Peutz-Jeghers syndrome pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==
===Genetics===
*Peutz-Jeghers syndrome is inherited in an [[autosomal dominant]] pattern.
===Pathogenesis===
===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>
*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>
*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.
*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).<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>
*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>
** The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.
** The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.


* Mucutaneous Pigmentation (macules)
* Mucutaneous Pigmentation (macules)
** Caused by pigment-laden macrophages in the dermis
**Caused by pigment-laden macrophages in the dermis


===Pathology===
===Genetics===
*Peutz-Jeghers syndrome is inherited in an [[autosomal dominant]] pattern.
 
==Associated Conditions==
*Breast Cancer
*Colon Cancer
*Pancreatic cancer
*Ovarian cancer
*Cervical cancer
*Testicular cancer
 
==Gross Pathology==
*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>
*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>
**These polyps can only be differentiated from other polyp types by histopathology.  
**These polyps can only be differentiated from other polyp types by histopathology.  
===Microscopic Pathology===
===Microscopic Pathology===
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>
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>

Revision as of 16:27, 20 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.

Pathophysiology

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.[1]
  • 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).[1]
    • The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.
  • Mucutaneous Pigmentation (macules)
    • Caused by pigment-laden macrophages in the dermis

Genetics

Associated Conditions

  • Breast Cancer
  • Colon Cancer
  • Pancreatic cancer
  • Ovarian cancer
  • Cervical cancer
  • Testicular cancer

Gross Pathology

  • Peutz-Jeghers syndrome associated polyps have a unique smooth muscle core that arborizes throughout the polyp.[1]
    • These polyps can only be differentiated from other polyp types by histopathology.

Microscopic Pathology

Polyps of Peutz-Jeghers syndrome are usually non-neoplastic hamartomas.[2] On microscopic histopathological analysis, polyps have the following characteristic findings:[3]

  • Frond-like polyp with all three components of mucosa:
    • Muscosal epithelium (melanotic mucosa, goblet cells)
    • Lamina propria
    • Muscularis mucosae
      Peutz-Jeghers Polyp Histology Source: By Nephron (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons[4]
      Colonic Polyp.
      Source:Libre Pathology[5]


References

  1. ↑ 1.0 1.1 1.2 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. ↑ 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
  3. ↑ 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.
  4. ↑ "By Nephron (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons". External link in |title= (help)
  5. ↑ "File:Colon histology with Peutz-Jeghers polyp.jpg - Libre Pathology".
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