Interobserver agreement in the cytologic grading of atypia in neoplastic pancreatic mucinous cysts with the 2‐tiered approach

Goyal, Abha; Abdul‐Karim, Fadi W.; Yang, Bin; Patel, Jinesh; Brainard, Jennifer

doi:10.1002/cncy.21767

Cited by 13 publications

(14 citation statements)

References 30 publications

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“…The presence of a TP53 variant in the pancreatic cyst with high‐grade cytologic atypia, although limited by sample size, suggests that the detection of a TP53 variant in pancreatic cysts could be a potential marker for high‐risk cysts meriting further investigation. In general, the use of ancillary genetic studies to identify high‐risk lesions following EUS‐FNA may be particularly helpful given the less than ideal interobserver reproducibility in the grading of high‐grade cytologic atypia in pancreatic aspirates 29 . How this translates in clinical practice remains to be seen, as only 6 of 42 (14.3%) cases in this cohort that had follow‐up underwent preoperative genetic testing.…”

Section: Discussionmentioning

confidence: 99%

Next‐generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study

Fulmer

Park

Dilcher

et al. 2020

Cancer Cytopathology

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Background Endoscopic ultrasound–guided fine needle aspiration (EUS‐FNA) is a sensitive and specific tool in the risk stratification of pancreatic lesions, including cysts. The sensitivity and specificity of EUS‐FNA has been shown to improve when cytology is combined with next‐generation sequencing (NGS). Ideally, fresh cyst fluid is used for NGS. In this pilot study, we explore the possibility of sequencing DNA derived from residual alcohol‐fixed pancreatic aspirates. Methods Residual cytologic fixatives (n = 42) from 39 patients who underwent EUS‐FNA for pancreatic lesions were collected along with demographics, imaging, and laboratory studies. Samples were designated as nonneoplastic/nonmucinous benign (NB), mucinous cyst (MC), pancreatic ductal adenocarcinoma (PDAC), or well‐differentiated neuroendocrine tumor (NET) on the basis of cytopathologic evaluation and sequenced on the Oncomine platform (ThermoFisher Scientific, Waltham, Massachusetts). Results Ten of 14 (71.4%) MCs exhibited clinically significant variants, including KRAS, GNAS, and TP53. Ten of 15 (66.7%) PDACs had KRAS alterations, and 9 of 15 (60%) showed variants in TP53. No variants were detected in any NETs. Only 1 of 9 (11.1%) NB aspirates showed variants in KRAS and MAP2K. Sequencing of formalin‐fixed, paraffin‐embedded tissue revealed variants identical to those detected in fixative‐derived DNA in 4 of 5 cases (80%). Conclusion Residual DNA from alcohol‐fixed aspirates are an underutilized source for NGS. Sequencing residual fixative‐derived DNA has the potential to be integrated into the workup of pancreatic aspirates, possibly impacting management.

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Section: Discussionmentioning

confidence: 99%

Next‐generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study

Fulmer

Park

Dilcher

et al. 2020

Cancer Cytopathology

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“…3,12,17 In one study looking at the overall agreement between cytopathologists when applying a two-tiered approach to grading mucinous cyst atypia (low or highgrade), a poor performance was noted particularly in histologically confirmed low-grade cysts, with many of the cytopathologists overinterpreting the grade of atypia. 18 In contrast, however, most studies have shown that the cytological grade of a mucinous cyst correlates well with histology, with high-grade atypia being the only statistically significant predictor of malignancy. 12,17,19 Grading the atypia of the cyst lining cells is of utmost importance, since low-grade lesions are usually managed conservatively, and high-grade lesions require prompt surgical intervention.…”

Section: Experience With the Use Of The Pb System Worldwidementioning

confidence: 95%

“…False positive interpretations are rare and, in the majority of the specimens, represent a discordance between cytology and final histological analysis of the grade of atypia of mucinous cysts . In one study looking at the overall agreement between cytopathologists when applying a two‐tiered approach to grading mucinous cyst atypia (low or high‐grade), a poor performance was noted particularly in histologically confirmed low‐grade cysts, with many of the cytopathologists over‐interpreting the grade of atypia . In contrast, however, most studies have shown that the cytological grade of a mucinous cyst correlates well with histology, with high‐grade atypia being the only statistically significant predictor of malignancy .…”

Section: Experience With the Use Of The Pb System Worldwidementioning

confidence: 99%

Experience and future perspectives on the use of the Papanicolaou Society of Cytopathology Terminology System for reporting pancreaticobiliary cytology

Saieg

Pitman

2020

Diagnostic Cytopathology

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The Papanicolaou Society of Cytopathology developed a set of guidelines for reporting pancreaticobiliary cytology in 2014 (PB System), with a six‐tiered system: Nondiagnostic, Negative, Atypical, Neoplastic (Benign or Other), Suspicious, and Positive. This proposed scheme incorporates ancillary testing such as biochemical testing of cyst fluids for diagnosis and provides terminology that standardizes the category of the various diseases of the pancreas, some of which are difficult to diagnose specifically by cytology alone. Since its initial publication five and half years ago, several groups have published their experiences on the use of the PB System and have shown that most objectives proposed by the original publication have been achieved. They have shown that there is a better understanding and definition of the diagnostic categories with an associated distribution and risk of malignancy. The diagnostic categories of Neoplastic: Other, Suspicious, and Malignant show a high sensitivity and specificity for the diagnosis of malignancy. The System also provides a multi‐specialist view of pancreatic lesions, with biochemical and radiological findings being incorporated into the final pathological report. The present review summarizes these findings and discusses the future perspectives and foreseen changes that are to be incorporated to a second edition of the reporting System.

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“…Previous studies reported that atypical cytological findings by pancreatic EUS‐FNA highly indicated pancreatic neoplasms (55%), including cancer (36%) 4 . Cytological diagnosis is also highly specific for the detection of pancreatic cystic tumours such as intraductal papillary mucinous neoplasm 5 and mucinous cyst neoplasm 6,7 . Thus, cytological diagnosis using pancreatic EUS‐FNA provides important information on indications for surgery 5,8,9 …”

Section: Introductionmentioning

confidence: 99%

Cytological scoring for pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration

et al. 2021

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Objective Cytological diagnosis of pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is often challenging because of the small sample size or well‐differentiated adenocarcinoma with weak cytological atypia. Therefore, the sensitivity and specificity of cytological diagnosis for pancreatic cancer should be improved. Hence, we aimed to clarify the utility of cytological scoring to distinguish malignant from benign lesions for cytological diagnosis of pancreatic EUS‐FNA specimens. Methods Seven reviewers, including four cytotechnologists and three medical doctors, evaluated 20 morphological indices in pancreatic specimens obtained by EUS‐FNA (malignant, n = 111; benign, n = 31). Statistical analyses were performed using Fisher's exact test, logistic regression analysis, the area under the receiver operating characteristic curve, and Youden index. Results Among the 20 indices, there was a high incidence rate (>40%) of the following 13 indices in malignant cases: irregular structure, hyperchromatic nucleus, irregular cell polarity, unclear cell boundaries, nuclear membrane thickening, anisonucleosis, overlapping, irregular nuclei, high nuclear‐cytoplasmic ratio, binding decline, the simultaneous appearance of malignant and benign cells, enlarged nucleoli, and background necrosis. When we diagnosed pancreatic specimens using these 13 cytological indices, the cut‐off value of 8/9 showed the highest Youden index (0.950) as well as high sensitivity and specificity in distinguishing malignant from benign specimens (98% and 97%, respectively). Conclusion Thirteen cytological indices showed high sensitivity and specificity in differentiating malignant and benign lesions using pancreatic EUS‐FNA samples. All 13 indices were important for diagnosing malignancy in the pancreatic cytology smear of EUS‐FNA. Further validation studies are required.

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Interobserver agreement in the cytologic grading of atypia in neoplastic pancreatic mucinous cysts with the 2‐tiered approach

Cited by 13 publications

References 30 publications

Next‐generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study

Next‐generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study

Experience and future perspectives on the use of the Papanicolaou Society of Cytopathology Terminology System for reporting pancreaticobiliary cytology

Cytological scoring for pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration

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