Uveal melanoma pathophysiology: Difference between revisions

Jump to navigation Jump to search
m (Bot: Removing from Primary care)
 
(4 intermediate revisions by one other user not shown)
Line 3: Line 3:
{{CMG}}{{AE}} {{Fs}},{{Simrat}}
{{CMG}}{{AE}} {{Fs}},{{Simrat}}
==Overview==
==Overview==
It is understood that [[Uvea (anatomy)|uveal]] [[melanoma]] is the result of [[genetic mutations]]. Activating [[Mutation|mutations]] in [[GNAQ]] or [[GNA11]], [[genes]] encoding for [[G protein]] alpha subunits. These [[mutations]] lead to activation of downstream signaling pathways including the [[MAPK]] pathway in [[Uvea (anatomy)|uveal]] [[melanoma]]. Inactivating [[Somatic mutation|somatic mutations]] are present in the [[gene]] encoding [[BRCA1]]-associated protein 1 ([[BAP1]]) on [[chromosome]] 3p21.1. The [[mutations]] in the [[gene]] ''[[BAP1]]'' are strongly linked to [[Metastasis|metastatic]] spread and patient survival. Conditions associated with [[Uvea (anatomy)|uveal]] [[melanoma]] include [[ocular]] [[nevi]], [[Immune system disorder|impaired immune system]], [[pregnancy]], and [[trauma]]. On microscopic histopathological analysis, we have 5 subtypes according to [[cell]] type into: [[Spindle cells|Spindle]] A, [[Spindle cells|spindle]] B, epitheliolid, mixed, and [[necrotic]].
It is understood that [[Uvea (anatomy)|uveal]] [[melanoma]] is the result of [[genetic mutations]]. Activating [[Mutation|mutations]] in [[GNAQ]] or [[GNA11]], [[genes]] encoding for [[G protein]] alpha subunits. These [[mutations]] lead to activation of downstream signaling pathways including the [[MAPK]] pathway in [[Uvea (anatomy)|uveal]] [[melanoma]]. Inactivating [[Somatic mutation|somatic mutations]] are present in the [[gene]] encoding [[BRCA1]]-associated protein 1 ([[BAP1]]) on [[chromosome]] 3p21.1. The [[mutations]] in the [[gene]] ''[[BAP1]]'' are strongly linked to [[Metastasis|metastatic]] spread and patient [[Survival rate|survival]]. Conditions associated with [[Uvea (anatomy)|uveal]] [[melanoma]] include [[ocular]] [[nevi]], [[Immune system disorder|impaired immune system]], [[pregnancy]], and [[trauma]]. On microscopic histopathological analysis, we have 5 subtypes according to [[cell]] type into [[Spindle cells|spindle]] A, [[Spindle cells|spindle]] B, epitheliolid, mixed, and [[necrotic]].
==Pathophysiology==
==Pathophysiology==
=== Pathogenesis ===
=== Pathogenesis ===
Line 14: Line 14:
== Genetics ==
== Genetics ==
[[Gene|Genes]] involved in the [[pathogenesis]] of uveal melanoma include:
[[Gene|Genes]] involved in the [[pathogenesis]] of uveal melanoma include:
* Activating [[mutations]] in [[GNAQ]] or [[GNA11]], [[genes]] encoding for [[G protein]] alpha subunits. <ref name="pmid21083380">{{cite journal| author=Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T et al.| title=Mutations in GNA11 in uveal melanoma. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 23 | pages= 2191-9 | pmid=21083380 | doi=10.1056/NEJMoa1000584 | pmc=PMC3107972 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21083380  }} </ref><ref name="pmid19078957">{{cite journal| author=Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM et al.| title=Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. | journal=Nature | year= 2009 | volume= 457 | issue= 7229 | pages= 599-602 | pmid=19078957 | doi=10.1038/nature07586 | pmc=PMC2696133 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19078957  }} </ref><ref name="pmid25304237">{{cite journal| author=Shoushtari AN, Carvajal RD| title=GNAQ and GNA11 mutations in uveal melanoma. | journal=Melanoma Res | year= 2014 | volume= 24 | issue= 6 | pages= 525-34 | pmid=25304237 | doi=10.1097/CMR.0000000000000121 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25304237  }} </ref>
* Activating [[mutations]] in [[GNAQ]] or [[GNA11]], [[genes]] encoding for [[G protein]] alpha subunits.<ref name="pmid21083380">{{cite journal| author=Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T et al.| title=Mutations in GNA11 in uveal melanoma. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 23 | pages= 2191-9 | pmid=21083380 | doi=10.1056/NEJMoa1000584 | pmc=PMC3107972 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21083380  }} </ref><ref name="pmid19078957">{{cite journal| author=Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM et al.| title=Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. | journal=Nature | year= 2009 | volume= 457 | issue= 7229 | pages= 599-602 | pmid=19078957 | doi=10.1038/nature07586 | pmc=PMC2696133 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19078957  }} </ref><ref name="pmid25304237">{{cite journal| author=Shoushtari AN, Carvajal RD| title=GNAQ and GNA11 mutations in uveal melanoma. | journal=Melanoma Res | year= 2014 | volume= 24 | issue= 6 | pages= 525-34 | pmid=25304237 | doi=10.1097/CMR.0000000000000121 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25304237  }} </ref>
* These [[mutations]] lead to activation of downstream signaling pathways including the [[MAPK]] pathway in uveal melanoma.
* These [[mutations]] lead to activation of downstream signaling pathways including the [[MAPK]] pathway in uveal melanoma.
* Inactivating somatic [[Mutation|mutations]] are present in the [[gene]] encoding [[BRCA1]]-associated protein 1 ([[BAP1]]) on [[chromosome]] 3p21.1.
* Inactivating somatic [[Mutation|mutations]] are present in the [[gene]] encoding [[BRCA1]]-associated protein 1 ([[BAP1]]) on [[chromosome]] 3p21.1.
Line 33: Line 33:


== Microscopic Pathology ==
== Microscopic Pathology ==
On microscopic [[Histopathology|histopathological]] analysis, we have 5 subtypes according to cell type into: [[Spindle]] A, [[spindle]] B, epitheliolid, mixed, and [[Necrosis|necrotic]].<ref name="McLeanFoster1983">{{cite journal|last1=McLean|first1=Ian W.|last2=Foster|first2=Walter D.|last3=Zimmerman|first3=Lorenz E.|last4=Gamel|first4=John W.|title=Modifications of Callender's Classification of Uveal Melanoma at the Armed Forces Institute of Pathology|journal=American Journal of Ophthalmology|volume=96|issue=4|year=1983|pages=502–509|issn=00029394|doi=10.1016/S0002-9394(14)77914-0}}</ref>
On microscopic [[Histopathology|histopathological]] analysis, we have 5 subtypes according to cell type include [[Spindle]] A, [[spindle]] B, epitheliolid, mixed, and [[Necrosis|necrotic]].<ref name="McLeanFoster1983">{{cite journal|last1=McLean|first1=Ian W.|last2=Foster|first2=Walter D.|last3=Zimmerman|first3=Lorenz E.|last4=Gamel|first4=John W.|title=Modifications of Callender's Classification of Uveal Melanoma at the Armed Forces Institute of Pathology|journal=American Journal of Ophthalmology|volume=96|issue=4|year=1983|pages=502–509|issn=00029394|doi=10.1016/S0002-9394(14)77914-0}}</ref>
{|
{|
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Cell type
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Cell type
Line 79: Line 79:
{{reflist|2}}
{{reflist|2}}


{{WH}}
[[Category:Medicine]]
{{WS}}
 
[[Category:Disease]]
[[Category:Ophthalmology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Up-To-Date]]
[[Category:Ophthalmology]]
[[Category:Surgery]]

Latest revision as of 00:37, 30 July 2020

Uveal melanoma Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Uveal melanoma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

Echocardiography and Ultrasound

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Uveal melanoma pathophysiology On the Web

Most recent articles

cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Uveal melanoma pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Uveal melanoma pathophysiology

CDC on Uveal melanoma pathophysiology

Uveal melanoma pathophysiology in the news

Blogs on Uveal melanoma pathophysiology

to Hospitals Treating Uveal melanoma

Risk calculators and risk factors for Uveal melanoma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.,Simrat Sarai, M.D. [2]

Overview

It is understood that uveal melanoma is the result of genetic mutations. Activating mutations in GNAQ or GNA11, genes encoding for G protein alpha subunits. These mutations lead to activation of downstream signaling pathways including the MAPK pathway in uveal melanoma. Inactivating somatic mutations are present in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1. The mutations in the gene BAP1 are strongly linked to metastatic spread and patient survival. Conditions associated with uveal melanoma include ocular nevi, impaired immune system, pregnancy, and trauma. On microscopic histopathological analysis, we have 5 subtypes according to cell type into spindle A, spindle B, epitheliolid, mixed, and necrotic.

Pathophysiology

Pathogenesis

Genetics

Genes involved in the pathogenesis of uveal melanoma include:

Associated Conditions

Conditions associated with uveal melanoma include:[7][8][9]

Gross Pathology


https://en.wikipedia.org/wiki/File:Malignant_melanoma.jpg

Microscopic Pathology

On microscopic histopathological analysis, we have 5 subtypes according to cell type include Spindle A, spindle B, epitheliolid, mixed, and necrotic.[10]

Cell type Explanation
Spindle A
Spindle B
  • Commen
Epithelioid
Mixed
Necrotic
  • uncommon


References

  1. 1.0 1.1 Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T; et al. (2010). "Mutations in GNA11 in uveal melanoma". N Engl J Med. 363 (23): 2191–9. doi:10.1056/NEJMoa1000584. PMC 3107972. PMID 21083380.
  2. 2.0 2.1 Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM; et al. (2009). "Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi". Nature. 457 (7229): 599–602. doi:10.1038/nature07586. PMC 2696133. PMID 19078957.
  3. 3.0 3.1 Shoushtari AN, Carvajal RD (2014). "GNAQ and GNA11 mutations in uveal melanoma". Melanoma Res. 24 (6): 525–34. doi:10.1097/CMR.0000000000000121. PMID 25304237.
  4. McGrath JJ (1986). "Nicotine and carbon monoxide: effects on the isolated rat heart". Alcohol. 3 (2): 157–60. PMID 3087380.
  5. Gupta MP, Lane AM, DeAngelis MM, Mayne K, Crabtree M, Gragoudas ES; et al. (2015). "Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations". JAMA Ophthalmol. 133 (8): 881–7. doi:10.1001/jamaophthalmol.2015.1119. PMID 25974357.
  6. Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM (2013). "Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma". Nat Genet. 45 (2): 133–5. doi:10.1038/ng.2523. PMC 3789378. PMID 23313955.
  7. Fisher, M.; Kripke, M. (1982). "Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice". Science. 216 (4550): 1133–1134. doi:10.1126/science.6210958. ISSN 0036-8075.
  8. Siegel, Ralph (1963). "Malignant Ocular Melanoma During Pregnancy". JAMA: The Journal of the American Medical Association. 185 (6): 542. doi:10.1001/jama.1963.03060060140028. ISSN 0098-7484.
  9. Baba, F. E.; Blumenkranz, M. (1986). "Malignant Melanoma at the Site of Penetrating Ocular Trauma". Archives of Ophthalmology. 104 (3): 405–409. doi:10.1001/archopht.1986.01050150105038. ISSN 0003-9950.
  10. McLean, Ian W.; Foster, Walter D.; Zimmerman, Lorenz E.; Gamel, John W. (1983). "Modifications of Callender's Classification of Uveal Melanoma at the Armed Forces Institute of Pathology". American Journal of Ophthalmology. 96 (4): 502–509. doi:10.1016/S0002-9394(14)77914-0. ISSN 0002-9394.