Chemically induced tumors of rat olfactory epithelium: a model for human esthesioneuroepithelioma.

N-Nitrosopiperidine (CAS: 100-75-4) and 2,6-dimethylnitrosomorpholine induced tumors of the olfactory epithelium in white Wistar rats. Some tumors were serially transplanted to NMRI nude mice (nu/nu) and passaged up to 16 times in a 1-year period. Tumor tissues from rats and mice were analyzed by conventional pathological stains, by electron microscopy, and by immunofluorescence microscopy with the use of antibodies specific for different intermediate filaments. Both carcinogens induced tumors built of undifferentiated small, round cells in which neuroblastic (Homer-Wright) rosettes and ependymal (Flexner) rosettes were visible. In some tumors areas of squamous cell metaplasia could be observed, which sometimes differentiated toward squamous cell carcinoma. Electron microscopy showed neurosecretory granules in some tumor cells, and biochemical studies of plasma showed in some instances elevated ACTH and calcitonin levels. Intermediate filament typing showed that in general the undifferentiated tumor cells lack intermediate filaments, although in 6 of 29 tumors a few cells that stained positively for neurofilaments were found. Flexner rosettes, the areas showing squamous cell differentiation, and occasional single tumor cells were positive with keratin antibodies. Neurofilament expression was observed in a minor population of tumor cells placed in tissue culture. These findings are used to argue that the chemically induced rat tumors are a model for human esthesioneuroepithelioma and furthermore that the light basal cells of the epithelium may be the stem cells of the rat tumors as well as of its rare counterparts in humans.