Neuroendocrinology

Research Article

A Consensus-Developed Morphological Re-Evaluation of 196 High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Its Clinical Correlations

Elvebakken H.a,b · Perren A.c · Scoazec J.-Y.d · Tang L.H.e · Federspiel B.f · Klimstra D.S.e · Vestermark L.W.g · Ali A.S.h · Zlobec I.c · Myklebust T.Å.i,j · Hjortland G.O.k · Langer S.W.l · Gronbaek H.m · Knigge U.n · Tiensuu Janson E.h · Sorbye H.o,p

Author affiliations

aDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
bDepartment of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
cInstitute of Pathology, University of Bern, Bern, Switzerland
dDepartment of Biopathology, Institut Gustave Roussy, Villejuif, France
eDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
fDepartment of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
gDepartment of Oncology, Odense University Hospital, Odense, Denmark
hDepartment of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
iDepartment of Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway
jDepartment of Registration, Cancer Registry Norway, Oslo, Norway
kDepartment of Oncology, Oslo University Hospital, Oslo, Norway
lDepartment of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
mDepartment of Hepatology & Gastroenterology, Aarhus University Hospital & ENETS Center of Excellence, Aarhus, Denmark
nDepartment of Surgery C and Endocrinology PE, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
oDepartment of Oncology, Haukeland University Hospital, Bergen, Norway
pDepartment of Clinical Science, University of Bergen, Bergen, Norway

Keywords: Neuroendocrine carcinomasGastroenteropancreatic neuroendocrine neoplasmsNeuroendocrine tumour grade 3Ki-67Morphology

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Neuroendocrinology 2021;111:883–894
https://doi.org/10.1159/000511905

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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: June 03, 2020
Accepted: September 29, 2020
Published online: October 01, 2020
Issue release date: August 2021

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 4

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are classified according to morphology as well-differentiated neuroendocrine tumours (NETs) G3 or poorly differentiated neuroendocrine carcinomas (NECs). Little data exist concerning which morphological criteria this subdivision should be based on. Uncertainty exists if the NEC group should be further subdivided according to proliferation rate. Clinical data on NET G3 and NEC with a lower Ki-67 range are limited. A total of 213 patients with high-grade GEP-NEN (Ki-67 >20%) were included from the Nordic NEC Registries. Four experienced NET pathologists re-evaluated the cases to develop the best morphological criteria to separate NET G3 from NEC, assuming longer survival in NET G3. Organoid growth pattern, capillary network in direct contact to tumour cells, and absence of desmoplastic stroma were found to best separate NET G3 from NEC. Of 196 patients with metastatic disease, NET G3 was found in 12.3%, NEC with a Ki-67 <55% (NEC < 55) in 29.6%, and NEC with a Ki-67 ≥55% (NEC ≥ 55) in 56.6%. Only in 1.5%, the morphology was ambiguous. Of 164 patients receiving first-line chemotherapy, 88% received platinum/etoposide treatment. Response rate was higher for NEC ≥ 55 (44%) than that of NEC < 55 (25%) and NET G3 (24%) (p = 0.025 and p = 0.026). Median progression-free survival was 5 months for all groups. Median overall survival was 33 months for NET G3 compared to 11 months for both NEC < 55 and NEC ≥ 55 (p = 0.004 and 0.003). Specific morphological criteria can separate NET G3 from NECs and show prognostic significance. High-grade GEP-NEN patients stratified by morphology and proliferation rate demonstrate significant differences in response to chemotherapy and survival.

© 2020 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: June 03, 2020
Accepted: September 29, 2020
Published online: October 01, 2020
Issue release date: August 2021

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 4

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

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2021, Vol.111, No. 9

August 2021

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Additional Information

Hege Elvebakken and Aurel Perren contributed equally to this work.

Eva Tiensuu Janson and Halfdan Sorbye shared last authorship.
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