Ki-67 cytological index can distinguish well-differentiated from poorly differentiated pancreatic neuroendocrine tumors: a comparative cytohistological study of 53 cases

Abstract

The Ki-67 labeling index has been found to bear prognostic significance in gastrointestinal neuroendocrine tumors (NETs), and it was recently incorporated in NET histological grading. Nevertheless, a reliable preoperative determination of NET grading could be useful in clinical practice. The aim of this study is to compare the results of Ki-67 labeling index, as measured on cytological samples and on surgical specimens of patients with pancreatic NETs (P-NETs). We also investigated whether concordance might be improved, using a 5 % (instead of 2 %) cutoff value for defining G2 tumors. We retrospectively identified 48 consecutive patients with 53 P-NETs, from our five institutions, and we measured Ki-67 labeling index on their cytological samples and surgical specimens. The traditional 2 % and the alternative 5 % cutoff values were used to classify G2 tumors. The concordance rate between cytological and histological grading was 46/53 (86.8 %; weighted κ statistic 0.77; 95 % confidence interval (95 % CI) 0.60-0.94). No cases of cytological G1-G2 NETs were upgraded to G3 neuroendocrine carcinoma (NEC) at histological grading. Cytology was found to be highly specific in the diagnosis of both G2 (94.1 %; 95 % CI 80.3-99.3) and G3 tumors (100.0 %; 95 % CI 92.8-100), but the sensitivity was poor for G2 NETs (66.7 %; 95 % CI 38.4-88.2) and high for the prediction of G3 NECs (100 %; 95 % CI 39.8-100.0). When the 5 % cutoff value was adopted, concordance rate was 49/53 (92.4 %; weighted κ 0.82; 95 % CI 0.64-1.00). In conclusion, Ki-67 cytological expression can distinguish well-differentiated (both G1 and G2) from poorly differentiated P-NETs, and it may be useful for their preoperative classification.

Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound-Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement

“…This is also largely described in the recent literature [2,15,16,[21][22][23][24] and seems to be due to tumour heterogeneity. Yang et al [25], studying tumour heterogeneity on 45 liver metastases from pNETs, showed that G1 tumours are relatively homogeneous, whereas 91% of their G2 cases harboured areas with <3% Ki67-LI.…”

“…Since 2014 and the publication of our first paper [17], a few groups have done comparative studies between the Ki67-LI obtained on FNA and the corresponding resection specimens [2,9,15,16,[20][21][22][23][24]. Our study represents the largest to date, not only in terms of comparison of grading, but also in terms of Ki67-LI absolute values, between cytology and corresponding resection specimens, studying the influence of tumour size, the number of counted cells on FNA and overall and progression-free survival.…”

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

“…Li et al in their meta-analysis showed that Ki67 LI assessment based on cytological samples had a pooled sensitivity of 64% for detection of G2/G3 vs. G1 tumours [19]. Carlinfante et al showed that Ki67 LI in cytological sample had poor sensitivity for detection of G2 NET, but allowed perfect distinction of NET and NEC [83]. Change of grade of NET is not rare at the stage of synchronous and especially metachronous metastatic disease [15].…”

Can Complementary 68Ga-DOTATATE and 18F-FDG PET/CT Establish the Missing Link Between Histopathology and Therapeutic Approach in Gastroenteropancreatic Neuroendocrine Tumors?

“…Thus, it is not always easy to identify a relation between the tracer uptake and histopathologic indices of tumor proliferation, which can guide therapeutic management. Multiple numbers of lesions with variable tracer uptake at different parts of the tumor, especially in the same organ, may cause the biopsy not to fully reflect in vivo tumor heterogeneity (5,6), thus leading to inaccurate Ki67 values. Likewise, tumors with lower proliferation are supposed to be less aggressive and vice versa, but that is not always the case.…”