Retinoblastoma screening: Difference between revisions

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Latest revision as of 23:59, 29 July 2020

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]

Overview

Early diagnosis of retinoblastoma is necessary to obtain the best outcomes for preservation of the vision and the eye. In 2018, a group of experts in clinical retinoblastoma care and ophthalmic pathology and genetics suggested 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.

Screening

In 2018, a group of experts in clinical retinoblastoma care and ophthalmic pathology and genetics suggested a risk-stratified schedule for ophthalmic screening examinations.^[1]
This panel of experts recommended that all children with an elevated risk of retinoblastoma (above the population risk) should be screened via regular fundoscopic examinations.
To schedule a screening plan, the risk of tumor development must be determined using the infant relationship to the family member with retinoblastoma.
The table below is an estimate of patients' risk for the development of retinoblastoma depending on the relation of the patient to the affected individual:


Relative of patient	Bilateral involvement (100%)	Unilateral involvement (15%)
Offspring (infant)	50	7.5
Parent	5	0.8
Sibling	2.5	0.4
Niece/nephew	1.3	0.2
Aunt/uncle	0.1	0.007
First cousin	0.05	0.007

The above table adopted from Ophthalmology journal ^[1]

Next step in assessing the risk of these children is to estimate the approximate relative risk of retinoblastoma development according to the percentage mentioned in the above table.

Relatives are categorized into three categories:
- High risk: Those with a risk percentage > 7.5%
- Intermediate risk: Those with a risk percentage between 1% and 7.5% (including 7.5%)
- Low risk: Those with a risk percentage < 1%
American Association of Ophthalmic Oncologists and Pathologists (AAOOP) guideline recommends scheduled eye examination for the screening of children at high risk of developing retinoblastoma. Screening should be initiated at birth and continued till the age of 7 years.^[1]
No further examination is required after the age of 7 years except for those who are known carriers of the RB1 gene mutation.
For those who are carries of the RB1 gene mutation, screening should be continued indefinitely after the age of 7 years and should be done annually or every 2 years.

The following table is the recommended eye examination schedule for unaffected children of families with retinoblastoma depending on their age and risk percentage of tumor development:


Risk category or Age	High risk	Intermediate risk	Low risk

Birth to 8 weeks	Every 2 - 4 weeks	Monthly	Monthly
> 8 - 12 weeks	Monthly	Monthly	Monthly
> 3 - 12 months	Monthly	Every 2 months	Every 3 months
> 12 - 24 months	Every 2 months	Every 3 months	Every 4 months
> 24 - 36 months	Every 3 months	Every 3 months	Every 6 months
> 36 - 48 months	Every 4 months	Every 4 - 6 months	Every 6 months
> 48 - 60 months	Every 6 months	Every 4 - 6 months	Annually
5 - 7 years	Every 6 months	Annually	Annually

This table is adopted from Ophthalmology journal^[1]

The schedule presented above is general guideline for at-risk children when no lesions of concern have been noted. Some children may require more frequent examinations.

The American Association of Ophthalmic Oncologists and Pathologists (AAOOP) guideline also suggests a single dilated fundus examination to evaluate for asymptomatic spontaneously regressed retinoblastoma or retinoma in all first-degree relatives of a patient with retinoblastoma, including older siblings if the RB1 genetic analysis of the relatives is not done.

Genetic Testing for Children with Retinoblastoma

Genetic testing for children with Retinoblastoma

Not available

Blood: RB1 mutation(+)
(germline mutation)

Blood: RB1 mutation(-)
Tumor: RB1 mutation(+)

Blood: RB1 mutation(-)
Tumor: RB1 mutation(-)

Blood: RB1 mutation(-)
Tumor: not available

Ophthalmic screening for all
the relatives with greater risk than the population

Assessment of relatives
for familial retinoblastoma

Ophthalmic screening and genetic analysis
not required for first degree relatives

No need for genetic analysis of first degree relatives

Relatives with RB1 mutation

Relatives without RB1 mutation

Ophthlamic screening for future offspring unless negative for parent's mutation

Future offspring of affected child require ophthalmic screening

Ophthalmic screening for children as high risk

Ophthalmic screening not required

The above table is the recommended genetic analysis guidline for families with affected individuals and adopted from Ophthalmology journal^[1]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 Skalet, Alison H.; Gombos, Dan S.; Gallie, Brenda L.; Kim, Jonathan W.; Shields, Carol L.; Marr, Brian P.; Plon, Sharon E.; Chévez-Barrios, Patricia (2018). "Screening Children at Risk for Retinoblastoma". Ophthalmology. 125 (3): 453–458. doi:10.1016/j.ophtha.2017.09.001. ISSN 0161-6420.

[SkaletGombos2018-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 Skalet, Alison H.; Gombos, Dan S.; Gallie, Brenda L.; Kim, Jonathan W.; Shields, Carol L.; Marr, Brian P.; Plon, Sharon E.; Chévez-Barrios, Patricia (2018). "Screening Children at Risk for Retinoblastoma". Ophthalmology. 125 (3): 453–458. doi:10.1016/j.ophtha.2017.09.001. ISSN 0161-6420.

[1]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Retinoblastoma}}
-{{CMG}},{{AE}}{{Simrat}}
+{{CMG}}; {{AE}} {{Sahar}} {{Simrat}}
 ==Overview==
-According to the United States Preventive Services Task Force, screening for retinoblastoma is not recommended. There is no widely accepted screening protocol of retinoblastoma for the general population. However, children at increased risk of retinoblastoma based on known 13q deletion or family history should be evaluated by an ophthalmologist shortly after birth.
+Early [[diagnosis]] of retinoblastoma is necessary to obtain the best outcomes for preservation of the [[vision]] and the eye. In 2018, a group of experts in clinical retinoblastoma care and [[ophthalmic]]
+[[pathology]] and [[genetics]] suggested a risk-stratified schedule for [[ophthalmic]] [[screening]] [[Examination|examinations]]. Estimated risk of retinoblastoma development is calculated according to the relativity of individuals to the family member with retinoblastoma.
 ==Screening==
-There is no widely accepted screening protocol of retinoblastoma for the general population. However, children at increased risk of retinoblastoma based on known 13q deletion or family history should be evaluated by an ophthalmologist shortly after birth.
+* In 2018, a group of experts in clinical retinoblastoma care and [[ophthalmic]] [[pathology]] and [[genetics]] suggested a risk-stratified schedule for [[ophthalmic]] [[Screening (medicine)|screening]] [[Examination|examinations]].<ref name="SkaletGombos2018">{{cite journal|last1=Skalet|first1=Alison H.|last2=Gombos|first2=Dan S.|last3=Gallie|first3=Brenda L.|last4=Kim|first4=Jonathan W.|last5=Shields|first5=Carol L.|last6=Marr|first6=Brian P.|last7=Plon|first7=Sharon E.|last8=Chévez-Barrios|first8=Patricia|title=Screening Children at Risk for Retinoblastoma|journal=Ophthalmology|volume=125|issue=3|year=2018|pages=453–458|issn=01616420|doi=10.1016/j.ophtha.2017.09.001}}</ref>
-*Screening should then be conducted every 1 to two months during the first two years of life. After that screening should be conducted  every three to four months until the child is three to four years of age, and every six months until five to six years of age unless genetic testing of the child reveals that he or she does not have the germline mutation identified in the affected relative, in which case screening examinations are not necessary. Retinoblastoma surveillance examinations are usually performed with the patient under general anesthesia to permit complete detailed examination of the ocular fundus.<ref>{{cite book | last = Pizzo | first = Philip | title = Principles and practice of pediatric oncology | publisher = Wolters Kluwer/Lippincott Williams & Wilkins Health | location = Philadelphia, PA | year = 2011 | isbn = 160547682X }}</ref>.
+* This panel of experts recommended that all [[Child|children]] with an elevated risk of retinoblastoma (above the population risk) should be [[Screening (medicine)|screened]] via regular [[Fundoscopy|fundoscopic examinations]].
-*There is 50 percent risk of passing the mutation on to their offspring in patients with bilateral retinoblastoma, unilateral retinoblastoma with a family history, or unilateral retinoblastoma with a proven RB1 somatic mutation. The risk of retinoblastoma may also be increased among siblings of a patient with retinoblastoma as one parent  may have somatic mosaicism for the RB1 deletion or may be a silent carrier of RB1 mutation.<ref name="pmid19280657">{{cite journal| author=Rushlow D, Piovesan B, Zhang K, Prigoda-Lee NL, Marchong MN, Clark RD et al.| title=Detection of mosaic RB1 mutations in families with retinoblastoma. | journal=Hum Mutat | year= 2009 | volume= 30 | issue= 5 | pages= 842-51 | pmid=19280657 | doi=10.1002/humu.20940 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19280657  }} </ref> The magnitude of risk among offspring of the proband depends upon the tumor presentation in the proband (ie, unilateral or bilateral; unifocal or multifocal). The magnitude of increased risk among siblings of the proband depends upon the genetic status of the parents and the proband.
+*To schedule a [[screening]] plan, the risk of [[tumor]] development must be determined using the [[infant]] relationship to the family member with retinoblastoma.
-*Trilateral retinoblastoma is a well-recognized syndrome that occurs in 5% to 15% of patients with heritable retinoblastoma and is defined by the development of an intracranial midline neuroblastic tumor, which typically develops between the ages of 20 and 36 months.
+*The table below is an estimate of [[Patient|patients']] risk for the development of retinoblastoma depending on the relation of the [[patient]] to the affected individual:
-*Given the poor prognosis of trilateral retinoblastoma and the short interval between the diagnosis of retinoblastoma and the occurrence of trilateral disease, routine neuroimaging could potentially detect most cases within 2 years of first diagnosis. Although it is not clear whether early diagnosis can impact survival, screening with MRI has been recommended as often as every 6 months for 5 years for those suspected of having heritable disease or those with unilateral disease and a positive family history. CT scans are generally avoided for routine screening in these children because of the perceived risk of exposure to ionizing radiation. At the time of diagnosis, patients who are asymptomatic of an intracranial tumor have a better outcome than do patients who are symptomatic.
+{| border="3"
-*Approximately 5% to 10% of children with heritable retinoblastoma develop pineal gland cysts detected by MRI; these cyst abnormalities must be distinguished from the pineoblastoma that typically defines trilateral retinoblastoma.
+|+
+! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF| Relative of patient}} !! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF| Bilateral involvement (100%)}} !! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF| Unilateral involvement (15%)}}
+|-
+! style="padding: 5px 5px; background: #DCDCDC; " |Offspring (infant)
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" | 50  || style="padding: 5px 5px; background: #F5F5F5;" align="center" | 7.5
+|-
+! style="padding: 5px 5px; background: #DCDCDC; " | Parent
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |5
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.8
+|-
+! style="padding: 5px 5px; background: #DCDCDC; " | Sibling
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |2.5
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.4
+|-
+! style="padding: 5px 5px; background: #DCDCDC; " | Niece/nephew
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |1.3
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.2
+|-
+! style="padding: 5px 5px; background: #DCDCDC; " | Aunt/uncle
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.1
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.007
+|-
+! style="padding: 5px 5px; background: #DCDCDC; " | First cousin
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.05
+| style="padding: 5px 5px; background: #F5F5F5;" align="center" |0.007
+|}
+{|
+! colspan="2" style="background:#DCDCDC;" align="center" + |The above table adopted from Ophthalmology journal <ref name="SkaletGombos2018">{{cite journal|last1=Skalet|first1=Alison H.|last2=Gombos|first2=Dan S.|last3=Gallie|first3=Brenda L.|last4=Kim|first4=Jonathan W.|last5=Shields|first5=Carol L.|last6=Marr|first6=Brian P.|last7=Plon|first7=Sharon E.|last8=Chévez-Barrios|first8=Patricia|title=Screening Children at Risk for Retinoblastoma|journal=Ophthalmology|volume=125|issue=3|year=2018|pages=453–458|issn=01616420|doi=10.1016/j.ophtha.2017.09.001}}</ref>
+|-
+|}
+* Next step in assessing the risk of these [[Child|children]] is to estimate the approximate relative risk of retinoblastoma development according to the percentage mentioned in the above table.
+*Relatives are categorized into three categories:
+**'''High risk:''' Those with a risk percentage > 7.5%
+**'''Intermediate risk:''' Those with a risk percentage between 1% and 7.5% (including 7.5%)
+**'''Low risk:''' Those with a risk percentage < 1%
+*American Association of [[Ophthalmic]] [[Oncologists]] and [[Pathologists]] (AAOOP) [[Medical guideline|guideline]] recommends scheduled [[eye examination]] for the [[screening]] of children at high risk of developing retinoblastoma. [[Screening (medicine)|Screening]] should be initiated at [[birth]] and continued till the age of 7 years.<ref name="SkaletGombos2018">{{cite journal|last1=Skalet|first1=Alison H.|last2=Gombos|first2=Dan S.|last3=Gallie|first3=Brenda L.|last4=Kim|first4=Jonathan W.|last5=Shields|first5=Carol L.|last6=Marr|first6=Brian P.|last7=Plon|first7=Sharon E.|last8=Chévez-Barrios|first8=Patricia|title=Screening Children at Risk for Retinoblastoma|journal=Ophthalmology|volume=125|issue=3|year=2018|pages=453–458|issn=01616420|doi=10.1016/j.ophtha.2017.09.001}}</ref>
+*No further [[Eye examination|examination]] is required after the age of 7 years except for those who are known carriers of the [[RB1]] [[gene]] [[mutation]].
+*For those who are carries of the [[RB1]] [[gene]] [[mutation]], [[screening]] should be continued indefinitely after the age of 7 years and should be done annually or every 2 years.
+* The following table is the recommended [[eye examination]] schedule for unaffected [[Child|children]] of families with retinoblastoma depending on their age and risk percentage of [[tumor]] development:
+{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center"
+| valign="top" |
+|+
+! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Risk category or Age}}
+! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|High risk}}
+! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Intermediate risk}}
+! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Low risk}}
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
+Birth to 8 weeks
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 2 - 4 weeks
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Monthly
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Monthly
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+> 8 - 12 weeks
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Monthly
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Monthly
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Monthly
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+> 3 - 12 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Monthly
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 2 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 3 months
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+> 12 - 24 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 2 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 3 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 4 months
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+> 24 - 36 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 3 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 3 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 6 months
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+> 36 - 48 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 4 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 4 - 6 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 6 months
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+> 48 - 60 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 6 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 4 - 6 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Annually
+|-
+| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
+- 7 years
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Every 6 months
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Annually
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Annually
+|}
+{|
+! colspan="2" style="background:#DCDCDC;" align="center" + |This table is adopted from Ophthalmology journal<ref name="SkaletGombos2018">{{cite journal|last1=Skalet|first1=Alison H.|last2=Gombos|first2=Dan S.|last3=Gallie|first3=Brenda L.|last4=Kim|first4=Jonathan W.|last5=Shields|first5=Carol L.|last6=Marr|first6=Brian P.|last7=Plon|first7=Sharon E.|last8=Chévez-Barrios|first8=Patricia|title=Screening Children at Risk for Retinoblastoma|journal=Ophthalmology|volume=125|issue=3|year=2018|pages=453–458|issn=01616420|doi=10.1016/j.ophtha.2017.09.001}}</ref>
+|-
+|}
+*The schedule presented above is general [[Medical guideline|guideline]] for at-risk [[Child|children]] when no [[Lesion|lesions]] of concern have been noted. Some [[Child|children]] may require more frequent [[Eye examination|examinations]].
+* The American Association of [[Ophthalmic]] [[Oncologists]] and [[Pathologists]] (AAOOP) [[Medical guideline|guideline]] also suggests a single dilated [[Fundus (eye)|fundus]] [[Physical examination|examination]] to evaluate for [[asymptomatic]] spontaneously regressed retinoblastoma or retinoma in all first-degree relatives of a [[patient]] with retinoblastoma, including older siblings if the [[RB1]] [[genetic analysis]] of the relatives is not done.
+===[[Genetic testing|Genetic Testing]] for Children with Retinoblastoma===
+{{familytree/start}}
+{{familytree | | | | | | | | | | | | | | | A01 | | | | | |A01=[[Genetic testing]] for children with Retinoblastoma}}
+{{familytree | | | | | | | | | | | | | | | |!| | | }}
+{{familytree | |,|-|-|-|-|-|v|-|-|-|-|-|-|-|+|-|-|-|-|v|-|-|-|.| | }}
+{{familytree | |!| | | | | |!| | | | | | | |!| | | | |!| | | |!| | | }}
+{{familytree | D01 | | | | D02 | | | | | | D03 | | | D04 | | D05 |D01=Not available|D02=[[Blood]]: [[RB1]] [[mutation]](+)<br>([[germline mutation]])|D03=Blood: [[RB1]] [[mutation]](-)<br>[[Tumor]]: [[RB1]] [[mutation]](+)|D04=[[Blood]]: [[RB1]] [[mutation]](-)<br>[[Tumor]]: [[RB1]] [[mutation]](-)|D05=[[Blood]]: [[RB1]] [[mutation]](-)<br>[[Tumor]]: not available}}
+{{familytree | |!| | | | | |!| | | | | | | |!| | | | |!| | | |!| }}
+{{familytree | E01 | | | | E02 | | | | | | E03 | | | |`| E04 |'| |E01=Ophthalmic [[screening]] for all<br>the relatives with greater risk than the population |E02=Assessment of relatives<br>for familial retinoblastoma|E03=Ophthalmic [[screening]] and [[genetic analysis]]<br>not required for first degree relatives|E04=No need for [[genetic analysis]] of first degree relatives}}
+{{familytree | | | | | |,|-|^|-|.| | | | | |!| | | | | | |!| }}
+{{familytree | | | | | F01 | | F02 | | | | F03 | | | | | F04 |F01=Relatives with [[RB1]] [[mutation]]|F02=Relatives without [[RB1]] [[mutation]]|F03=Ophthlamic [[screening]] for future offspring unless negative for parent's [[mutation]]|F04=Future offspring of affected child require ophthalmic [[screening]]}}
+{{familytree | | | | | |!| | | |!| | | |}}
+{{familytree | | | | | G01 | | G02 | | |G01=Ophthalmic [[screening]] for children as high risk|G02=Ophthalmic [[screening]] not required}}
+{{familytree/end}}
+{|
+! colspan="2" style="background:#DCDCDC;" align="center" + |The above table is the recommended genetic analysis guidline for families with affected individuals and adopted from Ophthalmology journal<ref name="SkaletGombos2018">{{cite journal|last1=Skalet|first1=Alison H.|last2=Gombos|first2=Dan S.|last3=Gallie|first3=Brenda L.|last4=Kim|first4=Jonathan W.|last5=Shields|first5=Carol L.|last6=Marr|first6=Brian P.|last7=Plon|first7=Sharon E.|last8=Chévez-Barrios|first8=Patricia|title=Screening Children at Risk for Retinoblastoma|journal=Ophthalmology|volume=125|issue=3|year=2018|pages=453–458|issn=01616420|doi=10.1016/j.ophtha.2017.09.001}}</ref>
+|-
+|}
 ==References==
 {{reflist|2}}
-{{WH}}
+[[Category:Medicine]]
-{{WS}}
+[[Category:Oncology]]
+[[Category:Up-To-Date]]
-[[Category:Disease]]
+[[Category:Surgery]]
-{{Nervous tissue tumors}}
-[[Category:Ophthalmology]]
-[[Category:Types of cancer]]
-[[Category:hereditary cancers]]
-[[Category:Oncology stub]]