Deoxyribonucleic Acid Cytometry Helps Identify Parathyroid Carcinomas*

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Abstract
It may be difficult in some patients with parathyroid tumors to distinguish between parathyroid carcinoma and parathyroid adenoma on the basis of clinical and histopathological findings. Patients initially diagnosed as having a parathyroid adenoma have subsequently occasionally developed metastases, and thereby their tumor was proven to be a carcinoma. To determine whether the nuclear DNA content would correlate with the clinical course and pathology of parathyroid tumors DNA cytometry was performed on parathyroid carcinomas (9 patients), histologically atypical adenomas (10 patients), adenomas associated with severe hypercalcemia [serum calcium, .gtoreq. 13.0 mg/dL (.gtoreq. 3.24 mmol/L); 11 patients], typical benign adenomas (11 patients), and incidentally removed normal parathyroid glands (6 patients). Sections were cut from the original paraffin-embedded surgical specimens and stained for nuclear DNA using the azure A Feulgen reaction. Nuclear DNA stain content was measured using and integrating imaging cytometer, and the results were plotted as histograms. Adjusted optical density (AOD) values were measured (in arbitrary units) to estimate the DNA content of whole nuclei in the specimens. The mean nuclear DNA content in the parathyroid carcinomas [24.6 .+-. 2.1 (.+-. SE) AOD] was significantly greater than that in the three groups of parathyroid adenomas (P < 0.005, by unpaired t test) and in the normal parathyroid glands (P < 0.0005). The mean nuclear DNA content in the atypical adenomas (15.8 .+-. 1.6 AOD), profoundly hypercalcemic adenomas (16.8 .+-. 1.3 AOD), and typical adenomas (16.0 .+-. 1.1 AOD) were similar, and all were significantly greater than that in the normal parathyroid glands (11.5 .+-. 0.7 AOD, P < 0.05). Five distinct DNA histogram patterns were present in the parathyroid specimens from these 47 patients. Four of the 9 parathyroid carcinomas had an aneuploid DNA pattern, an abnormal pattern not found in any of the other groups; 2 of these tumors were originally diagnosed as atypical parathyroid adenomas. Both patients developed recurrent disease, and 1 died from a hepatic metastasis. Therefore, DNA cytometry provides valuable information in differentiating some parathyroid carcinomas from adenomas and diagnosing certain parathyroid carcinomas before the appearance of grossly invasive or metastatic tumor.