Are G3 ENETS neuroendocrine neoplasms heterogeneous?

Abstract

The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index O20 and/or Ki67 index O20% 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 O20 and/or Ki67 O20% 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 (PZ0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (PZ0.049). 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.

Clinical outcomes and prognostic factors of resected pancreatic neuroendocrine neoplasms: A single-center experience in China

“…p-NEC exhibits a poor prognosis (24) and previous evidence has demonstrated the decreased survival rate of patients with p-NEC (25,26). Furthermore, increased lymph node metastasis in p-NEC was observed in the present study.…”

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

“…Each case was diagnosed as well-differentiated neuroendocrine tumour (NET) or poorly differentiated neuroendocrine carcinoma (NEC), based on histopathological criteria [35,36,37], but importantly without taking into account results of mitotic count and Ki67 LI. Details on tissue processing procedure and diagnostics are provided in SI -Methods.…”

Pancreatic neuroendocrine tumors

“…This classification system is simple and useful to standardize diagnosis and treatment. However, previous studies demonstrated that some pNENs with a high proliferative activity, but well-differentiated degree, are also classified into NEC (15,16). Furthermore, this subtype of pancreatic NEC, named well differentiated NET G3 normally, presented significantly better disease-specific survival than in the poorly differentiated subtype, which suggests that the biological behaviors of the two are different (17)(18)(19).…”