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Neuroendocrinology. 2018;107(2):114-126. doi: 10.1159/000489902. Epub 2018 Jun 12.

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up.

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Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy.
Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
Department of Internal Medicine, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy.
Clinical Epidemiology and Biometry Service, IRCCS San Matteo Hospital, Pavia, Italy.
Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore-Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Rome, Italy.
Anatomic Pathology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.



Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs.


Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival.


Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs.


Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease.


Gastric neuroendocrine neoplasms; Grading; Invasive behavior; Prognosis; Size; Stage


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