Atypical and suspicious diagnoses in solid pancreatic lesions: Cytomorphologic features and interobserver variability in FNA smears and biopsies

Abstract Background Atypical (ATY) and suspicious (SUS) diagnoses in fine‐needle aspiration/biopsy (FNA/B) of solid pancreatic lesions remain challenging to consistently apply. The most relevant cytomorphologic features and reproducibility of these interpretations across direct smears and FNBs are not well characterized. Methods In total, 124 FNA/B specimens (87 smears, 37 FNBs) from solid pancreatic masses originally diagnosed as ATY or SUS were identified (from 2014 to 2024). Clinical/pathologic follow‐up was reviewed, and morphologic features were systematically assessed. Interobserver variability was evaluated using blinded re‐interpretation of 40 smears and 20 FNBs by four cytopathologists and three cytopathology fellows. Results Non‐adenocarcinoma malignancies (16 smears and 3 FNBs) were excluded for outcomes and morphologic analysis. The risk of malignancy was high in both categories (smears: ATY, 72.3%; SUS, 90.0%; FNBs: ATY, 80.0%; SUS, 100%). ATY smears more often showed scant cellularity (87.8% vs. 59.1% of SUS smears; p = .011), whereas SUS cases more commonly demonstrated anisonucleosis ≥4:1 (54.5% vs. 20.4%; p = .010). On FNBs, background chronic pancreatitis was significantly more frequent in SUS cases (75.0% vs. 11.5%; p = .001). Interobserver agreement was fair for smears (κ = 0.355) and lower for FNBs (κ = 0.218), with fellows rendering ATY/SUS diagnoses more frequently than staff cytopathologists. Conclusions Both ATY and SUS interpretations in solid pancreatic lesions carry high malignancy risk. Smears show clearer morphologic features for upgrading from ATY to SUS, whereas FNBs demonstrate fewer discriminating features and lower reproducibility. These findings support continued refinement of specimen‐type‐specific morphologic criteria and ongoing education to reduce variability in reporting.