title: Are G3 ENETS neuroendocrine neoplasms heterogeneous?
abstract: The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Villejuif, France.
authors.forename: Fritz-Line
authors.initials: FL
authors.lastname: Vélayoudom-Céphise
authors.forename: Pierre
authors.initials: P
authors.lastname: Duvillard
authors.forename: Lydia
authors.initials: L
authors.lastname: Foucan
authors.forename: Julien
authors.initials: J
authors.lastname: Hadoux
authors.forename: Cecile N
authors.initials: CN
authors.lastname: Chougnet
authors.forename: Sophie
authors.initials: S
authors.lastname: Leboulleux
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.forename: Joël
authors.initials: J
authors.lastname: Guigay
authors.forename: Diane
authors.initials: D
authors.lastname: Goere
authors.forename: Thierry
authors.initials: T
authors.lastname: Debaere
authors.forename: Caroline
authors.initials: C
authors.lastname: Caramella
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.forename: Dominique
authors.initials: D
authors.lastname: Elias
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D053379:Chromogranin A / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053379:Chromogranin A; C569014:SYP protein, human; D016708:Synaptophysin; D010751:Phosphopyruvate Hydratase; D002945:Cisplatin
keywords: Ki67 index; WHO classification; grade 3 neuroendocrine carcinoma; mitotic count