Male Zebrafish


SIGNALMENT:
(age, breed, sex, species, and scientific name) 

  1. 5Z6/4A-37; 11 mo at necropsy, male, zebrafish Danio rerio, Florida wild-type line
  2. ZJS 43/3-1; 12.5 mo at necropsy, male, zebrafish Danio rerio, Tuebingen long fin (TL) line which is a double mutant with spotted skin and long fins (leopard; long fin)
  3. MK; 18 mo at necropsy, zebrafish Danio rerio, Tuebingen long fin (TL) line which is a double mutant with spotted skin and long fins (leopard; long fin)

TREATMENT PROTOCOL (including test compound identification, dose, and class of molecule):

  1. 5Z6/4A-37 fed dietary dibenzo[a,l]pyrene (polycyclic aromatic hydrocarbon) at 100 ppm for 4 weeks beginning at 2 months of age
  2. ZJS 43/3-1 untreated fish from prospective study of spontaneous tumors, sacrificed due to large mass on nose. (Lesions for this fish are similar to 5Z6/4A-37, so images are not presented for this fish.)
  3. MK diagnostic case submitted to the diagnostic service coordinated by the Zebrafish International Resource Center at the University of Oregon. Untreated broodstock with spontaneous mass on nose.


GROSS PATHOLOGY:
Typical gross lesion is a soft, white, smooth, polypoid mass protruding from the naris unilaterally.


LABORATORY RESULTS:
(clinical pathology, microbiology, etc…)

No ancillary tests conducted.

MORPHOLOGIC DIAGNOSI(E)S AND ETIOLOGY: 

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. 

  1. 5Z6/4A-37; Morphologic diagnosis: Esthesioneuroblastoma, nasal olfactory epithelium; etiology: carcinogen-induced tumor.  In over 10,000 Florida wild-type fish examined histologically in carcinogen studies at OSU, we never saw another tumor of this histologic type.  We never observed spontaneous olfactory neoplasms in over 3000 control zebrafish of this line.
  2. ZJS 43/3-1; Morphologic diagnosis: Esthesioneuroblastoma, nasal olfactory epithelium; etiology: spontaneous neoplasm—this histologic type of neoplasm probably occurs spontaneously in untreated fish more commonly in the TL line than in other lines that we have studied in carcinogen research at OSU and in diagnostic cases submitted through the Zebrafish International Resource Center.  More definitive data will be available when our 2-year prospective studies of spontaneous tumor incidences are completed.
  3. MK; Morphologic diagnosis: Esthesioneuroepithelioma, nasal olfactory epithelium; etiology: spontaneous neoplasm—this histologic type of neoplasm probably occurs spontaneously in untreated fish more commonly in the TL line than in other lines that we have studied in carcinogen research at OSU and in diagnostic cases submitted through the Zebrafish International Resource Center.  More definitive data will be available when our 2-year prospective studies of spontaneous tumor incidences are completed.

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.

REFERENCES:

Anderson, B. C. and D. R. Cordy (1981). "Olfactory neuroblastoma in a heifer." Vet Pathol 18(4): 536-40.

Argiris, A., J. Dutra, et al. (2003). "Esthesioneuroblastoma: the Northwestern University experience." Laryngoscope 113(1): 155-60.

Axe, S. and F. P. Kuhajda (1987). "Esthesioneuroblastoma. Intermediate filaments, neuroendocrine, and tissue-specific antigens." Am J Clin Pathol 88(2): 139-45.

Bhattacharyya, N. (2002). "Cancer of the nasal cavity: survival and factors influencing prognosis." Arch Otolaryngol Head Neck Surg 128(9): 1079-83.

Bunton, T. E. and M. J. Wolfe (1996). "N-methyl-N'-nitro-N-nitrosoguanidine-induced neoplasms in medaka (Oryzias latipes)." Toxicol Pathol 24(3): 323-30.

Carney, M. E., R. C. O'Reilly, et al. (1995). "Expression of the human Achaete-scute 1 gene in olfactory neuroblastoma (esthesioneuroblastoma)." J Neurooncol 26(1): 35-43.

Chaudhry, A. P., J. G. Haar, et al. (1979). "Olfactory neuroblastoma (esthesioneuroblastoma): a light and ultrastructural study of two cases." Cancer 44(2): 564-79.

Devoe, K. and N. Weidner (2000). "Immunohistochemistry of small round-cell tumors." Semin Diagn Pathol 17(3): 216-24.

Dulguerov, P., A. S. Allal, et al. (2001). "Esthesioneuroblastoma: a meta-analysis and review." Lancet Oncol 2(11): 683-90.

Gultekin, S. H., J. Rosai, et al. (2000). "Hu Immunolabeling as a Marker of Neural and Neuroendocrine Differentiation in Normal and Neoplastic Human Tissues: Assessment Using a Recombinant Anti-Hu Fab Fragment." Int J Surg Pathol 8(2): 109-117.

Herrold, K. M. (1964). "Induction of olfactory neuroepithelial tumors in Syrian hamsters by diethylnitrosamine." Cancer 17: 114-121.

Ingeholm, P., S. A. Theilgaard, et al. (2002). "Esthesioneuroblastoma: a Danish clinicopathological study of 40 consecutive cases." Apmis 110(9): 639-45.

Ivankovic, S., J. Seibel, et al. (1998). "Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine and dinitrosocaffeidine in bd-ix rats."

Koestner, A., T. Bilzer, et al. (1999). Histological Classification of Tumors of the Nervous System of Domestic Animals, World Health Organization/Armed Forces Institute of Pathology/American Registry of Pathology.

Koppang, N., A. Rivenson, et al. (1997). "A study of tobacco carcinogenesis, LIII: carcinogenicity of N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mink (Mustela vison)." Cancer Lett 111(1-2): 167-71.

Kounami, S., S. Douno, et al. (2001). "Olfactory neuroblastoma as a second malignant neoplasm in a patient previously treated for childhood acute leukemia." Pediatr Hematol Oncol 18(7): 459-63.

Kumar, M., R. J. Fallon, et al. (2002). "Esthesioneuroblastoma in children." J Pediatr Hematol Oncol 24(6): 482-7.

Llombart-Bosch, A., C. Carda, et al. (1989). "Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice. An immunohistochemical, electron microscopical, and cytogenetic analysis." Virchows Arch A Pathol Anat Histopathol 414(3): 199-208.

Love, L. A., W. Lijinsky, et al. (1977). "Chronic oral administration of 1-nitrosopiperazine at high doses to MRC rats." Cancer Res Clin Oncol [Z Krebsforsch Klin Onkol] 89(1): 69-73.

Mezzelani, A., S. Tornielli, et al. (1999). "Esthesioneuroblastoma is not a member of the primitive peripheral neuroectodermal tumour-Ewing's group." Br J Cancer 81(4): 586-91.

Mills, S. E., M. J. Gaffey, et al. (1997). Tumors of the upper aerodigestive tract and ear. Washington, D.C., Armed Forces Institute of Pathology.  Atlas of Tumor Pathology, vol. 26.

Miura, K., H. Mineta, et al. (2001). "Olfactory neuroblastoma with epithelial and endocrine differentiation transformed into ganglioneuroma after chemoradiotherapy." Pathol Int 51(12): 942-7.

Miyagami, M., Y. Katayama, et al. (2002). "An ultrastructural and immunohistochemical study of olfactory neuroepithelioma with rhabdomyoblasts." Med Electron Microsc 35(3): 160-6.

Nicholson, S. A., M. B. McDermott, et al. (2000). "CD31 immunoreactivity in small round cell tumors." Appl Immunohistochem Mol Morphol 8(1): 19-24.

Papadaki, H., S. Kounelis, et al. (1996). "Relationship of p53 gene alterations with tumor progression and recurrence in olfactory neuroblastoma." Am J Surg Pathol 20(6): 715-21.

Parham, D. M. (2001). "Neuroectodermal and neuroendocrine tumors principally seen in children." Am J Clin Pathol 115 Suppl: S113-28.

Pelfrene, A. and H. Garcia (1976). "Chemically induced esthesioneuroblastomas in rats." Cancer Res Clin Oncol [Z Krebsforsch Klin Onkol] 86(2): 113-9.

Riazimand, S. H., J. Brieger, et al. (2002). "Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization." Cancer Genet Cytogenet 136(1): 53-7.

Scherf, H. R., E. Frei, et al. (1989). "Carcinogenic properties of N-nitrodimethylamine and N-nitromethylamine in the rat." Carcinogenesis 10(11): 1977-81.

Schiff, D. and P. Y. Wen (1995). "Uncommon brain tumors." Neurol Clin 13(4): 953-74.

Schwartz, L. W., F. F. Hahn, et al. (1994). Proliferative lesions in the rat respiratory tract. Washington, D.C., STP/ARP/AFIP: 1-24.  In:  Guides for Toxicologic Pathology, R-1.

Simon, J. H., W. Zhen, et al. (2001). "Esthesioneuroblastoma: the University of Iowa experience 1978-1998." Laryngoscope 111(3): 488-93.

Takahashi, H., K. Wakabayashi, et al. (1988). "Esthesioneuroblastoma: a nasal catecholamine-producing tumor of neural crest origin. Demonstration of tyrosine hydroxylase-immunoreactive tumor cells." Acta Neuropathol (Berl) 76(5): 522-7.

Utsuki, S., N. Kawano, et al. (2000). "Olfactory neuroepithelioma arising from the olfactory placode." Clin Neuropathol 19(1): 7-12.

Vartanian, R. K. (1996). "Olfactory neuroblastoma: an immunohistochemical, ultrastructural, and flow cytometric study." Cancer 77(9): 1957-9.

Vollrath, M. (1989). "Chemically induced esthesioneuroepithelioma: a cytogenetic, cell culture and biochemical investigation with implications for tumor histogenesis." Arch Otorhinolaryngol 246(2): 71-8.

Vollrath, M. and M. Altmannsberger (1989). "Chemically induced esthesioneuroepithelioma: ultrastructural findings." Ann Otol Rhinol Laryngol 98(4 Pt 1): 256-66.

Vollrath, M. and M. Altmannsberger (1989). "[Esthesioneuroblastoma: histogenesis and diagnosis]." Strahlenther Onkol 165(6): 461-7.

Zeller, W. J. (1975). "[Investigation of the influence of copper and cobalt ions on the carcinogenesis by diethyl-nitrosamine (DENA) in Wistar rats (author's transl)]." Arch Geschwulstforsch 45(7): 634-6.

Zhao, S. P. and X. F. Zhou (2002). "Co-expression of trkA and p75 neurotrophin receptor in extracranial olfactory neuroblastoma cells." Neuropathol Appl Neurobiol 28(4): 301-7.

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IMAGES: 

 

r157a.jpg

Tissue from 5Z6/4A-37 fish. Gross lesion showing soft white, polypoid mass 7x4x3 mm protruding from naris. 

r157b.jpg

4X. H&E. Well-differentiated, circumscribed esthesioneuroepithelioma protruding from naris.  Variably-sized cystic spaces in mass are filled with proteinaceous secretory material..  


r157c.jpg

10X. H&E stain. Well-differentiated, esthesioneuroepithelioma comprised of sheets of neuroepithelial rosettes set in a highly vascular stroma.

r157d.jpg

25X. H&E.  Well-differentiated, esthesioneuroepithelioma comprised of sheets of neuroepithelial rosettes set in a highly vascular stroma.

r157e.jpg

4X. H&E.  Moderately well differentiated esthesioneuroblastoma protruding from naris.  Composed of sheets and cords of basophilic round primitive neuroepithelial cells interspersed with true neuroepithelial rosettes and bundles of well-diferentiated astrocytes set in a fine fibrovascular stroma.

 r157f.jpg
10X. H&E. Moderately well differentiated esthesioneuroblastoma protruding from naris.  Composed of sheets and cords of basophilic round primitive neuroepithelial cells interspersed with true neuroepithelial rosettes and bundles of well-diferentiated astrocytes set in a fine fibrovascular stroma.

r157g.jpg

25X. H&E. Tissue from 5Z6/4A-37 fish. Mass protruding from naris. Same as image above except 25X obj. 

r157h.jpg

40X. H&E.  Tissue from 5Z6/4A-37 fish. Mass protruding from naris. Same as image above except 40X obj.

s100olfactepith.jpg

S100 IHC. Moderately well differentiated esthesioneuroblastoma invading along olfactory tract into olfactory lobe of brain (telencephalon). Case 5Z6/4A-37, Florida wild-type zebrafish fed dietary dibenzo[a,l]pyrene (polycyclic aromatic hydrocarbon) at 100 ppm for 4 weeks beginning at 2 months of age and sampled at 11 mo of age.   

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November 8, 2019 03:58 PM by Santhipriyadarsini Sridharan, BVSc, MVSc, PhD, MVetSc, DACVP

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