Flow cytometric DNA analysis for the determination of malignant potential in adrenal and extra-adrenal pheochromocytomas or paragangliomas

DNA ploidy studies were performed by flow cytometry on extracted nuclei from 53 adrenal, 13 carotid body, 14 retroperitoneal, two intrathoracic, two urinary bladder, and one cauda equina pheochromocytomas (paragangliomas). A specific technique was used for preparation of paraffin-embedded tissue into single associated nuclei, and another specific method was used for propidium iodide staining. Twenty normal adrenal glands were also analyzed as controls. Six tumors in the adrenal medulla yielded uninterpretable histograms (coefficient of variation >7%) because of excessive cell debris or other technical failure. All control adrenal glands were diploid. Seventy-two tumors were clinically benign and seven were malignant as evidenced by regional or distant metastases and/or extensive local invasion. Fifty-six (71%) of 79 tumors disclosed a normal DNA diploidy pattern with a benign clinical course. Abnormal DNA histograms including tetraploidy and aneuploidy patterns were observed in the remaining 23 cases, including the seven malignant tumors. Significantly more malignant tumors occurred in the DNA tetraploid group and the DNA aneuploid group than in the normal DNA group; considered together, the two groups with abnormal DNA histograms differed significantly from the normal DNA group. On the basis of these results, nondiploid tumors are considered to be more prone to aggressive behavior than diploid tumors and, therefore, should be carefully monitored.