Interobserver variability between cytopathologists and cytotechnologists upon application and characterization of the indeterminate category in the Milan System for Reporting Salivary Gland Cytopathology.

BACKGROUND: The indeterminate categories in the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) are diagnostically challenging because of inherent heterogeneity and complexity, with wide interobserver variability (IOV). Herein, the authors explore the concordance rate (CR) between cytopathologists (CPs) and cytotechnologists (CTs) in interpreting indeterminate salivary gland lesions using the MSRSGC. METHODS: Between 2011 and 2016, 86 indeterminate fine-needle aspirations had slides available for review, of which 48 had follow-up. Four CPs and 2 CTs performed an independent, blinded review of these slides and categorized them according to the MSRSGC. The CRs between CTs and CPs with the final sign-out cytopathologist (FCP) were assessed, and interobserver agreement was categorized into uniform, majority, divided, minimal, or no agreement. RESULTS: The overall CR with the FCP ranged from 48.8% to 60.5% for CPs and from 22.1% to 36% for CTs. IOV κ scores for the entire group were 0.314 and, with the FCP as the reference, ranged from 0.403 to 0.539 for CPs and from 0.091 to 0.254 for CTs. Uniform, majority, divided, minimal, and no agreement was noted in 12.8%, 31.4%, 38.4%, 10.5%, and 6.9%, respectively, of all cases and in 16.7%, 35.4%, 31.3%, 8.3%, and 6.3%, respectively, of the cases with follow-up. Diagnostic challenges included distinguishing lymphoma from a reactive process and distinguishing mucin from mucin-like material. CONCLUSIONS: CPs had modestly higher CRs compared with CTs; and, although the variable CRs highlight indeterminate IOV, the MSRSGC enables reproducibility. Characterizing larger cohorts in the indeterminate categories will further improve MSRSGC criteria. Moreover, education on the MSRSGC should include CTs and CPs to improve overall diagnostic accuracy.

Endoscopic ultrasound-guided tissue acquisition of solid mass lesions of the pancreas: A retrospective comparison study of fine-needle aspiration and fine-needle biopsy.

BACKGROUND: Although endoscopic ultrasound guided fine-needle biopsy (EUS-FNB) has emerged as an alternative to fine-needle aspiration (FNA) for the sampling of solid pancreatic mass lesions, it remains unclear which method is more effective. We compared the diagnostic yields of FNA, FNB, and combined FNA/FNB at a tertiary care institution. METHODS: Specimens from EUS-FNA (04/2014-08/2017) and EUS-FNB (10/2015-08/2017) with SharkCore needle of pancreatic solid mass lesions were retrieved. Clinical, radiologic, and pathologic data was recorded. Pathology results of malignancy/neoplasms with uncertain malignant potential were considered as true positive. The "negative" cases included were with ≥6 months of follow-up. Nondiagnostic cases showed unremarkable pancreatic tissue, nonpancreatic elements, atypia, or features suspicious for malignancy. Diagnostic yield was defined as percentage of lesions sampled in which a benign or malignant tissue diagnosis, as defined above, was obtained. Statistical comparisons were performed using Fisher's exact test and univariable and multivariable logistic regression analysis. RESULTS: The study cohort included 76 FNA only cases, 88 FNB only cases, and 40 combined FNA/FNB cases. Diagnostic yields were 70% (FNA), 70% (FNB), and 83% (FNA/FNB), which were not statistically different. Increase in lesion size and presence of ROSE were significantly associated with a diagnostic outcome on both univariable and multivariable analysis, unlike the number of passes. CONCLUSION: Our results demonstrate that for solid pancreatic lesions, the diagnostic yields of FNA, FNB, and combined FNA and FNB are comparable. Presence of ROSE and increasing lesion size increased the diagnostic yield while the number of passes had no significant impact.

Cytological diagnosis of papillary thyroid carcinoma with tall cells on ThinPrep liquid-based cytology.

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (PTC-TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC-TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC-TC. METHODS: Preoperative cytology samples from 30 cases of histologically-proven PTC-TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features. RESULTS: Tall cells were present in the majority of PTC-TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap-bubble pseudoinclusions were very specific features of PTC-TC, when present. PTC-TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC-TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC-TC vs controls. CONCLUSION: Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value below 0.7 for positive for high-grade urothelial carcinoma and suspicious for high-grade urothelial carcinoma in urine cytology specimens.

BACKGROUND: Urinary cytology is sensitive and specific for diagnosing and screening high-grade urothelial carcinomas (HGUC). The Paris System (TPS) for urinary cytology was introduced in 2016 to standardize reporting. According to TPS diagnostic categories of HGUC and suspicious for HGUC (SHGUC), the average nuclear-to-cytoplasm (N:C) ratio of atypical cells should be ≥0.7. The objective of the current study was to measure the N:C ratio of urine cytology specimens with HGUC and SHGUC diagnoses and biopsy-proven HGUC follow-up. METHODS: A cohort of 64 cases (HGUC, 49 cases; SHGUC, 15 cases) from 57 patients was constructed. Urine cytology slides were scanned into whole-slide digital images. The nuclear and cytoplasmic areas were enumerated by digital image analysis (DIA), and the N:C ratios were measured. RESULTS: In total, 640 cells were analyzed by DIA (HGUC, 490 cells; SHGUC, 150 cells). For HGUC and SHGUC, the average N:C ratios were 0.57 and 0.53, respectively. The maximum average N:C ratio was 0.73 for HGUC and 0.68 for SHGUC. HGUC had higher average N:C ratio (P < .001), higher average nuclear area (P < .001), higher average maximum N:C ratio (P = .005), and higher average maximum nuclear area (P = .006) compared with SHGUC. CONCLUSIONS: The N:C ratios for the HGUC (0.57) and SHGUC (0.53) categories are lower than those previously suggested in TPS. The authors advocate reducing the N:C ratio below the current threshold of 0.7.

Decreased UCHL1 expression as a cytologic biomarker for aggressive behavior in pancreatic neuroendocrine tumors.

BACKGROUND: There are currently no reliable markers associated with aggressive behavior in well-differentiated and moderately differentiated pancreatic neuroendocrine tumors. We aimed to determine whether expression of ubiquitin carboxyl-terminal hydrolase L1 in conjunction with Ki67 can identify metastatic potential of well-differentiated and moderately differentiated pancreatic neuroendocrine tumors from fine-needle aspiration samples obtained by endoscopic ultrasound. METHODS: Retrospective review of 48 patients with well-differentiated and moderately differentiated pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound fine-needle aspiration at a single center identified 35 biopsy samples with adequate material for analysis. Ubiquitin carboxyl-terminal esterase L1 immunocytochemistry of primary pancreatic neuroendocrine tumors was performed along with Ki67 staining and scored semiquantitatively. The combination of ubiquitin carboxyl-terminal esterase L1 score ≤4 (weak) and Ki67 ≥3% (high) was considered a positive test for predicting tumors associated with metastases. RESULTS: Weak ubiquitin carboxyl-terminal hydrolase L1 staining had 80% sensitivity, 65% specificity, 63% positive predictive value, and 81% negative predictive value to identify primary tumors associated with metastatic disease. The combination of weak ubiquitin carboxyl-terminal hydrolase L1 staining and high Ki67 staining increased the test specificity to 95%. On multivariable analysis, combined positive test of weak ubiquitin carboxyl-terminal esterase L1 staining and high Ki67 staining was an independent predictor of metastatic disease (P = .047). CONCLUSION: Ubiquitin carboxyl-terminal hydrolase L1 is a novel biomarker for identifying malignant potential of primary well-differentiated and moderately differentiated pancreatic neuroendocrine tumors and in combination with Ki67 is an independent predictor of development of metastatic disease.