Esthesioneuroblastoma pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]
Overview
Pathophysiology
Gross Pathology
- On gross examination of the tumor, biopsy material from olfactory neuroblastoma is soft and hemorrhagic.
- Resection specimens may show a polypoid appearance.
- The vascular supply of the tumor is rich and fragile, accounting for the hemorrhagic gross appearance.
Microscopic Pathology
- Olfactory neuroblastomas are of neural crest cell origin. They are mulilobulated pink-grey tumours.
- Histology demonstrates variable differentiation, from well formed neural tissue to undifferentiated neuroblasts with pseudorosette formation. It has been suggested that olfactory neuroblastoma is actually part of the Ewing sarcoma group of tumors, rather than being related to neuroblastoma.[1]
- Microscopically, the tumor grows beneath the surface respiratory epithelium and may produce focal ulceration.
- Small round (blue) cell tumour with:
- Stippled chromatin.
- High NC ratio.
- +/-Flexner-Wintersteiner rosette - rosette with empty centre (donut hole).
- +/-Fibrillary, eosinophilic material (neuropil-like).[2]
- Esthesioneuroblastomas (ENBs) can display various histologic presentations.
- The hallmark of well-differentiated esthesioneuroblastoma is arrangements of cells into rosettes or pseudorosettes.
- True rosettes (Flexner-Wintersteiner rosettes) refer to a ring of columnar cells circumscribing a central oval-to-round space, which appears clear on traditional pathologic sections.
- Pseudorosettes (Homer-Wright rosettes) are characterized by a looser arrangement and the presence of fibrillary material within the lumen.
- In low-grade lesions, the growth pattern is lobulated with transitions into sheets or discrete nests of tumor cells, which are small and round with high nuclear cytoplasmic ratios.[3][4]
- In well-differentiated tumors, the nuclei show uniform chromatin distribution with small unremarkable nucleoli. The nuclei become progressively more pleomorphic, with prominent nucleoli and coarse chromatin clumping, with increasing tumor grade. The stroma in well-differentiated tumors is distinctly fibrillary, reflecting the neuronal processes made by the tumor cells. This stroma decreases in quantity as the tumor becomes less well-differentiated. Mitoses and areas of necrosis also become more frequent with increasing tumor grade.
Homer Wright pseudorosettes, which are composed of tumor cells surrounding a center of pink fibrillary material, are seen in one-half of olfactory neuroblastomas; true (Flexner type) rosettes, composed of tumor cells surrounding a central lumen, are best seen in higher grade tumors. Necrosis, dystrophic calcification, and vascular or lymphatic invasion are more common with increasing tumor grade. In rare instances, a few admixed ganglion cells may be present. Electron microscopy of olfactory neuroblastomas demonstrates numerous axonal-type cytoplasmic processes, which contain neurofilaments, neurotubules, and dense-core neurosecretory granules (100 to 200 nm in diameter) [21,22]. The S100 immunoreactivity corresponds to Schwann cells enveloping cell bodies and axonal processes (see 'Differential diagnosis' below).
Genetics
Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. To date, no certain genetic factor has been identified that can accurately assist in the diagnosis or predict prognosis. This is partially due to the ability to analyze cancer genomes on a whole genome basis. Recently, a tool called array comparative genomic hybridization was applied to the analysis of esthesioneuroblastomass. Although many alterations were identified in this study, chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q have been confirmed by at least 2 other studies. Interestingly, 20q is a region that has been implicated in other cancers, including breast, ovarian, and squamous cell carcinoma. Still, further experimentation will be required to determine the role of these genomic regions in esthesioneuroblastoma.
The demonstration of human achaete-scute homologue (HASH1) gene expression, although still investigational, could become the diagnostic procedure of choice.[5] The HASH1 gene is involved in olfactory neuronal differentiation and is expressed in immature olfactory cells[6] ; therefore, it could be useful in distinguishing ENB from other poorly differentiated small blue cell tumors. Esthesioneuroblastomas stain positive for S-100 protein and/or neuron-specific enolase, while the stain usually is negative for cytokeratin, desmin, vimentin, actin, glial fibrillary acidic protein, UMB 45, and the common leukocytic antigen. For difficult cases, electron microscopy can be useful. Common features are small, round neuroepithelial cells arranged in rosette or pseudorosette patterns, separated by fibrous elements. Rosettes consist of a central space ringed by columnar cells with radially oriented nuclei. The Hyams histologic grading system grades tumors from I to IV based upon pathologic features such as mitotic activity and necrosis [21].
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Associated Conditions
- Associated with Trisomy 8.
References
- ↑ Esthesioneuroblastoma. Radiopedia(2015) http://radiopaedia.org/articles/olfactory-neuroblastoma Accessed on January 25, 2016
- ↑ Esthesioneuroblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Olfactory_neuroblastoma Accessed on January 25, 2015
- ↑ Hyams, V. J. (1988). Tumors of the upper respiratory tract and ear. Washington, D.C.: Armed Forces Institute of Pathology.
- ↑ Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Harner SG; et al. (1995). "Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study". Cancer. 76 (1): 4–19. PMID 8630875.