RAS-Mutant Follicular Thyroid Tumors: A Continuous Challenge for Pathologists

Area of Science:

• Pathology
• Endocrinology
• Oncology

Background:

• Thyroid nodule classification, particularly for follicular-patterned tumors with RAS mutations, presents diagnostic challenges.
• Histological features like nuclear atypia, invasion, mitotic activity, and necrosis are critical but often ambiguous.
• Distinguishing benign from malignant follicular neoplasms requires careful evaluation of specific criteria.

Purpose of the Study:

• To review the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors.
• To address challenges in classifying follicular nodules with worrisome features and RAS mutations.
• To clarify diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and follicular thyroid carcinoma (FTC).

Main Methods:

• Review of histological features and diagnostic criteria for RAS-mutant thyroid nodules.
• Discussion of nuclear characteristics, invasion assessment (capsular and vascular), and mitotic activity.
• Evaluation of ancillary techniques like immunohistochemistry and multi-level sectioning.

Main Results:

• RAS-mutant follicular-patterned tumors range from benign adenomas to malignant carcinomas.
• Nuclear features in encapsulated tumors aid in differentiating follicular thyroid adenoma (FTA) from NIFTP.
• Angioinvasion is a key indicator of malignancy in RAS-mutant follicular neoplasms, though its assessment can be challenging.

Conclusions:

• Accurate classification of RAS-mutant thyroid nodules relies on meticulous histological assessment, especially of invasion and nuclear features.
• Nomenclature for certain follicular nodules with high-risk mutations and worrisome features remains debated.
• Improved diagnostic criteria and potentially revised nomenclature are needed for precise thyroid cancer classification.