Nuclear Features of Papillary Thyroid Carcinoma (BRAF-Like Tumors), Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (RAS-Like Tumors), and Follicular Adenoma/Follicular Thyroid Carcinoma (RAS-Like Tumors)

In seminal papers for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and the fourth edition WHO classification, NIFTP was defined by the following four features: (1) noninvasive, (2) encapsulated, (3) follicular pattern, and (4) papillary thyroid carcinoma-type nuclear features (PTC-N). However, most Asian pathologists have difficulty in diagnosing NIFTP and are often unable to distinguish noninvasive encapsulated classic papillary thyroid carcinoma (PTC) with predominant follicular pattern from NIFTPs. This is because most Asian pathologists accept only those features seen in classic PTC as PTC-N. This was evidenced by some NIFTP cases from Asian series being reported as cases of NIFTP with nodal metastasis and/or BRAFV600E mutation. The nuclear features of NIFTP (papillary-like nuclear features or dysplastic nuclear features of RAS-like tumors) are clearly different from those (florid nuclear features or fully developed nuclear features of BRAF-like tumors) observed in classic PTC, although they are both scored as 3 by the nuclear score guide. PTC-N can be divided into two types: nuclear features seen in classic PTC (true PTC-N in BRAF-like tumors) and those in NIFTP (dysplastic nuclear changes in RAS-like tumors). This difference is emphasized particularly for Asian readers in order to recognize the following delicate nuclear changes seen in RAS-like tumors: (1) mild nuclear enlargement, (2) mild nuclear irregularity, (3) delicate grooves, (4) faintly pale chromatin, and (5) very rare or no nuclear cytoplasmic pseudo-inclusions. This wide definition of PTC-N in Western practice encompasses nuclear features of classic PTC (BRAF-like tumors) and NIFTP (RAS-like tumors) in contrast to the narrow definition in Asian practice, which is observed in classic PTC at the invasive stage.