Evidence for the founder effect of RET533 as the common Greek and Brazilian ancestor spreading multiple endocrine neoplasia 2A.

OBJECTIVES: About one-quarter of patients with medullary thyroid cancer (MTC) have inherited disease due to mutations in the RET gene. A rare mutation in exon 8 (G533C) of RET, previously described in a large Brazilian family with MEN2A, also appeared to be clustering in Greece, whereas it was rarely reported in other ethnic groups. The aim of this study was to identify a possible common ancestry between these carriers. PATIENTS AND METHODS: Twelve RET G533C mutation carriers, four randomly selected from the Brazilian cohort and eight from apparently unrelated Greek families, were studied for a possible common ancestral origin. RET flanking microsatellite markers at chromosome 10q (D10S197, D10S196, D10S1652 and D10S537) were used. RESULTS: Genomic DNA analysis using these markers showed that many of these apparently unrelated individuals shared a common haplotype indicating a common ancestral origin. CONCLUSION: Our data suggest that Brazilian and Greek patients with MTC carrying the G533C mutation in exon 8 of RET gene originate from a common ancestor. Due to historical reasons, we speculate that the more plausible explanation for the origin of this mutation is in Greece.

Papillary thyroid carcinomas in patients under 21 years of age: clinical and histologic characteristics of tumors ≤10 mm.

OBJECTIVE: To compare clinical and histologic characteristics of papillary thyroid carcinomas (PTCs) ≤10 mm in patients ≤21 years old with larger ones and with microcarcinomas in adults. STUDY DESIGN: Retrospective study of patients with PTC diagnosed between 1983 and 2012. Medical records were reviewed and information about age, sex, tumor size, intra/extrathyroid extension, lymph node, and distant metastases were collected. RESULTS: Patients ≤21 years old (n = 93) and adults (n = 1235) with PTC were identified. Among the former, 34 had PTC ≤10 mm (37.4%) and among the latter, 584 had papillary thyroid microcarcinoma (PTM) (47.3%), P = .082. Patients with tumors ≤10 mm less frequently had extrathyroidal extension and lymph node metastases compared with larger tumors (8.8% vs 33.3%, P = .017, and 60.0% vs 95.2%, P = .001, respectively). The percentage of PTC ≤10 mm increased with age (7.1%, 32.0%, and 48.1% in age groups ≤15, 15-18, and >18 to ≤21 years old, respectively; P = .016). Mean tumor size was larger (6.8 ± 2.7 vs 5.8 ± 2.8 mm, P = .030), and lymph nodes metastases were more frequent (41.2% vs 18.6%, P = .003) in patients ≤21 years of age compared with adults with PTM. The frequency of multifocal cancers decreased between 1983-1992, 1993-2002, and 2003-2012 (66.7%, 53.6%, and 27.1%, respectively, P = .019). CONCLUSIONS: The frequency of PTC ≤10 mm is low in children, increases in adolescents, and reaches that of adults at 18-21 years of age. Mean tumor size is larger and metastases to regional lymph nodes more frequent in comparison with PTM in adults. Whether their treatment and follow-up could be based on guidelines used for PTM in adults is questionable.