Small Bowel Polyposis Without Diagnosis

Abstract

A 19 year old male presents with nausea and vomiting. He is treated for gastroenteritis but returns with intussusception and small bowel obstruction that is managed conservatively. Two months later the intussusception recurs with 30 pound weight loss and hematochezia. An exploratory laparotomy is performed and a segment of jejunum with carpeting polyps is resected. He denies a history of cognitive delay and mucocutaneous freckling. On physical exam he is well-developed with a head circumference of 62cm. He has normal abdominal, skin, genital and neurologic exams. Upper endoscopy shows H. pylori gastritis and a stricture at the surgical anastomosis which is dilated. A colonoscopy and capsule endoscopy reveal only lymphoid follicles in the terminal ileum. Pathology from the jejunal resection is significant for hamartomatous polyps containing gastric type tissue. The patient's clinical condition is most consistent with Cowden Syndrome/PTEN Hamartoma Syndrome. He undergoes genetic testing that reveals a variant of uncertain significance (VUS) in the phosphatase and tensin homolog (PTEN) gene. Cowden syndrome is a rare genetic condition that carries an increased risk for multiple cancers. Our patient had two major clinical criteria, macrocephaly (>97th percentile) and hamartomatous intestinal polyps. Approximately 85% of individuals with an operational diagnosis of Cowden syndrome have autosomal dominant mutations identified in the PTEN gene on chromosome 10, which acts as a negative regulator of cell cycle pathways including mTOR and PI3K-AKT. Mutations can be deleterious or a VUS. Our case is unique in that the polyps architecturally resembled Peutz-Jeghers Syndrome (PJS) with an arborizing lamina propria and a lack of significant inflammation or dysplasia. However, the polyps were almost entirely composed of gastric foveolar and pyloric type mucosa, which is highly atypical in small bowel PJS. Furthermore, there have been few reports of small bowel hamartomas associated with Cowden syndrome, and none involving the jejunum to our knowledge. The patient also did not have any classic mucocutaneous findings or family members with a similar phenotype. Up to 44% of CS/PTHS cases arise from de novo PTEN mutations. It is not yet known if his VUS impacts protein function and/or predisposes to increased cancer risk. It is also unclear if the H. pylori infection contributed to his polyposis, however polyp regression after antibiotic therapy is reported.Figure 1Figure 2Figure 3