DNA ploidy and proliferating cell nuclear antigen in islet cell tumors

It is often difficult for pathologists to differentiate between benign and malignant islet cell tumors solely by histopathological criteria. The unequivocal evidence of malignancy is still the presence of metastases since cellular morphology or pleomorphism does not often render the biological clues of malignancy. Recently, nuclear DNA patterns have been reported for islet cell tumors using flow cytometry and image analysis to differentiate between benign and malignant tumors, yet conclusions are still controversial. With 28 surgically resected islet cell tumors, including 20 primary and eight metastatic tumors, nuclear DNA ploidy was analyzed and compared for the S-phase by image analysis and immunocytochemical staining for proliferating cell nuclear antigen (PCNA). Five additional autopsy cases were included for image analysis study. Small insulinomas (< 5 cm) were all benign, whereas gastrinomas were more frequently malignant. One-half of all islet cell tumors (14 of 28) were diploid and S-phase values by image analysis did not correspond with the comparable data obtained by PCNA staining. With cumulative information on tumor size, hormone secretion, mitotic figures, and PCNA positivity, islet cell tumors can be classified as benign or malignant with confidence.