Retinoblastoma overview: Difference between revisions
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{{Retinoblastoma}} | {{Retinoblastoma}} | ||
==Overview== | ==Overview== | ||
==Historic Perspective== | ==Historic Perspective== | ||
[[Retinoblastoma]] was first described in 1809 by Dr. James Wardrop. Then, Dr. Flexner, in 1891, was the first to discover the rosette structure within the [[tumor]].In 1953, Dr. Kupfer was the first [[ophthalmologist]] who tried a combination of [[chemotherapy]] and [[radiotherapy]] for the treatment of the [[tumor]]. | [[Retinoblastoma]] was first described in 1809 by Dr. James Wardrop. Then, Dr. Flexner, in 1891, was the first to discover the rosette structure within the [[tumor]].In 1953, Dr. Kupfer was the first [[ophthalmologist]] who tried a combination of [[chemotherapy]] and [[radiotherapy]] for the treatment of the [[tumor]]. | ||
==Classification== | ==Classification== | ||
There are several [[classification]] system available for [[retinoblastoma]]. As the treatment of the [[tumor]] has evolved, a new [[classification]] system has been introduced. For intraocular [[diseases]] the available grouping systems include the International Intraocular [[Retinoblastoma]] [[Classification]] (IIRC), Intraocular [[Classification]] of Retinoblastoma (ICRB) and [[TNM|cTNMH systems]]. For extraocular [[diseases]], the International [[Retinoblastoma]] [[Cancer staging|Staging]] System (IRSS) and [[TNM Staging System|cTNMH]] schemes can be used. | There are several [[classification]] system available for [[retinoblastoma]]. As the treatment of the [[tumor]] has evolved, a new [[classification]] system has been introduced. For intraocular [[diseases]] the available grouping systems include the International Intraocular [[Retinoblastoma]] [[Classification]] (IIRC), Intraocular [[Classification]] of Retinoblastoma (ICRB) and [[TNM|cTNMH systems]]. For extraocular [[diseases]], the International [[Retinoblastoma]] [[Cancer staging|Staging]] System (IRSS) and [[TNM Staging System|cTNMH]] schemes can be used. | ||
==Pathophysiology== | ==Pathophysiology== | ||
[[Retinoblastoma]] is a [[neoplasm]] which is caused by the inactivation of [[RB1]] [[gene]], a [[tumor suppressor gene]], located on the long arm of the [[chromosome 13]]. [[Mutation]] in both [[alleles]] of the [[RB1]] [[gene]] is necessary for the inactivation of the [[gene]]. This [[disorder]] may occur in the [[familial]] or sporadic form. ([[Rb]]) [[gene]] product limits the [[cell]] progression from the [[G1 phase]] to the [[S phase]] of the [[cell cycle]]. Loss of this active, functional [[protein]] ([[Rb]]) causes [[cell cycle]] [[dysregulation]] and subsequent overgrowth and [[tumor]] formation. | [[Retinoblastoma]] is a [[neoplasm]] which is caused by the inactivation of [[RB1]] [[gene]], a [[tumor suppressor gene]], located on the long arm of the [[chromosome 13]]. [[Mutation]] in both [[alleles]] of the [[RB1]] [[gene]] is necessary for the inactivation of the [[gene]]. This [[disorder]] may occur in the [[familial]] or sporadic form. ([[Rb]]) [[gene]] product limits the [[cell]] progression from the [[G1 phase]] to the [[S phase]] of the [[cell cycle]]. Loss of this active, functional [[protein]] ([[Rb]]) causes [[cell cycle]] [[dysregulation]] and subsequent overgrowth and [[tumor]] formation. | ||
==Causes== | ==Causes== | ||
[[Retinoblastoma]] may be caused by [[mutation]] in both [[allels]] of [[RB1]] [[tumor suppressor gene]] or due to somatic amplification of the ''MYCN'' [[oncogene]]. | [[Retinoblastoma]] may be caused by [[mutation]] in both [[allels]] of [[RB1]] [[tumor suppressor gene]] or due to somatic amplification of the ''MYCN'' [[oncogene]]. | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
[[Retinoblastoma]] must be differentiated from other [[diseases]] that cause [[leukocoria]]. [[leukocoria]] may occur in several ocular [[conditions]] including [[tumors]], vascular [[disease]], [[inflammatory]] [[disorders]], and also due to [[trauma]]. | [[Retinoblastoma]] must be differentiated from other [[diseases]] that cause [[leukocoria]]. [[leukocoria]] may occur in several ocular [[conditions]] including [[tumors]], vascular [[disease]], [[inflammatory]] [[disorders]], and also due to [[trauma]]. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
The [[incidence]] of [[retinoblastoma]] in the United States has been reported 1.2 cases per 100,000 child aged 4 years or younger. The median age at [[diagnosis]] of [[retinoblastoma]] is 18 months. The average age at [[diagnosis]] of [[retinoblastoma]] for children with unilateral [[disease]] and [[bilateral]] [[disease]] is 24 months and 12 months respectively. [[Retinoblastoma]] affects males and females equally. There is no [[racial]] predilection to the development of [[retinoblastoma]]. | The [[incidence]] of [[retinoblastoma]] in the United States has been reported 1.2 cases per 100,000 child aged 4 years or younger. The median age at [[diagnosis]] of [[retinoblastoma]] is 18 months. The average age at [[diagnosis]] of [[retinoblastoma]] for children with unilateral [[disease]] and [[bilateral]] [[disease]] is 24 months and 12 months respectively. [[Retinoblastoma]] affects males and females equally. There is no [[racial]] predilection to the development of [[retinoblastoma]]. | ||
==Risk factors== | ==Risk factors== | ||
[[Risk factors]] associated with the development of [[retinoblastoma]] are [[mutation]] in [[RB1 gene]], a positive [[family history]] of [[retinoblastoma]], living in areas with high [[incidence rate]] of the [[disease]], [[HPV]] viral exposure and other environmental factors. | [[Risk factors]] associated with the development of [[retinoblastoma]] are [[mutation]] in [[RB1 gene]], a positive [[family history]] of [[retinoblastoma]], living in areas with high [[incidence rate]] of the [[disease]], [[HPV]] viral exposure and other environmental factors. | ||
==Screening== | ==Screening== | ||
Early [[diagnosis]] of [[retinoblastoma]] is necessary to obtain the best outcomes for [[vision]] and eye salvage. In 2018, a group of experts in clinical [[retinoblastoma]] care and [[ophthalmic]] | Early [[diagnosis]] of [[retinoblastoma]] is necessary to obtain the best outcomes for [[vision]] and eye salvage. In 2018, a group of experts in clinical [[retinoblastoma]] care and [[ophthalmic]] | ||
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==Natural history,Complications and Prognosis== | ==Natural history,Complications and Prognosis== | ||
If left untreated, retinoblastoma may progress to develop seeding in the [[eye]], leading to [[retinal detachment]], [[necrosis]] and [[invasion]] of the [[orbit]], [[optic nerve]] [[invasion]], and [[central nervous system]] invasion. The majority of untreated patients die of intracranial extension and disseminated [[disease]] within one year. Spontaneous regression of the [[tumor]] is a rare occurrence but may occur in a small number of cases. Common [[complications]] of [[retinoblastoma]] include [[metastasis]], [[tumor]] recurrence, trilateral [[retinoblastoma]], and subsequent [[neoplasms]]. [[Prognosis]] is generally good, and the [[survival rate]] of [[patients]] with [[retinoblastoma]] with treatment is approximately 95% in the United States. | If left untreated, retinoblastoma may progress to develop seeding in the [[eye]], leading to [[retinal detachment]], [[necrosis]] and [[invasion]] of the [[orbit]], [[optic nerve]] [[invasion]], and [[central nervous system]] invasion. The majority of untreated patients die of intracranial extension and disseminated [[disease]] within one year. Spontaneous regression of the [[tumor]] is a rare occurrence but may occur in a small number of cases. Common [[complications]] of [[retinoblastoma]] include [[metastasis]], [[tumor]] recurrence, trilateral [[retinoblastoma]], and subsequent [[neoplasms]]. [[Prognosis]] is generally good, and the [[survival rate]] of [[patients]] with [[retinoblastoma]] with treatment is approximately 95% in the United States. | ||
==History and Symptoms== | ==History and Symptoms== | ||
The hallmark of retinoblastoma is [[leukocoria]] which is an abnormal appearance of the [[retina]] as viewed through the [[pupil]], also known as amaurotic cat's eye reflex. Other common [[symptoms]] include [[strabismus]] and [[proptosis]]. The [[clinical]] presentation depends on the stage of the [[disease]]. | The hallmark of retinoblastoma is [[leukocoria]] which is an abnormal appearance of the [[retina]] as viewed through the [[pupil]], also known as amaurotic cat's eye reflex. Other common [[symptoms]] include [[strabismus]] and [[proptosis]]. The [[clinical]] presentation depends on the stage of the [[disease]]. | ||
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Patients with [[retinoblastoma]] usually appear normal. [[Physical examination]] of patients is usually remarkable for [[leukocoria]], [[strabismus]], and [[proptosis]], particularly in advanced cases. | Patients with [[retinoblastoma]] usually appear normal. [[Physical examination]] of patients is usually remarkable for [[leukocoria]], [[strabismus]], and [[proptosis]], particularly in advanced cases. | ||
Other findings in [[physical examination]] of retinoblastoma include [[anisocoria]], [[orbital cellulitis]], [[hyphema]], [[heterochromia iridis]], poor [[visual acuity]], unilateral [[mydriasis]], [[rubeosis iridis]], [[vitreous]] [[hemorrhage]], and findings of intrinsic [[calcification]] on fundoscopic examination. | Other findings in [[physical examination]] of retinoblastoma include [[anisocoria]], [[orbital cellulitis]], [[hyphema]], [[heterochromia iridis]], poor [[visual acuity]], unilateral [[mydriasis]], [[rubeosis iridis]], [[vitreous]] [[hemorrhage]], and findings of intrinsic [[calcification]] on fundoscopic examination. | ||
==Laboratory Tests== | ==Laboratory Tests== | ||
There are no diagnostic lab findings associated with retinoblastoma. | There are no diagnostic lab findings associated with retinoblastoma. | ||
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==Other Imaging Studies== | ==Other Imaging Studies== | ||
[[Optical coherence tomography]] may be helpful in the [[diagnosis]] of [[Retinoblastoma]]. | [[Optical coherence tomography]] may be helpful in the [[diagnosis]] of [[Retinoblastoma]]. | ||
==Other Diagnostic Studies== | ==Other Diagnostic Studies== | ||
Other diagnostic studies for retinoblastoma include [[fluorescein angiography]]. | Other diagnostic studies for retinoblastoma include [[fluorescein angiography]]. | ||
==Medical therapy== | |||
==Surgical therapy== | ==Surgical therapy== | ||
The feasibility of | There are different modalities of treatment available for the treatment of [[retinoblastoma]]. The feasibility of each strategy depends on the stage of [[retinoblastoma]] at the time of [[diagnosis]]. | ||
==Primary Prevention== | ==Primary Prevention== | ||
There are no primary preventive measures available for retinoblastoma. | There are no primary preventive measures available for retinoblastoma. | ||
Revision as of 16:40, 19 May 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] 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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Retinoblastoma overview On the Web |
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American Roentgen Ray Society Images of Retinoblastoma overview |
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Risk calculators and risk factors for Retinoblastoma overview |
Overview
Historic Perspective
Retinoblastoma was first described in 1809 by Dr. James Wardrop. Then, Dr. Flexner, in 1891, was the first to discover the rosette structure within the tumor.In 1953, Dr. Kupfer was the first ophthalmologist who tried a combination of chemotherapy and radiotherapy for the treatment of the tumor.
Classification
There are several classification system available for retinoblastoma. As the treatment of the tumor has evolved, a new classification system has been introduced. For intraocular diseases the available grouping systems include the International Intraocular Retinoblastoma Classification (IIRC), Intraocular Classification of Retinoblastoma (ICRB) and cTNMH systems. For extraocular diseases, the International Retinoblastoma Staging System (IRSS) and cTNMH schemes can be used.
Pathophysiology
Retinoblastoma is a neoplasm which is caused by the inactivation of RB1 gene, a tumor suppressor gene, located on the long arm of the chromosome 13. Mutation in both alleles of the RB1 gene is necessary for the inactivation of the gene. This disorder may occur in the familial or sporadic form. (Rb) gene product limits the cell progression from the G1 phase to the S phase of the cell cycle. Loss of this active, functional protein (Rb) causes cell cycle dysregulation and subsequent overgrowth and tumor formation.
Causes
Retinoblastoma may be caused by mutation in both allels of RB1 tumor suppressor gene or due to somatic amplification of the MYCN oncogene.
Differential Diagnosis
Retinoblastoma must be differentiated from other diseases that cause leukocoria. leukocoria may occur in several ocular conditions including tumors, vascular disease, inflammatory disorders, and also due to trauma.
Epidemiology and Demographics
The incidence of retinoblastoma in the United States has been reported 1.2 cases per 100,000 child aged 4 years or younger. The median age at diagnosis of retinoblastoma is 18 months. The average age at diagnosis of retinoblastoma for children with unilateral disease and bilateral disease is 24 months and 12 months respectively. Retinoblastoma affects males and females equally. There is no racial predilection to the development of retinoblastoma.
Risk factors
Risk factors associated with the development of retinoblastoma are mutation in RB1 gene, a positive family history of retinoblastoma, living in areas with high incidence rate of the disease, HPV viral exposure and other environmental factors.
Screening
Early diagnosis of retinoblastoma is necessary to obtain the best outcomes for vision and eye salvage. In 2018, a group of experts in clinical retinoblastoma care and ophthalmic pathology and genetics suggest a risk-stratified schedule for ophthalmic screening examinations. Estimated risk of retinoblastoma development is calculated according to the relativity of individuals to the family member with retinoblastoma.
Natural history,Complications and Prognosis
If left untreated, retinoblastoma may progress to develop seeding in the eye, leading to retinal detachment, necrosis and invasion of the orbit, optic nerve invasion, and central nervous system invasion. The majority of untreated patients die of intracranial extension and disseminated disease within one year. Spontaneous regression of the tumor is a rare occurrence but may occur in a small number of cases. Common complications of retinoblastoma include metastasis, tumor recurrence, trilateral retinoblastoma, and subsequent neoplasms. Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95% in the United States.
History and Symptoms
The hallmark of retinoblastoma is leukocoria which is an abnormal appearance of the retina as viewed through the pupil, also known as amaurotic cat's eye reflex. Other common symptoms include strabismus and proptosis. The clinical presentation depends on the stage of the disease.
Physical Examination
Patients with retinoblastoma usually appear normal. Physical examination of patients is usually remarkable for leukocoria, strabismus, and proptosis, particularly in advanced cases. Other findings in physical examination of retinoblastoma include anisocoria, orbital cellulitis, hyphema, heterochromia iridis, poor visual acuity, unilateral mydriasis, rubeosis iridis, vitreous hemorrhage, and findings of intrinsic calcification on fundoscopic examination.
Laboratory Tests
There are no diagnostic lab findings associated with retinoblastoma.
Chest X Ray
There are no chest x-ray findings associated with retinoblastoma.
CT scan
CT scan has been the standard imaging study of retinoblastoma. Retinoblastoma usually appears as an intra-ocular mass with calcification (in 80% of the cases).
MRI scan
On head and neck MRI, retinoblastoma is characterized by hyperintense mass on T1-weighted MRI and hypointense mass on T2-weighted MRI.
Ultrasound
On ultrasound, retinoblastoma is characterized by echogenic soft-tissue masses with variable shadowing due to calcifications and heterogeneity due to necrosis and/or hemorrhage.
Other Imaging Studies
Optical coherence tomography may be helpful in the diagnosis of Retinoblastoma.
Other Diagnostic Studies
Other diagnostic studies for retinoblastoma include fluorescein angiography.
Medical therapy
Surgical therapy
There are different modalities of treatment available for the treatment of retinoblastoma. The feasibility of each strategy depends on the stage of retinoblastoma at the time of diagnosis.
Primary Prevention
There are no primary preventive measures available for retinoblastoma.
Secondary Prevention
Early diagnosis of retinoblastoma is necessary to obtain the best outcomes for vision and eye salvage. In 2018, a group of experts in clinical retinoblastoma care and ophthalmic pathology and genetics suggest a risk-stratified schedule for ophthalmic screening examinations. Estimated risk of retinoblastoma development is calculated according to the relativity of individuals to the family member with retinoblastoma.
References