RESUMO
Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAFV600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAFK601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAFV600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAFV600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type.
RESUMO
BACKGROUND: A systematic analysis of the clinical and pathologic patterns of childhood "sporadic" thyroid carcinoma in Belarus, in the absence of the "Chernobyl radioactive iodine factor," has never been performed. The aim of this study was to establish the essential features of "sporadic" papillary thyroid carcinoma (PTC) in Belarusian children and adolescents, and the relationship of tumor pathology to extrathyroidal extension (ETE) and lymph node metastases. METHODS: This was a retrospective population-based study with assessment of histological samples of 119 cases of thyroid cancer in Belarusian children and adolescents of 0-18 years old registered during 2005-2008 years. Sporadic PTC was noted in 94 children who were not exposed to the Chernobyl radiation release. None of the 119 cases of thyroid were follicular thyroid cancer. RESULTS: The incidence rate of PTC was 1.13 per 100,000 persons. The median age at diagnosis was 15.1 years with fourfold predominance of diagnosis in female patients. Relapse was detected in 2% of cases with median follow-up of 4.2 years. Median tumor size was 12 mm. Three percent of the cases of PTC had multifocal growth. The classical variant of PTC was registered in 46% of the patients with thyroid cancer, the follicular variant of PTC was noted in 20% of the cases. The percent of rare types of PTC (tall cell and diffuse sclerosing) were equal to that for solid PTCs (13%, 12%, and 10%, respectively). Adolescents had a pure papillary carcinoma more often compared to children who represented tumors with mixed papillary/follicular patterns more frequently (p<0.05). Two-thirds of the patients with PTC had regional lymph node metastases. ETE was established in 39 of 74 patients in whom ETE could be assessed by morphology. Multivariate analysis showed that lymphatic invasion was the strongest independent factor associated with both ETE (p<0.0001) and lymph node metastases (p<0.0001). CONCLUSION: In 2005-2008, sporadic thyroid cancer in children of Belarus was represented by high prevalence of PTC and absence of follicular thyroid cancer. Sporadic cases of PTC in Belarus were characterized by smaller tumor size, a small number of cases with multifocal growth, an equal number of rare types and solid PTCs, a relatively high prevalence of pure papillary variant of PTC in adolescents, and a low frequency of early relapses. A high frequency of ETE and lymph node metastases was detected. The strongest morphologic factor associated with both of them was lymphatic invasion.
