Background Identifying high grade features in pancreatic mucinous neoplasms (MN) is important for patient management. It is not clear if MNs can be graded with reproducibility in routine practice. We evaluated interobserver variability in grading MNs and identification of neoplastic mucin in endoscopic ultrasound guided fine needle aspirations (EUS-FNA). Methods We created a 54 case grading set from histologically confirmed MNs (N=44) and nonmucinous lesions (NML) with abundant gastrointestinal contamination (N=10). Six observers received a tutorial, reviewed pre-screened slides, and recorded: 1) a diagnosis according to a 6-tiered system (TS) (nondiagnostic (NDX), atypical (ATP), mucinous cyst low grade (LG), mucinous cyst high grade (HG), suspicious for adenocarcinoma (SSPA), positive for adenocarcinoma (PA)); 2) a diagnosis with cyst fluid CEA (CEADX); and 3) the presence of neoplastic mucin. Interobserver agreement (IOA ) was evaluated by calculation of Kappa coefficients. Diagnostic accuracy was not evaluated. Results IOA was lowest for 6-TS (K=0.13, P<.001). CEADX was available for 18 (33%) cases, including 6/24 (25%) of LG. CEADX modestly improved IOA for combined tiers of the 6-TS with ATP and LG as separate categories. The highest IOA was with a 3-TS (NDX, ATP/LG, HG/SSPA/PA; K=0.28, P<.001) and various 4-TS (K=0.22-0.23). IOA was low for neoplastic mucin (K=0.15, P<.001). Conclusions In a study using simulated cytology practice, observers showed fair IOA for grading MNs and low IOA for identifying neoplastic mucin. Knowledge of cyst fluid CEA level modestly improved IOA for low grade lesions.

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BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) guide the clinical management of breast cancer metastases. Decalcification of bone core needle biopsies (CNBs) can affect IHC. In the current study, the authors sought to define whether fine-needle aspiration (FNA) would be a better alternative to CNB for reliable IHC. METHODS: Patients with breast cancer metastases to bone that were sampled by both CNB and FNA were selected. ER, PR, and HER2 were performed in FNA cell blocks (FNA-CBs) and concurrent decalcified CNBs. Discrepancies were classified as minor when there was a difference of up to 30% nuclear staining in IHC for ER and PR between paired samples and as major when a clinically relevant change was observed (ie, positive vs negative). Quantitative reverse transcriptase-polymerase chain reaction of ESR1 messenger RNA levels was performed on FNA/ CNB pairs with discrepancies for ER IHC. IHC status of the primary breast carcinoma was recorded. RESULTS: Concordance rates for ER, PR, and HER2 were 89%, 67%, and 93%, respectively, between FNA-CB and CNB pairs from 27 patients. Major discrepancies were noted in approximately 11% of FNA/CNB pairs for ER IHC and in 33% of FNA/CNB pairs for PR. ESR1 messenger RNA levels of FNA/CNB matched samples were similar and did not explain the differences in ER IHC expression in the majority of cases. Two of 27 FNA/CNB pairs had different results for HER2 IHC that changed from negative on CNB to equivocal (2+) on FNA-CB. Both cases had prior HER2 amplification by fluorescence in situ hybridization. CONCLUSIONS:FNA-CB and CNB appear to constitute acceptable methods for the assessment of ER, PR, and HER2 for clinical decision making. Cancer Cytopathol 2020;128:133-145. Edelweiss performed the immunohistochemical staining review and the protein quantification. Salvatore Piscuoglio performed the quantitative real-time polymerase chain reaction.