Hamartomatous Polyposis Syndromes
Peutz-Jeghers Syndrome (PJS)
PJS occurs in an estimated 1 in 10,000 to 1 in 100,000 patients, but there is a highly variable penetrance even within family members. Patients with PJS present typical freckling mucocutaneous hyperpigmentation in lips, buccal mucosa, vulva, fingers, and toes.
Gastrointestinal polyps occur in almost all individuals with PJS and they exhibit a unique morphology consisting of mucosa with interdigitating smooth muscle bundles that yield a characteristic branching tree appearance termed "arborization". Polyps start developing during the first decade and symptoms usually present between the ages of 11 and 29 due to polyp growth and subsequent obstruction or intussuception. Patients have an increased risk of developing gastrointestinal cancers, such as colon (40%), stomach (30-60%), small intestine (15-30%), and esophagus (0.5-30%). Cancers of the breast, endometrial, pancreatic and lung are also common. Therefore, a cancer surveillance protocol should be instituted.
PJS is diagnosed when hamarmatous polyps are present and at least two of the following clinical criteria are fulfilled: (1) family history, (2) hyperpigmentation, and (3) small bowel polyposis.
Genetic testing and PFS
Peutz-Jeghers syndrome is caused by germ-line mutations in the serine threonine kinase STK11 or LKB1, located in chromosome 19p. This tumor suppressor gene encodes a protein involved in the transduction of intracellular growth signals. Mutations in this gene have been identified in 50-75% of familial cases. However, up to 25% of documented cases are not familial and these would be due to de novo mutations.
In these patients an attempt is done to locate and remove all polyps larger than 1cm in diameter.
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