Retinoblastoma pathophysiology: Difference between revisions
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Revision as of 15:24, 27 November 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [3]
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Retinoblastoma Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Retinoblastoma pathophysiology On the Web |
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American Roentgen Ray Society Images of Retinoblastoma pathophysiology |
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Risk calculators and risk factors for Retinoblastoma pathophysiology |
Overview
On gross pathology, viable tumor cells near blood vessels and zones of necrosis in avascular areas are characteristic findings of retinoblastoma. On microscopic histopathological analysis, small, round-cell tumor of neuroepithelial origin, Flexner-Wintersteiner rosettes, and Homer-Wright rosettes are characteristic findings of retinoblastoma. Retinoblastoma can be bilateral or unilateral, spontaneous or familial. In 30% to 40% of cases, retinoblastoma is accompanied by a germinal mutation in the RB1 gene.[1]
Pathogenesis
Retinoblastoma may be sporadic or secondary to a germline mutation of the RB tumor suppressor gene which is usually inherited. Children with non-germline retinoblastoma incur new somatic mutations in the retinal cell from which the tumor arises.[2][3]
Genetics
Usually retinoblastoma is caused by mutational inactivation of both alleles of the retinoblastoma (RB1) gene.[4] The RB1 gene maps to chromosome 13q14 and encodes a nuclear protein (Rb) that acts as a tumor suppressor.[5][6][7] This protein (Rb) restricts the cell's ability to progress from the G1 phase to the S phase of the cell cycle.[8] Rb binds to E2F, a transcription factor, when active. Loss of this active, functional protein (Rb) causes cell cycle dysregulation. The inherited form of retinoblastoma is due to a germline mutation that can be either familial or sporadic.[9] Retinoblastoma may be unilateral or bilateral.
- Bilateral tumors (30-40% of cases) essentially always have a germline mutation. In 10 percent of bilateral patients, a positive history of retinoblastoma is seen, which suggests that the majority of bilateral cases arise from a new germline mutation.
- Unilateral tumors (60-70% of cases) are caused by a germline mutation in approximately 15% of cases, whereas 85% are sporadic. Patients with unilateral disease can also have the heritable form of the disease; these are often multifocal, and account for 12 to 15 percent of retinoblastoma cases. The remaining children with retinoblastoma have the unilateral, non-germline, and non-heritable form of the disease.
- Thus, approximately 30% to 40% of cases are due to a germline mutation. This mutation is inherited in an autosomal dominant fashion with approximately 90% penetrance (i.e the child of a retinoblastoma survivor who has a germline mutation has a 50% chance of inheriting a mutation, and if they do so a 90% chance of developing a retinoblastoma. Thus there is an overall chance of 45% of having a retinoblastoma (50% x 90%).[10]
Gross Pathology
Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. Macroscopic examination reveals a white elevated mass with fine surface vessels. Early retinoblastoma presents as a solitary or multifocal, well-circumscribed translucent mass. The tumor becomes more pink in color, with dilated feeding blood vessels as the disease advances. The tumor may exhibit three patterns of growth, which is tabulated below:[10]
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Microscopic Pathology
Microscopically, both undifferentiated and differentiated elements may be present.[12]
- Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei
- Differentiated elements include:
- Flexner-Wintersteiner rosettes
- Homer-Wright rosettes
- Fluerettes from photoreceptor differentiation
![Retinoblastoma 400 X magnification[13]](/index.php/File:Retinoblastoma_Pathology_(2).jpg)
![Flexner- Wintersteiner Rosettes in retinoblastoma[13]](/index.php/File:Flexner-_Wintersteiner_Rosettes_in_Retinoblastoma.jpg)
References
- ↑ Schefler AC, Abramson DH (2008). "Retinoblastoma: what is new in 2007-2008". Curr Opin Ophthalmol. 19 (6): 526–34. doi:10.1097/ICU.0b013e328312975b. PMID 18854698.
- ↑ Knudson AG, Hethcote HW, Brown BW (1975). "Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma". Proc Natl Acad Sci U S A. 72 (12): 5116–20. PMC 388887. PMID 1061095.
- ↑ Smith BJ, O'Brien JM (1996). "The genetics of retinoblastoma and current diagnostic testing". J Pediatr Ophthalmol Strabismus. 33 (2): 120–3. PMID 8965236.
- ↑ Finger, Paul T; Harbour, J.William; Karcioglu, Zeynel A (2002). "Risk Factors for Metastasis in Retinoblastoma". Survey of Ophthalmology. 47 (1): 1–16. doi:10.1016/S0039-6257(01)00279-X. ISSN 0039-6257.
- ↑ Friend, Stephen H.; Bernards, Rene; Rogelj, Snezna; Weinberg, Robert A.; Rapaport, Joyce M.; Albert, Daniel M.; Dryja, Thaddeus P. (1986). "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma". Nature. 323 (6089): 643–646. doi:10.1038/323643a0. ISSN 0028-0836.
- ↑ Fung, Y.; Murphree, A.; T'Ang, A; Qian, J; Hinrichs, S.; Benedict, W. (1987). "Structural evidence for the authenticity of the human retinoblastoma gene". Science. 236 (4809): 1657–1661. doi:10.1126/science.2885916. ISSN 0036-8075.
- ↑ Lee, W.; Bookstein, R.; Hong, F.; Young, L.; Shew, J.; Lee, E. (1987). "Human retinoblastoma susceptibility gene: cloning, identification, and sequence". Science. 235 (4794): 1394–1399. doi:10.1126/science.3823889. ISSN 0036-8075.
- ↑ Goodrich, David W.; Wang, Nan Ping; Qian, Yue-Wei; Lee, Eva Y.-H.P.; Lee, Wen-Hwa (1991). "The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle". Cell. 67 (2): 293–302. doi:10.1016/0092-8674(91)90181-W. ISSN 0092-8674.
- ↑ Leiderman, Yannek I.; Kiss, Szilárd; Mukai, Shizuo (2007). "Molecular Genetics ofRB1——The Retinoblastoma Gene". Seminars in Ophthalmology. 22 (4): 247–254. doi:10.1080/08820530701745165. ISSN 0882-0538.
- ↑ 10.0 10.1 Retinoblastoma. Radiopedia(2015) http://radiopaedia.org/articles/retinoblastoma Accessed on October 10, 2015
- ↑ Image courtesy of Dr. Frank Gaillard Radiopaedia (original file [1]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC
- ↑ Retinoblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Retinoblastoma Accessed on October 10 2015
- ↑ 13.0 13.1 Images of microscopic appearance of retinoblastoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Retinoblastoma