Peutz-Jeghers syndrome pathophysiology: Difference between revisions

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{{Peutz-Jeghers syndrome}}
{{Peutz-Jeghers syndrome}}
{{CMG}} {{AE}} {{HQ}}
{{CMG}}; {{AE}} {{HQ}}


==Overview==
==Overview==
Peutz-Jeghers syndrome is transmitted in an [[autosomal dominant]] pattern. Polyps of Peutz-Jeghers syndrome are usually non-neoplastic [[hamartomas]].
Peutz-Jeghers syndrome is transmitted in an [[autosomal dominant]] pattern. [[Polyps]] of Peutz-Jeghers syndrome are usually non-neoplastic [[hamartomas]]. It is thought that Peutz-Jeghers syndrome is the result of [[Deletion (genetics)|deletion]] or [[Deletion (genetics)|partial deletion]] of [[STK11]] (LBK1) gene, located on [[chromosome]] 19p13.3. Mucutaneous [[pigmentation]] ([[macules]]) are caused by [[pigment]]-laden [[macrophages]] in the [[dermis]].  


==Pathophysiology==
==Pathophysiology==
===Pathogenesis===
*It is thought that Peutz-Jeghers syndrome is the result of [[Deletion (genetics)|deletion]] or [[Deletion (genetics)|partial deletion]] of [[STK11]] (LBK1) gene, located on [[chromosome]] 19p13.3.<ref name="KopacovaTacheci2009">{{cite journal|last1=Kopacova|first1=Marcela|last2=Tacheci|first2=Ilja|last3=Rejchrt|first3=Stanislav|last4=Bures|first4=Jan|title=Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach|journal=World Journal of Gastroenterology|volume=15|issue=43|year=2009|pages=5397|issn=1007-9327|doi=10.3748/wjg.15.5397}}</ref><ref name="BuckHarned1992">{{cite journal|last1=Buck|first1=J L|last2=Harned|first2=R K|last3=Lichtenstein|first3=J E|last4=Sobin|first4=L H|title=Peutz-Jeghers syndrome.|journal=RadioGraphics|volume=12|issue=2|year=1992|pages=365–378|issn=0271-5333|doi=10.1148/radiographics.12.2.1561426}}</ref>
*[[STK11]] [[protein]] plays an important role in [[second messenger]] [[signal transduction]] and is found to regulate [[cellular]] [[proliferation]], controls [[cell]] polarity, and responds to low energy states.
*In Mammalian studies, [[STK11]] is shown in the inhibition of [[AMP-activated protein kinase]] (AMPK), and signals downstream to inhibit the [[mammalian target of rapamycin]] ([[mTOR]]).
** The [[Mammalian target of rapamycin|mTOR pathway]] is dysregulated in Peutz-Jeghers syndrome.
* Pathogenesis of mucutaneous [[pigmentation]] ([[Macule|macules]])
**Caused by [[pigment]]-laden [[Macrophage|macrophages]] in the [[dermis]].
===Genetics===
===Genetics===
*Peutz-Jeghers syndrome is inherited in an [[autosomal dominant]] pattern.
*Peutz-Jeghers syndrome is [[inherited]] in an [[autosomal dominant]] pattern.
===Pathogenesis===
 
*It is thought that Peutz-Jeghers syndrome is the result of deletion or partial deletion of STK11 (LBK1) gene, located on chromosome 19p13.3.<ref name="KopacovaTacheci2009">{{cite journal|last1=Kopacova|first1=Marcela|last2=Tacheci|first2=Ilja|last3=Rejchrt|first3=Stanislav|last4=Bures|first4=Jan|title=Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach|journal=World Journal of Gastroenterology|volume=15|issue=43|year=2009|pages=5397|issn=1007-9327|doi=10.3748/wjg.15.5397}}</ref>
==Associated Conditions==
*STK11 protein plays an important role in second messenger signal transduction and is found to regulate cellular proliferation, controls cell polarity, and responds to low energy states.
Conditions associated with Peutz-Jeghers syndrome include:
*In Mammalian studies, STK11 is shown in the inhibition of AMP-activated protein kinase (AMPK), and signals downstream to inhibit the mammalian target of rapamycin (mTOR).<ref name="KopacovaTacheci2009">{{cite journal|last1=Kopacova|first1=Marcela|last2=Tacheci|first2=Ilja|last3=Rejchrt|first3=Stanislav|last4=Bures|first4=Jan|title=Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach|journal=World Journal of Gastroenterology|volume=15|issue=43|year=2009|pages=5397|issn=1007-9327|doi=10.3748/wjg.15.5397}}</ref>
*[[Breast Cancer]]
**The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.
*[[Colorectal cancer|Colon Cancer]]
===Pathology===
*[[Pancreatic cancer]]
*Peutz-Jeghers syndrome associated polyps have a unique smooth muscle core that arborizes throughout the polyp.<ref name="KopacovaTacheci2009">{{cite journal|last1=Kopacova|first1=Marcela|last2=Tacheci|first2=Ilja|last3=Rejchrt|first3=Stanislav|last4=Bures|first4=Jan|title=Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach|journal=World Journal of Gastroenterology|volume=15|issue=43|year=2009|pages=5397|issn=1007-9327|doi=10.3748/wjg.15.5397}}</ref>
*[[Ovarian cancer]]
**These polyps can only be differentiated from other polyp types by histopathology.  
*[[Cervical cancer]]
===Microscopic Pathology===
*[[Testicular cancer]]
Polyps of Peutz-Jeghers syndrome are usually non-neoplastic [[hamartomas]].<ref>Pathology of Peutz-Jeghers syndrome. Dr Amir Rezaee and Dr Alexandra Stanislavsky et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/peutz-jeghers-syndrome-2</ref> On microscopic histopathological analysis, polyps have the following characteristic findings:<ref name="BuckHarned1992">{{cite journal|last1=Buck|first1=J L|last2=Harned|first2=R K|last3=Lichtenstein|first3=J E|last4=Sobin|first4=L H|title=Peutz-Jeghers syndrome.|journal=RadioGraphics|volume=12|issue=2|year=1992|pages=365–378|issn=0271-5333|doi=10.1148/radiographics.12.2.1561426}}</ref>
 
*Frond-like polyp with all three components of mucosa:
==Gross Pathology==
**Muscosal epithelium (melanotic mucosa, goblet cells)
*On gorss pathology, Peutz-Jeghers syndrome associated [[Polyp|polyps]] have a unique [[smooth muscle]] core that arborizes throughout the [[polyp]].<ref name="KopacovaTacheci2009">{{cite journal|last1=Kopacova|first1=Marcela|last2=Tacheci|first2=Ilja|last3=Rejchrt|first3=Stanislav|last4=Bures|first4=Jan|title=Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach|journal=World Journal of Gastroenterology|volume=15|issue=43|year=2009|pages=5397|issn=1007-9327|doi=10.3748/wjg.15.5397}}</ref>
**Lamina propria
**These [[Polyp|polyps]] can only be differentiated from other [[polyp]] types by [[histopathology]].  
**Muscularis mucosae
 
==Microscopic Pathology==
* [[Polyp|Polyps]] of Peutz-Jeghers syndrome are usually non-neoplastic [[hamartomas]].<ref>Pathology of Peutz-Jeghers syndrome. Dr Amir Rezaee and Dr Alexandra Stanislavsky et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/peutz-jeghers-syndrome-2</ref>
* On microscopic histopathological analysis, [[Polyp|polyps]] have the following characteristic findings:<ref name="BuckHarned1992">{{cite journal|last1=Buck|first1=J L|last2=Harned|first2=R K|last3=Lichtenstein|first3=J E|last4=Sobin|first4=L H|title=Peutz-Jeghers syndrome.|journal=RadioGraphics|volume=12|issue=2|year=1992|pages=365–378|issn=0271-5333|doi=10.1148/radiographics.12.2.1561426}}</ref>
 
*Frond-like [[polyp]] with all three components of [[mucosa]]:
**Muscosal [[epithelium]] (melanotic [[mucosa]], [[goblet cells]])
**[[Lamina propria]]
**[[Muscularis mucosae]]


[[File:Peutz-Jeghers syndrome polyp.jpg|400px|PJ polyps]]
[[File:Peutz-Jeghers syndrome polyp .jpg|none|thumb|260x260px|Peutz-Jeghers Polyp Histology [https://upload.wikimedia.org/wikipedia/commons/c/c6/Peutz-Jeghers_syndrome_polyp.jpg Source: By Nephron (Own work), via Wikimedia Commons]]]
[[File:Colon histology with Peutz-Jeghers polyp.jpg|200x200px|thumb|Peutz-Jeghers Polyp Histology [https://www.wikidoc.org/images/0/03/Colon_histology_with_Peutz-Jeghers_polyp.jpg Source:Libre Pathology]]]


== References ==
== References ==
{{reflist|2}}
{{reflist|2}}
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[[Category:Gastroenterology]]
[[Category:Surgery]]
[[Category:Oncology]]
[[Category:Disease]]
[[Category:Pediatrics]]
[[Category:Up-To-Date]]

Latest revision as of 15:16, 21 December 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2]

Overview

Peutz-Jeghers syndrome is transmitted in an autosomal dominant pattern. Polyps of Peutz-Jeghers syndrome are usually non-neoplastic hamartomas. It is thought that Peutz-Jeghers syndrome is the result of deletion or partial deletion of STK11 (LBK1) gene, located on chromosome 19p13.3. Mucutaneous pigmentation (macules) are caused by pigment-laden macrophages in the dermis.

Pathophysiology

Pathogenesis

Genetics

Associated Conditions

Conditions associated with Peutz-Jeghers syndrome include:

Gross Pathology

Microscopic Pathology

  • Polyps of Peutz-Jeghers syndrome are usually non-neoplastic hamartomas.[3]
  • On microscopic histopathological analysis, polyps have the following characteristic findings:[2]
Peutz-Jeghers Polyp Histology Source: By Nephron (Own work), via Wikimedia Commons
Peutz-Jeghers Polyp Histology Source:Libre Pathology

References

  1. 1.0 1.1 Kopacova, Marcela; Tacheci, Ilja; Rejchrt, Stanislav; Bures, Jan (2009). "Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach". World Journal of Gastroenterology. 15 (43): 5397. doi:10.3748/wjg.15.5397. ISSN 1007-9327.
  2. 2.0 2.1 Buck, J L; Harned, R K; Lichtenstein, J E; Sobin, L H (1992). "Peutz-Jeghers syndrome". RadioGraphics. 12 (2): 365–378. doi:10.1148/radiographics.12.2.1561426. ISSN 0271-5333.
  3. Pathology of Peutz-Jeghers syndrome. Dr Amir Rezaee and Dr Alexandra Stanislavsky et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/peutz-jeghers-syndrome-2

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