Peutz-Jeghers Phenotype Caused by an Unknown Variant APC Gene

Abstract

Peutz-Jeghers syndrome is an autosomal dominant condition, characterized by hamartomatous polyps, mucocutanous pigmentation, and increased predisposition to both Gastrointestinal (GI) and Non-Gastrointestinal malignancies. Most cases are due to a mutation of the STK11 tumor suppressor gene. Diagnosis is based on clinical findings, while genetic studies are used to confirm the diagnosis. We present a rare case of Peutz-Jeghers phenotype with an APC gene mutation variant of unknown significance. A 56-year old male with significant past medical history of prior sigmoidectomy for a benign colon mass and hemorrhoidectomy, was evaluated for intermittent rectal bleeding. He described vague abdominal pain, and intermittent dark stools with concurrent bright red blood per rectum. Laboratory findings were consistent with iron deficiency anemia. Esophagogastroduodenoscopy revealed gastritis and a duodenal polyp, which on histology showed hamartomatous polyp with features of a Peutz-Jeghers polyp. Colonoscopy findings showed internal hemorrhoids. Retrospectively, on detailed physical examination, the patient was found to have brown pigmented macular lesions on his buccal mucosa. Molecular studies were performed for common hereditary cancer syndromes and revealed no STK11 mutation but showed an APC gene variant of unknown significance. Specifically, a c.2297C>T (P.Ala766Val) mutation. With the presence of classic Peutz-Jeghers polyp histology and mucocutaneous pigmentation, the patient was treated as a Peutz-Jeghers phenotype. He was discharged home on iron supplementation and is currently on an intensive surveillance regimen for cancers involving the thyroid, pancreas, colon, and testes. Hamartomatous polyps in Peutz-Jeghers syndrome can occur anywhere in the GI tract, yet they tend to have a strong predilection for the small intestine. Patients with Peutz-Jeghers are at an increased risk for cancers manifesting both within the intestinal tract and externally. Routine surveillance with endoscopy and polypectomy is indicated to screen for malignancy, and to help prevent polyp related complications including; bowel obstructions, intussusception, and bleeding. Genetically, STK11 mutation is present in between 50 to 80 percent of Peutz-Jeghers cases. We present a case of Peutz-Jeghers phenotype in the presence of an APC gene variant of unknown significance.