Esthesioneuroblastoma pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. On gross pathology, soft and hemorrhagic, polypoid appearance, and rich and fragile vascular supply of the tumor are characteristic findings of esthesioneuroblastoma. | |||
==Pathophysiology== | ==Pathophysiology== | ||
===Gross Pathology=== | ===Gross Pathology=== | ||
*On gross examination | *On gross examination, biopsy material from olfactory neuroblastoma is soft and hemorrhagic. | ||
*Resection specimens may show a polypoid appearance. | *Resection specimens may show a polypoid appearance. | ||
*The vascular supply of the tumor is rich and fragile, accounting for the hemorrhagic gross appearance. | *The vascular supply of the tumor is rich and fragile, accounting for the hemorrhagic gross appearance. | ||
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*In one-half of olfactory neuroblastomas, Homer Wright pseudorosettes, which are composed of tumor cells surrounding a center of pink fibrillary material are seen. | *In one-half of olfactory neuroblastomas, Homer Wright pseudorosettes, which are composed of tumor cells surrounding a center of pink fibrillary material are seen. | ||
*In higher grade tumors, true (Flexner type) rosettes, composed of tumor cells surrounding a central lumen are seen. | *In higher grade tumors, true (Flexner type) rosettes, composed of tumor cells surrounding a central lumen are seen. | ||
*Vascular or lymphatic invasion, necrosis, and dystrophic calcification are more common with increasing tumor grade. | *Vascular or lymphatic invasion, necrosis, and dystrophic calcification are more common with increasing tumor grade. | ||
*A few admixed ganglion cells may be present, on rare instances. | |||
*Electron microscopy of olfactory neuroblastomas demonstrates numerous axonal-type cytoplasmic processes, which contain neurotubules, neurofilaments, and dense-core neurosecretory granules (100 to 200 nm in diameter). The S100 immunoreactivity corresponds to Schwann cells enveloping axonal processes and cell bodies.<ref>Hyams, V. J. (1988). Tumors of the upper respiratory tract and ear. Washington, D.C.: Armed Forces Institute of Pathology.</ref><ref name="pmid8630875">{{cite journal| author=Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Harner SG et al.| title=Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study. | journal=Cancer | year= 1995 | volume= 76 | issue= 1 | pages= 4-19 | pmid=8630875 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8630875 }} </ref> | |||
==Genetics== | ==Genetics== | ||
*A tool called array comparative genomic hybridization was applied to the analysis of esthesioneuroblastomass. Although many alterations were identified by this study, chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q have been confirmed by at least two other studies. | |||
*Although still investigational, the demonstration of human achaete-scute homologue (HASH1) gene expression, could become the diagnostic procedure of choice. The HASH1 gene is involved in olfactory neuronal differentiation and is expressed in immature olfactory cells; therefore, it could be useful in distinguishing ENB from other poorly differentiated small blue cell tumors.<ref name="pmid18408657">{{cite journal| author=Guled M, Myllykangas S, Frierson HF, Mills SE, Knuutila S, Stelow EB| title=Array comparative genomic hybridization analysis of olfactory neuroblastoma. | journal=Mod Pathol | year= 2008 | volume= 21 | issue= 6 | pages= 770-8 | pmid=18408657 | doi=10.1038/modpathol.2008.57 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18408657 }} </ref><ref name="pmid15272537">{{cite journal| author=Mhawech P, Berczy M, Assaly M, Herrmann F, Bouzourene H, Allal AS et al.| title=Human achaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract. | journal=Am J Clin Pathol | year= 2004 | volume= 122 | issue= 1 | pages= 100-5 | pmid=15272537 | doi=10.1309/QD0K-9Q1J-BH6B-5GQQ | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15272537 }} </ref><ref name="pmid8583243">{{cite journal| author=Carney ME, O'Reilly RC, Sholevar B, Buiakova OI, Lowry LD, Keane WM et al.| title=Expression of the human Achaete-scute 1 gene in olfactory neuroblastoma (esthesioneuroblastoma). | journal=J Neurooncol | year= 1995 | volume= 26 | issue= 1 | pages= 35-43 | pmid=8583243 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8583243 }} </ref> | |||
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. | 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]. | The Hyams histologic grading system grades tumors from I to IV based upon pathologic features such as mitotic activity and necrosis [21]. | ||
Revision as of 20:48, 25 January 2016
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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
Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. On gross pathology, soft and hemorrhagic, polypoid appearance, and rich and fragile vascular supply of the tumor are characteristic findings of esthesioneuroblastoma.
Pathophysiology
Gross Pathology
- On gross examination, 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.
- In one-half of olfactory neuroblastomas, Homer Wright pseudorosettes, which are composed of tumor cells surrounding a center of pink fibrillary material are seen.
- In higher grade tumors, true (Flexner type) rosettes, composed of tumor cells surrounding a central lumen are seen.
- Vascular or lymphatic invasion, necrosis, and dystrophic calcification are more common with increasing tumor grade.
- A few admixed ganglion cells may be present, on rare instances.
- Electron microscopy of olfactory neuroblastomas demonstrates numerous axonal-type cytoplasmic processes, which contain neurotubules, neurofilaments, and dense-core neurosecretory granules (100 to 200 nm in diameter). The S100 immunoreactivity corresponds to Schwann cells enveloping axonal processes and cell bodies.[5][4]
Genetics
- A tool called array comparative genomic hybridization was applied to the analysis of esthesioneuroblastomass. Although many alterations were identified by this study, chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q have been confirmed by at least two other studies.
- Although still investigational, the demonstration of human achaete-scute homologue (HASH1) gene expression, could become the diagnostic procedure of choice. The HASH1 gene is involved in olfactory neuronal differentiation and is expressed in immature olfactory cells; therefore, it could be useful in distinguishing ENB from other poorly differentiated small blue cell tumors.[6][7][8]
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].
| Grade | Features |
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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.
- ↑ 4.0 4.1 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.
- ↑ Hyams, V. J. (1988). Tumors of the upper respiratory tract and ear. Washington, D.C.: Armed Forces Institute of Pathology.
- ↑ Guled M, Myllykangas S, Frierson HF, Mills SE, Knuutila S, Stelow EB (2008). "Array comparative genomic hybridization analysis of olfactory neuroblastoma". Mod Pathol. 21 (6): 770–8. doi:10.1038/modpathol.2008.57. PMID 18408657.
- ↑ Mhawech P, Berczy M, Assaly M, Herrmann F, Bouzourene H, Allal AS; et al. (2004). "Human achaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract". Am J Clin Pathol. 122 (1): 100–5. doi:10.1309/QD0K-9Q1J-BH6B-5GQQ. PMID 15272537.
- ↑ Carney ME, O'Reilly RC, Sholevar B, Buiakova OI, Lowry LD, Keane WM; et al. (1995). "Expression of the human Achaete-scute 1 gene in olfactory neuroblastoma (esthesioneuroblastoma)". J Neurooncol. 26 (1): 35–43. PMID 8583243.