Peutz-Jeghers syndrome pathophysiology

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

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.

• 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][2]
• 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 mTOR pathway is dysregulated in Peutz-Jeghers syndrome.

• Pathogenesis of mucutaneous pigmentation (macules)
  • Caused by pigment-laden macrophages in the dermis.

• Peutz-Jeghers syndrome is inherited in an autosomal dominant pattern.

Conditions associated with Peutz-Jeghers syndrome include:

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

• On gorss 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.

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

• Frond-like polyp with all three components of mucosa:
  • Muscosal epithelium (melanotic mucosa, goblet cells)
  • Lamina propria
  • Muscularis mucosae

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