IMMUNOHISTOCHEMICAL AND MORPHOLOGICAL CHARACTERIZATION OF SPONTANEOUSLY OCCURRING PHEOCHROMOCYTOMAS IN THE AGING MOUSE

Pheochromocytomas in mice are rare tumors, and their expression of fun ctional markers has not previously been assessed. In this study, 29 sp ontaneously occurring mouse pheochromocytomas were characterized morph ologically and immunohistochemically to determine whether there are fu nctional correlates to previously described morphological features and to provide a database for comparison with tumors that arise in geneti cally engineered animals. The tumors were derived from 28 mice 828-1,4 89 days old, of three genotypes. Considerable cytological and architec tural polymorphism was observed both within and between tumors. Most o f the tumor cells were comparable in size to normal chromaffin cells o r were larger. Small basophilic cells, which are the predominant cell type in rat pheochromocytomas, were usually in the minority. All of th e tumors and most of the cells within individual tumors expressed immu noreactive tyrosine hydroxylase (TH). The tumors were variably positiv e for phenylethanolamine-N-methyltransferase (PNMT) and chromogranin A (CGA). There did not appear to be a global association of specific cy tological features with expression of TH, PNMT, or CGA, although cells of similar appearance often shared similar immunoreactivities within individual tumors. Small basophilic cells could be either PNMT-positiv e or PNMT-negative. The frequency, morphology, and immunophenotype of mouse pheochromocytomas suggest that the mouse may be more appropriate than the rat as a model for human adrenal medullary pathology. In add ition, the expression of immunoreactive PNMT by mouse pheochromocytoma s suggests that these tumors are a potential source of epinephrine-pro ducing cell lines, for which adequate models currently do not exist.