Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Stefano Crippa, Stefano Partelli, Giulio Belfiori, Marco Palucci, Francesca Muffatti, Olga Adamenko, Luca Cardinali, Claudio Doglioni, Giuseppe Zamboni, Massimo Falconi, Stefano Crippa, Stefano Partelli, Giulio Belfiori, Marco Palucci, Francesca Muffatti, Olga Adamenko, Luca Cardinali, Claudio Doglioni, Giuseppe Zamboni, Massimo Falconi

Abstract

Neuroendocrine carcinomas (NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.

Keywords: Chemotherapy; Metastases; Morphology; Neuroendocrine carcinomas; Pancreatic neuroendocrine tumors; Prognosis; Proliferation; Surgery.

Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest, no financial support.

Figures

Figure 1
Figure 1
Pancreatic poorly differentiated neuroendocrine carcinomas of the pancreatic body-tail associated with neoplastic thrombosis of the splenic vein/portal vein, and with a lymphadenopathy along the stomach. The patients underwent left pancreatectomy with splenectomy, portal vein resection with portal vein thrombectomy and partial gastric resection.
Figure 2
Figure 2
A small cell poorly differentiated neuroendocrine carcinoma of the pancreas (A) (haematoxylin-eosin stain) and a small cell poorly differentiated neuroendocrine carcinoma of the pancreas with high ki67 proliferative index (B, Ki67: 90%).
Figure 3
Figure 3
Shows a large cell poorly differentiated neuroendocrine carcinoma of the pancreas (A, haematoxylin-eosin stain) and a large cell poorly differentiated neuroendocrine carcinoma of the pancreas with its Ki67 proliferative index (B, Ki67: 80%).
Figure 4
Figure 4
Morphological well differentiated neuroendocrine carcinoma of the pancreas (A, haematoxylin-eosin stain) and morphological well differentiated neuroendocrine carcinoma of the pancreas with Ki67 proliferative index of 30% (B).
Figure 5
Figure 5
Diagnostic flowchart algorithm in patients with pancreatic neuroendocrine carcinomas.
Figure 6
Figure 6
Different therapeutic options in patients with morphological poorly differentiated neuroendocrine carcinomas of the pancreas. 18FDG-PET: 18F-fluorodeoxyglucose positron emission tomography.
Figure 7
Figure 7
Management flowchart algorithm in patients with morphological well differentiated neuroendocrine carcinomas of the pancreas. PRRT: Peptide receptor radionuclide therapy; TAE: Transarterial embolization; TACE: Transarterial chemoembolization; SSA: Somatostatin analogues.

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