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__NOTOC__
__NOTOC__
{{Myxoma}}
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
{{CMG}} {{AE}} {{S.G.}} {{MV}}{{CZ}}{{AAM}}
==Overview==
==Overview==


Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>. Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, [[bones]], and source of extramedullary [[hematopoiesis]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref>. The primary distribution of cardiac myxoma is the left atrium (75%) of the heart.
Cardiac myxoma is a [[benign]] intracavitary [[endocardial]] [[mass]] that represents the most common [[primary tumor]] of the [[heart]]. Myxoma cells are characterized by [[undifferentiated]] [[Mesenchymal cell|mesenchymal cells]], which potentially [[differentiate]] into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]]. The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the [[heart]]; regularly, they tend to be located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].


==Pathophysiology==
==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of [[subendocardial]] vasoformative reserve [[Cell (biology)|cells]], which are primitive [[mesenchymal]] [[Cell (biology)|cells]] that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref><ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* The exact [[pathogenesis]] of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the [[neoplastic]] theory, dysembryoplastic theory, histopathogenesis of [[glandular]] [[Cell (biology)|cells]] in myxoma or the [[thrombotic]] theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of [[Tumor cell|tumor]] attachment, normally the [[foramen ovale]], is considered to be consistent with an origin from [[multipotent]] [[Mesenchymal cell|mesenchymal cells]] or from [[embryonic]] rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>


Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]]. <ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref> <ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref> Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].
==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several [[chromosome]] and [[gene]] alterations which involve [[Heart|cardiac]] development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] [[gene]] inactivation [[mutation]] that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The [[gene]] 17q24.2-q24.3 plays an important role in [[Heart|cardiac]] development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the [[endocardium]].<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of [[protein kinase]] A.Inactivating [[Germline mutation|germline mutations]] of this [[gene]] are found in 70% of people with Carney complex.<ref name="pmid26130139">{{cite journal |vauthors=Correa R, Salpea P, Stratakis CA |title=Carney complex: an update |journal=Eur. J. Endocrinol. |volume=173 |issue=4 |pages=M85–97 |date=October 2015 |pmid=26130139 |pmc=4553126 |doi=10.1530/EJE-15-0209 |url=}}</ref>
* Less commonly, the molecular pathogenesis of Carney complex is a variety of [[genetic]] changes at chromosome 2p16.<ref name="StratakisKirschner2001">{{cite journal|last1=Stratakis|first1=Constantine A.|last2=Kirschner|first2=Lawrence S.|last3=Carney|first3=J. Aidan|title=Clinical and Molecular Features of the Carney Complex: Diagnostic Criteria and Recommendations for Patient Evaluation|journal=The Journal of Clinical Endocrinology & Metabolism|volume=86|issue=9|year=2001|pages=4041–4046|issn=0021-972X|doi=10.1210/jcem.86.9.7903}}</ref>
* Both types of Carney complex are [[autosomal dominant]].
* Despite dissimilar [[genetics]], there appears to be no [[phenotype|phenotypic]] difference between [[PRKAR1A]] and [[chromosome]] 2p16 [[Mutation|mutations]].<ref name="StratakisKirschner20012">{{cite journal|last1=Stratakis|first1=Constantine A.|last2=Kirschner|first2=Lawrence S.|last3=Carney|first3=J. Aidan|title=Clinical and Molecular Features of the Carney Complex: Diagnostic Criteria and Recommendations for Patient Evaluation|journal=The Journal of Clinical Endocrinology & Metabolism|volume=86|issue=9|year=2001|pages=4041–4046|issn=0021-972X|doi=10.1210/jcem.86.9.7903}}</ref>


===Gross Pathology===
==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms ([[cardiac]], [[endocrine]], [[cutaneous]], and [[neural]]), and a host of [[pigmented lesions]] of the [[skin]] and [[Mucous membrane|mucosae]], including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL.  The complex of myxomas, spotty pigmentation, and endocrine overactivity.  ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al.  (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150  http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with [[Carney complex]].<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>


On gross pathology, external appearance, consistency size and weight are extremely variable findings of cardiac myxoma. Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (It can be smooth, lobulated, friable or gelatinous). <ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref> Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface thrombi and embolize.   
==Gross Pathology==
 
* On gross [[pathology]], external appearance, consistency size, and [[weight]] are extremely variable findings of cardiac myxoma.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk. In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile. Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.
*[[Tumor]] consistency depends on the quantity and distribution of [[fibrous tissue]] and [[calcification]] (it can be smooth, lobulated, friable or gelatinous).
 
* Myxomas are usually described as having a gelatinous, irregular surface.  
Cardiac myxomas are intracavitary tumors. The distribution is normally within the interatrial septum or adjacent to foramen ovale (75%). However, they can also be found in other cardiac chambers, such as right atrium (15%),ventricles(˜2%)or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> Large cardiac myxomas are usually located in [[fossa ovalis]]. The average tumor size is from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and [[Embolization|embolize]].<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256  }} </ref>
 
* Morphologically, these [[Lesion|lesions]] tend to be attached to the [[endocardium]] by a broad-based [[pedunculated]] stalk.<ref name="pmid7477198" />
 
* In some cases, the attachment to the [[endocardium]] can also be without a clear stalk, or [[sessile]].<ref name="pmid7477198" />
[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
* Cardiac myxomas are [[Non-invasive (medical)|non-invasive]] [[Tumor|tumors]], thus there is no [[Infiltration (medical)|infiltration]] to underlying [[Tissue (biology)|tissues]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
<div align="center">
* Cardiac myxomas are intracavitary [[tumors]].
* The distribution is normally within the [[interatrial septum]] or adjacent to [[foramen ovale]] (75%).
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.
*  [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium.
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left Atrial Myxoma
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology Atrial Myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</gallery>
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===Microscopic Pathology===
==Microscopic Pathology==
*On [[microscopic]] [[histopathological]] analysis, myxoma cells have an ovoid [[nucleus]] with large [[nucleoli]], abundant [[eosinophilic]] cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>
 
*They are usually arranged in perivascular ring structures (typically, infiltrated by [[lymphocytes]] and [[macrophages]]).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
 
*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
 
*Other frequent histological findings, are [[hemosiderin]] within the [[histiocytes]], [[thrombosis]], [[fibrosis]] and [[Calcification|calcifications]].<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
 
*In some cases, [[extramedullary hematopoiesis]] is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
 
*The [[extracellular matrix]] forms an [[alcian blue]]-positive myxoid stroma, composed of variable amounts of [[Proteoglycan|proteoglycans]], [[elastin]] and [[collagen]].<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
 
{|
|
[[Image:800px-Atrial myxoma edge high mag.jpg|200px|thumb|none|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage. [https://upload.wikimedia.org/wikipedia/commons/7/74/Atrial_myxoma_edge_high_mag.jpg Source: Case courtesy by Nephron, via Wikimedia Commons]]]
|
[[Image: Cardiac myxoma mic 2.jpg|200px|thumb|none|'''Gamna Bodies:''' A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image: Cardiac myxoma mic 3.jpg|200px|thumb|none|'''Cardiac myxoma:''' Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick-walled vessels which angiographically may look like neovascularization. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image: Cardiac myxoma mic 4.jpg|200px|thumb|none|'''Cardiac myxoma:''' The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology]]]
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[[Image:Cardiac myxoma mic 5.jpg|200px|thumb|none|'''Cardiac myxoma:''' Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology]]]
|}
 
==Immunohistochemistry==
 
*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by [[vimentin]] (>50%), [[NOTCH1]], alpha-1 antichymotrypsin and [[Plakophilin-2|plakophilin- 2]].<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>


On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders. They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.
*[[Calretinin]] plays an important role in the [[discrimination]] of [[Mural thrombus|mural thrombi]] and [[papillary fibroelastoma]].<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>


The extracellular matrix forms an Alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen. There is a diffuse reticulated stroma with fine collagen fibrils on which iron encrustation often occurs. <ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
*Another [[immunohistochemical]] marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>


It is also common to find hemosiderin within the histiocytes. Thrombosis, fibrosis and calcification are a frequent histological finding. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.
{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''


<div align="center">
! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''
<gallery heights="225" widths="225">
 
Image:800px-Atrial myxoma edge high mag.jpg|1) Black arrow(top):Endothelium 2) Black arrow(bottom): Hemosiderin macrophage. <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
|-
</gallery>
 
</div>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular [[cellular]] borders, mild or no [[atypia]], absence of [[mitosis]]
:*Myxoma requires the presence of lepidic [[Cell (biology)|cells]]
|-


| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in [[Heart|cardiac]] development and myxomagenesis
|-


[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated [[mass]] can be friable or gelatinous
:*No [[Infiltration (medical)|infiltration]] to underlying [[Tissue (biology)|tissues]]
|-


<div align="center">
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
<gallery heights="150" widths="150">
:*[[Inflammatory]] infiltrates with [[hemosiderin]], [[calcification]]s, and [[extramedullary hematopoiesis]]
Image:Cardiac myxoma mic 2.jpg|Cardiac Myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
:*Scattered thin-walled vessels
Image:Cardiac myxoma mic 3.jpg|Cardiac Myxoma Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
|-
Image:Cardiac myxoma mic 4.jpg|Cardiac Myxoma The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac Myxoma Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma
</gallery>
</div>


==Immunohistochemistry==
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
Cardiac myxoma cells exhibit immuno-reactivity mainly for calretinin (75–100%) followed by vimentin (>50%), Notch-1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>. Another  immunohistochemical marker, survivin (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>
:*[[Calretinin]] (75–100%)
:*[[Vimentin]] (>50%)


==Genetics==
|}
Single cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.
Inherited myxomas are usually presented in the [[Carney complex]]. The development of this syndrome is a result of [[PRKAR1A]] gene inactivation mutation that is associated  with [[chromosome]] 17q24.2-q24.3. This gene plays an important role in cardiac development and myxomagenesis. The expression of PRKAR1A causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>


==References==
==References==
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[[Category:Cardiology]]
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[[Category:Oncology]]
[[Category:Medicine]]
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Latest revision as of 17:08, 9 July 2020

Myxoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2] Maria Fernanda Villarreal, M.D. [3]Cafer Zorkun, M.D., Ph.D. [4]Ahmad Al Maradni, M.D. [5]

Overview

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart. Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many tissues such as blood vessels, glandular structures, and bones. The primary distribution of cardiac myxoma is the left atrium (75%) of the heart; regularly, they tend to be located in the fossa ovalis and endocardium of the atrial septum.

Pathogenesis

Pathogenesis

Genetics

Associated Conditions

Gross Pathology

  • A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium

    A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium

  • Left atrial myxoma

    Left atrial myxoma

  • Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus

    Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus

Microscopic Pathology

  • The Gamna-Bodies which consist of fibrosis and deposition of iron pigments are a characteristic finding of myxoma tumors.[17]
Black arrow (top): Endothelium Black arrow (bottom): Hemosiderin macrophage. Source: Case courtesy by Nephron, via Wikimedia Commons
Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma. Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology
Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick-walled vessels which angiographically may look like neovascularization. Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology
Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas. Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology
Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma. Image courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology

Immunohistochemistry

  • Another immunohistochemical marker, survivin (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.[22]
Cardiac Myxoma Summary
Features Description
General aspects
  • Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
  • Myxoma requires the presence of lepidic cells
Genetics
  • PRKAR1A gene plays an important role in cardiac development and myxomagenesis
Gross Pathology
Micropathology
Inmunohistochemistry

References

  1. ↑ Bulkley BH, Hutchins GM (1979). "Atrial myxomas: a fifty year review". Am. Heart J. 97 (5): 639–43. PMID 433739.
  2. ↑ Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR (2000). "Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation". Radiographics. 20 (4): 1073–103, quiz 1110–1, 1112. doi:10.1148/radiographics.20.4.g00jl081073. PMID 10903697.
  3. ↑ Roscher AA, Kato NS, Quan H, Padmanabhan M (1996). "Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review". J Cardiovasc Surg (Torino). 37 (6 Suppl 1): 131–7. PMID 10064365.
  4. ↑ Acebo E, Val-Bernal JF, Gómez-Román JJ (2001). "Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma". Histopathology. 39 (5): 529–35. PMID 11737312.
  5. ↑ 5.0 5.1 5.2 Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR (2000). "Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation". Radiographics. 20 (4): 1073–103, quiz 1110–1, 1112. doi:10.1148/radiographics.20.4.g00jl081073. PMID 10903697.
  6. ↑ Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G (2006). "Cardiac myxoma cells exhibit embryonic endocardial stem cell features". J. Pathol. 209 (2): 231–9. doi:10.1002/path.1959. PMID 16508920.
  7. ↑ Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K (2003). "Cardiac myxoma: its origin and tumor characteristics". Ann Thorac Cardiovasc Surg. 9 (4): 215–21. PMID 13129418.
  8. ↑ 8.0 8.1 8.2 Reynen K (1995). "Cardiac myxomas". N. Engl. J. Med. 333 (24): 1610–7. doi:10.1056/NEJM199512143332407. PMID 7477198.
  9. ↑ 9.0 9.1 9.2 9.3 Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y (2015). "A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family". Can J Cardiol. 31 (11): 1393–401. doi:10.1016/j.cjca.2015.05.018. PMID 26416542.
  10. ↑ Correa R, Salpea P, Stratakis CA (October 2015). "Carney complex: an update". Eur. J. Endocrinol. 173 (4): M85–97. doi:10.1530/EJE-15-0209. PMC 4553126. PMID 26130139.
  11. ↑ Stratakis, Constantine A.; Kirschner, Lawrence S.; Carney, J. Aidan (2001). "Clinical and Molecular Features of the Carney Complex: Diagnostic Criteria and Recommendations for Patient Evaluation". The Journal of Clinical Endocrinology & Metabolism. 86 (9): 4041–4046. doi:10.1210/jcem.86.9.7903. ISSN 0021-972X.
  12. ↑ Stratakis, Constantine A.; Kirschner, Lawrence S.; Carney, J. Aidan (2001). "Clinical and Molecular Features of the Carney Complex: Diagnostic Criteria and Recommendations for Patient Evaluation". The Journal of Clinical Endocrinology & Metabolism. 86 (9): 4041–4046. doi:10.1210/jcem.86.9.7903. ISSN 0021-972X.
  13. ↑ Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985;64(4):270-83.
  14. ↑ Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. British Journal of Dermatology 2005;152:391-393.
  15. ↑ Gaissmaier et al. (letter and response) Carney Complex. Circulation 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150
  16. ↑ Reynen, K. (1995). "Cardiac Myxomas". New England Journal of Medicine. 333 (24): 1610–1617. doi:10.1056/NEJM199512143332407. PMID 7477198.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 17.5 Di Vito A, Mignogna C, Donato G (2015). "The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology". Histopathology. 66 (3): 321–32. doi:10.1111/his.12531. PMID 25297937.
  18. ↑ He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B; et al. (2015). "Risk factors for embolism in cardiac myxoma: a retrospective analysis". Med Sci Monit. 21: 1146–54. doi:10.12659/MSM.893855. PMC 4418206. PMID 25900256.
  19. ↑ Yoon DH, Roberts W (2002). "Sex distribution in cardiac myxomas". Am. J. Cardiol. 90 (5): 563–5. PMID 12208428.
  20. ↑ Vaideeswar P, Butany JW (2008). "Benign cardiac tumors of the pluripotent mesenchyme". Semin Diagn Pathol. 25 (1): 20–8. PMID 18350919.
  21. ↑ 21.0 21.1 Acebo E, Val-Bernal JF, Gómez-Roman JJ (2001). "Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma". Histol. Histopathol. 16 (4): 1031–6. PMID 11642722.
  22. ↑ Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH (2011). "Survivin expression in cardiac myxoma". Chang Gung Med J. 34 (4): 360–6. PMID 21880190.


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