Hürthle cell neoplasms

Abstract Hurthle cells (HC) are characterized by abundant granular eosinophilic cytoplasm containing accumulated dysfunctional mitochondria and large nuclei with prominent nucleoli. Based on the distinct clinicopathologic and molecular characteristics of Hurthle cell neoplasms (HCN), the 2017 Endocrine World Health Organization (WHO) moved to categorizing HCN as a separate group of tumors. Hurthle cell carcinomas (HCC) are now subclassified as minimally invasive, encapsulated angioinvasive, and widely invasive. HCC have a low rate of driver mutations associated with follicular thyroid carcinoma. Instead, these neoplasms are characterized by widespread loss of heterozygosity due to whole-chromosome alterations and a high rate of mitochondrial DNA mutations. Increased understanding of the genomic underpinnings of HCC has translated into improvements in molecular testing of HCN. This review will focus on clinical, cytologic, and histopathologic features of HCN, concentrating on diagnostic challenges and prognostic parameters. In addition, the molecular characteristics and molecular testing of HCN will be reviewed.