TREATMENT PROTOCOL (including test compound identification, dose, and class of molecule):
No ancillary tests conducted.
Histologically, the nasal masses are comprised of sheets of well-differentiated to poorly differentiated true neuroepithelial rosettes (Flexner-Wintersteiner rosettes) set in a fine fibrovascular stroma. Variably-sized cysts filled with proteinaceous secretory fluid may be present in larger masses. Although nearly all sensory neural neoplasms of olfactory tissue in mammals are histologically malignant and often relatively poorly differentiated, certain large olfactory neoplasms of zebrafish are histologically quite benign, with little evidence of local invasion, so would perhaps be best classified as esthesioneuroepithelioma rather than esthesioneuroblastoma.
CONTRIBUTOR'S COMMENTS: (Proposed pathogenesis of the lesion(s), important considerations and diagnostic features, discussion of controversial issues).
Esthesioneuroblastoma is an uncommon malignant neuroendocrine neoplasm arising from olfactory mucosa, showing a bimodal peak of occurrence in humans at ages 15 and 55 years (Mills et al, 2000). These neoplasms occur occasionally in domestic veterinary species including dog, cat, horse, and cattle (Koestner et al, 1999; Anderson and Cordy, 1981). Experimental laboratory induction of these tumors in rodents and other mammalian species is documented following parenteral or respiratory exposure to a variety of N-nitroso carcinogens, including N-nitrosodiethylamine (diethylnitrosamine; DEN) in Syrian hamsters, N-nitrosodimethylamine (dimethylnitrosamine; DMN), N-nitromethylamine, N-nitrosopiperidine, N-nitrosopiperazine, the caffeine-derived carcinogen mononitrosocaffeidine in rats, and the tobacco smoke-related agent nitrosonornicotine in mink (Herrold, 1964; Koppang et al, 1997; Love et al, 1977; Pelfrene and Garcia, 1976; Scherf et al, 1989; Schwartz et al, 1994; Vollrath and Altsmannberger, 1989a and b; Vollrath et al, 1989; Zeller, 1975). Immersion exposure of medaka fry to MNNG (N-methyl-N’-nitro-N-nitrosoguanidine) results in a low incidence of nasal esthesioneuroblastoma (Bunton and Wolfe, 1996).
In our studies with zebrafish, we have observed spontaneous sensory neural neoplasms of nasal tissue only in the TL line. We have observed these neoplasms in carcinogen studies in several wild-type and mutant lines of zebrafish at incidences up to 30% at 9-12 months following fry immersion exposure to MNNG. We have also observed the single case reported here following dietary exposure of juvenile zebrafish to the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene. In the carcinogenesis studies with MNNG, small lesions visible only histologically showing hyperplasia and dysplasia of sensory nasal epithelium precede frank neoplasms.
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Tissue from 5Z6/4A-37 fish. Gross lesion showing soft white, polypoid mass 7x4x3 mm protruding from naris.
4X. H&E. Well-differentiated, circumscribed esthesioneuroepithelioma protruding from naris. Variably-sized cystic spaces in mass are filled with proteinaceous secretory material..