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 Evaluation Endoscopy with biopsy histology hamartomas proliferation of smooth muscle into lamina propria Complete blood count iron-deficiency anemia due to blood loss 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 Differential Diagnosis Familial adenomatous polyposis Juvenile polyposis Cowden syndrome Treatment Routine evaluation with cancer screening every 1-2 years Endoscopic resection of polyps if extensive, surgical resection Prognosis, Prevention, and Complications Prognosis high risk of malignant transformation of polyps good with routine screening Complications malignant transformation of macules are rare increased risk of (from most to least) colorectal cancer breast stomach small bowel gonadal pancreas