Massive gastric polyposis associated with a germline SMAD4 gene mutation

Abstract

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. Polyps are most common in the colorectum (98% of patients) and the stomach (14%). Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are associated with a higher incidence of gastric polyposis. In this case report, we describe two patients with massive gastric polyposis associated with a SMAD4 mutation. Both presented with anaemia and both had colonic polyps. Initial endoscopic findings revealed giant rugal folds suggestive of Ménétrier disease. However, as other possible gastropathies could not be differentiated on the basis of histology, a definitive diagnosis of JPS required additional mutation analysis. In patients with polyposis predominant in or limited to the stomach, establishing a diagnosis based solely on the pathological features of polyps can be challenging due to difficulties in differentiating JPS from other hypertrophic gastropathies. Mutation analysis should be considered early in the diagnostic process in cases of suspected juvenile polyposis, thus facilitating rapid diagnosis and adequate follow-up.

Massive gastric juvenile‐type polyposis: a clinicopathological analysis of 22 cases

“…As seen in our cohort, patients with massive gastric juvenile‐type polyposis can present with a variety of complaints, including iron deficiency anaemia, upper gastrointestinal bleeding, abdominal pain, haematemesis, vomiting, early satiety, weight loss, melena, hypoproteinaemia, and hypergastrinaemia . However, they can occasionally be asymptomatic and discovered incidentally (by screening), as in some patients from our cohort.…”

“…The terminology used in describing this syndrome has varied. Terms that have been used include ‘massive gastric polyposis’, ‘diffuse gastric polyposis’, ‘juvenile polyposis of the stomach’/‘gastric juvenile polyposis’, ‘hyperplastic gastric polyposis’, and ‘massive hyperplastic and juvenile polyposis of the stomach’ . This variability is not entirely surprising, as hyperplastic and juvenile polyps can be difficult if not impossible to distinguish in the stomach on the basis solely of histology .…”

“…Although that organ does not often bear the brunt of JPS, rare patients develop massive gastric polyposis, with a large portion of the gastric volume being occupied by several polyps; this type of polyposis can also occur in patients not formally diagnosed with JPS. This has been reported sporadically in the clinical and surgical literature, mostly in the form of case reports . It has been little explored in the English‐language pathology literature, aside from a case series/literature review totalling 12 patients from 1997 and mention of four patients with a ‘huge [gastric] polyp burden’ in a recent review of JPS of the upper gastrointestinal tract .…”

Ménétrier’s disease presenting as recurrent unprovoked venous thrombosis: a case report

“…Juvenile polyposis syndrome is an autosomal dominant disorder characterized by multiple hamartomatous polyps, nearly always involving the colon. However, 14% of patients with this syndrome also have gastric involvement [54]. An entity known as “massive gastric juvenile-type polyposis” has also been described in patients with and without known juvenile polyposis syndrome [55].…”

First report of an Asian family with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) revealed with the germline mutation of the APC exon 1B promoter region

“…However, familial clustering is observed in almost 10% of patients with gastric cancer and heritability is seen in 1% of patients [10]. There have been several reports on familial gastrointestinal cancers such as, hereditary diffuse gastric cancer [11], FAP [1,12], Lynch syndrome [13], Li-Fraumeni syndrome [14], Peutz-Jeghers syndrome [15], and juvenile polyposis [16]. In 2012, Worthley et al [5] proposed GAPPS as a novel familial gastric cancer.…”