Kaposi's sarcoma pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
Line 67: Line 67:


==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:
:* 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"
Line 85: Line 85:
'''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 [[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:
:* 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  

Revision as of 19:23, 19 January 2016

Kaposi's sarcoma Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Kaposi's sarcoma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Echocardiograph and Ultrasound

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Kaposi's sarcoma pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Kaposi's sarcoma pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Kaposi's sarcoma pathophysiology

CDC on Kaposi's sarcoma pathophysiology

Kaposi's sarcoma pathophysiology in the news

Blogs on Kaposi's sarcoma pathophysiology

Directions to Hospitals Treating Kaposi's sarcoma

Risk calculators and risk factors for Kaposi's sarcoma pathophysiology

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 interior surface of blood vessels and lymphatic vessels.[1][2][3] 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).[4] 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.[5][6][7][8]

Pathogenesis

  • The high vascularity of the tumor which leads to leakage of RBC and haemosiderin into the surrounding tissue
  • The inflammatory process which 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).[6][9]
  • Other viral latent genes involved in the induction of malignant cellular proliferation include:
  • vcyclin gene
  • vFLIP gene[10]
  • ORF K12 gene (kaposins gene)[11]
  • KSHV miRNAs[12][13]

Associated Conditions

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

Gross Pathology

  • On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi's sarcoma.
  • The cutaneous lesions start distally and progressively spread and coalesce to form nodules or plaques.
  • Kaposi's sarcoma patient presenting with a redish/violaceous macules

    Kaposi's sarcoma patient presenting with a redish/violaceous macules

  • Kaposi's sarcoma located on the nose

    Kaposi's sarcoma located on the nose

  • An HIV-positive patient presented with an intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection

    An HIV-positive patient presented with an intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection

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:
  • 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:
  • Positive CD31
  • Positive CD34
  • Positive HHV-8
  • Positive D2-40
  • Positive Ki-67
  • Positive ERG

Gallery

  • Illustrated below is a series of microscopic images demonstrating Kaposi's sarcoma:[13]
  • Kaposi sarcoma observed under low magnification[13]

    Kaposi sarcoma observed under low magnification[13]

  • Kaposi sarcoma observed under high magnification[13]

    Kaposi sarcoma observed under high magnification[13]

References

  1. ↑ 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. ↑ Kaposi's sarcoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Kaposi's_sarcoma Accessed on January, 17 2015
  4. ↑ Toth Z, Brulois K, Jung JU (2013). "The chromatin landscape of Kaposi's sarcoma-associated herpesvirus". Viruses. 5 (5): 1346–73. doi:10.3390/v5051346. PMC 3712311. PMID 23698402.
  5. ↑ Rossetto CC, Pari GS (2014). "PAN's Labyrinth: Molecular biology of Kaposi's sarcoma-associated herpesvirus (KSHV) PAN RNA, a multifunctional long noncoding RNA". Viruses. 6 (11): 4212–26. doi:10.3390/v6114212. PMC 4246217. PMID 25375885.
  6. ↑ 6.0 6.1 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.
  7. ↑ 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.
  8. ↑ Kaposi's Sarcoma. Radiopaedia (2015) http://radiopaedia.org/articles/kaposi-sarcoma Accessed on January, 19 2016
  9. ↑ LANA. Wikipedia (2015) https://en.wikipedia.org/wiki/LANA Accessed January, 19 2015
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 13.0 13.1 13.2 13.3 Libre Pathology. Kaposi's sarcoma (2015) http://librepathology.org/wiki/index.php/File:Kaposi_sarcoma_low_intermed_mag.jpg Accessed on January, 19 2016


Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Kaposi%27s_sarcoma_pathophysiology&oldid=1203824"