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

Elvebakken, Hege; Perren, A.; Scoazec, Jean-Yves; Tang, Laura H; Federspiel, Birgitte; Klimstra, David S; Vestermark, Lene W; Ali, Abir S; Zlobec, I.; Myklebust, Tor Å; Hjortland, Geir O; Langer, Seppo W; Gronbæk, Henning; Knigge, Ulrich; Tiensuu Janson, Eva; Sorbye, Halfdan (2021). A consensus developed morphological re-evaluation of 196 high-grade gastroenteropancreatic neuroendocrine neoplasms and its clinical correlations. Neuroendocrinology, 111(9), pp. 883-894. Karger 10.1159/000511905

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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).

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