Upper Tract Juvenile Polyps in Juvenile Polyposis Patients

Abstract

Patients with juvenile polyposis syndrome (JPS), a hereditary autosomal dominant hamartomatous polyposis syndrome, are at increased risk for colorectal adenocarcinoma. The upper gastrointestinal tract is less often involved by JPS than the colorectum, and, consequently, upper tract juvenile polyps (JPs) are not well studied. We reviewed upper endoscopies and corresponding biopsies in JPS patients documented in our Polyposis Registry. A total of 199 upper gastrointestinal biopsies from 69 endoscopies were available in 22 of 41 (54%) JPS patients. Thirteen of the 22 patients (59%) had ≥1 gastric JP; 5 also had 6 small bowel JPs. Gastric JP was identified as early as age 7 in a patient with an SMAD4 gene mutation. Two patients (9%) had high-grade dysplasia in gastric JP. Invasive adenocarcinoma was diagnosed in the gastrectomy specimen of 1 patient. Five patients had a huge gastric polyp burden; 3 underwent total gastrectomy. Three patients died of complications associated with extensive upper JP. Histologically, 8 of the 56 (14%) gastric JPs identified had dysplasia. All of the 8 polyps demonstrated intestinalized and pyloric gland differentiation intermixed with foveolar epithelium. Dysplasia was seen arising in all 3 types of epithelium. The flat gastric mucosa in 11 patients was unremarkable without inflammation or intestinal metaplasia. The 6 small bowel JPs had no dysplasia. Our findings suggest that JPS patients are at increased risk for gastric adenocarcinoma. Detection of malignancy in syndromic gastric JP indicates that the current screening procedures are insufficient in removal of precursor lesions to prevent progression to carcinoma.

Non-familial juvenile polyposis of the stomach with gastric cancers: a case report

“…Although juvenile polyposis is a nonneoplastic lesion, several cases have suggested that it represents a predisposition to gastrointestinal cancer [ 6 – 8 ]. The risk of gastric cancer in patients with juvenile polyposis was reported to be approximately 11–21% [ 27 ], with a higher risk in patients with a SMAD4 germline mutation [ 28 ]. The current patient had no germline mutations of SMAD4 or BMPR1A , but did have somatic mutations in APC , KRAS , TP53 , and ERBB2 genes.…”

A case report of adult juvenile polyposis syndrome with SMAD4 pathogenic variant

“…Compared to the general population, the JPS has an increased risk of developing cancers such as colorectal cancer ( 16 ). Studies have shown that the incidence of colorectal and gastric cancer in JPS patients is 39% ( 17 ) and 21% ( 18 ), respectively. In addition, pancreatic, duodenal and small bowel cancers also occur in a smaller proportion of patients ( 19 , 20 ).…”

Some Morphology Frontiers of Dysplasia in the Tubular Gastrointestinal Tract

“…PGAs are also a manifestation of FAP, including gastric adenocarcinoma proximal polyposis syndrome (GAPPS), a variant 39. Gastric polyps with pyloric differentiation are also found in patients with McCune-Albright syndrome (fibrous dysplasia of bone, café-au-lait skin spots, and precocious puberty; mosaic pattern of germline GNAS mutations40) and even juvenile polyposis 41. Not surprisingly, syndromic (FAP-associated) PGAs arise in younger patients than sporadic examples,22,23,42 developing predominantly in gastric oxyntic mucosa.…”

“…39 Gastric polyps with pyloric differentiation are also found in patients with McCune-Albright syndrome (fibrous dysplasia of bone, café-au-lait skin spots, and precocious puberty; mosaic pattern of germline GNAS mutations 40 ) and even juvenile polyposis. 41 Not surprisingly, syndromic (FAP-associated) PGAs arise in younger patients than sporadic examples, 22,23,42 developing predominantly in gastric oxyntic mucosa. At least in western patients, they develop in mucosa without gastritis, often in association with fundic gland polyps.…”