Molecular Pathology of Thyroid Follicular Epithelial Cell-Derived Neoplasia: An Update.

CONTEXT.—: Thyroid gland neoplasia comprises the most common group of tumors arising within organs of the endocrine system. Pathogenic molecular changes can now be identified in up to 90% of thyroid carcinomas. These alterations not only shape our understanding of tumor biology and classification, but also increasingly guide therapeutic approaches to these diseases.

OBJECTIVE.—: To revisit a frequently cited review article from 2011 that outlined fundamental differences between tumor types-primarily papillary thyroid carcinoma and follicular neoplasia-in terms of their underlying genetic profiles. The present review discusses the aspects of the preceding manuscript that have remained salient, as well as advances in thyroid molecular pathology that have transpired in the intervening years.

DATA SOURCES.—: Primary literature and review articles were evaluated in order to consider topics addressed in the original review, and to gauge progress that has occurred since its publication.

CONCLUSIONS.—: The distinction between the respective molecular signatures of papillary thyroid carcinoma and follicular neoplasia, and the specter of alterations associated with aggressive cancers, remain pertinent in the present era. Important changes since 2011 relate to the reorganization of diagnostic categories, the prospect of molecular alterations in (or their incompatibility with) nonneoplastic processes, and the variety of available molecular testing platforms. Molecular analysis of thyroid nodules now factors into every step along the gamut from initial assessment to definitive classification to subsequent guidance of management. Nikiforov's review established a conceptual framework around thyroid neoplasia that has evolved over time, but endures as the dominant paradigm regarding these tumors.