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==Overview== | ==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. | 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. | ||
==Pathogenesis== | |||
Retinoblastoma may be sporadic or secondary to a germline mutation of the RB tumour suppressor gene which is usually inherited. It may be unilateral or bilateral: | |||
*Bilateral (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 tumours (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 55% 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. They thus an overall chance of 45% of having a retinoblastoma (50% x 90%). | |||
The inherited form of retinoblastoma is due to a germline mutation that can be either: | |||
*Familial (inherited from one of the parents) | |||
*Sporadic (the result of a new mutation in an embryo) | |||
Children with non-germline retinoblastoma incur new somatic mutations in one retinal cell from which the tumor arises. Less than 10 percent of retinoblastoma patients have a positive family history for the disease [30] | |||
==Pathophysiology== | ==Pathophysiology== | ||
Usually retinoblastoma is caused by mutational inactivation of both alleles of the retinoblastoma (''RB1'') gene. <ref name="FingerHarbour2002">{{cite journal|last1=Finger|first1=Paul T|last2=Harbour|first2=J.William|last3=Karcioglu|first3=Zeynel A|title=Risk Factors for Metastasis in Retinoblastoma|journal=Survey of Ophthalmology|volume=47|issue=1|year=2002|pages=1–16|issn=00396257|doi=10.1016/S0039-6257(01)00279-X}}</ref> The ''RB1'' gene maps to chromosome 13q14 and encodes a nuclear protein (Rb) that acts as a tumor suppressor <ref name="FriendBernards1986">{{cite journal|last1=Friend|first1=Stephen H.|last2=Bernards|first2=Rene|last3=Rogelj|first3=Snezna|last4=Weinberg|first4=Robert A.|last5=Rapaport|first5=Joyce M.|last6=Albert|first6=Daniel M.|last7=Dryja|first7=Thaddeus P.|title=A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma|journal=Nature|volume=323|issue=6089|year=1986|pages=643–646|issn=0028-0836|doi=10.1038/323643a0}}</ref><ref name="FungMurphree1987">{{cite journal|last1=Fung|first1=Y.|last2=Murphree|first2=A.|last3=T'Ang|first3=A|last4=Qian|first4=J|last5=Hinrichs|first5=S.|last6=Benedict|first6=W.|title=Structural evidence for the authenticity of the human retinoblastoma gene|journal=Science|volume=236|issue=4809|year=1987|pages=1657–1661|issn=0036-8075|doi=10.1126/science.2885916}}</ref><ref name="LeeBookstein1987">{{cite journal|last1=Lee|first1=W.|last2=Bookstein|first2=R.|last3=Hong|first3=F.|last4=Young|first4=L.|last5=Shew|first5=J.|last6=Lee|first6=E.|title=Human retinoblastoma susceptibility gene: cloning, identification, and sequence|journal=Science|volume=235|issue=4794|year=1987|pages=1394–1399|issn=0036-8075|doi=10.1126/science.3823889}}</ref> This protein (Rb) restricts the cell's ability to progress from the G1 phase to the S phase of the cell cycle.<ref name="GoodrichWang1991">{{cite journal|last1=Goodrich|first1=David W.|last2=Wang|first2=Nan Ping|last3=Qian|first3=Yue-Wei|last4=Lee|first4=Eva Y.-H.P.|last5=Lee|first5=Wen-Hwa|title=The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle|journal=Cell|volume=67|issue=2|year=1991|pages=293–302|issn=00928674|doi=10.1016/0092-8674(91)90181-W}}</ref> Rb binds to E2F, a transcription factor, when active. Loss of this active, functional protein (Rb) causes cell cycle dysregulation. | Usually retinoblastoma is caused by mutational inactivation of both alleles of the retinoblastoma (''RB1'') gene. <ref name="FingerHarbour2002">{{cite journal|last1=Finger|first1=Paul T|last2=Harbour|first2=J.William|last3=Karcioglu|first3=Zeynel A|title=Risk Factors for Metastasis in Retinoblastoma|journal=Survey of Ophthalmology|volume=47|issue=1|year=2002|pages=1–16|issn=00396257|doi=10.1016/S0039-6257(01)00279-X}}</ref> The ''RB1'' gene maps to chromosome 13q14 and encodes a nuclear protein (Rb) that acts as a tumor suppressor <ref name="FriendBernards1986">{{cite journal|last1=Friend|first1=Stephen H.|last2=Bernards|first2=Rene|last3=Rogelj|first3=Snezna|last4=Weinberg|first4=Robert A.|last5=Rapaport|first5=Joyce M.|last6=Albert|first6=Daniel M.|last7=Dryja|first7=Thaddeus P.|title=A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma|journal=Nature|volume=323|issue=6089|year=1986|pages=643–646|issn=0028-0836|doi=10.1038/323643a0}}</ref><ref name="FungMurphree1987">{{cite journal|last1=Fung|first1=Y.|last2=Murphree|first2=A.|last3=T'Ang|first3=A|last4=Qian|first4=J|last5=Hinrichs|first5=S.|last6=Benedict|first6=W.|title=Structural evidence for the authenticity of the human retinoblastoma gene|journal=Science|volume=236|issue=4809|year=1987|pages=1657–1661|issn=0036-8075|doi=10.1126/science.2885916}}</ref><ref name="LeeBookstein1987">{{cite journal|last1=Lee|first1=W.|last2=Bookstein|first2=R.|last3=Hong|first3=F.|last4=Young|first4=L.|last5=Shew|first5=J.|last6=Lee|first6=E.|title=Human retinoblastoma susceptibility gene: cloning, identification, and sequence|journal=Science|volume=235|issue=4794|year=1987|pages=1394–1399|issn=0036-8075|doi=10.1126/science.3823889}}</ref> This protein (Rb) restricts the cell's ability to progress from the G1 phase to the S phase of the cell cycle.<ref name="GoodrichWang1991">{{cite journal|last1=Goodrich|first1=David W.|last2=Wang|first2=Nan Ping|last3=Qian|first3=Yue-Wei|last4=Lee|first4=Eva Y.-H.P.|last5=Lee|first5=Wen-Hwa|title=The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle|journal=Cell|volume=67|issue=2|year=1991|pages=293–302|issn=00928674|doi=10.1016/0092-8674(91)90181-W}}</ref> Rb binds to E2F, a transcription factor, when active. Loss of this active, functional protein (Rb) causes cell cycle dysregulation. | ||
Revision as of 16:32, 11 October 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]
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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.
Pathogenesis
Retinoblastoma may be sporadic or secondary to a germline mutation of the RB tumour suppressor gene which is usually inherited. It may be unilateral or bilateral:
- Bilateral (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 tumours (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 55% 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. They thus an overall chance of 45% of having a retinoblastoma (50% x 90%). The inherited form of retinoblastoma is due to a germline mutation that can be either:
- Familial (inherited from one of the parents)
- Sporadic (the result of a new mutation in an embryo)
Children with non-germline retinoblastoma incur new somatic mutations in one retinal cell from which the tumor arises. Less than 10 percent of retinoblastoma patients have a positive family history for the disease [30]
Pathophysiology
Usually retinoblastoma is caused by mutational inactivation of both alleles of the retinoblastoma (RB1) gene. [1] The RB1 gene maps to chromosome 13q14 and encodes a nuclear protein (Rb) that acts as a tumor suppressor [2][3][4] This protein (Rb) restricts the cell's ability to progress from the G1 phase to the S phase of the cell cycle.[5] Rb binds to E2F, a transcription factor, when active. Loss of this active, functional protein (Rb) causes cell cycle dysregulation.
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:[6]
| Growth patterns | Features |
|---|---|
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Microscopic Pathology
Microscopically, both undifferentiated and differentiated elements may be present:[7]
- 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
See also
References
- ↑ 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.
- ↑ Retinoblastoma. Radiopedia(2015) http://radiopaedia.org/articles/retinoblastoma
- ↑ Retinoblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Retinoblastoma Accessed on October 10 2015