Prognostic criteria in nonfunctioning pancreatic endocrine tumours

Abstract

To identify prognostic subgroups among non-functioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index > 2%, mitotic rate > or = 2, size > or = 4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of non-functioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases.

Neuroendocrine tumor disease: an evolving landscape

“…Validation of the prognostic ability of Ki-67 has shown differences in 5-year survival using a binary schema of !2 or O2%: pancreatic NENs (PNENs) showed 100 vs 54% survival at 5 years (La Rosa et al 1996); a mixed group of GEP-NENs showed 56 vs 14% and 90 vs 54%, and a mixed group of pancreatic, SI, and colorectal NENs showed 76 vs 29% (Arnold et al 2008a). More recently, the use of Ki-67 was defined for PNENs in a study on 1072 patients with at least 2 years of follow-up (Rindi et al 2012).…”

Highlights of the biology of endocrine tumours of the gut and pancreas.

“…Finally, there is no histological tumour grading for welldifferentiated endocrine tumours of the digestive tract, although it has been tentatively developed for pancreatic and gastric tumours (La Rosa et al 1996, Rindi et al 1999a. Further, a number of clinicopathological criteria proved to be useful predictors of malignant behaviour (La Rosa et al 1996, Rindi et al 1999a and included: tumour size (larger tumours tend to be more aggressive); invasion of nearby tissue (pancreas or appendix) or deep wall invasion; angioinvasion and invasion of perineural spaces; presence of spotty necrosis; overt cell atypia; more than two mitoses in 10 microscopic high power fields (HPF); Ki-67 index of more than 100/10 HPF or more than 2%; loss of chromogranin A immunoreactivity or hormone expression; nuclear p53 protein accumulation; and aneuploid status of tumour cells.…”

“…Further, a number of clinicopathological criteria proved to be useful predictors of malignant behaviour (La Rosa et al 1996, Rindi et al 1999a and included: tumour size (larger tumours tend to be more aggressive); invasion of nearby tissue (pancreas or appendix) or deep wall invasion; angioinvasion and invasion of perineural spaces; presence of spotty necrosis; overt cell atypia; more than two mitoses in 10 microscopic high power fields (HPF); Ki-67 index of more than 100/10 HPF or more than 2%; loss of chromogranin A immunoreactivity or hormone expression; nuclear p53 protein accumulation; and aneuploid status of tumour cells. These variables should all be considered in assigning a tentative risk class for each specific case.…”

“…The lack of concomitant detectable p53 mutations and a detailed 17p allelotyping led these authors to suggest that an additional, malignancyinvolved tumour suppressor gene may occur in 17p telomeric to p53. p53 nuclear hyperexpression/accumulation was frequently observed in poorly differentiated cases (La Rosa et al 1996).…”

Feasibility of Mesenteric Vein Reconstruction with PTFE Prosthesis for Non Functioning Endocrine Pancreatic Tumor Surgery

“…EPTs have been recently stratified, on the basis of the WHO classification, in 3 categories: benign tumors, well-differentiated carcinomas with low-grade malignant behaviour and poorly-differentiated carcinomas with high grade malignant behaviour [10]. Malignancy is assessed by the presence of invasiveness of adjacent structures or viscera and/ or metastases or, in their absence, by the following criteria: vascular or perineural microinvasion, tumor size >4 cm., Ki 67 proliferative index >2%, presence of necrosis and/or clear cellular atypia, capsular penetration, mitotic rate >2, loss of chromogranin A (CgA) and calcitonin immunoreactivity, argyrophilia and nuclear p53 protein accumulation [11]. Surgeons approaching EPTs must firstly address the problem of a correct diagnosis that could be uncertain when facing a bulky pancreatic mass with charachteristics resembling the more common pancreatic adenocarcinoma.…”