Cytology-histology correlation of cervical Papanicolaou smears and biopsies performed at a single institution compared to those performed at different institutions.

OBJECTIVE: Cytology-histology correlation (CHC) is the gold standard of quality assurance in cytology laboratories to ensure appropriate patient treatment, and as an educational tool for cytology laboratory personnel. If cervical Pap smears (CPs) and cervical biopsies (CBs) are performed at different institutions, these benefits may be lost. METHODS: All CBs performed at our institution from 1 January 2019 to 31 December 2019 with adequate CPs performed in the 6 months prior to the CB were included in this retrospective review. We compared the CHC for CPs and CBs performed at a single institution to the CHC for CPs and CBs performed at different institutions, with a focus on the proportion of overcalls on CPs, as those are the most challenging discrepant CHC to manage clinically. We used the American Society of Cytology guidelines for our discrepancy assessment grid. A Chi-squared test was used to compare the proportions of the populations. The P-value was set at < 0.05. RESULTS: Of the 305 CBs in our study population, 69 had a CP performed at our institution and 236 had a CP performed at an outside institution. The CHC for CBs and CPs performed at a single institution showed statistically significantly less disagreement than the CHC for those performed at different institutions (P < 0.05). Further, CBs and CPs performed at a single institution had statistically significantly fewer overcalls than CBs and CPs performed at different institutions (P < 0.05). CONCLUSION: This study further supports the use of CHC, and in light of our findings we recommend that a patient's CPs and CBs are performed at the same institution. If performing a CP and CB at the same institution is not feasible, a prospective consultation review of the CP by the institution performing the CB should be strongly considered. Further study, including an evaluation of the reason for the discrepancy in discordant cases may better elucidate the reasons for better CHC agreement when CP and CB are performed at the same institution.

Characterization and Clinical Significance of EIF1AX Mutations and Co-Mutations in Cytologically Indeterminate Thyroid Nodules: A 5-Year Retrospective Analysis.

OBJECTIVE: Mutations in the EIF1AX gene have been recently detected in a small percentage of benign and malignant thyroid lesions. We sought to investigate the prevalence and clinical significance of EIF1AX mutations and co-mutations in cytologically indeterminate thyroid nodules at our institution. MATERIALS AND METHODS: A 5-year retrospective analysis was performed on thyroid nodules with a cytologic diagnosis of Bethesda category III or IV, which had undergone testing by our in-house next generation sequencing panel. Surgically resected nodules with EIF1AX mutations were identified, and mutation type and presence of co-mutations were correlated with histopathologic diagnosis. RESULTS: 41/904 (4.5%) cases overall and 26/229 (11.4%) surgically resected nodules harbored an EIF1AX mutation. The most common histologic diagnoses were follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma. 11/26 (42.3%) of nodules had isolated EIF1AX mutation. Comutations were found in RAS (12/26; 46.2%), TERT (5/26; 19.2%) and TP53 (2/26; 7.7%). EIF1AX mutation alone conferred a 36.4% risk of malignancy (ROM) and 54.5% ROM or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), while the ROM was significantly higher in nodules with concurrent RAS (71.4%), TERT, TP53 and RAS+TERT (100%) mutations. CONCLUSION: EIF1AX mutations occur in benign and malignant follicular thyroid neoplasms. In our cohort, the majority of mutations occurred at the splice acceptor site between exons 5 and 6. Importantly, the coexistence of EIF1AX mutations with other driver pathogenic mutations in RAS, TERT and TP53 conferred a 100% ROM or NIFTP, indicating that such nodules require surgical removal.