Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma

SummaryAimsThis study was undertaken to investigate the genetic factors underlying the development of multifocality and phenotypic diversity in multifocal papillary thyroid carcinoma (mPTC).MethodsLoss of heterozygosity (LOH) and BRAFV600E mutation status were analysed in a total of 55 individual tumour foci from 18 cases of mPTC. The genetic findings and morphology of tumour foci were then compared.ResultsMultifocal PTC LOH rates were higher than observed previously in solitary PTC. Different patterns of LOH and BRAFV600E positivity separated follicular variant tumours and tumour foci from other PTC histological subtypes. In five cases, genetic alterations were detected in morphologically normal thyroid epithelium.ConclusionsThese findings support the concept that multifocal PTCs develop through clonal selection from a field of pre-neoplastic cells, with morphotype differentiation correlating with specific tumour-genetic alterations. The relatively high genetic disarray in multifocal PTC may underlie their ability to spread throughout the thyroid gland.