TY - JOUR

T1 - A consensus developed morphological re-evaluation of 196 high-grade gastroenteropancreatic neuroendocrine neoplasms and its clinical correlations

AU - Elvebakken, Hege

AU - Perren, Aurel

AU - Scoazec, Jean-Yves

AU - Tang, Laura H

AU - Federspiel, Birgitte

AU - Klimstra, David S

AU - Vestermark, Lene W

AU - Ali, Abir S

AU - Zlobec, Inti

AU - Myklebust, Tor Å

AU - Hjortland, Geir O

AU - Langer, Seppo W

AU - Gronbæk, Henning

AU - Knigge, Ulrich

AU - Tiensuu Janson, Eva

AU - Sorbye, Halfdan

N1 - © 2020 S. Karger AG, Basel.

PY - 2021

Y1 - 2021

N2 - High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are classified according to morphology as well differentiated neuroendocrine tumours (NET) G3 or poorly differentiated neuroendocrine carcinomas (NEC). 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. 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 1-line chemotherapy, 88% received platinum/etoposide treatment. Response-rate was higher for NEC ≥55 (44%) compared to 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).

AB - High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are classified according to morphology as well differentiated neuroendocrine tumours (NET) G3 or poorly differentiated neuroendocrine carcinomas (NEC). 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. 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 1-line chemotherapy, 88% received platinum/etoposide treatment. Response-rate was higher for NEC ≥55 (44%) compared to 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).

U2 - 10.1159/000511905

DO - 10.1159/000511905

M3 - Journal article

C2 - 33002892

VL - 111

SP - 883

EP - 894

JO - Neuroendocrinology

JF - Neuroendocrinology

SN - 0028-3835

ER -