Signalment:  
Gross Description:  
Histopathologic Description:
Tumor cells are pleomorphic: those in rosettes tend to be elongate to triangular, with a wider base and scant cytoplasm; apical processes are sometimes present. The nuclei are basal, round to ellipsoid, with coarsely clumped chromatin or multiple nucleoli. There is a second population of tumor cells that is smaller and rounder, with very scant cytoplasm and multiple nucleoli; these are most often outside of the rosettes. The mitotic index is high (up to 25 mitotic figures per 0.238 mm2 high power field).
Adjacent to the main tumor mass, the architecture of many submucosal (Bowmans) glands is disorganized, with loss of cellular polarity and no apparent lumen. In some areas the cells are piled into more than one layer or even extend away from the basement membrane. These cells are enlarged and basophilic, with nuclei containing multiple nucleoli or coarsely-clumped chromatin. Although not nearly as common as in the main tumor mass, mitotic figures are not rare in these glands.
Cells in the overlying epithelium range from normal to containing eosinophilic granules, pyknotic nuclei or nuclear remnants, and lacking microvilli. There are intact neutrophils and nuclear remnants within the eosinophilic material (fluid) within the nasal cavities.
Morphologic Diagnosis:  
Condition:  
Contributor Comment:  
This tumor in the nasal sections is a good example of an esthesioneuroblastoma(1), with occasional true rosettes (Flexner-Wintersteiner rosettes) and more common pseudorosettes (Homer-Wright rosettes). This is an exceedingly rare tumor in mice, as in all mammals(2), and is likely present here in part because the strain is heterozygous for p53 gene knockout. The diagnosis in the brain was made more difficult as there the tumor adopted a solid sheet-type architecture, with only rare rosettes, a situation apparently typical of esthesioneuroblastomas in animals other than humans(2).
JPC Diagnosis:  
Conference Comment:  
Ultrastructural features include cytoplasmic membrane-bound dense core neurosecretory granules which contain neurotubules and neurofilaments. Olfactory differentiation with olfactory vesicles and microvilli or apical cilia on apical borders may be seen in Flexner-Wintersteiner rosettes. The fibrillary stroma corresponds to the immature nerve processes, and Schwann-like cells are uncommonly encountered(4,5).
The differential diagnosis of ONB includes the group of small round blue cell malignant neoplasms that can occur in the sinonasal tract, such as sinonasal undifferentiated carcinoma, extranodal NK/T cell lymphoma, rhabdomyosarcoma, Ewing/primitive neuroectodermal tumor (PNET), mucosal melanoma and neuroendocrine carcinomas (NEC)4. Other tumors considered in the differential diagnosis are paraganglioma, extramedullary plasmacytoma, pituitary adenoma, extracranial meningioma, mesenchymal chondrosarcoma, and granulocytic sarcoma. In cats, feline leukemia virus has been identified in association with olfactory neuroblastoma, but a causal role has not been established(3).
References:
1. Maronpot RR, editor. Pathology of the Mouse. (1999). Cache River Press, Vienna, IL 62995.
2. Reznik GK, Schuller HM, & Stinson SF. Tumors of the nasal cavities, IARC Sci Publ. 1994;(111):305-24.
3. Schrenzel MD, Higgins RJ, Hinrichs SH, Smith MO, Torten M. Type C retroviral expression in spontaneous feline olfactory neuroblastomas. Acta Neuropathol. 1990;80(5):547-53.
4. Thompson LD. Olfactory neuroblastoma. Head Neck Pathol. 2009 Sep;3(3):252-9.
5. Wippold FJ 2nd, Perry A. Neuropathology for the neuroradiologist: rosettes and pseudorosettes. AJNR Am J Neuroradiol. 2006 Mar;27(3):488-92.