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

Abstract

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.

WITHDRAWN: Survival Nomograms for Patients with Pancreatic Neuroendocrine Tumors: A Population-based Study

“…Over the last two decades, the incidence of PNETs has increased due to improved diagnostic techniques, while the mortality has decreased due to the progress in understanding the pathophysiology and natural history of PNETs as well as better treatment and management [3]. Although PNETs are considered long-term indolent tumors, the outcomes of patients with PNETs are highly variable because of their high genetic heterogeneity [4], tissue histological differentiation, Ki-67 proliferation index, and tumor stage [5]. Thus, a personalized management strategy for PNET patients is urgently needed along with a relevant statistical predictive model [6].…”

Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms

“…Stratified analysis for tumors ≤ 2 cm was also performed; of the 22 articles, 10 reports showed the individual size or details of the classification ≤ 2 cm. Pooling the data of the studies, the concordance rate was 77.5% and the kappa correlation index was 0.65 (95% confidence interval (CI) = 0.59-0.71, p < 0.01) (Table 3) [55,[61][62][63][67][68][69][70][72][73][74][75][76][77][78][79][80][81][82][83][84]87]. The sensitivity of G1 was good at 91.4% (338/370), but it was poor in G2 and G3 at 55.7% and 59.5%, respectively.…”

“…FNA, fine-needle aspiration; FNB, fine-needle biopsy. Concordance of PNEN grading between EUS-FNAB specimens and surgical specimens in pooling data[55,[61][62][63][67][68][69][70][72][73][74][75][76][77][78][79][80][81][82][83][84]87]. Concordance of PNEN grading between EUS-FNAB specimens and surgical specimens in pooling data with small tumor sizes (2 cm or less)[55,61,62,67,69,73,[75][76][77]81,84].…”

Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms

“…However, it is almost impossible to count in 50 HPFs with FNA samples, and the Ki-67 proliferation index is usually used in clinical practice. The concordance rate of the Ki-67 index between PNENs measured from EUS-FNA samples and surgical specimens was reported to be 54%-100% [37,[43][44][45][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] (Table 1), whereas a systematic review reported a rate of 83% [68]. Pooling the data of the studies which compared the Ki-67 LI grades obtained both in EUS-FNA samples and surgical specimen, the concordance rate was 77.5% and the kappa correlation index was 0.65 (95% confidence interval = 0.59 -0.71, P < 0.01) ( Table 2) [37,[43][44][45][49][50][51][52][54][55][56][57][58][59][60][61][62][63][64]…”

“…Table 2. Concordance of PNEN grading between EUS-FNAB specimens and surgical specimens in pooling data [37,[43][44][45][49][50][51][52][54][55][56][57][58][59][60][61][62][63][64][65][66]69]. Grade 1 Grade 2 Grade 3 Total Grade 1 338 88 5 431 Grade 2 32 111 12 155 Grade 3 0 0 23 23 Total 370 199 40 609…”