Kaposi's sarcoma pathophysiology: Difference between revisions

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__NOTOC__
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{{Kaposi's sarcoma}}
{{Kaposi's sarcoma}}
{{CMG}} {{AE}} {{HL}}
{{CMG}} {{AE}} {{HL}} {{Hudakarman}}


==Overview==
==Overview==
Kaposi's sarcoma arises from [[endothelial cell]]s, which are [[epithelial cell]]s that normally lines the interior surface of [[blood vessel]]s and [[lymphatic]] vessels.<ref name="pmid23806158">{{cite journal| author=Ruocco E, Ruocco V, Tornesello ML, Gambardella A, Wolf R, Buonaguro FM| title=Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies. | journal=Clin Dermatol | year= 2013 | volume= 31 | issue= 4 | pages= 413-22 | pmid=23806158 | doi=10.1016/j.clindermatol.2013.01.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23806158  }} </ref><ref name="patho2"> Kaposi's Sarcoma. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/skintumornonmelanocytickaposisarcoma.html Accessed on January, 19 2015</ref><ref name="wiki">Kaposi's sarcoma. Wikipedia (2015)  https://en.wikipedia.org/wiki/Kaposi's_sarcoma Accessed on January, 17 2015</ref> Kaposi's sarcoma is mainly caused by an [[infection]] with Human herpes virus 8 (HHV8), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV). The main [[gene]] involved in the pathogensis of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated [[nuclear]] [[antigen]] (LANA-1).<ref name="pmid23698402">{{cite journal| author=Toth Z, Brulois K, Jung JU| title=The chromatin landscape of Kaposi's sarcoma-associated herpesvirus. | journal=Viruses | year= 2013 | volume= 5 | issue= 5 | pages= 1346-73 | pmid=23698402 | doi=10.3390/v5051346 | pmc=PMC3712311 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23698402  }} </ref> Kaposi's sarcoma is commonly associated with acquired immune deficiency syndrome ([[AIDS]]). On gross pathology, reddish, violaceous, or bluish-black [[macule]]s and patches are characteristic findings of Kaposi's sarcoma. On microscopic histopathological analysis the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi's sarcoma.<ref name="pmid25375885">{{cite journal| author=Rossetto CC, Pari GS| title=PAN's Labyrinth: Molecular biology of Kaposi's sarcoma-associated herpesvirus (KSHV) PAN RNA, a multifunctional long noncoding RNA. | journal=Viruses | year= 2014 | volume= 6 | issue= 11 | pages= 4212-26 | pmid=25375885 | doi=10.3390/v6114212 | pmc=PMC4246217 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25375885  }} </ref><ref name="pmid23685018">{{cite journal| author=Cancian L, Hansen A, Boshoff C| title=Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming. | journal=Trends Cell Biol | year= 2013 | volume= 23 | issue= 9 | pages= 421-32 | pmid=23685018 | doi=10.1016/j.tcb.2013.04.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23685018  }} </ref><ref name="pmid25068226">{{cite journal| author=Zattra E Coati I, Alaibac M, Piaserico S| title=Kaposi's sarcoma and other rare skin cancers in organ transplant patients. | journal=G Ital Dermatol Venereol | year= 2014 | volume= 149 | issue= 4 | pages= 395-400 | pmid=25068226 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25068226  }} </ref><ref name="radio"> Kaposi's Sarcoma. Radiopaedia (2015) http://radiopaedia.org/articles/kaposi-sarcoma Accessed on January, 19 2016</ref>
Kaposi's sarcoma arises from [[endothelial cell]]s, which are [[epithelial cell]]s that normally lines the [[luminal]] surface of [[blood vessel]]s and [[lymphatic]] vessels. Kaposi's sarcoma is mainly caused by an [[infection]] with [[Human herpes virus 8]] ([[HHV-8]]), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV). The main [[gene]] involved in the [[pathogenesis]] of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated [[nuclear]] [[antigen]] (LANA-1). Kaposi's sarcoma is commonly associated with acquired immune deficiency syndrome ([[AIDS]]). On [[Gross pathology|gross pathology,]] reddish, violaceous, or bluish-black [[macule]]s and patches are characteristic findings of Kaposi's sarcoma. On [[microscopic]] [[histopathological]] analysis, the presence of [[spindle cell]]s with minimal [[nuclear]] atypia are characteristic findings of Kaposi's sarcoma.


==Pathogenesis==
==Pathophysiology==
* Kaposi's sarcoma arises from endothelial cells, which are epithelial cells that normally lines the interior surface of blood vessels and lymphatic vessels.  
===Pathogenesis===
* Kaposi's sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV8), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV).
* Kaposi's sarcoma arises from [[endothelial cell]]s, which are [[epithelial cell]]s that normally lines the luminal surface of [[blood vessel]]s and [[lymphatic]] [[vessels]].
* HHV8 is usually transmitted through both saliva and semen via close sexual contact.
* Kaposi's sarcoma is mainly caused by an [[infection]] with Human herpes virus 8 ([[HHV-8]]), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV).<ref name="pmid23806158">{{cite journal| author=Ruocco E, Ruocco V, Tornesello ML, Gambardella A, Wolf R, Buonaguro FM| title=Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies. | journal=Clin Dermatol | year= 2013 | volume= 31 | issue= 4 | pages= 413-22 | pmid=23806158 | doi=10.1016/j.clindermatol.2013.01.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23806158  }} </ref><ref name="patho2">Kaposi's Sarcoma. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/skintumornonmelanocytickaposisarcoma.html Accessed on January, 19 2015</ref>
* Another minor route of transmission for HHV8 is through organ transplantation.  
* HHV-8 is usually transmitted through both [[saliva]] and [[semen]] via close sexual contact.
* A state of immunosuppression facilitates the development of Kaposi's sarcoma among patients infected with virus.  
* Another minor routes of [[transmission]] for [[HHV-8]] are through [[organ transplantation]] and [[blood transfusion]].
* Kaposi's sarcoma is a widely disseminated malignancy that may involve the skin, oral cavity, gastrointestinal tract, and respiratory airways.
* A state of [[immunosuppression]] facilitates the development of Kaposi's sarcoma among [[patients]] infected with the [[virus]].<ref name="pmid23806158">{{cite journal| author=Ruocco E, Ruocco V, Tornesello ML, Gambardella A, Wolf R, Buonaguro FM| title=Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies. | journal=Clin Dermatol | year= 2013 | volume= 31 | issue= 4 | pages= 413-22 | pmid=23806158 | doi=10.1016/j.clindermatol.2013.01.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23806158  }} </ref>
* Kaposi's sarcoma is characterised by abnormal proliferation of endothelial cells, neoangiogenesis, and inflammation.  
* Kaposi's sarcoma is a widely disseminated [[malignancy]] that may involve the [[skin]], [[oral cavity]], [[gastrointestinal tract]], and [[lungs|respiratory airways]].
* Cutaneous manifestations of Kaposi's sarcoma is due to:
* Kaposi's sarcoma is characterized by abnormal [[proliferation]] of [[endothelial cells]], [[angiogenesis|neoangiogenesis]], and [[inflammation]].<ref name="pmid23685018">{{cite journal| author=Cancian L, Hansen A, Boshoff C| title=Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming. | journal=Trends Cell Biol | year= 2013 | volume= 23 | issue= 9 | pages= 421-32 | pmid=23685018 | doi=10.1016/j.tcb.2013.04.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23685018  }} </ref><ref name="pmid25068226">{{cite journal| author=Zattra E Coati I, Alaibac M, Piaserico S| title=Kaposi's sarcoma and other rare skin cancers in organ transplant patients. | journal=G Ital Dermatol Venereol | year= 2014 | volume= 149 | issue= 4 | pages= 395-400 | pmid=25068226 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25068226  }} </ref>
:* The high vascularity of the tumor which leads to leakage of RBC and haemosiderin into the surrounding tissue
* [[Cutaneous]] manifestations of Kaposi's sarcoma are due to:
:* The inflammatory process which surrounds the tumor leads to a mild painful swelling of the area
 
* The oncogenesis of HHV8 infection is due to a number of human cellular genes that have been incorporated through molecular piracy into the viral DNA sequence.
:* The high [[vascularity]] of the [[tumor]] that leads to the leakage of [[RBC]] and [[haemosiderin]] into the surrounding tissue
* The genes acquired by HHV8 will augment the cellular proliferation pathways of infected cells through various mediators and DNA synthesis proteins such as:  
:* The [[inflammatory]] process that surrounds the tumor leads to a mild [[painful]] [[swelling]] of the area
:* Complement-binding protein
* The [[oncogenesis]] of HHV-8 infection is due to a number of human cellular [[genes]] that have been incorporated through [[molecular]] piracy into the viral [[DNA]] sequence.
:* IL-6
* The [[genes]] acquired by [[HHV-8]] will augment the cellular proliferation pathways of infected [[cells]] through various mediators and [[DNA synthesis]] [[protein]]s such as:
:* BCL-2
 
:* Cyclin-D
:*[[Complement]]-binding protein
:* VEGF
:* [[IL-6]]
:* PDGF
:* [[BCL-2]]
:* βFGF
:* [[Cyclin D]]
:* TGFβ
:* v[[cyclin]] <ref name="pmid19261774">{{cite journal |vauthors=Burbelo PD, Leahy HP, Groot S, Bishop LR, Miley W, Iadarola MJ, Whitby D, Kovacs JA |title=Four-antigen mixture containing v-cyclin for serological screening of human herpesvirus 8 infection |journal=Clin. Vaccine Immunol. |volume=16 |issue=5 |pages=621–7 |date=May 2009 |pmid=19261774 |pmc=2681582 |doi=10.1128/CVI.00474-08 |url=}}</ref>
:* Interferon regulatory factor
:* [[VEGF]]
:* [[PDGF]]
:* FGF
:* [[TGF β]]
:* [[Interferon]] regulatory factor
:* Flice inhibitory protein (FLIP)
:* Flice inhibitory protein (FLIP)
:* Dihydrofolate reductase
:* [[Dihydrofolate reductase]]
:* Thymidine kinase
:* [[Thymidine kinase]]
:* Thymidylate synthetase
:* [[Thymidylate synthetase]]
:* DNA polymerase
:* [[DNA polymerase]]
* The augmentation of such cellular proliferation pathways will protect the virus from the immune system and allow a continuous viral replication during the latency period.
* The augmentation of such [[cellular]] [[proliferation]] pathways will protect the [[virus]] from the [[immune system]] and allow a continuous [[viral replication]] during the [[latent period| latency period]].
* During the latent period, HHV8 will express a viral latency-associated nuclear antigen (LANA-1) that acts as transcriptional modulator.  
* During the [[latent period]], [[HHV-8]] will express a [[viral]] latency-associated nuclear antigen (LANA-1) that acts as [[transcription|transcriptional modulator]].<ref name="pmid30682185">{{cite journal |vauthors=De Leo A, Deng Z, Vladimirova O, Chen HS, Dheekollu J, Calderon A, Myers KA, Hayden J, Keeney F, Kaufer BB, Yuan Y, Robertson E, Lieberman PM |title=LANA oligomeric architecture is essential for KSHV nuclear body formation and viral genome maintenance during latency |journal=PLoS Pathog. |volume=15 |issue=1 |pages=e1007489 |date=January 2019 |pmid=30682185 |doi=10.1371/journal.ppat.1007489 |url=}}</ref>
* The functions of HHV8 viral latency-associated nuclear antigen (LANA-1) include:  
* The functions of [[HHV-8]] [[viral]] latency-associated [[nuclear]] [[antigen]] (LANA-1) include:
:* A tethering molecule that stabilize the viral DNA to the cellular chromosome
 
:* An inhibitor of p53 tumor suppressor protein
:* A tethering [[molecule]] that stabilize the [[viral]] [[DNA]] to the cellular [[chromosome]]
:* An inhibitor of retinoblastoma (Rb) tumor suppressor protein
:* An [[inhibitor]] of [[p53]] tumor suppressor protein
:* A suppressor of the viral lytic phase of replication
:* An [[inhibitor]] of [[retinoblastoma]] (Rb) [[tumor suppressor]] [[protein]]
:* A suppressor of the [[viral]] [[lytic]] phase of [[replication]]


==Genetics==  
==Genetics==  
* The main gene involved in the pathogensis of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1).<ref name="pmid23685018">{{cite journal| author=Cancian L, Hansen A, Boshoff C| title=Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming. | journal=Trends Cell Biol | year= 2013 | volume= 23 | issue= 9 | pages= 421-32 | pmid=23685018 | doi=10.1016/j.tcb.2013.04.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23685018  }}</ref><ref name="W">LANA. Wikipedia (2015) https://en.wikipedia.org/wiki/LANA Accessed January, 19 2015</ref>  
* The main [[gene]] involved in the [[pathogenesis]] of Kaposi's sarcoma is ORF73 [[gene]]<ref name="pmid10191203">{{cite journal |vauthors=Zhu L, Wang R, Sweat A, Goldstein E, Horvat R, Chandran B |title=Comparison of human sera reactivities in immunoblots with recombinant human herpesvirus (HHV)-8 proteins associated with the latent (ORF73) and lytic (ORFs 65, K8.1A, and K8.1B) replicative cycles and in immunofluorescence assays with HHV-8-infected BCBL-1 cells |journal=Virology |volume=256 |issue=2 |pages=381–92 |date=April 1999 |pmid=10191203 |doi=10.1006/viro.1999.9674 |url=}}</ref>, which encodes the [[viral]] latency-associated [[nuclear]] [[antigen]] (LANA-1).<ref name="pmid23685018">{{cite journal| author=Cancian L, Hansen A, Boshoff C| title=Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming. | journal=Trends Cell Biol | year= 2013 | volume= 23 | issue= 9 | pages= 421-32 | pmid=23685018 | doi=10.1016/j.tcb.2013.04.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23685018  }}</ref>
* Other viral latent genes involved in the induction of malignant cellular proliferation include:  
* Other [[viral]] latent [[genes]] involved in the induction of [[malignant]] [[cellular]] [[proliferation]] include:
:* vcyclin gene
 
:* vFLIP gene<ref name="pmid16809323">{{cite journal| author=Grossmann C, Podgrabinska S, Skobe M, Ganem D| title=Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype. | journal=J Virol | year= 2006 | volume= 80 | issue= 14 | pages= 7179-85 | pmid=16809323 | doi=10.1128/JVI.01603-05 | pmc=PMC1489050 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16809323  }} </ref>
:* vCyclin [[gene]]<ref name="pmid19261774" />
:* ORF K12 gene (kaposins gene)<ref name="pmid10738139">{{cite journal| author=Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ| title=Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12). | journal=J Clin Virol | year= 2000 | volume= 16 | issue= 3 | pages= 203-13 | pmid=10738139 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10738139  }} </ref>
:* vFLIP [[gene]]<ref name="pmid16809323">{{cite journal| author=Grossmann C, Podgrabinska S, Skobe M, Ganem D| title=Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype. | journal=J Virol | year= 2006 | volume= 80 | issue= 14 | pages= 7179-85 | pmid=16809323 | doi=10.1128/JVI.01603-05 | pmc=PMC1489050 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16809323  }} </ref>
:* ORF K12 [[gene]] (kaposins [[gene]])<ref name="pmid10738139">{{cite journal| author=Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ| title=Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12). | journal=J Clin Virol | year= 2000 | volume= 16 | issue= 3 | pages= 203-13 | pmid=10738139 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10738139  }} </ref>
:* KSHV miRNAs<ref name="pmid25341664">{{cite journal| author=Plaisance-Bonstaff K, Choi HS, Beals T, Krueger BJ, Boss IW, Gay LA et al.| title=KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors. | journal=Viruses | year= 2014 | volume= 6 | issue= 10 | pages= 4005-23 | pmid=25341664 | doi=10.3390/v6104005 | pmc=PMC4213575 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25341664  }} </ref><ref name="patho">Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016</ref>
:* KSHV miRNAs<ref name="pmid25341664">{{cite journal| author=Plaisance-Bonstaff K, Choi HS, Beals T, Krueger BJ, Boss IW, Gay LA et al.| title=KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors. | journal=Viruses | year= 2014 | volume= 6 | issue= 10 | pages= 4005-23 | pmid=25341664 | doi=10.3390/v6104005 | pmc=PMC4213575 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25341664  }} </ref><ref name="patho">Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016</ref>


==Associated Conditions==
==Associated Conditions==
* Kaposi's sarcoma is associated with a number of conditions that include:
* Kaposi's sarcoma is associated with a number of conditions that include:<ref name="pmid23806158">{{cite journal| author=Ruocco E, Ruocco V, Tornesello ML, Gambardella A, Wolf R, Buonaguro FM| title=Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies. | journal=Clin Dermatol | year= 2013 | volume= 31 | issue= 4 | pages= 413-22 | pmid=23806158 | doi=10.1016/j.clindermatol.2013.01.008 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23806158  }} </ref>
:* Acquired immune deficiency syndrome (AIDS)  
 
:* Patients receiving immunosuppressive therapy
:*[[Acquired Immunodeficiency Syndrome|Acquired immune deficiency syndrome]] ([[AIDS]])
:*[[Patients]] receiving [[immunosuppression|immunosuppressive therapy]]


==Gross Pathology==
==Gross Pathology==
* On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi's sarcoma.
* On [[gross pathology]], reddish, violaceous, or bluish-black [[macule]]s and patches are characteristic findings of Kaposi's sarcoma.<ref name="patho">Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016</ref>
* The cutaneous lesions start distally and progressively spread and coalesce to form nodules or plaques.
* The [[cutaneous]] lesions start to develop distally then progressively spread and coalesce to form [[nodule]]s or [[plaque]]s.
<gallery>
Image:
Kaposis Sarcoma Lesions.jpg| Kaposi's sarcoma patient presenting with a redish/violaceous macules
Image:
Kaposis sarcoma.jpg| Kaposi's sarcoma located on the nose
Image:
Kaposi’s sarcoma intraoral AIDS 072 lores.jpg|An HIV-positive patient presented with an intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection
</gallery>


==Microscopic Pathology==
==Microscopic Pathology==
* On microscopic histopathological analysis the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi's sarcoma.
* On [[microscopic]] [[histopathological]] analysis the presence of [[spindle cell]]s with minimal [[nuclear]] atypia are characteristic findings of Kaposi's sarcoma.
* Other findings of Kaposi's sarcoma on light microscopy may include:
* Other findings of Kaposi's sarcoma on [[light microscopy]] may include:<ref name="patho">Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016</ref>
:* Excessive vascular proliferation  
:* Excessive [[vascular]] proliferation  
:* Abundant red blood cells
:* Abundant [[red blood cell]]s
:* Red blood cell and hemosiderin extravasation  
:* Red blood cell and [[hemosiderin]] extravasation  
:* Abundant lymphocytes and monocytes
:* Abundant [[lymphocyte]]s and [[monocyte]]s
:* Premonitory sign (a neovascular lesion wrapped around a pre-existing space with abnormal protrusions)
:* Premonitory sign (a neovascular lesion wrapped around a pre-existing space)
:* Intracytoplasmic PAS +ve hyaline globules (pale pink globs that are paler than red blood cells)
:* Intracytoplasmic PAS +ve [[hyaline]] globules (pale pink globs that are paler than red blood cells)
* The table below differentiates between the four main lesion stages of development for Kaposi's sarcoma:<ref name="patho2"> Kaposi's Sarcoma. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/skintumornonmelanocytickaposisarcoma.html Accessed on January, 19 2015</ref>
* The table below differentiates between the four main [[lesion]] stages of development for Kaposi's sarcoma:<ref name="patho2">Kaposi's Sarcoma. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/skintumornonmelanocytickaposisarcoma.html Accessed on January, 19 2015</ref>
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
|valign=top|
| valign="top" |
|+
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Lesion Stage  }}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Lesion Stage  }}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Histologic Features}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Histologic Features}}
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align=center |
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" |
'''Macular stage'''  
'''Macular stage'''  
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Thin vessel wall
* Thin [[vessel wall]]
* Angulated vessels throughout dermis
* Angulated [[vessels]] throughout the [[dermis]]
* Plasma cell and hemosiderin infiltrates
* [[Plasma cell]] and [[hemosiderin]] infiltrates
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" align=center |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" align="center" |
'''Patch stage'''
'''Patch stage'''
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Angulated lumina that dissect dermal collagen
* Angulated lumina that dissect [[dermal]] [[collagen]]
* Premonitory sign
* Premonitory sign
* Spindle cells surround angiomatoid vascular spaces filled with RBC  
*[[Spindle cells]] surround [[angioma|angiomatoid]] [[vascular]] spaces filled with [[RBC]]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" align=center |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" align="center" |
'''Tumor stage'''  
'''Tumor stage'''  
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Solid nodules
*[[Solid]] [[nodule]]s
* The presence of spindle cells and red blood cells in a slit-like lumina
* The presence of [[spindle cells]] and [[red blood cell]]s in a slit-like lumina
* Abscence of cellular atypia or mitotic activity  
* Abscence of [[cellular]] atypia or [[mitotic]] activity
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" align=center |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" align="center" |
'''Lymphangioma-like variant'''  
'''Lymphangioma-like variant'''  
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Thin walled, angulated vessels
* Thin walled, angulated [[vessel]]s
* Absence of red blood cells
* Absence of [[red blood cells]]
|}
|}


* On immunohistochemistry Kaposi's sarcoma is characterized by:
* On [[immunohistochemistry]] Kaposi's sarcoma is characterized by:<ref name="patho">Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016</ref>
:* Positive CD31  
:* Positive [[CD31]]
:* Positive CD34  
:* Positive [[CD34]]
:* Positive HHV-8  
:* Positive [[HHV-8]]
:* Positive D2-40  
:* Positive D2-40  
:* Positive Ki-67  
:* Positive Ki-67  
:* Positive ERG
:* Positive ERG
* Detection of the LANA protein antigen in tumor cells confirms the diagnosis.


==Gallery==
==Gallery==
* Illustrated below is a series of microscopic images demonstrating Kaposi's sarcoma:<ref name="patho">Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016</ref>
* The following images show the different gross pathological findings and different sites:
<gallery widths="300px">
File:Kaposi’s sarcoma intraoral AIDS 072 lores.jpg| Intraoral lesion depicting Kaposi Sarcoma. Source: Wikimedia Commons <ref>Photo Credit: Sol Silverman, Jr., D.D.S.Content Providers: CDC/ Sol Silverman, Jr., D.D.S., University of California, San Francisco [Public domain], https://upload.wikimedia.org/wikipedia/commons/d/d5/Kaposi%E2%80%99s_sarcoma_intraoral_AIDS_072_lores.jpg </ref>
File:Kaposi'sSarcoma.jpg|Violaceous lesions on the nose of Kaposi sarcoma. Source: Wikimedia Commons<ref> Photo courtesy: Michael Sand, Daniel Sand, Christina Thrandorf, Volker Paech, Peter Altmeyer, Falk G Bechara [CC BY 2.5https://creativecommons.org/licenses/by/2.5)],https://commons.wikimedia.org/wiki/File:Kaposi%27sSarcoma.jpg</ref>
File:Kaposi sarcoma (3944996124).jpg|Pulmonary lesion of Kaposi sarcoma. Source: Wikimedia Commons <ref>Photo courtesy: Yale Rosen from USA [CC BY-SA 2.0 https://creativecommons.org/licenses/by-sa/2.0)],https://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_(3944996124).jpg</ref>
File:Kaposi sarcoma new photo to help in diagnosis.jpg| Lesion in a foot. Source: Wikimedia Commons.<ref> Photo courtesy:Mohammad2018 [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]https://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_new_photo_to_help_in_diagnosis.jpg</ref>
File:Kaposi's sarcoma lesion.jpg|Kaposi sarcoma lesion  Source: Wikimedia Commons.<ref> Photo Credit:Content Providers: CDC/ Dr. Steve Kraus [Public domain]https://commons.wikimedia.org/wiki/File:Kaposi%27s_sarcoma_lesion.jpg</ref>
File:Kaposis Sarcoma Lesions.jpg|Kaposi sarcoma lesion  Source: Wikimedia Commons.<ref> Photo Credit:OpenStax College [CC BY 3.0(https://creativecommons.org/licenses/by/3.0)]https://commons.wikimedia.org/wiki/File:Kaposis_Sarcoma_Lesions.jpg</ref>
</gallery>
 
* Illustrated below is a series of microscopic images demonstrating Kaposi's sarcoma:
<gallery>
<gallery>
Image:  
Image:  
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Latest revision as of 21:15, 10 October 2019

Kaposi's sarcoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Huda A. Karman, M.D.

Overview

Kaposi's sarcoma arises from endothelial cells, which are epithelial cells that normally lines the luminal surface of blood vessels and lymphatic vessels. Kaposi's sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV-8), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV). The main gene involved in the pathogenesis of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1). Kaposi's sarcoma is commonly associated with acquired immune deficiency syndrome (AIDS). On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi's sarcoma. On microscopic histopathological analysis, the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi's sarcoma.

Pathophysiology

Pathogenesis

Genetics

Associated Conditions

  • Kaposi's sarcoma is associated with a number of conditions that include:[1]

Gross Pathology

Microscopic Pathology

  • Excessive vascular proliferation
  • Abundant red blood cells
  • Red blood cell and hemosiderin extravasation
  • Abundant lymphocytes and monocytes
  • Premonitory sign (a neovascular lesion wrapped around a pre-existing space)
  • Intracytoplasmic PAS +ve hyaline globules (pale pink globs that are paler than red blood cells)
  • The table below differentiates between the four main lesion stages of development for Kaposi's sarcoma:[2]
Lesion Stage Histologic Features

Macular stage

Patch stage

Tumor stage

Lymphangioma-like variant

  • Positive CD31
  • Positive CD34
  • Positive HHV-8
  • Positive D2-40
  • Positive Ki-67
  • Positive ERG
  • Detection of the LANA protein antigen in tumor cells confirms the diagnosis.

Gallery

  • The following images show the different gross pathological findings and different sites:
  • Intraoral lesion depicting Kaposi Sarcoma. Source: Wikimedia Commons [12]

    Intraoral lesion depicting Kaposi Sarcoma. Source: Wikimedia Commons [12]

  • Violaceous lesions on the nose of Kaposi sarcoma. Source: Wikimedia Commons[13]

    Violaceous lesions on the nose of Kaposi sarcoma. Source: Wikimedia Commons[13]

  • Pulmonary lesion of Kaposi sarcoma. Source: Wikimedia Commons [14]

    Pulmonary lesion of Kaposi sarcoma. Source: Wikimedia Commons [14]

  • Lesion in a foot. Source: Wikimedia Commons.[15]

    Lesion in a foot. Source: Wikimedia Commons.[15]

  • Kaposi sarcoma lesion Source: Wikimedia Commons.[16]

    Kaposi sarcoma lesion Source: Wikimedia Commons.[16]

  • Kaposi sarcoma lesion Source: Wikimedia Commons.[17]

    Kaposi sarcoma lesion Source: Wikimedia Commons.[17]

  • Illustrated below is a series of microscopic images demonstrating Kaposi's sarcoma:
  • Kaposi sarcoma observed under low magnification[11]

    Kaposi sarcoma observed under low magnification[11]

  • Kaposi sarcoma observed under high magnification[11]

    Kaposi sarcoma observed under high magnification[11]

References

  1. ↑ 1.0 1.1 1.2 Ruocco E, Ruocco V, Tornesello ML, Gambardella A, Wolf R, Buonaguro FM (2013). "Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies". Clin Dermatol. 31 (4): 413–22. doi:10.1016/j.clindermatol.2013.01.008. PMID 23806158.
  2. ↑ 2.0 2.1 Kaposi's Sarcoma. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/skintumornonmelanocytickaposisarcoma.html Accessed on January, 19 2015
  3. ↑ 3.0 3.1 Cancian L, Hansen A, Boshoff C (2013). "Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming". Trends Cell Biol. 23 (9): 421–32. doi:10.1016/j.tcb.2013.04.001. PMID 23685018.
  4. ↑ Zattra E Coati I, Alaibac M, Piaserico S (2014). "Kaposi's sarcoma and other rare skin cancers in organ transplant patients". G Ital Dermatol Venereol. 149 (4): 395–400. PMID 25068226.
  5. ↑ 5.0 5.1 Burbelo PD, Leahy HP, Groot S, Bishop LR, Miley W, Iadarola MJ, Whitby D, Kovacs JA (May 2009). "Four-antigen mixture containing v-cyclin for serological screening of human herpesvirus 8 infection". Clin. Vaccine Immunol. 16 (5): 621–7. doi:10.1128/CVI.00474-08. PMC 2681582. PMID 19261774.
  6. ↑ De Leo A, Deng Z, Vladimirova O, Chen HS, Dheekollu J, Calderon A, Myers KA, Hayden J, Keeney F, Kaufer BB, Yuan Y, Robertson E, Lieberman PM (January 2019). "LANA oligomeric architecture is essential for KSHV nuclear body formation and viral genome maintenance during latency". PLoS Pathog. 15 (1): e1007489. doi:10.1371/journal.ppat.1007489. PMID 30682185.
  7. ↑ Zhu L, Wang R, Sweat A, Goldstein E, Horvat R, Chandran B (April 1999). "Comparison of human sera reactivities in immunoblots with recombinant human herpesvirus (HHV)-8 proteins associated with the latent (ORF73) and lytic (ORFs 65, K8.1A, and K8.1B) replicative cycles and in immunofluorescence assays with HHV-8-infected BCBL-1 cells". Virology. 256 (2): 381–92. doi:10.1006/viro.1999.9674. PMID 10191203.
  8. ↑ Grossmann C, Podgrabinska S, Skobe M, Ganem D (2006). "Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype". J Virol. 80 (14): 7179–85. doi:10.1128/JVI.01603-05. PMC 1489050. PMID 16809323.
  9. ↑ Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ (2000). "Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12)". J Clin Virol. 16 (3): 203–13. PMID 10738139.
  10. ↑ Plaisance-Bonstaff K, Choi HS, Beals T, Krueger BJ, Boss IW, Gay LA; et al. (2014). "KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors". Viruses. 6 (10): 4005–23. doi:10.3390/v6104005. PMC 4213575. PMID 25341664.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016
  12. ↑ Photo Credit: Sol Silverman, Jr., D.D.S.Content Providers: CDC/ Sol Silverman, Jr., D.D.S., University of California, San Francisco [Public domain], https://upload.wikimedia.org/wikipedia/commons/d/d5/Kaposi%E2%80%99s_sarcoma_intraoral_AIDS_072_lores.jpg
  13. ↑ Photo courtesy: Michael Sand, Daniel Sand, Christina Thrandorf, Volker Paech, Peter Altmeyer, Falk G Bechara [CC BY 2.5https://creativecommons.org/licenses/by/2.5)],https://commons.wikimedia.org/wiki/File:Kaposi%27sSarcoma.jpg
  14. ↑ Photo courtesy: Yale Rosen from USA [CC BY-SA 2.0 https://creativecommons.org/licenses/by-sa/2.0)],https://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_(3944996124).jpg
  15. ↑ Photo courtesy:Mohammad2018 [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]https://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_new_photo_to_help_in_diagnosis.jpg
  16. ↑ Photo Credit:Content Providers: CDC/ Dr. Steve Kraus [Public domain]https://commons.wikimedia.org/wiki/File:Kaposi%27s_sarcoma_lesion.jpg
  17. ↑ Photo Credit:OpenStax College [CC BY 3.0(https://creativecommons.org/licenses/by/3.0)]https://commons.wikimedia.org/wiki/File:Kaposis_Sarcoma_Lesions.jpg


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