Pancreatic neuroendocrine tumors: accurate grading with Ki-67 index on fine-needle aspiration specimens using the WHO 2010/ENETS criteria

Abstract

Background: The natural history of pancreatic neuroendocrine tumors (panNETs) is extremely variable. One of the most controversial problems in diagnosis is the accurate prediction of the clinical behavior of these tumors. PanNETs that behave aggressively with a malignant course may have bland cytologic features, while some tumors with previously described "malignant" features may behave in a benign or indolent fashion. Various classification schemes have been proposed for grading panNETs. The European Neuroendocrine Tumor Society (ENETS) and 2010 World Health Organization (WHO) classification schemes include counting the mitotic index and/or the Ki-67 proliferation index for grading. The current study was undertaken to determine whether tumors sampled by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be accurately graded based on the Ki-67 index when compared to surgical samples.

Methods: Corresponding EUS-FNA cytology and surgical tissue specimens were obtained for 22 tumors and stained for hematoxylin and eosin (H&E) and the Ki-67 proliferation marker (MIB-1 antibody). Samples were graded by scoring Ki-67 staining indices in accordance with the 2010 ENETS/WHO criteria. The grading scores assigned to the EUS-FNA cytology samples were compared with the scores assigned to the corresponding histological samples.

Results: The majority (86%) of EUS-FNA cytology samples and corresponding surgical tissue specimens demonstrated concordant grading based on Ki-67 indices.

Conclusions: These results indicate that EUS-FNA cytology samples can be accurately graded based on the WHO Ki-67 labeling scheme. Thus, Ki-67 scoring in EUS-FNA cytology samples is an alternative approach for establishing the grade of panNETs. Accurate grading of panNETs is critical for predicting tumor biology, patient prognosis, and making informed decisions regarding patient management and treatment.

Keywords: Ki-67; cytology; fine-needle aspiration; grading; pancreatic neuroendocrine tumor; proliferation index.