Kaposi's sarcoma pathophysiology: Difference between revisions

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==Overview==
==Overview==
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.<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 ([[HHV-8]]), 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 cell]]s 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 pathogensis 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 [[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==
==Pathogenesis==
* 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 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).<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 ([[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>
* HHV-8 is usually transmitted through both [[saliva]] and [[semen]] via close sexual contact.
* HHV-8 is usually transmitted through both [[saliva]] and [[semen]] via close sexual contact.
* Another minor routes of transmission for HHV-8 are through [[organ transplantation]] and [[blood transfusion]].  
* Another minor routes of transmission for HHV-8 are through [[organ transplantation]] and [[blood transfusion]].  
* 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>   
* 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 a widely disseminated malignancy that may involve the skin, [[oral cavity]], [[gastrointestinal tract]], and [[lungs|respiratory airways]].
* Kaposi's sarcoma is a widely disseminated malignancy that may involve the skin, [[oral cavity]], [[gastrointestinal tract]], and [[lungs|respiratory airways]].
* Kaposi's sarcoma is characterised 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><ref name="radio"> Kaposi's Sarcoma. Radiopaedia (2015) http://radiopaedia.org/articles/kaposi-sarcoma Accessed on January, 19 2016</ref>  
* Kaposi's sarcoma is characterised 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><ref name="radio">Kaposi's Sarcoma. Radiopaedia (2015) http://radiopaedia.org/articles/kaposi-sarcoma Accessed on January, 19 2016</ref>  
* [[Cutaneous]] manifestations of Kaposi's sarcoma are due to:
* [[Cutaneous]] manifestations of Kaposi's sarcoma are due to:
:* The high [[vascularity]] of the [[tumor]] that leads to the leakage of [[RBC]] and [[haemosiderin]] into the surrounding tissue
:* The high [[vascularity]] of the [[tumor]] that leads to the leakage of [[RBC]] and [[haemosiderin]] into the surrounding tissue
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:* [[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 [[latent period| latency period]].<ref name="wiki">Kaposi's sarcoma. Wikipedia (2015)  https://en.wikipedia.org/wiki/Kaposi's_sarcoma Accessed on January, 17 2015</ref>
* 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, HHV-8 will express a viral latency-associated nuclear antigen (LANA-1) that acts as [[transcription|transcriptional modulator]].  
* During the latent period, HHV-8 will express a viral latency-associated nuclear antigen (LANA-1) that acts as [[transcription|transcriptional modulator]].  
* The functions of HHV-8 viral latency-associated nuclear antigen (LANA-1) include:<ref name="W">LANA. Wikipedia (2015) https://en.wikipedia.org/wiki/LANA Accessed January, 19 2015</ref>  
* 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]]   
:* A tethering molecule that stabilize the viral DNA to the cellular [[chromosome]]   
:* An inhibitor of [[p53]] tumor suppressor protein
:* An inhibitor of [[p53]] tumor suppressor protein
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==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 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>  
* 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
:* vCyclin gene
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==Associated Conditions==
==Associated Conditions==
* 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><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 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]])  
:* Acquired immune deficiency syndrome ([[AIDS]])  
:* Patients receiving [[immunosuppression|immunosuppressive therapy]]
:* Patients receiving [[immunosuppression|immunosuppressive therapy]]


==Gross Pathology==
==Gross Pathology==
* On gross pathology, reddish, violaceous, or bluish-black [[macule]]s and patches are characteristic findings of Kaposi's sarcoma.<ref name="wiki">Kaposi's sarcoma. Wikipedia (2015)  https://en.wikipedia.org/wiki/Kaposi's_sarcoma Accessed on January, 17 2015</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>
* 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 to develop distally then progressively spread and coalesce to form [[nodule]]s or [[plaque]]s.
* The [[cutaneous]] lesions start to develop distally then progressively spread and coalesce to form [[nodule]]s or [[plaque]]s.


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:* Premonitory sign (a neovascular lesion wrapped around a pre-existing space)
:* 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;" |
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* [[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;" |
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* Spindle cells surround [[angioma|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;" |
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* 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;" |
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:* Positive Ki-67  
:* Positive Ki-67  
:* Positive ERG
:* Positive ERG
* Detection of the LANA protein antigen in tumor cells confirms the diagnosis.<ref name="wiki">Kaposi's sarcoma. Wikipedia (2015)  https://en.wikipedia.org/wiki/Kaposi's_sarcoma Accessed on January, 17 2015</ref>
* Detection of the LANA protein antigen in tumor cells confirms the diagnosis.


==Gallery==
==Gallery==

Revision as of 21:21, 10 February 2019

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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]

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 pathogensis 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.

Pathogenesis

  • The high vascularity of the tumor that leads to the leakage of RBC and haemosiderin into the surrounding tissue
  • The inflammatory process that surrounds the tumor leads to a mild painful swelling of the area
  • 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.
  • The genes acquired by HHV-8 will augment the cellular proliferation pathways of infected cells through various mediators and DNA synthesis proteins such as:
  • 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.
  • During the latent period, HHV-8 will express a viral latency-associated nuclear antigen (LANA-1) that acts as transcriptional modulator.
  • 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
  • An inhibitor of retinoblastoma (Rb) tumor suppressor protein
  • A suppressor of the viral lytic phase of replication

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).[3]
  • Other viral latent genes involved in the induction of malignant cellular proliferation include:
  • vCyclin gene
  • vFLIP gene[6]
  • ORF K12 gene (kaposins gene)[7]
  • KSHV miRNAs[8][9]

Associated Conditions

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

Gross Pathology

  • On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi's sarcoma.[9]
  • The cutaneous lesions start to develop distally then progressively spread and coalesce to form nodules or plaques.

Microscopic Pathology

  • On microscopic histopathological analysis the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi's sarcoma.
  • Other findings of Kaposi's sarcoma on light microscopy may include:[9]
  • 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

  • Thin walled, angulated vessels
  • Absence of red blood cells
  • On immunohistochemistry Kaposi's sarcoma is characterized by:[9]
  • 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

  • Illustrated below is a series of microscopic images demonstrating Kaposi's sarcoma:
  • Kaposi sarcoma observed under low magnification[9]

    Kaposi sarcoma observed under low magnification[9]

  • Kaposi sarcoma observed under high magnification[9]

    Kaposi sarcoma observed under high magnification[9]

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. ↑ Kaposi's Sarcoma. Radiopaedia (2015) http://radiopaedia.org/articles/kaposi-sarcoma Accessed on January, 19 2016
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016


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