Background Molecular testing (MT) of thyroid fine‐needle aspiration (FNA)‐derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. Methods Neoplasia‐associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS‐like mutations (HRAS, NRAS, or KRAS mutations or non‐V600E BRAF mutations), or other mutations. Results Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1‐8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4‐9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8‐89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS‐like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. Conclusions Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.
Background The Paris system (TPS) has provided a standardized classification for reporting urinary cytology, specifically high‐grade urothelial carcinoma (HGUC). While hyperchromasia is well described in HGUC, there exists little data on nuclear hypochromasia in HGUC. Our focus was to investigate the incidence of hypochromasia in HGUC and if it should become a criterion for HGUC. Design All cases of HGUC at our institution for a 3‐year interval (2017–2019) using TPS were reviewed. Each case had a single ThinPrep slide and concurrent biopsy or resection specimen to confirm the diagnosis within 30 days. The presence of hypochromasia was evaluated, and cases with hypochromasia were stratified based on the tumor cell percentage. Cases with hypochromasia in 5% or greater of the tumor cells were considered “positively identified” for hypochromasia. Results We reviewed 117 cases of HGUC and identified nuclear hypochromasia in 12 cases (10.2%) within 5% or greater of the tumor cells. These 12 cases were further assessed based on if tumor cells showed hypochromasia in 5%–49% of the sample, or greater than 50% of the sample. Hypochromasia in 5%–49% of tumor cells was present in 8/117 cases (6.8%); whereas in 50% or greater samples 4/117 cases (3.4%) showed hypochromasia. No cases were identified where hypochromasia was noted in less than 5% of the tumor cells. Conclusion TPS and use of hyperchromasia as a feature of HGUC is affirmed. However, hypochromasia, while not diagnostic in isolation, is present in a sub‐set of patients with HGUC (10.2%) and should be considered as a variance noted in the nuclei of HGUC.
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