Publication: Gastric neoplasm with foveolar-cell differentiation in Helicobacter pylori-naïve patients
Authors
Kotaro Shibagaki ; Ryoji Kushima ; Tsuyoshi Mishiro ; Kenichi Kishimoto ; Yusuke Takahashi ; Norihisa Ishimura ; Asuka Araki ; Mamiko Nagase ; Daisuke Niino ; Shunji Ishihara ; Satoshi Kotani
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-966
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info:eu-repo/semantics/article
Description
Abstract
The incidence of Helicobacter pylori (Hp)
naïve gastric neoplasms (HpNGNs) is increasing due to
a growing Hp-naïve population and improved
recognition. Among these, HpNGNs that predominantly
exhibit foveolar-cell differentiation include foveolar-type
gastric adenomas (FGA) and fundic gland polyps with
dysplasia (FGPD).
Traditionally, FGAs have been considered large,
whitish, flat lesions (flat-type FGA), primarily
associated with syndromic conditions, such as familial
adenomatous polyposis (FAP) and gastric adeno
carcinoma and proximal polyposis of the stomach
(GAPPS), while sporadic cases are rare. This type
exhibits a gastric immunophenotype with diverse
differentiation, mainly toward foveolar cells, and harbors
APC and KRAS mutations in all sporadic and most
syndromic cases.
A distinct subset of FGAs, termed foveolar-type
gastric adenoma with a raspberry-like appearance (FGA
RA), has been identified. It presents as small, reddish
polyps with unique macroscopic and microscopic
features and only occurs sporadically. FGA-RA often
mimics gastric hyperplastic polyps macroscopically and
typically exhibits low-grade dysplasia, making biopsy
based diagnosis challenging and leading to its historical
underrecognition. It shows pure foveolar differentiation
and consistently harbors Krüppel-like factor 4 (KLF4)
mutations.
FGPD primarily develops sporadically in Hp-naïve
individuals with long-term proton pump inhibitor use. A
syndromic form, resembling flat-type FGAs, is also
associated with FAP and GAPPS. Histologically, FGPD
features dysplasia confined to the superficial foveolar
epithelium and mucus neck cells overlying fundic gland
polyps, with APC mutations detected in approximately
50% of cases.
This review explores the clinicopathological and
molecular characteristics of HpNGNs with predominant
foveolar cell differentiation, emphasizing the need for an
updated histological diagnostic framework
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