Grading of pancreatic neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspiration using Ki-67 index and 2017 World Health Organization criteria: An analysis of 32 cases

Objectives: Biological behavior of pancreatic neuroendocrine tumors (Pan NETs) is difficult to predict on morphology alone. The assessment of proliferation by the Ki-67 proliferation index (PI) is considered to be an important prognostic parameter in these tumors and has been endorsed by the 2017 World Health Organization (WHO) grading system for Pan NETs. Although widely accepted on surgical specimens, there is varied opinion on grading of these tumors on cytology samples. This study aimed at classification and grading of Pan NETs on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using the recent 2017 WHO criteria and assess the reliability of Ki-67 grading by comparing it with histology samples wherever available. Material and Methods: Search of cytopathology lab records over a 3-year period (June 2015-May 2018) revealed 33 cases of pancreatic NETs diagnosed on EUS-FNA specimens. Using the guidelines of 2017 WHO classification and grading of Pan NETs, retrospective grading of these Pan NETs was done. They were graded as Grades 1, 2, and 3 well differentiated Pan NETs and poorly differentiated Grade 3 neoplasms based on Ki-67 PI and cytomorphology. Cytomorphological features were compared across the three grades. The cytological grading was then compared with the histological grading where available. Results: Ki-67 grading on cytology was done in 32 cases (22 on cell block and 10 on smears), of which 19 (59.4%) were Grade 1, 8 (25%) were Grade 2, and 5 (15.6%) were Grade 3 tumors. The most common cytomorphological features observed in Grade 1 tumors were small round uniform cells with granular chromatin and prominent plasmacytoid morphology. As the grade increased, tumor cells showed increased pleomorphism, angulated nuclei, and less frequent plasmacytoid cells. Histopathology (biopsy/resected specimens) was available in 11 of the 32 cases. Comparison of grading on cytology and histology showed concordance in ten of the 11 cases (k value = 0.862). Conclusion: Our data suggest that grading of Pan NETs by assessing Ki-67 PI on cytology samples collected by EUS-FNA shows good agreement with that measured on histology samples.