Ki‐67 proliferation index in neuroendocrine tumors: Can augmented reality microscopy with image analysis improve scoring?

Abstract

BackgroundThe Ki‐67 index is important for grading neuroendocrine tumors (NETs) in cytology. However, different counting methods exist. Recently, augmented reality microscopy (ARM) has enabled real‐time image analysis using glass slides. The objective of the current study was to compare different traditional Ki‐67 scoring methods in cell block material with newer methods such as ARM.MethodsKi‐67 immunostained slides from 50 NETs of varying grades were retrieved (39 from the pancreas and 11 metastases). Methods with which to quantify the Ki‐67 index in up to 3 hot spots included: 1) “eyeball” estimation (EE); 2) printed image manual counting (PIMC); 3) ARM with live image analysis; and 4) image analysis using whole‐slide images (WSI) (field of view [FOV] and the entire slide).ResultsThe Ki‐67 index obtained using the different methods varied. The pairwise kappa results varied from no agreement for image analysis using digital image analysis WSI (FOV) and histology to near‐perfect agreement for ARM and PIMC. Using surgical pathology as the gold standard, the EE method was found to have the highest concordance rate (84.2%), followed by WSI analysis of the entire slide (73.7%) and then both the ARM and PIMC methods (63.2% for both). The PIMC method was the most time‐consuming whereas image analysis using WSI (FOV) was the fastest method followed by ARM.ConclusionsThe Ki‐67 index for NETs in cell block material varied by the method used for scoring, which may affect grade. PIMC was the most time‐consuming method, and EE had the highest concordance rate. Although real‐time automated counting using image analysis demonstrated inaccuracies, ARM streamlined and hastened the task of Ki‐67 quantification in NETs.

Digital Image Analysis of the Proliferation Markers Ki67 and Phosphohistone H3 in Gastroenteropancreatic Neuroendocrine Neoplasms: Accuracy of Grading Compared With Routine Manual Hot Spot Evaluation of the Ki67 Index

“…13,34,35 For breast cancers, there is a debate about whether the manual analysis of Ki67 should be the gold standard since several studies have shown superior prognostic information from DIA. 39,40 In conclusion, standardized DIA Ki67 scoring gave similar results as subjective scoring but may be a time-saving supplementary tool in surgical pathology 29 that can improve the poor intraobserver and interobserver reliability with manual evaluation methods. 41 DIA PHH3 do not agree so well with routine grading and is not recommended as an alternative to MAI or Ki67 in routine practice.…”

“…This study confirms an excellent agreement between the DIA Ki67 and the pathology Ki67, a finding that is supported by other studies. 13 , 29 DIA can improve the reliability and reproducibility of grading in routine practice. 30 Thus, likely the pathology departments with this method or similar DIA available, can use DIA Ki67 as a part of their routine diagnostics.…”

Ki-67 assessment of pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis of manual vs. digital pathology scoring

“…Guidelines established using histological samples have been extrapolated to grading PanNENs in cytology material (e.g., cell blocks) procured by FNA. Several studies have demonstrated that Ki-67 assessment by manual counting of tumor cells in cell blocks can result in under-grading of these neoplasms when compared with matched surgical resection specimens 36 , 42 , with discrepancies more often observed in G2 cases 20 , 29 . Intriguingly, Abi-Raad and colleagues demonstrated that counting hotspots instead of the complete cell block can provide a higher concordance with surgical specimens, especially for FNA samples that contain ≥ 1000 cells 43 .…”

Mitotic count of fine needle aspiration material of gastrointestinal stromal tumours of the stomach underestimates actual mitotic count

“…The assistance of artificial intelligence in digital image analysis has shown increased efficiency with comparable results to manual mitotic counts in breast cancer and melanoma 23‐25 . Artificial intelligence has been used in cell block material of gastric neuroendocrine tumours in the calculation of the Ki‐67 proliferation index 26,27 . However, there is no set risk stratification in GISTs for the use of the Ki‐67 proliferation index and artificial intelligence for mitotic counts has not yet been studied in either GISTs or cytology cell block material.…”

“…[23][24][25] Artificial intelligence has been used in cell block material of gastric neuroendocrine tumours in the calculation of the Ki-67 proliferation index. 26,27 However, there is no set risk stratification in GISTs for the use of the Ki-67 proliferation index and artificial intelligence for mitotic counts has not yet been studied in either GISTs or cytology cell block material.…”