Childhood thyroid carcinoma with BRAFT1799A mutation shows unique pathological features of poor differentiation

Abstract

The prevalence of BRAFT1799A mutation in papillary thyroid carcinomas (PTCs) displays a marked age association: relatively high in adults and exceedingly low in childhood. We report a case of a 12-year-old Japanese female with PTC, the only one case that harbored BRAFT1799A mutation in a series of 46 childhood thyroid cancer tissues. On histology, the findings were so atypical that pathologists had repeatedly examined tumor sections to agree on the diagnosis of poorly differentiated follicular carcinoma. Upon molecular investigation, BRAFT1799A was detected in DNA extracted from paraffin-embedded material, whereas TP53 was wild-type. Since BRAFT1799A is strictly limited to PTCs, immunohistochemical staining for CD15, a specific marker for papillary carcinoma, was performed to verify the diagnosis. A small tumor area with papillary-like structure was stained positive. These findings strongly suggest that this case is a poorly differentiated carcinoma that arose from PTC and implies a possible association of BRAF mutation with dedifferentiated phenotype of PTCs.