Update on Molecular Diagnostics in Thyroid Pathology: A Review

Abstract

Thyroid nodules are quite common, and the determination of a nodule of concern is complex, involving serum testing, radiology and, in some cases, pathological evaluation. For those nodules that raise clinical concern of neoplasia, fine needle aspiration biopsy is the gold standard for evaluation; however, in up to 30% of cases, results are indeterminate for malignancy, and further testing is needed. Advances in molecular testing have shown it to be of benefit for both diagnostic and prognostic purposes, and its use has become an integral part of thyroid cancer management in the United States and in several global nations. After The Cancer Genome Atlas (TCGA) consortium published its molecular landscape of papillary thyroid carcinoma (PTC) and reduced the “black matter” in PTC from 25% to 3.5%, further work ensued to clarify the remaining fraction not neatly attributed to the BRAFV600E-like or RAS-like phenotypes of the TCGA. Over the past decade, commercial molecular platforms have been refined as data accrues, and they increasingly cover most genetic variants of thyroid carcinomas. Molecular reporting focuses on the nodule tested, including related clinical information for that nodule (size of nodule, Bethesda category, etc.). This results in a comprehensive report to physicians that may also include patient-directed, clear language that facilitates conversations about nodule management. In cases of advanced or recurrent disease, molecular testing may become essential for devising an individual therapeutic plan. In this review, we focus on the evolution of integrated molecular testing in thyroid nodules, and how our understanding of tumor genetics, combined with histopathology, is driving the next generation of rational patient management, particularly in the context of emerging small, targetable therapeutics.