Cytological features and nuclear scores: diagnostic tools in preoperative fine-needle aspiration of indeterminate thyroid nodules with RAS or BRAF K601E mutations?

BACKGROUND Cytological diagnosis of follicular-patterned thyroid lesions is challenging, moreover since the WHO classification has recognized NonInvasive Follicular Thyroid neoplasm with Papillary like features (NIFTP). These entities are often classified as indeterminate on cytology. Molecular testing has been proposed to help classifying indeterminate nodules. RAS and K601E BRAF mutations are mostly encountered in follicular-patterned lesions, but their diagnostic value is not well established. Nuclear scores have also been proposed to help classifying indeterminate lesions. OBJECTIVE To investigate the correlation between cytological features and histology and to assess nuclear scores in a series of indeterminate RAS or BRAF K601E positive thyroid nodules. METHODS We evaluated the cytological parameters of 69 indeterminate RAS or BRAF K601E positive thyroid nodules. The Strickland, the Maletta, and a new nuclear score were assessed. Diagnosis of malignant, benign or indolent neoplasms was confirmed in each case by histology. Malignant and indolent nodules were considered "surgical nodules", and adenomas "non-surgical nodule". RESULTS Surgical nodules were associated with the presence of ground glass nuclei (p=0.001), grooves (p<0.001), irregular nuclear membranes (p=0.01) on cytology. Nuclear scores were more often ≥ 2 in surgical nodules compared to benign ones (p<0.001), with high sensitivity, but a low negative predictive value. CONCLUSIONS Analysis of nuclear features is useful to distinguish non-surgical from surgical nodules in indeterminate FNAs. Although nuclear scores are not ideal rule-out tests for indeterminate RAS or BRAF K601E positive nodules, they seem useful to screen non-molecular tested or non-mutated indeterminate FNAs.