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Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases With a Proposal for Low-Grade and Intermediate-Grade Groups

From the Department of Surgery, University of Florida College of Medicine, Gainesville, FL, and Departments of Pathology and Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to David S. Klimstra, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; email: klimstrd{at}mskcc.org

PURPOSE: In some organs (eg, the lung), endocrine tumors are classified on the basis of mitotic rate and necrosis. The purpose of this study was to evaluate prognostic factors in pancreatic endocrine neoplasms recently treated at a single institution.

PATIENTS AND METHODS: In 136 patients undergoing surgery from 1979 to 1998, the influence on disease-free survival (DFS) and disease-specific survival (DSS) of tumor size, mitotic rate, vascular invasion, necrosis, metastases, and nuclear grade was determined. Cases were further grouped according to an existing proposed classification system and then regrouped on the basis of mitotic rate (< 2 mitoses per 50 high-power fields v higher) and necrosis (present or absent) into low- and intermediate-grade groups.

RESULTS: Correlations with DFS and DSS in univariate analysis included 2 mitoses per 50 high-power fields (P = .001, P = .002), vascular invasion (P = .02, P = .04), size 2 cm (P = .01, P = .05), metastases (P = .0002, P = .07), necrosis (P = .002, P = .16), and nuclear grade (P = .04, P = .33), respectively. By multivariate analysis, for DFS, tumor necrosis and presence of metastases retained significance (P = .01, P = .04, respectively). For DSS, only mitotic rate was a prognostic factor (P = .02). Among the 18 macroadenomas, eight borderline tumors, and 48 low-grade carcinomas, there was no significant difference in DSS between any groups (P = .3). However, in evaluating our newly proposed groups, the differences in DFS and DSS between low- and intermediate-grade groups were highly significant (P = .0007, P = .006, respectively).

CONCLUSION: Pancreatic endocrine neoplasms exhibit a spectrum of biologic behavior, and the proposed benign (macroadenoma) and borderline groups contain potentially aggressive tumors. An alternative system based on mitotic rate and necrosis correlates strongly with survival without specifically designating any group as benign.

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