Search

Background: Thyroid fine‐needle aspiration (FNA) is a reliable and cost‐effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7‐gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis. Methods: In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting Thyroid Cytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow‐up. Results: In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7‐gene test confirmed the high positive predictive value of BRAFV600E and BRAF‐like mutations (80%) and the moderate positive predictive value of RAS‐like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation‐positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. Conclusions: The 7‐gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation‐positive FNAs is related to the risk of malignancy of each diagnostic class. The 7‐gene panel test improves the preoperative risk stratification of indeterminate thyroid fine‐needle aspirations, especially when considering the biologic significance of the different types of mutations (ie, BRAF‐like and RAS‐like alterations). Moreover, the rate of mutation‐positive thyroid fine‐needle aspirations is related to the risk of malignancy of each diagnostic class, supporting the establishment, from a molecular standpoint, of prognostically relevant cytologic diagnostic categories. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) includes fine‐needle aspiration (FNA) specimens that cannot straightforwardly be classified as benign or malignant. To determine whether morphological subcategorization based on atypia qualifiers and molecular testing could improve malignancy risk stratification of AUS/FLUS patients, this study assessed the correlation between these qualifiers and the molecular alterations commonly harbored by thyroid neoplasms. METHODS: A total of 162 AUS/FLUS cases were subcategorized by atypia qualifiers (Hürthle cell changes, architectural atypia, and cytologic atypia [CyA]) and were tested for BRAF, N‐H‐KRAS, RET/PTC, and paired box 8 (PAX8)/peroxisome proliferator activated receptor γ (PPARg) mutations. RESULTS: CyA was observed more frequently in mutation‐positive AUS/FLUS (14 of 37 [37.84%]) than mutation‐negative AUS/FLUS (20 of 125 [16.00%]; P < .0084), and it specifically harbored the BRAFV600E point mutation. Malignancy was confirmed in the available follow‐up. Conversely, although RAS was the most frequent mutation identified in AUS/FLUS FNA specimens (26 of 37 cases [70.27%]; P < .0001), it was distributed across various AUS/FLUS subcategories and was not significantly associated with a specific atypia qualifier or malignant outcome according to the available follow‐up. Rearrangements of both RET/PTC (n = 1) and PAX8/PPARg (n = 3) were rarely retrieved in the FNA samples. CONCLUSIONS: BRAF and RAS mutations are associated with different AUS/FLUS qualifiers and hence have different risks of malignancy. Consequently, a hybrid molecular and morphological subcategorization system could improve the malignancy risk stratification of thyroid FNA samples diagnosed as AUS/FLUS. Cancer Cytopathol 2018;126:317‐25. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]