Kaposi's sarcoma pathophysiology: Difference between revisions

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


==Overview==
==Overview==
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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]].
* 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]].<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>
* 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 [[HHV-8]] 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]]
:* 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
:* An inhibitor of [[retinoblastoma]] (Rb) tumor suppressor protein
:* An [[inhibitor]] of [[retinoblastoma]] (Rb) [[tumor suppressor]] [[protein]]
:* A suppressor of the viral lytic phase of replication
:* A suppressor of the [[viral]] [[lytic]] phase of [[replication]]


==Genetics==  
==Genetics==  
* 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>
* 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<ref name="pmid19261774" />
:* vCyclin [[gene]]<ref name="pmid19261774" />
:* 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>
:* 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>
:* 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:<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 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 [[immunosuppression|immunosuppressive therapy]]
:*[[Acquired Immunodeficiency Syndrome|Acquired immune deficiency syndrome]] ([[AIDS]])
:*[[Patients]] receiving [[immunosuppression|immunosuppressive therapy]]


==Gross Pathology==
==Gross Pathology==
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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" |
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| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Thin [[vessel wall]]
* Thin [[vessel wall]]
* Angulated vessels throughout the [[dermis]]
* Angulated [[vessels]] throughout the [[dermis]]
* [[Plasma cell]] and [[hemosiderin]] infiltrates
* [[Plasma cell]] and [[hemosiderin]] infiltrates
|-
|-
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'''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 [[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;" |
* Solid [[nodule]]s  
*[[Solid]] [[nodule]]s
* The presence of spindle cells and [[red blood cell]]s 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" |
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| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Thin walled, angulated [[vessel]]s
* Thin walled, angulated [[vessel]]s
* Absence of red blood cells
* Absence of [[red blood cells]]
|}
|}


Latest revision as of 21:15, 10 October 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] 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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