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Determining Prognosis in Patients With Pancreatic Endocrine Neoplasms: Can the WHO Classification System Be Simplified?

Cristina R. Ferrone, Laura H. Tang, James Tomlinson, Mithat Gonen, Steven N. Hochwald, Murray F. Brennan, David S. Klimstra, Peter J. Allen

From the Departments of Surgery, Pathology, and Epidemiology/Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Peter J. Allen, MD, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Howard 1223, 1275 York Ave, New York, NY 10021; e-mail: allenp{at}mskcc.org

Purpose The WHO classification for well-differentiated pancreatic endocrine neoplasms (PENs) incorporates both stage and grade. This study compares the prognostic value of a simplified staging and grading system with the WHO system in a large single-institution study.

Patients and Methods A prospective database (1982 to 2005) identified 183 patients who underwent operative treatment for PENs. Tumors were staged (< 2 cm primary, 2 cm primary, or metastases) and graded (low grade: no necrosis and < two mitoses/50 high-powered fields [HPF]; or intermediate grade: necrosis and/or two mitoses/50 HPF) with a simplified schema. Influence of stage and grade on recurrence and disease-specific survival (DSS) was determined. Prognostic strength was assessed with the concordance index (CI).

Results Median age of the 183 patients was 56 years, and 53% were women. Median follow-up time was 44 months (range, 1 to 226 months). Classification identified 28 patients (15%) with WHO 1.1 disease, 74 (41%) with 1.2 disease, and 81 (44%) with 2.0 disease. Classification by stage identified 35 patients (19%) with tumors less than 2 cm, 96 (52%) with tumors 2 cm, and 52 (29%) with nodal or distant metastases. Tumors were low grade in 102 patients (56%). Earlier stage tumors were more likely to be low grade (< 2 cm, 83%; 2 cm, 61%; metastases, 28%; P < .001). The WHO classification, tumor stage, and grade were associated with 5-year DSS (P < .001). Tumors 2 cm or metastases are stratified by grade (5-year DSS rate for low v intermediate grade: 2 cm, 97% v 80%, respectively; P < .001; metastases, 93% v 62%, respectively; P = .05). The CI was 0.72 for WHO, 0.71 for stage, 0.66 for grade, and 0.76 for stage combined with grade.

Conclusion Accurate prognostic information can be obtained by combining tumor size and metastases with simple grading information based on necrosis and mitotic rate.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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