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Non-medullary thyroid cancers (NMTCs) originate from the follicular cells of the thyroid gland and account for over 90% of all thyroid cancers. About 3-10% of NMTCs are of familial origin, and familial NMTC (FNMTC) is defined as two or more affected first-degree relatives with NMTC. Clinicopathological correlations have resulted in a further subclassification of FNMTCs into two groups. FNMTC may occur as a minor component of familial cancer syndromes (Gardner and Cowden syndrome, Carney complex type 1, Werner and DICER1 syndromes) or as a nonsyndromic familial disease. The majority of FNMTC cases are non-syndromic with unknown susceptibility gene(s). Overall, the definition, clinical behavior, and genetic mechanisms underlying FNMTC are still unclear and, thus, familial non-medullary thyroid cancer represents an interesting field of basic and clinical research. Outstanding experts in the field contributed to the Special Research Topic titled “NonSyndromic Familial Non-Medullary Thyroid Carcinoma: Clinical and Genetic Update”. In this Editorial, we discuss the main messages from three original research articles and one review, as reported below. The clinical characteristics of FNMTC are controversial. Some, but not all, authors have reported an earlier age of onset, higher incidence of multifocality and lymph node metastases, and more aggressive features than sporadic thyroid cancer. Interestingly, FNMTC might be more aggressive, with higher thyroid cancer–specific mortality, in families with three or more members affected by FNMTC compared to families with “only” two members affected. Cirello et al. reported a statistically significant difference between familial papillary thyroid cancer (FPTC) and sporadic disease in terms of more aggressive presentation at diagnosis. In particular, in FPTCs, histological variants, other than the classical one, were more represented (19% vs 10%, p< 0.0001), multifocality was significantly more frequent (56% vs 38%, p= 0.02), T3-T4 tumors were more prevalent (28% vs 8%, p= 0.0003), and had a more advanced AJCC III-IV stage at diagnosis (12% vs 2%, p <0.0001). However, they conclude that these more aggressive features of FPTCs did not result in a worst outcome in the presence of appropriate treatments. The genetic basis of FNMTC is complex and heterogeneous, involving not only a monogenic, but also a polygenic mode of inheritance in some families. The pathogenesis of non-syndromic familial non-medullary carcinoma has been revised by Sánchez-Ares et al. emphasizing those aspects that