Introduction. The 2022 WHO Classification categorizes oncocytic (OTC) and follicular thyroid carcinoma (FTC) based on the degree of capsular and vascular invasion into minimally invasive (MI), encapsulated angio-invasive (EA) and widely invasive tumors (WI). While associations with clinical outcomes have extensively been studied in FTC, for OTC robust clinical data is lacking. Aim of this study is to investigate the effect of extent of invasiveness on clinical outcomes in OTC compared to FTC.

Methods. All adult FTC and OTC patients treated at the Erasmus MC between 2000 and 2016 were retrospectively included (n=142). All tumors were thoroughly revised independently by two pathologists applying the 2022 WHO Classification. Kaplan Meier curves were used to study the association between 2004 and 2022 WHO Classification and overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and radioactive iodine refractory disease (RAI-R).

Results. 52 OTC and 90 FTC patients were included. Mean age was 61.7 years for OTC and 51.9 years for FTC (p<0.001) and 26 (50%) OTC and 20 (24.4%) FTC patients were male (p=0.005). For OTC, 8 (15.4%) tumors were reclassified from MI to EA and 22 (40.3%) from WI to EA, resulting in 6 MIOTC, 29 EAOTC and 17 WIOTC. In FTC, 22 (24.4%) tumors were reclassified from MI to EA and 26 (28.9%) from WI to EA, resulting in 32 MIFTC, 48 EAFTC and 10 WIFTC. Compared to the 2004 WHO Classification, for all clinical outcomes but RFS, the 2022 WHO classification showed better separation of the data. Ten-year DSS for 2022 WHO Classification were 100% for MI-OTC, 75.3% for EA-OTC and 53.5% for WI-OTC, compared to 98.0% (MI-OTC) and 89.1% (WI-OTC) according to the 2004 WHO Classification. For FTC and other clinical outcomes, similar trends were observed.

Conclusion. Classification of OTC and FTC into three subcategories based on the extent of invasiveness (i.e. MI, EA and WI), as defined by the 2022 WHO Classification, better discriminates b