Snapshot A 20-year-old woman presents with fatigue and pallor. On routine blood tests, she is found to have iron-deficiency anemia. On physical exam, she has multiple freckles around her lips and some inside her mucosa. Her primary care physician is concerned that the freckles may not actually be freckles but a lesion of something else. She is referred to a GI doctor, who schedules her for an endoscopy. Introduction Inherited syndrome with multiple nonmalignant hamartomatous polyps in GI tract mucocutaneous hyperpigmentation Genetics autosomal dominant mutation in STK11, a tumor suppressor gene Associated conditions ↑ risk for multiple malignancies colon cancer breast pancreas gynecologic Presentation Symptoms/physical exam hyperpigmented mucocutaneous macules blue-gray or brown spots most common spots lips buccal mucosa soles palms hamartomatous polyps most common in small bowel may be sessile, pedunculated, or lobulated bowel obstruction intussusception abdominal pain infarction chronic bleeding IMAGING Endoscopy with biopsy Upper GI endoscopy, video capsule endoscopy, and colonoscopy beginning at 8 years of age if polyps detected, repeat screening every 3 years if no polyps, repeat screening at 18 years of age or sooner if symptoms arise histology hamartomas proliferation of smooth muscle into lamina propria STUDIES Complete blood count iron-deficiency anemia due to blood loss Predictive genetic testing offered to at-risk individuals in whom diagnosis is not already clinically apparent by age 8 years, provided a pathogenic STK11 mutation has been identified in an affected family member Differential Diagnosis Familial adenomatous polyposis Juvenile polyposis Cowden syndrome DIAGNOSIS Diagnostic criteria using any of these two or more histologically confirmed Peutz-Jeghers (PJ) polyps family history + any number PJ polyps family history + mucocutaneous pigments any number PJ polyps + mucocutaneous pigments Treatment Routine evaluation with cancer screening every 1-2 years Endoscopic resection of polyps if extensive, surgical resection Complications Malignant transformation of macules are rare Increased risk of extraintestinal cancers (from most to least) breast gonadal pancreas Prognosis High risk of malignant transformation of polyps Good with routine screening