the most predominant feature and thyroid cancer is associated with known frequency. Most patients with syndromic NMTCs are asymptomatic, but genetic screening for the syndrome allows an early diagnosis and adequate surgery. Syndromic and non-syndromic FNMTC may represent 5-15% from all follicular cell-derived thyroid carcinomas. Four susceptibility loci for pure FNMTC have been described: TCO – familial thyroid carcinoma with oxyphilia on chromosome 19p13.2, FPTC/PRN – familial papillary thyroid carcinoma with papillary renal neoplasia (carcinoma) on chromosome 1q13.2-1q22, NMTC1 – non medullary thyroid carcinoma type 1 on chromosome 2q21, NMG1 – multinodular goiter with papillary thyroid carcinoma on chromosome 14q32. Inheritance is autosomal dominant, but the candidate genes are unknown. Most authors agree that pure FNMTC have a more aggressive behavior: multifocality, bilaterality, association with other thyroid disease (nodules and thyroiditis), trend to spread locally and in lymph nodes, higher recurrence rate, lower disease-free survival. Syndromic FNMTCs occur in the following syndromes in which FNMTC occurs with a known frequency: Familial Adenomatous Polyposis and Gardner’s syndrome (associated FNMTC - 5%), PTEN-hamartoma tumor syndrome (PTEN/PHTS - associated FNMTC - 10%), Carney’s complex (associated FNMTC - 10-25%), Werner’s syndrome (associated FNMTC - up to 18%). Knowing the aggressiveness of FNMTCs, affected individuals must be prospectively researched by screening, aggressively treated and closely monitored. Their relatives must be also monitored for early diagnosis known the phenomenon of genetic anticipation.