Romanian Journal of Morphology and Embryology 2010, 51(2):365–369
Pancreatic metaplasia of gastric mucosa
associated with gastroduodenal ulcer
L. MOGOANTĂ1), C. T. STREBA1), D. PIRICI1), RODICA DÎRNU2),
1)Department of Histology,
University of Medicine and Pharmacy of Craiova
2)County Hospital, Târgu-Jiu
PhD candidate, University of Medicine and Pharmacy of Craiova
Metaplasia represents the process of transforming a well-differentiated adult tissue into another type of adult tissue. Pancreatic metaplasia
of the gastric mucosa represents the process in which the normal mucosa of the stomach is replaced with pancreatic formations, which
mimic the structure of pancreatic acini. We describe the case of a male patient aged 39 who was admitted for abdominal pain, vomiting,
hematemesis, melena, pale teguments, intense perspiration and nausea. The patient underwent surgery for suturing a perforated duodenal
ulcer five years prior to this episode (2002). A gastric ulcer complicated with superior digestive bleeding and a chronic duodenal ulcer
complicated with partial stenosis and perivisceritis were found during surgery. Gastric wall fragments were harvested and underwent usual
histological techniques and immunohistochemistry. We found an ulceration from the gastric mucosa to the submucosa, covered by fibrino-
leukocytic detritus. In the mucosal chorion we found numerous round or oval shaped nested formations which occupied the lower two
thirds of the chorion, to the muscularis mucosae. Some metaplasic acini contain cel s variable in shape, color and immunophenotype.
Surrounding the nested acini we found tubular formations, formed of cubic shaped cells, representing excretory canals which were
continued by gastric glands or opened directly in the crypts of the gastric epithelium.
Keywords: pancreatic metaplasia, gastric mucosa, gastroduodenal ulcer, acinar pancreatic cells.
Clinic at the Emergency County Hospital of Craiova.
He presented a deteriorated condition, intense abdo-
Pancreatic metaplasia of the gastric mucosa repre-
minal pain, vomiting, hematemesis, melena, pale tegu-
sents the process in which the normal mucosa of the ments, intense perspiration and nausea. The acute
stomach is replaced with pancreatic formations, which symptoms debuted five days prior to admission,
mimic the structure of pancreatic acini.
following several abundant meals accompanied by large
Currently, intestinal metaplasia is the most common alcohol intake. During anamnesis, we found out that the
type of gastric mucosal transformation. It can contain patient was suffering from an older gastric condition,
both sialomucin secreting goblet cells and non-secretory
five years prior to this episode (2002) being admitted
absorptive cells. Sometimes the transition from the and treated by surgery for a perforated duodenal ulcer,
normal gastric mucosa to the intestinal type occurs when the suture of said ulcer was performed.
abruptly, both types of cells appearing concomitantly;
Clinical examination revealed an underweight
in other cases, it is a progressive transition. In the latter patient, with pale teguments and mucosae, little adipose
case columnar cells with increased sulphomucin secre-
tissue, presenting diffuse abdominal pain, both sponta-
tion and goblet cells that can secret either sialomucin or
neous and on palpatory examination.
sulphomucin can be found [1, 2].
Endoscopic examination showed intense brown-
In recent years, there have been an increased number
colored sanguinolent secretions (hematemesis debris)
of reports concerning cases of pancreatic metaplasia in the esophagus, and an ulcer of about 3–4 cm bleeding
appearing in chronic atrophic gastritis and autoimmune ulcer situated on the incisura angularis, on the lesser
gastritis [3–5]. This type of metaplasia mainly consists curvature, having prominent margins, with great
of nested acin formations that can be found in the lower
malignisation potential. A large quantity of blood
thirds of the gastric chorion. They are usually and secretions was found in the gastric cavity
accompanied by tubular cell clusters that resemble (hematemesis).
glandular ducts that usually reach the gastric crypts or
Laboratory tests showed normal, except a moderated
are continued by gastric fundic glands [3, 5].
anemia (Hemoglobin level 10.24 g/L), anizocytosis with
anisochromia and hypokalemia with hyponatremia.
Patient and Methods
After correcting the hydroelectrolitic imbalance and
We describe the case of a male patient (CP) aged 39,
hemostatic treatment, surgery was performed, finding a
coming from a rural environment, who was admitted in double ulcer (gastric ulcer complicated with superior
the Emergency Ward in August 2007 in the 2nd Surgery
digestive bleeding and a chronic duodenal ulcer
L. Mogoantă et al.
complicated with partial stenosis and perivisceritis). formaldehyde solution for 48 hours, followed by
Two-thirds gastric resection was performed, followed paraffin inclusion. After performing 3–5 micrometer
by gastroduodenal Péan-type anastomosis.
thick sections, some of the histologic cups were stained
For the histopathology study we harvested gastric with Hematoxylin–Eosin and PAS–Hematoxylin dyes.
wall fragments from the lesion site, three centimeters
For the immunohistochemistry study, sections
above (line of gastric resection), from the antral area placed on poly-Lysine slides were deparaffinated and
and from adjacent ganglia on the lesser curvature. rehydrated. Antigenic retrieval was performed accor-
All biologic material was fixated in neutral 10% ding the producers specifications (Table 1).
Table 1 – Characteristics of the antibodies used in the present study
Digestion with K proteinase, 5 minutes
Alpha 1 antitrypsin
Boiling in citrate buffer, pH 6
Boiling in EDTA buffer, pH 9
Boiling in citrate buffer, pH 6
Boiling in citrate buffer, pH 7
Digestion with K proteinase, 5 minutes
Endogenous peroxidase was inactivated by incuba-
ting in oxygenated water 1%; afterwards non-specific
antigen situs were blocked with 1% non-fat milk
solution. The primary antibody was added in optimal
dilution, and sections were incubated at 40C overnight.
On the second day, after washing the excess primary
antibody, sections were incubated with secondary
polyclonal polymeric antibodies labeled with peroxidase
Actual staining was performed using Diamino-
benzidine (DAB) under the optic microscope for each
section. Afterwards, sections were counterstained with
Hematoxylin, dehydrated, clarified and mounted in
DPX (Merck) mounting environment.
For the histology and immunohistochemistry study,
we used the Nikon 55i microscope.
The histopathology exam of the gastric wall at
ulcer level and the surrounding area evidentiated the
existence of an ulceration reaching from the gastric
mucosa to the submucosa, covered by fibrino-leukocytic
detritus, underneath which we found granulation
Figure 1 – Overview image of gastric mucosa with
tissue. At the level of the gastric corpus, at a distance
pancreatic metaplasia (HE staining, ×100).
of about 3 cm from the ulcerous lesion, we found
hypertrophic mucosa with a rich inflammatory
infiltrate containing polymorphonucleated cells in
the chorion (lamina propria) and moderated vascular
Study of the gastric mucosa fragments coming from
the antral region showed an atrophic mucosa, with
fewer and smaller glandular crypts and small and rare
In the mucosal chorion we found numerous round
or oval shaped nested formations, with diameters
between 150 and 350 microns, which occupied
the lower two thirds of the chorion, to the muscularis
mucosae (Figure 1). These formations were separated
by variable amounts of lax conjunctive tissue with
rare vascular vessels, conjunctive fibers and cells
Figure 2 – Nest of metaplasic pancreatic acini (HE
(Figures 2 and 3).
Pancreatic metaplasia of gastric mucosa associated with gastroduodenal ulcer
Figure 3 – Metaplasic pancreatic acini (HE staining,
Figure 5 – Metaplasic pancreatic acini with PAS-
positive granules in the apical two thirds (PAS–
Hematoxylin staining, ×400).
To evidentiate the shape of the cells in these acinar
formations we marked the cellular limits with
Immunohistochemistry showed a positive, neverthe-
E-cadherin and contrasted with Hematoxylin–Eosin, less variable reaction to alpha-trypsin between acini
knowing that E-cadherin or epithelial cadherin is an (Figure 6), while reactions to cytokeratins 7, 18 and 20
intercellular adherence glycoprotein made up of a long and lysozyme were negative.
extracellular domain, a transmembranary domain and a
short intracellular domain. They form homotypical
extracellular interactions, creating a functional link
between epithelial cells. Hence, immunostaining of
E-cadherin will mark the external surfaces of epithelial
As it can be seen in our images (Figure 4), the acinar
formations were formed by pyramid or pyramid body
shaped cells with slight basophilic cytoplasm, fine
granules, with round nuclei frequently found in the
basal region, with distinct nucleoli. Cells were delimited
by a thin basal membrane which continuated with the
basal membrane of the gastric glands. Acinar cells have
delimited a small round or star shaped lumen at their
Figure 6 – Metaplasic acini. Positive immunostain-
ing with alpha-trypsin, ×400.
On some slides, histology staining as well as
immunostaining for alpha-trypsin allowed us to
evidentiate the fact that some metaplasic acini contain
cells variable in shape, color and immunophenotype.
Therefore, in the structure of some acini we identified
oval shaped cells, with a round, central nucleus, more
hypochromic cytoplasm, which can be either endocrine
or oxyntic cells (Figure 6), while other cells had
columnar shapes, clear cytoplasm, basal nuclei, aspect
similar to that of mucinous cells found in the epithelium
of the neck of pyloric glands (Figure 7). Additionally,
we found cells with two or even three nuclei in the
Figure 4 – Metaplasic pancreatic acini (immuno-
Surrounding the nested acini, we found tubular
staining with E-cadherin; counterstaining with HE,
formations 80–120 microns in diameter, formed of
cubic shaped cells, which paved a lumen of approxima-
The PAS–Hematoxylin staining revealed acinar tely 25–40 microns in diameter, representing excretory
cells, numerous small acidophilic granules, usually canals of these acin formations. These tubular shapes
found in the middle third and apical regions. We have to
were continued by gastric glands or opened directly in
account for the fact that the PAS reaction was not the crypts of the gastric epithelium. Unlike pancreatic
homogenous between acini, hence the number of canalicules, these canals did not have other cellular of
granules found in each acinar cell was different fibrillary structures surrounding them (smooth muscle
cells or collagen fibers).
L. Mogoantă et al.
between 8 and 18 years, who presented digestive symp-
toms. If pancreatic metaplasia in adults is associated
with atrophic or autoimmune gastritis phenomena, it is
considered for children that the presence of pancreatic
metaplasia is caused by developing and differentiating
problems of the gastric mucosa.
Other authors  consider that pancreatic acinar
cells can also develop within the gastric mucosa of the
antral region and is often associated with intestinal
metaplasia or gastric atrophy. These focal points of
metaplasia contain isolated or multiple nests of acini or
lobules, measuring up to 1.7 mm in diameter. More
rarely, acinar cells appear isolated or in small cellular
nests amongst the gastric glands.
Our study aimed at demonstrating that pancreatic
Figure 7 – Metaplasic acin containing numerous cells
with clear cytoplasm (HE staining, ×200).
metaplasia can be localized in the antral mucosa and can
be associated with grave pathologies of the stomach.
On some histological cups, we remarked that metaplasic
tissue merges imperceptibly with gastric glands in which
Metaplasia represents the process of transforming a it sends synthesized products, but larger lobules contain
well-differentiated adult tissue into another type of adult
collector tubes, which communicate with gastric crypts.
tissue. The term of metaplasia signifies that the trans-
Leys CM et al. (2006)  showed that both pancre-
formation process takes place in postnatal life, that it atic metaplasia and gastric endocrine cells hyperplasia
consists of a tissue that appears in a place it is not are associated with atrophic gastritis of the gastric body.
normally found and that it can be part of both physio-
A study performed by Doglioni C et al. (1993) 
logical and pathological processes. Some researchers showed that metaplasic acinar cells are localized within
consider it a process of adapting structures to new con-
the same basal membrane and are joined with gastric
ditions in the local environment. In experimental biolo-
cells through desmosomes, which might be a hint that
gy, the term of metaplasia is often replaced with “trans-
progenitor cells for pancreatic metaplasia are part of
differentiation” . In histopathology, for humans, normal gastric epithelium. Authors have also observed a
metaplasic processes are frequently encountered. They striking similarity between parietal and metaplasic cells.
always occur in tissue that has been subjected to chronic
We consider that the diagnosis of pancreatic meta-
trauma, infections or hormonal stimulations, therefore plasia is quite difficult on gastric biopsies, especially
places that are subject to a continuous process of rege-
when the inflammatory process is abundant, because
neration. In some processes, it is unclear whether the acinar cells can be mistaken with parietal cells from the
metaplasic tissue has occurred because of local cellular bottom of gastric glands. In these situations, immuno-
differentiation or has migrated from elsewhere .
histochemistry techniques can bring a considerable
Metaplasia of gastric mucosa is frequently encount-
advantage, highlighting the presence of enzymes cha-
ered in chronic inflammatory processes (gastritis), ulcer
racteristic to pancreatic acinar cells. All authors agree
or gastric cancer. The one most often quoted is intestinal
that the islands of acinar epithelial cells produce
metaplasia that consists of replacing gastric epithelium pancreatic enzymes like amylase, lipase and trypsinogen
with enterocytes, caliciform cells and Paneth cells.
. Molecular pathogenesis of pancreatic metaplasia is
Pancreatic metaplasia is much rarer than the intesti-
insufficiently known. Metaplasic cells probably result
nal one. According to some authors, Doglioni C et al.
from an aberrant differentiation of stem cells present at
(1993) , it is present in approximately 12% of the neck of gastric glands .
patients with autoimmune gastritis, usually occurring in
Our study confirms that hypothesis as we observed a
the cardia region and co-existing with other types of direct continuation between the acin pancreatic structu-
metaplasia . Jhala NC et al. (2003)  offer similar res and cells from gastric glands or crypts.
data and consider that pancreatic acinar cells metaplasia
Johansson J et al. (2010) , while examining
mainly occurs in patients with autoimmune gastritis.
biopsies coming from eso-gastric junctions of 644
Jhala NC et al. (2003) , while investigating the patients, found pancreatic acinar metaplasia in 19% of
presence of pancreatic metaplasia at the level of the the patients, out of which 8% in the esophageal mucosa,
oxyntic mucosa on fragments of gastric biopsy from associating Barrett esophagus, and 11% on gastric mu-
adult patients, finds an incidence of 11%, out of which cosa surrounding the cardia. Pancreatic acin metaplasia
9% is found in patients with autoimmune gastritis, 1% above the eso-gastric junction was associated with the
in patients with multifocal atrophic chronic gastritis and
female gender, while the one below the junction
1% in a patient with normal gastric mucosa.
positively correlated with the presence of Helicobacter
Pancreatic metaplasia has been evidenced in chil-
pylori. The author considers that eso-gastric pancreatic
dren. Thus, Integlia MJ et al. (1997)  has shown metaplasia may be an age-dependent lesion, associated
through studies of histology and immunohistochemistry
with Helicobacter pylori, female gender and gastro-
the presence of islands of exocrine pancreas within the esophageal reflux. However, the nature of the
gastric mucosa on a number of eight children aged metaplasia at this level remains obscure.
Pancreatic metaplasia of gastric mucosa associated with gastroduodenal ulcer
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Laurenţiu Mogoantă, Professor, MD, PhD, Department of Histology, University of Medicine and Pharmacy, 2–4
Petru Rareş Street, 200349 Craiova, Romania; Phone +40251–523 654, e-mail: email@example.com
Received: March 25th, 2010
Accepted: May 20th, 2010