reviews

Management of gastric polyps: a pathology-

based guide for gastroenterologists
Susanne W. Carmack, Robert M. Genta, David Y. Graham and Gregory Y. Lauwers
abstract | 1–4% of patients who undergo gastric biopsy have gastric polyps. These lesions may be true
epithelial polyps, heterotopias, lymphoid tissue, or stromal lesions. Hyperplastic polyps, which arise in
patients with underlying gastritis, and fundic-gland polyps, which are associated with PPi therapy, are the most
common gastric polyps; however, prevalence varies widely relative to the local prevalence of Helicobacter
pylori infection and use of PPi therapy. some polyps have characteristic topography, size, and endoscopic
appearance. Approximately 20% of biopsy specimens identified endoscopically as polyps have no definite
pathological diagnosis. evaluation of the phenotype of the gastric mucosa that surrounds a lesion will provide
significant information crucial to the evaluation, diagnosis and management of a patient. The presence of
a gastric adenoma should prompt the search for a coexistent carcinoma. The endoscopic characteristics,
histopathology, pathogenesis, and management recommendations of polyps and common polypoid lesions in
the stomach are discussed in this review.
Carmack, s. w. et al. Nat. Rev. Gastroenterol. Hepatol. 6, 331–341 (2009); published online 5 May 2009; doi:10.1038/nrgastro.2009.70

Classic studies and the majority of textbooks on gastro­

Continuing Medical Education online
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learning objectives
Upon completion of this activity, participants should be able to:
1 List the variables associated with a higher rate of gastric
adenoma.
2 identify the endoscopic features of different gastric polyps.
3 identify the histologic features of different gastric polyps.
4 Describe the appropriate management of different gastric
polyps.
Introduction
most biopsy specimens of presumed gastric polyps
have distinctive clinical characteristics that enable their
easy categorization into one of the major established
classes of epithelial or stromal gastric lesions (table 1).
Competing interests
The authors, the Locum Journal editor r. Jones and the CMe
questions author C. P. vega declare no competing interests.
intestinal pathology indicate that although adenoma­
tous polyps1 have a high malignant potential and are
frequently associated with synchronous gastric adeno­
carcinomas, risk of malignant transformation is very low
for hyperplastic gastric polyps and is virtually absent
in sporadic fundic­gland polyps (FGPs).2 as a conse­
quence, the diagnosis of an adenomatous gastric polyp
may trigger inclusion of the patient into an endoscopic
surveillance program, whereas only limited follow­up is
generally proposed for patients with diagnoses of hyper­
plastic polyps, inflammatory polyps, or FGPs.3 However,
molecular studies contest this long­held management
approach. Gastric polyps other than adenomatous
polyps display molecular alterations that may lead to
neoplastic progression, and might carry unknown risks veterans Affairs North
of malignant transformation. Texas Health Care
system, University of
southwestern Medical
Clinical and pathological correlations Center, Dallas, TX, UsA
substantial information on the etiology of a gastric (s. W. Carmack,
r. M. genta).
polyp or lesion and correlations between clinical and Michael e. DeBakey
pathological findings can be gathered by histological veterans Affairs
Medical Center, Baylor
and pathological evaluation of an appropriately College of Medicine,
representative range of biopsy samples taken from the Houston, TX, UsA
unaffected gastric mucosa. (D. y. graham).
Massachusetts
although most gastroenterologists are aware of the General Hospital,
value of examining the mucosa that surrounds a gastric Harvard Medical
school, Boston, MA,
polyp or lesion, in our experience a thorough examina­ UsA (g. y. lauwers).
tion of the affected gastric mucosa is not commonly
performed at the time a polyp is discovered. the clini­ Correspondence:
r. M. Genta, Caris
cal characteristics of gastric polyps or lesions, and the Diagnostics, 8400
possible pathological findings of the gastric mucosa esters Blvd, irving,
TX 75063, UsA
adjacent to these entities, are highlighted in tables 2 robert.genta@
and 3. utsouthwestern.edu

nature reviews | gastroenterology & hepatology volume 6 | June 2009 | 331

© 2009 Macmillan Publishers Limited. All rights reserved

 reviews
Key points
■ Multiple entities may present as a gastric polypoid lesion, and many have
subtle yet characteristic endoscopic features
■ in western countries, fundic-gland polyps are now more common than
hyperplastic polyps, resulting from the increase in PPi therapy and decrease in
gastritis associated with Helicobacter pylori infection
■ Biopsy specimens of the gastric mucosa adjacent to a lesion are extremely
important in establishing an etiology when hyperplastic polyps, adenomas, and
carcinoids are present
■ surveillance is indicated in patients with polyposis syndromes and adenomas;
patients with gastrointestinal stromal tumors and carcinoids may be followed
up endoscopically, but management approach should be tailored to each
individual
Table 1 | Classification of gastric polyps and polypoid lesions
Classification polyp or lesion
Neoplastic Adenomatous carcinoma (primary or metastatic)
Carcinoid
Hyperplastic or Usual (gastritis-related)
inflammatory Polypoid hyperplasia near sites of repair (i.e. stomas, ulcers)
Cardiac (reflux)
inflammatory fibroid polypa
Hamartomatous or Fundic-gland polypa
developmental Peutz–Jeghers
Juvenile
Cowden disease
Pancreatic heterotopia
Mesenchymal Gastrointestinal stromal tumor
smooth-muscle tumors
Glomus tumor
Neural tumors (schwannoma/neuroma, ganglioneuroma,
granular-cell tumor)
Miscellaneous Xanthoma
Lymphoid hyperplasia or lymphoma
Hemangioma or lymphangioma
a
Considered benign, but genetic mutations are common.
Epidemiology
Published data on the epidemiology of gastric polyps
diverge substantially with regard to both absolute and
relative prevalence. among the variables that influence
epidemiological data, we must consider the populations
studied, which will have wide variations in age and sex,
and the prevalence of underlying gastric conditions, such
as Helicobacter pylori infection. the methodology of
studies and the accuracy of pathological diagnoses should
also be considered. thus, we must be aware that we are
comparing unevenly obtained data. a detailed discus­
sion on the effects of these variables is beyond the scope
of this review, but it should be noted that problems exist
with the two most common types of studies: pathology­
based series and retrospective studies. Pathology­based
series, in which the denominator is the total of gastric
biopsy samples available, cannot be used to establish the
absolute prevalence of gastric polyps, but are adequate
to determine the relative frequency of the various types
of polyps.4 retrospective reviews of endoscopic reports
are likely to underestimate the true prevalence of gastric
332 | JUNE 2009 | volUmE 6
© 2009 Macmillan Publishers Limited. All rights reserved
polyps, because not all polyps may have been described
and excised.5,6
similarly to other gastric diseases, important geo­
graphical differences in the prevalence of gastric polyps
exist. rates of gastric adenomas and adenocarcinomas
are much higher in eastern europe and asia than in
western populations, with figures approaching 27%
compared with 0.5–3.75%, respectively.7–9 a retrospec­
tive review of 13,000 endoscopies performed on Greek
adults yielded 258 gastric polyps (1.2%).5 up to 27% of
patients had more than one polyp, and 75.6% had hyper­
plastic polyps. adenomas (6.6% of all polyps) were pre­
dominantly found in males (2:1 male to female ratio),
and were found only in patients over 50 years of age.
stromal polyps were present in 5.2% of patients who
had previously undergone gastrectomy or gastrojejuno­
stomy. a large, pathology­based, German study ana­
lyzed 5,515 gastric polyps collected between 1969 and
1989 and found 47% to be FGPs and 28.3% to be hyper­
plastic polyps; high representations of gastric adenomas
(9.0%) and adenocarcinomas (7.2%) were found.4 a
2007 Brazilian study of the findings of 26,000 endo­
scopies identified a mere 153 patients with gastric polyps
(0.58%). the relative frequency of polyps in this popula­
tion reflected the high rate of H. pylori infection: 71.3%
of polyps were hyperplastic polyps, 16.3% were FGPs,
and 12.4% were gastric adenomas.6 recently, we exam­
ined data on gastric polyps obtained over a 12­month
period in a nationwide pathology laboratory in the
us.10 in approximately 200,000 patients who underwent
esophago gastroduodenoscopy (eGD), 8,000 gastric
polyps were excised or biopsied from 7,500 patients, with
an overall gastric­polyp prevalence of 3.75%—somewhat
higher than the amount previously reported for western
populations. in this population with a low prevalence
of H. pylori infection (12.3% among the 78,909 patients
who had gastric biopsies), the overwhelming major­
ity of gastric polyps (77.2%) were FGPs, 14.4% were
inflammatory or hyperplastic polyps, and only 0.7%
were gastric adenomas.
Classification and key features
a diverse array of polyps and polypoid lesions may be
found in the stomach. table 1 illustrates the various
entities that may appear endoscopically as a polyp or
nodule. epithelial polyps (hyperplastic, fundic gland, and
adenomatous) are the classic gastric polyps, but clusters
of endocrine cells (carcinoids), infiltrates (xanthomas,
lymphoid proliferations) or mesenchymal prolifera­
tions (gastrointestinal stromal tumors [Gists], leio­
myoma and inflammatory fibroid polyps) may produce a
mucosal protrusion. this review excludes discussion of
carcinomas, lymphomas, and other malignancies.
Fundic-gland polyps
Clinical characteristics
FGPs are the most common type of polyp detected
by eGD in western countries. 10 endoscopically they
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 reviews

Table 2 | Clinical characteristics of gastric polyps

polyp type prevalence gastric location size endoscopic appearance pathological Comments
(frequency features of
relative to background
other polyps) gastric mucosa
Fundic gland 13–77% Fundus and upper <1 cm smooth, glassy, transparent; Helicobacter Associated with PPi
body usually multiple polyps are pylori-associated use; may regress;
found gastritis is rare dysplasia found in
patients with FAP
Hyperplastic 18–70% random, adjacent Generally small polyps have a smooth Atrophic gastritis with Found in patients with
to ulcers or stoma <1 cm dome; large polyps are intestinal metaplasia; gastritis; dysplasia is
sites, or in the lobulated, and erosions Helicobacter rare (<3%) and found in
cardia if related are common pylori-associated polyps <2 cm
to acid reflux gastritis (25%)
Adenoma 0.50–3.75% Incisura angularis, <2 cm velvety, lobular surface; Atrophic gastritis with May be accompanied by
(in western found more in the exophytic, sessile or intestinal metaplasia coexistent carcinoma
hemisphere) antrum than pedunculated; usually
fundus solitary (82%)
inflammatory 0.1–3.0% submucosal, Median 1.5 cm; single, firm, sessile, Pernicious anemia etiology is believed
fibroid found near the generally <3 cm well-circumscribed, commonly found; to be reactive, but
pyloric sphincter ulceration is common atrophic gastritis genetic mutations
are common
Peutz–Jeghers rare random <1 cm Pedunculated with a velvety Normal risk of
or papillary surface adenocarcinoma, but
rare in gastric polyps
Juvenile rare Found more in variable More rounded than Normal Polyps may exclusively
the body than hyperplastic polyps; involve stomach; risk of
in the antrum superficial erosions; multiple adenocarcinoma but
polyps are usually found rare in gastric polyps
Abbreviations: FAP, familial adenomatous polyposis; MeN, multiple endocrine neoplasia; Zes, Zollinger–ellison syndrome.

Table 3 | Clinical characteristics of gastric polypoid lesions

polypoid lesion prevalence gastric location size endoscopic appearance pathological Comments
(frequency features of
relative to background
other polyps) gastric mucosa
Xanthoma 0.3–3.9% Antrum, lesser <3 mm Can be multiple in groups; Chronic gastritis No association with
curvature, sessile, pale-yellow nodule hyperlipidemia. Lesions
prepyloric or plaque represent a reparative
response
Pancreatic 0.80% Antrum, prepyloric 0.2–4.0 cm solitary; dome-shaped Normal very rare instances of
heterotopia with central dimple; associated pancreatitis,
smooth surface islet-cell tumors,
adenocarcinoma
Gastrointestinal 1% of all random, variable well-circumscribed; Normal 25% are malignant:
stromal tumor gastrointestinal submucosal (median 6 cm) overlying mucosa may risk of aggressive
malignancies be ulcerated behavior depends on
size and mitotic count
Carcinoid <0.5% Body and fundus <2 cm, larger if Hypergastrinemic lesions: Autoimmune atrophic Associated with
sporadic firm, yellow, broad-based gastritis with intestinal hypergastrinemia,
and multiple metaplasia; parietal autoimmune atrophic
sporadic lesions: cell hyperplasia in gastritis, Zes or MeN
large and single Zes; normal mucosa
if lesion is sporadic
Abbreviations: MeN, multiple endocrine neoplasia; Zes, Zollinger–ellison syndrome.

appear as smooth, glassy, sessile, circumscribed eleva­
tions (usually measuring <0.5 cm) in the oxyntic mucosa
(Figure 1a). Histologically, the basic lesion consists of
one or more cystically dilated oxyntic glands, with
the lining cells appearing flattened and difficult to
recognize when markedly dilated (Figure 1b,c). FGPs
may occur sporadically, in association with PPi use, and
in patients with familial adenomatous polyposis (FaP)
syndrome.11–13 sporadic polyps are either single or few
in number, and are found almost exclusively in patients

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 reviews
a b
Figure 1 | A fundic-gland polyp. a | endoscopically, they appear as glassy, smooth, round polyps (often multiple) in the
gastric body and fundus. b | A low-power histological view displaying dilated glands that may be lined by parietal cells (p) or
mucous cells (m). c | A high-power histological view showing both flattened parietal cells (thin black arrows) and mucous
cells (thick black arrow).
without H. pylori infection.14 in PPi users, large numbers
of polyps might exist, but these may regress with cessa­
tion of therapy.15 little is known about the etiology of
FGPs. in the past, these polyps were considered to be
hamartomatous; however, the recognized association
of FGPs with long­term PPi use suggests that mech­
anisms related to the suppression of acid secretion may
be involved in their pathogenesis.16,17 However, this view
is not shared by all researchers.18,19 our understanding
of the pathogenesis of these polyps has been further
complicated by the finding that sporadic FGPs with dys­
plasia exhibit germ­line mutations in the APC tumor­
suppressor gene (a finding also observed in patients with
FaP),20 rather than somatic mutations in the β­catenin
gene, which had previously been described in association
with these polyps.21,22
Management
although dissenting opinions have been expressed, spor­
adic and PPi­associated FGPs are traditionally believed
to have low malignant potential and no ominous associ­
ations.23 in patients on PPi therapy with typical, small
(<0.5 cm) FGPs, diagnosis is confirmed by taking a
biopsy specimen from one polyp. Biopsy specimens are
taken from all polyps 0.5–1.0 cm in size. PPi therapy is
not discontinued in patients with smaller polyps. larger
polyps (>1 cm) are removed and, if clinically appropriate,
PPi therapy is discontinued in these patients. By contrast,
a definite risk of dysplasia (between 30% and 50%) is
present in FaP­associated FGPs.11 in a 2008 study of 75
patients undergoing surveillance for FaP, 88% had FGPs,
38% had low­grade dysplasia and 3% had high­grade
dysplasia.12 Dysplasia in FGPs was associated with large
polyp size (>1 cm), increased severity of duodenal poly­
posis, and antral gastritis. PPi therapy use seemed to have
a protective effect against dysplasia in FGPs. although no
official guidelines have been issued, the general consen­
sus is that all pediatric, and perhaps also adult, patients
with FaP warrant upper gastrointestinal screening
334 | JUNE 2009 | volUmE 6
© 2009 Macmillan Publishers Limited. All rights reserved
c
p
p
and surveillance endoscopy from the time of initial
colonoscopy, irrespective of referable symptoms.13
when multiple FGPs are diagnosed in a young patient,
FaP should be considered. the responsibility of alerting
the clinician to this possibility and performing a careful
search for dysplasia is incumbent upon a conscientious
pathologist. no immunohistochemical or molecular
studies are warranted outside a research setting.
hyperplastic polyps
Clinical characteristics
Hyperplastic polyps arise most frequently in patients
with an inflamed and often atrophic gastric mucosa.24
in the industrialized world, both their absolute and rela­
tive prevalence has decreased along with the declining
prevalence of H. pylori infection.25
Hyperplastic polyps are more frequently observed in
the antrum than in other parts of the stomach and are
often multiple; these polyps are usually smooth, dome­
shaped and small in diameter (measuring 0.5–1.5 cm),
but they may reach much larger dimensions, wherein
they become lobulated and pedunculated (Figure 2a).26 in
larger hyperplastic polyps, the surface epithelium is often
eroded. this erosion may result in chronic blood loss
and iron­deficiency anemia, one of the most common
clinical manifestations of hyperplastic polyps. rarely,
patients with large hyperplastic polyps may present with
gastric obstruction.27,28
Histologically, hyperplastic polyps consist of elongated,
grossly distorted, branching and dilated hyperplastic
foveolae lying in an edematous stroma rich in vascula­
ture, and small, haphazardly distributed smooth­muscle
bundles; they contain varying degrees of chronic and
active inflammation (Figure 2b,c). owing to this often
prominent inflammatory component, some clinicians and
researchers prefer the term hyperplastic­inflammatory
polyps to hyperplastic polyps, and a few refer to them
simply as inflammatory polyps. some confusion has
resulted from these loosely interchanged terms.
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 reviews

a b c f

Figure 2 | A hyperplastic polyp. a | An endoscopic view showing lobulations with an irregular surface. b | A low-power
histological view showing irregular, distorted, branching foveolae, which may form mucous-cell-lined cysts (m); the
stroma is vascular and edematous with chronic and active inflammation. c | A high-power histological view showing an
eroded branch of a hyperplastic polyp. The epithelial surface is replaced by a thick deposit of fibrin (f), which overlays
a richly vascular granulation tissue. such erosions, which are universal in larger polyps, often result in blood loss and
iron-deficiency anemia.

a hyperproliferative response to tissue injury (erosions
or ulcers) accompanied by increased cellular exfoliation
results in the histopathological appearance of fove­
olar hyperplasia.29 Foveolar hyperplasia has long been
recognized as a prominent feature of chemical gastro­
pathy (caused by bile reflux or nsaiDs), and to a lesser
extent in H. pylori gastritis.30 Polypoid foveolar hyper­
plasia, gastric foveolar polyps, gastritis cystica polyposa
(characteristic of post­Billroth i and ii gastric stumps),
and gastric hyperplastic polyps are considered variants of
the same basic hyperproliferative disturbance.
Management
removal of the underlying injury (that is, eradication of
H. pylori infection) results in regression of hyperplastic
polyps in a high proportion of patients (up to 70% in
one study).31,32
Both isolated hyperplastic polyps and the polypoid
lesions found at gastrectomy sites have a low but definite
potential for development of malignancy. Between 1%
and 20% of hyperplastic polyps have been found to harbor
foci of dysplasia; furthermore, mutations of the p53 gene,
chromosomal aberrations, and microsatellite instability
have been detected in these polyps.33–36 molecular studies
examining these polyps were designed to acquire insights
into possible neoplastic mechanisms, not to develop pre­
dictive tests: thus, in the clinical setting, the perform­
ance of immunostaining to detect p53 accumulation,
microsatellite instability testing (both easily available and
accurate) or gene arrays, would yield results whose full
clinical implications could not be interpreted. the overall
prevalence of dysplasia in hyperplastic polyps is believed
to be <2%, and more frequent in large polyps (>2 cm).37,38
large, hyperplastic polyps should be completely excised
for thorough histological evaluation. if dysplasia, or even
intramucosal carcinoma, was present, it will have been
removed and most likely will have been cured.
when a hyperplastic polyp of any size, with or without
dysplasia, is diagnosed, a full set of topographically
defined biopsy specimens (‘gastric mapping’) should be
obtained. if H. pylori gastritis is present, eradication of
H. pylori is warranted with a follow­up endoscopy after a
few months to monitor not only cure of the infection, but
also recurrence or regression of remaining polyps.31,32 if
extensive atrophy and metaplasia are found, the patient
should be considered at risk for gastric cancer, as the
polyp could be viewed as an alarming lesion, and an
individualized surveillance plan (for which guidelines
do not yet exist) should be implemented.24 if the polyp
is obtained from a gastrectomy site in the absence of
dysplasia, optimal management remains uncertain.
adenomatous polyps
Clinical characteristics
adenomatous polyps may occur sporadically and in
association with FaP. only the former are discussed
in this review. endoscopically, adenomatous polyps
have a velvety, lobulated appearance, are usually solitary
(82%), located in the antrum, and <2 cm in diameter
(Figure 3a).1 these polyps are circumscribed lesions,
pedunculated or sessile and histology will reveal dys­
plastic epithelium without detectable invasion of the
lamina propria (Figure 3b). their prevalence varies
widely and is estimated to be 0.5–3.75% in western
countries and 9–27% in areas with higher rates of gastric
carcinoma, such as China and Japan.4,7,39
sporadic, gastric adenomatous polyps may be viewed
as one of the possible steps in the development of gastric
adenocarcinoma. Both conditions arise most often in
patients with chronic, atrophic, metaplastic gastritis and
they share a common epidemiological pattern. the larger
an adenomatous polyp, the greater the probability that it
contains foci of adenocarcinoma. a synchronous adeno­
carcinoma in another area of the stomach has been found

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 reviews
a b
Figure 3 | An adenomatous polyp. a | An endoscopic view showing a velvety
surface. b | A low-power histological view. Not unlike their colonic counterparts,
gastric adenomatous polyps are usually exophytic lesions composed of interlacing
sheets of irregular tubular epithelium that may form complex structures with a
cribriform architecture (arrows). Cells are crowded in a disorderly arrangement
(inset high-power histological view), often elongated, with hyperchromatic nuclei
and occasional mitoses. Paneth cells, and rarely oxyntic cells, may be found in
various proportions.
in up to 30% of patients with an adenomatous polyp, and
up to 50% of adenomatous polyps >2 cm harbor a focus
of adenocarcinoma.40,41
Management
the management of gastric adenomas has not been
markedly changed by molecular studies that have con­
firmed their neoplastic nature. a 2003 molecular study
reported that distinction of the type of gastrointestinal
adenoma (intestinal versus gastric) might further define
the risk of cancer (an increased risk of cancer is associ­
ated with intestinal adenomas). 41 Gastric mapping is
useful to determine the phenotype of gastritis on which
an adenoma arises; the finding of metaplastic atrophic
gastritis is an indication for surveillance.42 in addition, a
thorough search for synchronous adenocarcinoma should
be performed and the endoscopist should confirm com­
plete excision of the adenoma with a repeat endoscopy
if necessary. the guidelines of the american society of
Gastrointestinal endoscopy (asGe) recommend endo­
scopic surveillance at 1 year follow­up for patients with
gastric adenoma, and that specific biopsy techniques be
implemented when large or multiple polyps exist.42
polyposis syndromes
Clinical characteristics
Polyposis syndromes that affect the stomach are rare, and
patients with these syndromes often present with clini­
cal manifestations unrelated to gastric polyps. However,
some cases of juvenile polyposis may affect the stomach
alone.43,44 the hamartomatous polyps found in juvenile
polyposis, Cronkite–Canada syndrome and Cowden
disease have subtle histological findings that closely
mimic hyperplastic gastric polyps and might easily be
overlooked if the diagnosis is not suggested by the clini­
cal context.45,46 Patients with FaP can have FGPs with
dysplasia as well as adenocarcinoma. Hamartomatous
polyps in patients with the Peutz–Jeghers syndrome
336 | JUNE 2009 | volUmE 6
© 2009 Macmillan Publishers Limited. All rights reserved
are easily recognized by their characteristic arborizing
pattern of muscle fibers between hyperplastic glands.44
Management
a detailed discussion of the management of different
polyposis syndromes is beyond the scope of this review.
However, we will summarize the recommendations for
screening and surveillance of the upper gastrointestinal
tract for the three most­studied conditions: FaP, Peutz–
Jeghers syndrome, and juvenile polyposis. the presence
of gastroduodenal polyposis is well recognized in patients
with FaP. However, the dearth of published studies pre­
vents an accurate assessment of the potential benefits
of surveillance, particularly in light of the relatively low
risk of gastric cancer found in these patients in western
countries. 47,48 a reasonable management approach
involves the performance of an upper gastrointestinal
endoscopy at 3­year intervals from 30 years of age, with
the aim of detecting early curable cancers. Patients
with large numbers of gastric and duodenal polyps and
those with dysplastic polyps (FGPs with epithelial dys­
plasia and adenomas) are recommended to undergo
surveillance yearly.43
individuals with Peutz–Jeghers syndrome are at risk of
a wide variety of cancers at a young age, including cancer
of the breast, colon, pancreas, stomach, small intestine,
ovaries, uterus, and testes. the lifetime risk for gastric
cancer has been estimated to be ~30% in patients with
Peutz–Jeghers syndrome;49 most authorities, therefore,
suggest surveillance of the stomach and small intestine
with upper endoscopy and small­bowel series every
2–3 years, starting at 18 years of age. 50 surveillance
should continue every 2–3 years if polyps are noted at
baseline evaluation.43, 51
Juvenile polyposis is rare and data regarding gastric
malignancy are limited. as the risk of gastric cancer in
patients with this condition is estimated to be 15–20%,
it seems reasonable to offer gastric endoscopic surveil­
lance at intervals of 1–2 years, with simultaneous
colonoscopy.43,52
recommendations for the management of Cronkite–
Canada syndrome have focused on pharmacological
therapy and surgical resection. 53 Cowden disease has
no documented association with gastrointestinal malig­
nancies; screening is, therefore, aimed at detecting breast
and thyroid cancers.54
Inflammatory fibroid polyps
Clinical characteristics
inflammatory fibroid polyps (also known as vanek
tumors) are rare lesions that represent <1% of all gastric
polyps. although these polyps can form throughout
the gastrointestinal tract, 80% arise in the antropyloric
region.55 these polyps are firm, solitary, sessile or pedun­
culated, and are often ulcerated (Figure 4a); they have
been associated with hypochlorydia or achlorhydria, as
well as with adenomas.55 inflammatory fibroid polyps
are usually found incidentally, although symptoms
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 reviews

of bleeding and gastric­outlet obstruction have been a b

reported.56 Histologically, these lesions consist of a sub­
mucosal proliferation of spindle cells, small vessels, and
a striking inflammatory infiltrate, in which eosinophils
predominate (Figure 4b). owing to the massive eosino­
philic infiltrates, these polyps are occasionally referred
to as eosinophilic granulomas; however, this term is
incorrect, as these polyps are not granulomas and confu­
sion might occur with langerhan cell histiocytosis (also
known as eosinophilic granuloma).
the etiology of inflammatory fibroid polyps is
unknown. a familial tendency has been suggested by
researchers, owing to the finding of a family in Devon,
uK, whose female members have a high rate of these
polyps.57 the presence of eosinophils in a lesion is sure to
Figure 4 | An inflammatory fibroid polyp. a | endoscopic view showing a firm,
elicit allergy­related speculations; however, no support­
well-circumscribed, vascular, submucosal polyp. b | A low-power histological view
ive evidence is currently available. immunohistochemical showing a compact aggregate of concentrically organized spindle cell (fibroblasts),
staining suggests these polyps originate in dendritic prominent vascularity and abundant inflammatory cells, predominantly eosinophils
cells.58 the mucosa adjacent to these polyps is often (inset high-power histological view). The surface mucosa might be normal,
unremarkable, but associations with chronic atrophic hyperplastic, or eroded.
gastritis have been reported. a recent study found that
70% of inflammatory fibroid polyps contain gain­of­
function mutations in the gene encoding PDGF­α poly­ a b
peptide, similar to those found in KIT­negative Gists,
which suggests the possibility of a neoplastic process.59

Management
as most inflammatory fibroid polyps are found inci­
dentally and do not recur after excision, neither further
treatment beyond local excision nor surveillance is
recommended.60

gastrointestinal stromal tumors

Clinical characteristics
Gists are rare tumors of the gastrointestinal tract and
comprise 1–3% of gastric neoplasms.61,62 these tumors
are most commonly found in men and in the gastric
fundus, although they can be found in other regions
of the stomach. the gastric mucosa that surrounds
these lesions is usually normal. microscopic Gists are
common in the upper stomach of Japanese patients who
have undergone gastric resection for gastric cancers,
which suggests that only a few lesions enlarge and
develop malignant potential.63
endoscopically, Gists are well­circumscribed sub­
mucosal lesions (median diameter 6 cm) that occa­
sionally show an eroded or ulcerated overlying mucosa
(Figure 5a). the gastric mucosa tends to slide over
benign, submucosal tumors, which might be missed
by the biopsy forceps. thus, representative tissue is
best obtained by endosonographic fine­needle aspira­
tion. Histologically, Gists are composed of spindle cells
(Figure 5b), in some cases with an epithelioid (rounding­
up) morphology.61 these lesions are believed to originate
from the interstitial cells of Cajal, the gut’s pacemaker
cells. Gists have unique immunostaining character­
istics that allow a specific diagnosis: the stain for KIT
gene product, CD117, is positive in approximately 95%
Figure 5 | A gastrointestinal stromal tumor. a | An endoscopic view showing a
well-circumscribed, hard, submucosal polyp with normal overlying mucosa. These
polyps are often large when detected, and their surface may be ulcerated.
b | Histological view (low power) of the tumor. A high-power image (inset) shows
that the lesion is formed by a compact mass of whirling CD117-positive spindle
cells, which usually infiltrate the submucosa. The overlying mucosa is edematous
with distorted glands displaced by the infiltrating neoplastic cells.
of cases.61 on the basis of size and mitotic activity, Gists
are categorized for risk of malignancy (very low risk to
high risk).
Management
all Gists must be considered as having malignant
potential, with up to 50% of patients having metastatic
disease at presentation, usually of the liver.64 in practice,
a strong correlation exists between the mitotic activity,
size, and clinical behavior of Gists. surgical resection is
recommended for lesions >2 cm; endoscopic enucleation
followed by surveillance is an option for small Gists.
endoscopic removal is controversial, however, because
of reports of positive resection margins and tumor spill­
age.65 tyrosine kinase inhibitors are used as targeted
therapy in cases of metastasis and surgically unresect­
able Gists.66 neoadjuvant therapy with use of tyrosine

nature reviews | gastroenterology & hepatology volume 6 | June 2009 | 337

© 2009 Macmillan Publishers Limited. All rights reserved

 reviews
a b
Figure 6 | A carcinoid. a | An endoscopic view showing the broad-based
appearance of these polyps with a yellowish tinge. b | A low-power histological view
showing that these polyps are formed by ribbons and clusters (nests) of small
monotonous cells (clearly visible at higher power [inset]) that displace the normal
mucosal glands. Larger lesions expand into and beyond the muscularis mucosae.
a b
X
X
X
Figure 7 | A xanthoma. a | endoscopic view. As their name indicates, xanthomas
are pale-yellow plaques or nodules, and are often multiple (arrows). b | A low-power
histological view showing irregular expansions of the lamina propria (X), which is
filled by macrophages laden with foamy-appearing lipids (inset high-power view).
The overlying epithelium is usually made of normal mucosa.
kinase inhibitors after surgical resection of high­risk
Gists deters recurrence, but the optimal duration of
therapy remains unknown.67
Carcinoids
Clinical characteristics
Carcinoids comprise less than 2% of gastric polypoid
lesions.4,68 the term carcinoid is used here in the tradi­
tional connotation of a type of neuroendocrine tumor
derived from enterochromaffin­like (eCl) cells.69 three
types of carcinoids are recognized: type i are associated
with chronic autoimmune atrophic gastritis (65–80% of
all gastric carcinoid tumors, female predominance, often
accompanied by pernicious anemia); type ii are associ­
ated with Zollinger–ellison syndrome and multiple
endocrine neoplasia type 1 (3–15% of tumors); type iii
are sporadic (~20% of tumors, male predominance).70
type i carcinoids are associated with hypergastrinemia,
which results from loss of negative feedback to the
G cells in the antrum secondary to the destruction of
parietal cells and increasing gastric pH. type ii carci­
noids are also associated with hypergastrinemia, but as a
result of a gastrinoma—a gastrin­producing tumor that
leads to the development of hypertrophic parietal cells
338 | JUNE 2009 | volUmE 6
© 2009 Macmillan Publishers Limited. All rights reserved
and eCl­cell hyperplasia. Carcinoids associated with
hypergastrinemia are usually multiple, broad­based,
firm, yellowish lesions located in the body and fundus
of the stomach, and rarely measure >2 cm (Figure 6a).
sporadic carcinoid tumors occur in a normal gastric
mucosa with no apparent associations; they are typi­
cally single, tend to be prepyloric, and are usually >2 cm
when detected.71,72
Histologically, carcinoids are composed of nests or
ribbons of endocrine cells (small polygonal cells with
round nuclei featuring ‘salt and pepper’ chromatin)
(Figure 6b). necrosis, anaplasia, increased mitotic activ­
ity, and size >2 cm are markers of aggressive behavior,
and are found exclusively in sporadic carcinoids.71 the
carcinoid syndrome (which is characterized by cutane­
ous flushing, diarrhea, bronchospasm and cardiac valvu­
lar lesions) is present almost exclusively in patients with
sporadic carcinoids.70
Management
Prognosis and therapy depend on the type of carcinoid.73
type i carcinoids rarely metastasize, 5­year survival rates
of 95% are reported, and patients may be followed up
endoscopically after local excision and biopsy specimens
have been obtained from the surrounding mucosa.72–74
surveillance is not recommended in patients with perni­
cious anemia, although according to asGe guidelines,
the performance of one endoscopy is appropriate. 42
antrectomy might be considered if a patient has multi­
ple carcinoids. the prognosis of patients with type ii
carcinoids is excellent when the underlying gastrinoma
can be successfully removed; when this is not possible,
endoscopic polypectomy followed by surveillance is the
accepted therapy and management. 75 sporadic carci­
noids behave like neuroendocrine carcinomas, with a
propensity for invasion and metastases. the therapy
of choice is gastrectomy, but the 5­year survival rate
remains below 50%.68
Xanthomas
Clinical characteristics
Xanthomas (also known as xanthelasmas) are small
(<3 mm), yellowish nodules or plaques that barely
protrude from the surrounding pink gastric mucosa
(Figure 7a). these sessile lesions, which rarely attain the
size and shape of a polyp, are often found near the site
of mucosal repair, such as gastrectomy stomas, ulcers,
or, less commonly, the mucosa adjacent to an adeno­
carcinoma. Xanthomas are also commonly associated
with chronic gastritis and may be found in small clusters
along the lesser curvature, antrum, and prepyloric areas
of the stomach. Histologically, they consist of aggre­
gates of lipid­laden macrophages that contain chole­
sterol and neutral fat loosely embedded in the lamina
propria (Figure 7b). their prevalence is low in the west;
however, for unknown reasons, possibly related to the
high prevalence of chronic gastritis, these lesions are
common in asia.76
www.nature.com/nrgastro

Xanthomas represent a reparative response and are
not associated with hypercholesterolemia. in cases of
chronic gastritis, they might be associated with intestinal
metaplasia and hyperplastic polyps.77
Management
Xanthomas are, in themselves, clinically insignificant
lesions. However, because of their possible associ­
ation with other potentially serious conditions of the
stomach, the remainder of the gastric mucosa should be
examined carefully.77
pancreatic heterotopia
Clinical characteristics
Pancreatic heterotopia can be found in two clinical set­
tings in the stomach. the first presentation, only rarely
seen endoscopically as a polyp, consists of small, sub­
mucosal nodules (single or multiple, usually containing
only a few glands) of pancreatic tissue at the cardio­
esophageal junction; this finding is known as pancre­
atic metaplasia, although whether it represents real
metaplasia or heterotopia is unclear. this condition is
found in 5–15% of individuals who undergo endoscopy
for GerD and have a biopsy specimen taken from the
esophageal junction. in some studies, pancreatic meta­
plasia at the cardioesophageal junction has been related
to inflammation at the gastroesophageal junction. the
significance of this condition is unclear, but no indica­
tion that pancreatic metaplasia has neoplastic potential
has been found.78,79
the other type of pancreatic heterotopia is usually
discovered as a submucosal lesion in the antral and
prepyloric regions of the stomach, sometimes with a
central dimple if a duct is present (Figure 8a). this type
is uncommon; it represents <1% of all gastric polyps.80
these lesions are solitary and composed mostly of acinar
tissue, often with ducts and seldom with islet cells. the
histology resembles normal pancreatic tissue. as is
the case with all submucosal lesions, they are easily missed
in superficial biopsies (Figure 8b). the gastric mucosa
that surrounds these lesions is usually unremarkable.
Management
Pancreatic heterotopia is a benign and usually asymptom­
atic lesion; thus, no therapy is warranted.80 symptomatic
lesions (large enough to cause gastric­outlet obstruc­
tion) are rare, and can be treated by resection.81 Ductal
adenocarcinomas, islet­cell tumors, and pancreatitis
that arises in heterotopic pancreatic tissue have been
reported, but the rarity of such occurrences suggests that
neither surgical excision nor endoscopic surveillance
are warranted.82,83
When a polyp is not a polyp
in our 2009 series,10 16.1% of 7,925 gastric biopsy speci­
mens identified endoscopically as a polyp or nodule had
no histopathological features that could meet the diag­
nostic criteria of one of the recognized gastric polyps.
nature reviews | gastroenterology & hepatology
© 2009 Macmillan Publishers Limited. All rights reserved
reviews
a b
Figure 8 | A pancreatic heterotopia. a | endoscopic view showing a pyloric channel
polyp with a central dimple, which may be a draining pancreatic duct. Although
considered typical, this endoscopic appearance is by no means the most common.
Most pancreatic heterotopias are seen as small, smooth nodules lined by normal
gastric mucosa. b | Histological features of a nodule of pancreatic acinar tissue
(limited by converging black arrows) completely surrounded by normal oxyntic
mucosa. This is the most common microscopic appearance of pancreatic
heterotopia in the stomach, with neither ducts nor islets readily visible.
the overwhelming majority of these specimens con­
sisted of normal or inflamed gastric mucosa. mucosal
folds, edema of the lamina propria, foveolar hyperplasia,
and prominent lymphoid follicles might have the endo­
scopic appearance of a small polyp. the practice, now
routine in many centers, to attach an endoscopic picture
or a detailed description of the lesion to the pathol­
ogy requisition is crucial to formulation of an informed
report. For example, if endoscopy shows a smooth,
round antral nodule and the biopsy specimen reveals
a perfectly normal mucosa, a sensible pathologist will
add a comment to suggest that the biopsy specimen may
not be representative of the lesion, and a submucosal
lesion may not have been sampled. if a malignant­
looking, necrotic ulcerated lesion is seen endoscopi­
cally, but the biopsy specimen shows only dysplastic,
but not invasive, epithelium, the pathology report
should clearly state that a repeat biopsy is necessary.
Gastroenterologists who routinely receive diag noses
of polypoid mucosa, mild hyperplastic features, and
similar vacuous expressions should suspect that their
pathologist is trying to appease them with a diagnosis
that fits the endoscopy. a frank conversation with the
pathologist and a few sessions at the microscope could
go a long way to improve the specificity of diagnoses
and, ultimately, care of patients.
Conclusions
although no precise epidemiologic data exist, gastric
polyps are common, and most often fall into the cate­
gories of fundic­gland, hyperplastic, and adenomatous
polyps. However, an impressive variety of gastric lesions
might present as a polyp, and understanding the need
to obtain a biopsy specimen from the gastric mucosa
volume 6 | June 2009 | 339
 reviews

adjacent to a lesion is critical for a cohesive pathological Review criteria

diagnosis. although polyps are occasionally the cause
of symptoms that require endoscopic investigation,
they are often a marker of underlying gastritis that may
require diagnosis and treatment. appropriate surveil­
lance proto cols, detailed above, exist for polyps with
a known neoplastic risk, and the asGe surveillance
recommendations for polyps and polyposis syndromes
are also available online.84
The MeDLiNe and PubMed databases were searched in
October 2008 for english-language articles. The terms
“polyp”, “fundic-gland polyp”, “hyperplastic polyp”,
“adenoma”, “gastrointestinal stromal tumor”, “polyposis”,
“pancreatic heterotopia”, “xanthoma”, “inflammatory
fibroid” and “carcinoid” were combined with “stomach”
and “gastric” to locate articles. reference lists were
checked for additional relevant papers.

1. Park, D. Y. & Lauwers, G. Y. Gastric polyps:
classification and management. Arch. Pathol.
Lab. Med. 132, 633–640 (2008).
2. Ming, s. C. The classification and significance
of gastric polyps. Monogr. Pathol. 18, 149–175
(1977).
3. stolte, M. Clinical consequences of the
endoscopic diagnosis of gastric polyps.
Endoscopy 27, 32–37 (1995).
4. stolte, M. et al. Frequency, location, and age
and sex distribution of various types of gastric
polyp. Endoscopy 26, 659–665 (1994).
5. Archimandritis, A. et al. Gastric epithelial
polyps: a retrospective endoscopic study of
12974 symptomatic patients. Ital. J.
Gastroenterol. 28, 387–390 (1996).
6. Morais, D. J. et al. Gastric polyps:
a retrospective analysis of 26,000 digestive
endoscopies. Arq. Gastroenterol. 44, 14–17
(2007).
7. Nakamura, T. & Nakano, G. Histopathological
classification and malignant change in gastric
polyps. J. Clin. Pathol. 38, 754–764 (1985).
8. Farinati, F. et al. early and advanced gastric
cancer in the follow-up of moderate and severe
gastric dysplasia patients. A prospective study.
i. G. G. e. D.—-interdisciplinary Group on
Gastric epithelial Dysplasia. Endoscopy 25,
261–264 (1993).
9. Lauwers, G. Y. & srivastava, A. Gastric
preneoplastic lesions and epithelial dysplasia.
Gastroenterol. Clin. North Am. 36, 813–829
(2007).
10. Carmack, s. w. et al. The current spectrum of
gastric polyps: a one-year national study of over
120,000 patients. Am. J. Gastroenterol. (in
press).
11. Bertoni, G. et al. Dysplastic changes in gastric
fundic gland polyps of patients with familial
adenomatous polyposis. Ital. J. Gastroenterol.
Hepatol. 31, 192–197 (1999).
12. Bianchi, L. K. et al. Fundic gland polyp
dysplasia is common in familial adenomatous
polyposis. Clin. Gastroenterol. Hepatol. 6,
180–185 (2008).
13. Attard, T. M. et al. Multicenter experience with
upper gastrointestinal polyps in pediatric
patients with familial adenomatous polyposis.
Am. J. Gastroenterol. 99, 681–686 (2004).
14. Fossmark, r. et al. serum gastrin and
chromogranin A levels in patients with fundic
gland polyps caused by long-term proton-pump
inhibition. Scand. J. Gastroenterol. 43, 1–5
(2007).
15. Kim, J. s. et al. spontaneous resolution of
multiple fundic gland polyps after cessation
of treatment with omeprazole. Korean J.
Gastroenterol. 51, 305–308 (2008).
16. el-Zimaity, H. M. et al. Fundic gland polyps
developing during omeprazole therapy. Am. J.
Gastroenterol. 92, 1858–1860 (1997).
17. raghunath, A. s. et al. review article: the long-
term use of proton-pump inhibitors. Aliment.
Pharmacol. Ther. 22 (suppl. 1), 55–63 (2005).
18. Declich, P. et al. Fundic gland polyps and PPi:
the Mozart effect of gastrointestinal
pathology? Pol. J. Pathol. 57, 181–182 (2006).
19. vieth, M. & stolte, M. Fundic gland polyps are
not induced by proton pump inhibitor therapy.
Am. J. Clin. Pathol. 116, 716–720 (2001).
20. Abraham, s. C. et al. sporadic fundic gland
polyps with epithelial dysplasia: evidence for
preferential targeting for mutations in the
adenomatous polyposis coli gene. Am. J.
Pathol. 161, 1735–1742 (2002).
21. Abraham, s. C. et al. sporadic fundic gland
polyps: common gastric polyps arising through
activating mutations in the β-catenin gene. Am.
J. Pathol. 158, 1005–1010 (2001).
22. Torbenson, M. et al. sporadic fundic gland
polyposis: a clinical, histological, and
molecular analysis. Mod. Pathol. 15, 718–723
(2002).
23. Declich, P. et al. Fundic gland polyps: a not so
innocuous entity worth a careful evaluation.
Am. J. Gastroenterol. 93, 2641 (1998).
24. Dirschmid, K. et al. why is the hyperplastic
polyp a marker for the precancerous condition
of the gastric mucosa? Virchows Arch. 448,
80–84 (2006).
25. Malaty, H. M. epidemiology of Helicobacter
pylori infection. Best Pract. Res. Clin.
Gastroenterol. 21, 205–214 (2007).
26. Abraham, s. C. et al. Hyperplastic polyps of the
stomach: associations with histologic patterns
of gastritis and gastric atrophy. Am. J. Surg.
Pathol. 25, 500–507 (2001).
27. Cerwenka, H. et al. Pyloric obstruction caused
by prolapse of a hyperplastic gastric polyp.
Hepatogastroenterology 49, 958–960 (2002).
28. Chen, H. w. et al. Gastric outlet obstruction
due to giant hyperplastic gastric polyps.
J. Formos. Med. Assoc. 104, 852–855 (2005).
29. Dixon, M. F. et al. reflux gastritis:
distinct histopathological entity? J. Clin. Pathol.
39, 524–530 (1986).
30. Genta, r. M. Differential diagnosis of reactive
gastropathy. Semin. Diagn. Pathol. 22,
273–283 (2005).
31. Ljubicic, N. et al. The effect of eradicating
Helicobacter pylori infection on the course of
adenomatous and hyperplastic gastric polyps.
Eur. J. Gastroenterol. Hepatol. 11, 727–730
(1999).
32. Ohkusa, T. et al. Disappearance of hyperplastic
polyps in the stomach after eradication of
Helicobacter pylori. A randomized, clinical trial.
Ann. Intern. Med. 129, 712–715 (1998).
33. Lauwers, G. Y. et al. p53 expression in
precancerous gastric lesions:
an immunohistochemical study of PAb 1801
monoclonal antibody on adenomatous and
hyperplastic gastric polyps. Am. J.
Gastroenterol. 88, 1916–1919 (1993).
34. Nogueira, A. M. et al. Microsatellite instability in
hyperplastic and adenomatous polyps of the
stomach. Cancer 86, 1649–1656 (1999).
35. Murakami, K. et al. p53, but not c‑Ki‑ras,
mutation and down-regulation of p21wAF1/
CiP1 and cyclin D1 are associated with
malignant transformation in gastric hyperplastic
polyps. Am. J. Clin. Pathol. 115, 224–234
(2001).
36. Yao, T. et al. Malignant transformation of gastric
hyperplastic polyps: alteration of phenotypes,
proliferative activity, and p53 expression. Hum.
Pathol. 33, 1016–1022 (2002).
37. Hattori, T. Morphological range of hyperplastic
polyps and carcinomas arising in hyperplastic
polyps of the stomach. J. Clin. Pathol. 38,
622–630 (1985).
38. Zea-iriarte, w. L. et al. Carcinoma in gastric
hyperplastic polyps. A phenotypic study. Dig. Dis.
Sci. 41, 377–386 (1996).
39. Yoshihara, M. et al. Correlation of ratio of serum
pepsinogen i and ii with prevalence of gastric
cancer and adenoma in Japanese subjects. Am.
J. Gastroenterol. 93, 1090–1096 (1998).
40. Laxen, F. et al. Gastric polyps; their
morphological and endoscopical characteristics
and relation to gastric carcinoma. Acta Pathol.
Microbiol. Immunol. Scand. [A]. 90, 221–228
(1982).
41. Abraham, s. C. et al. Genetic alterations in
gastric adenomas of intestinal and foveolar
phenotypes. Mod. Pathol. 16, 786–795 (2003).
42. Hirota, w. K. et al. AsGe guideline: the role of
endoscopy in the surveillance of premalignant
conditions of the upper Gi tract. Gastrointest.
Endosc. 63, 570–580 (2006).
43. Dunlop, M. G. Guidance on gastrointestinal
surveillance for hereditary non-polyposis
colorectal cancer, familial adenomatous
polypolis, juvenile polyposis, and Peutz–Jeghers
syndrome. Gut 51 (suppl. 5), v21–v27 (2002).
44. Hizawa, K. et al. Juvenile polyposis of the
stomach: clinicopathological features and its
malignant potential. J. Clin. Pathol. 50, 771–774
(1997).
45. Johnson, G. K. et al. Cronkite–Canada
syndrome: gastrointestinal pathophysiology and
morphology. Gastroenterology 63, 140–152
(1972).
46. Hizawa, K. et al. Gastrointestinal manifestations
of Cowden’s disease. report of four cases.
J. Clin. Gastroenterol. 18, 13–18 (1994).
47. Jagelman, D. G. et al. Upper gastrointestinal
cancer in familial adenomatous polyposis.
Lancet 1, 1149–1151 (1988).
48. Offerhaus, G. J. et al. The risk of upper
gastrointestinal cancer in familial adenomatous
polyposis. Gastroenterology 102, 1980–1982
(1992).

340 | JUNE 2009 | volUmE 6 www.nature.com/nrgastro

© 2009 Macmillan Publishers Limited. All rights reserved


49. Giardiello, F. M. et al. very high risk of cancer in
familial Peutz–Jeghers syndrome.
Gastroenterology 119, 1447–1453 (2000).
50. McGrath, D. r. & spigelman, A. D. Preventive
measures in Peutz–Jeghers syndrome. Fam.
Cancer 1, 121–125 (2001).
51. Giardiello, F. M. & Trimbath, J. D. Peutz–Jeghers
syndrome and management recommendations.
Clin. Gastroenterol. Hepatol. 4, 408–415 (2006).
52. Howe, J. r. et al. The risk of gastrointestinal
carcinoma in familial juvenile polyposis. Ann.
Surg. Oncol. 5, 751–756 (1998).
53. ward, e. M. & wolfsen, H. C. Pharmacological
management of Cronkhite–Canada syndrome.
Expert Opin. Pharmacother. 4, 385–389 (2003).
54. wirtzfeld, D. A. et al. Hamartomatous polyposis
syndromes: molecular genetics, neoplastic risk,
and surveillance recommendations. Ann. Surg.
Oncol. 8, 319–327 (2001).
55. Hasegawa, T. et al. CD34 expression by
inflammatory fibroid polyps of the stomach.
Mod. Pathol. 10, 451–456 (1997).
56. Puri, A. s. et al. Giant inflammatory fibroid polyp
of stomach causing massive upper
gastrointestinal bleeding. Indian J. Gastroenterol.
10, 23–24 (1991).
57. Allibone, r. O. et al. Multiple and recurrent
inflammatory fibroid polyps in a Devon family
(‘Devon polyposis syndrome’): an update. Gut
33, 1004–1005 (1992).
58. Pantanowitz, L. et al. inflammatory fibroid polyps
of the gastrointestinal tract: evidence for a
dendritic cell origin. Am. J. Surg. Pathol. 28,
107–114 (2004).
59. schildhaus, H. U. et al. inflammatory fibroid
polyps harbour mutations in the platelet-derived
growth factor receptor α (PDGFrA) gene.
J. Pathol. 216, 176–182 (2008).
60. Paikos, D. et al. inflammatory fibroid polyp or
vanek’s tumour. Dig. Surg. 24, 231–233 (2007).
61. Miettinen, M. & Lasota, J. Gastrointestinal
stromal tumors-—definition, clinical, histological,
immunohistochemical, and molecular genetic
features and differential diagnosis. Virchows
Arch. 438, 1–12 (2001).
62. Nilsson, B. et al. Gastrointestinal stromal
tumors: the incidence, prevalence, clinical
course, and prognostication in the preimatinib
nature reviews | gastroenterology & hepatology
© 2009 Macmillan Publishers Limited. All rights reserved
mesylate era-—a population-based study in
western sweden. Cancer 103, 821–829 (2005).
63. Kawanowa, K. et al. High incidence of microscopic
gastrointestinal stromal tumors in the stomach.
Hum. Pathol. 37, 1527–1535 (2006).
64. DeMatteo, r. P. et al. Two hundred gastrointestinal
stromal tumors: recurrence patterns and
prognostic factors for survival. Ann. Surg. 231,
51–58 (2000).
65. Demetri, G. D. et al. NCCN Task Force report:
management of patients with gastrointestinal
stromal tumor (GisT)-—update of the NCCN
clinical practice guidelines. J. Natl Compr. Canc.
Netw. 5 (suppl. 2), 1–9 (2007).
66. Hueman, M. T. & schulick, r. D. Management of
gastrointestinal stromal tumors. Surg. Clin. North
Am. 88, 599–614 (2008).
67. Nilsson, B. et al. Adjuvant imatinib treatment
improves recurrence-free survival in patients with
high-risk gastrointestinal stromal tumours (GisT).
Br. J. Cancer 96, 1656–1658 (2007).
68. Gilligan, C. J. et al. Gastric carcinoid tumors:
the biology and therapy of an enigmatic and
controversial lesion. Am. J. Gastroenterol. 90,
338–352 (1995).
69. Kloppel, G. et al. The gastroenteropancreatic
neuroendocrine cell system and its tumors:
the wHO classification. Ann. NY Acad. Sci. 1014,
13–27 (2004).
70. Kloppel, G. et al. Pathology and nomenclature of
human gastrointestinal neuroendocrine
(carcinoid) tumors and related lesions. World J.
Surg. 20, 132–141 (1996).
71. rindi, G. et al. eCL cell tumor and poorly
differentiated endocrine carcinoma of the
stomach: prognostic evaluation by pathological
analysis. Gastroenterology 116, 532–542
(1999).
72. rindi, G. et al. Gastric carcinoids and
neuroendocrine carcinomas: pathogenesis,
pathology, and behavior. World J. Surg. 20,
168–172 (1996).
73. Borch, K. et al. Gastric carcinoids:
biologic behavior and prognosis after
differentiated treatment in relation to type. Ann.
Surg. 242, 64–73 (2005).
74. Modlin, i. M. et al. Gastric carcinoids. The Yale
experience. Arch. Surg. 130, 250–255 (1995).
reviews
75. schindl, M. et al. Treatment of gastric
neuroendocrine tumors: the necessity of a type-
adapted treatment. Arch. Surg. 136, 49–54
(2001).
76. Yi, s. Y. Dyslipidemia and H. pylori in gastric
xanthomatosis. World J. Gastroenterol. 13,
4598–4601 (2007).
77. Lin, P. Y. et al. Gastric xanthelasma in
hyperplastic gastric polyposis. Arch. Pathol. Lab.
Med. 113, 428–430 (1989).
78. el-serag, H. B. et al. Prevalence and
determinants of histological abnormalities of
the gastric cardia in volunteers. Scand. J.
Gastroenterol. 42, 1158–1166 (2007).
79. Polkowski, w. et al. intestinal and pancreatic
metaplasia at the esophagogastric junction in
patients without Barrett’s esophagus. Am. J.
Gastroenterol. 95, 617–625 (2000).
80. Christodoulidis, G. et al. Heterotopic pancreas in
the stomach: a case report and literature review.
World J. Gastroenterol. 13, 6098–6100 (2007).
81. Ormarsson, O. T. et al. Diagnosis and treatment
of gastric heterotopic pancreas. World J. Surg.
30, 1682–1689 (2006).
82. Ayantunde, A. A. et al. symptomatic pyloric
pancreatic heterotopia: report of three cases
and review of the literature. Med. Sci. Monit. 12,
Cs49–Cs52 (2006).
83. Chetty, r. & weinreb, i. Gastric neuroendocrine
carcinoma arising from heterotopic pancreatic
tissue. J. Clin. Pathol. 57, 314–317 (2004).
84. AsGe guideline: the role of endoscopy in the
surveillance of premalignant conditions of the
upper Gi tract. National Guidelines
Clearinghouse [online] http://www.guideline.
gov/summary/summary.aspx?doc_id=9306
(2009).
acknowledgments
we would like to thank Dr A. Horiuchi, showa inan
General Hospital, Komagane, Japan for providing the
endoscopic photographs of a gastric adenoma
(Figure 3a) and a gastric carcinoid (Figure 6a).
Charles P. vega, University of California, irvine, CA, is
the author of and is solely responsible for the content
of the learning objectives, questions and answers of
the Medscape-accredited continuing medical
education activity associated with this article.
volume 6 | June 2009 | 341