RAS-positive thyroid nodules.

Purpose Of Review: The current review focuses on the uncertainty regarding the management of rat sarcoma viral oncogene homolog RAS-positive thyroid nodules. The application of oncogene testing has been heralded for improving risk assessment for indeterminate cytology thyroid nodules and has grown in clinical use. RAS mutations are historically considered oncogenic.

Qualifiers of atypia in the cytologic diagnosis of thyroid nodules are associated with different Afirma gene expression classifier results and clinical outcomes.

Background: Thyroid nodules with atypia of undetermined significance (AUS) on fine-needle aspiration (FNA) have a low risk of malignancy that appears to vary based on specific features described in the AUS diagnosis. The Afirma gene expression classifier (GEC) is a molecular test designed to improve preoperative risk stratification of thyroid nodules, but its performance for different patterns of AUS has not been defined. The objective of this study was to assess GEC results and clinical outcomes in AUS nodules with architectural atypia (AUS-A), cytologic atypia (AUS-C) or both (AUS-C/A).

The variable phenotype and low-risk nature of RAS-positive thyroid nodules.

Background: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed.

Loss of negative regulators amplifies RAS signaling.

A new study identifies SPRY4 as a tumor suppressor in acute myeloid leukemia and shows that loss of SPRY4 acts as an alternative mechanism to drive RAS signaling. In addition, a paradigm of cooperativity in which combined loss of multiple negative regulators of the RAS pathway supplants the need for RAS mutations is suggested.