The role of cytomorphology and proliferative activity in predicting biologic behavior of pancreatic neuroendocrine tumors

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Abstract
BACKGROUND: The biologic behavior of pancreatic neuroendocrine tumors (NETs) is difficult to predict in the absence of metastases or invasion into adjacent organs. In this study, the authors retrospectively evaluated the cytopathology and proliferative activity in cytology specimens obtained by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). METHODS: Thirty-five patients who were diagnosed with pancreatic NET based on EUS-guided FNA were studied retrospectively (2002-2007). Cytopathology and proliferative activity (Ki-67) in cytology specimens were reviewed. Patients were divided into 2 groups: Group A (all patients with simultaneous, suspicious, metastatic masses [unresectable tumors]) and Group B (patients with final histopathologic diagnosis). Moreover, the patients in Group B were classified into 4 risk subgroups according to the 2004 World Health Organization (WHO) classification (Subgroups 1a, 1b, 2, and 3). RESULTS: Thirteen of 35 patients who were diagnosed with unequivocally malignant tumors were placed in Group A (unresectable tumors), and 22 of 35 patients were placed in Group B. In Group A, >2% Ki-67–positive cells were present in 12 of 13 patients (92.3%). In Group B, >2% Ki-67–positive cells were present in 0 of 6 patients in WHO Subgroup 1a (0%), in 3 of 7 patients in WHO Subgroup 1b (42.86%), in 7 of 7 patients in WHO Subgroup 2 (100%), and in 2 of 2 patients in WHO Subgroup 3 (100%). In Group A, nuclear pleomorphism/multinucleation was observed in 8 or 13 patients (61.53%). In Group B, nuclear pleomorphism/multinucleation was observed in 4 of 7 patients in WHO Subgroup 2 (57.14%) and in 2 of 2 patients in WHO Subgroup 3 (100%). In Group A, nucleoli were present in 7 of 13 patients (53.85%); whereas, in Group B, nucleoli were present in 6 of 7 patients in WHO Subgroup 2 (85.7%) and in 2 of 2 patients in WHO Subgroup 3 (100%). None of the remaining cytologic features that were evaluated (necrosis, mitoses, spindle cells, and molding/crush artifact) were observed consistently in malignant NETs. CONCLUSIONS: The current results indicated that Ki-67 evaluation in routine EUS-FNA cytology specimens can be used as a potential prognostic marker in pancreatic NETs. Nuclear pleomorphism/multinucleation and the presence of nucleoli also are reliable for predicting malignant pancreatic NETs. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.