Heterotopic Pancreas of the Gallbladder

Thanasis Klimis
, Nikolaos Roukounakis
, Ilias Kafetzis
Vasileios Mouziouras
, Ilias Karantonis
, Nikolaos Andromanakos
Department of Pathology, Third Hospital of Social Insurance Institute;
Department of Surgery, “Polykliniki” General Hospital. Athens, Greece
Context Heterotopic pancreas of the gallbladder is an extremely rare entity, especially when pancreatic tissue appears histologically
with an exclusively exocrine structure. Case report We report the case of a 35-year-old man who presented with symptoms of
acalculous gallbladder disease with high levels of amylasuria. Immunohistochemical analysis of the surgical specimen of the
cholecystectomy revealed pancreatic tissue at the gallbladder wall. Conclusions Heterotopic pancreatic tissue is a rare pathological
finding in the gallbladder. It requires consideration and sensitization in the differential diagnosis of acalculous gallbladder disease,
which can explain hyperamylasuria in cases of unknown origin.
Heterotopic pancreas is defined as the presence of
pancreatic tissue which lacks anatomic and vascular
continuity with the main pancreas [1]. In 90% of
reported cases, heterotopic pancreas has been found in
the upper gastrointestinal tract [2, 3, 4]. In addition,
other locations of aberrant pancreatic tissue have
occasionally been detected in the spleen, omentum,
mediastinum, lungs, umbilicus, gallbladder and bile
ducts [3, 5, 6, 7].
Heterotopic pancreas in the gallbladder is an extremely
rare entity. Only thirty-three cases have been reported
in the literature [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16]. In the majority of cases, the heterotopic
pancreas was an incidental finding following a
cholecystectomy performed for symptomatic
gallbladder disease.
We report the case of heterotopic pancreas which
presented with clinical symptoms of cholecystitis and
high levels of amylasuria.
A 35-year-old man was admitted to the hospital
complaining of anorexia, nausea and abdominal pain.
The onset of the pain was insidious, starting 48 hours
previously and gradually worsening. On physical
examination, the abdominal pain was located in the
right upper quadrant. Palpation of the abdomen
revealed tenderness and guarding in the right upper
quadrant, and the Murphy sign was positive.
Furthermore, examination of the other systems did not
disclose pathological findings. The patient’s
temperature was 37.2°C. Laboratory data other than
amylasuria (1,030 IU/L; reference range: 0-500 IU/L)
were within the reference limits. The ultrasonographic
study showed a small well-defined, non-mobile
echogenic structure of 4 mm in diameter attached to the
wall of the gallbladder. The features of the echogenic
structure were suggestive of a gallbladder polyp
(Figure 1) but not of a gallstone. Therefore, the most
likely diagnosis was a gallbladder polyp and a
laparoscopic cholecystectomy was carried out.
Received February 13th - Accepted April 20th, 2011
Key words Choristoma; Gallbladder, Immunohistochemistry;
Correspondence Nicolaos Roukounakis
Department of Surgery; General Hospital “Polykliniki”; Athens;
Phone: +30-21.0204.4123; Fax: +30-21.0524.0130
E-mail: nicrouk@hotmail.com
Document URL http://www.joplink.net/prev/201109/03.html
Figure 1. An echogenic non-mobile structure attached to the
gallbladder wall: features suggestive of a polyp.

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JOP. J Pancreas (Online) 2011 Sep 9; 12(5):458-460.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 5 - September 2011. [ISSN 1590-8577]
On macroscopic examination, the gallbladder was 70
mm long and 30 mm wide with a mural thickness of 60
µm. Gallstones were not present in the gallbladder
lumen. An 8 mm intramural, yellow nodule was found
in the body of the gallbladder. Its consistency was firm
and it was protruding under the serosa.
On microscopic examination of the gallbladder, a
mixed chronic inflammation in the lamina propria,
submucosa and muscular wall was found. The nodule
showed ectopic pancreatic tissue, consisting of acini,
ducts without any connection to the gallbladder lumen,
and no islet cells (Figure 2).
Immunohistochemical analysis was performed using a
series of immunologic markers to identify this
heterotopia. The ductal epithelium was surrounded by a
smooth muscle component and exhibited a typical
pancreatic duct-like immunophenotype, characterized
by immunoreactivity to cytokeratins 7, 8, 18, 19 and to
carbohydrate antigen (CA) 19-9. No reactivity against
CEA, vimentin and CK20 was found. The pancreatic
acini, composed of polygonal cells arranged in a single
layer, with typical exocrine differentiation, were
positive for alpha-1-antitrypsin and alpha-1-
chymotrypsin (Figure 3). The other immuno-
histochemical markers, such as somatostatin, insulin
and chromogranin A, were negative for endocrine
A subsequent diagnosis of chronic cholecystitis with
heterotopic pancreas was reached. The patient’s
postoperative course was uneventful and he was
discharged on the 3rd postoperative day. After a follow-
up of three months, the patient was asymptomatic
without any discomfort.
Heterotopic pancreas is believed to result from early
separation of the pancreas during rotation of the
gastrointestinal tract in the embryonic stage. There is
not a universally accepted theory as to the exact origin
of this aberrant tissue [3, 4, 6].
Heterotopic pancreas can be found in all age groups. It
is more frequent in men than in women [2, 7]. In one
series of 212 cases of aberrant pancreas, only one case
was found to be located in the gallbladder [4].
Heterotopic pancreas in the gallbladder presents as an
exophytic growth and may be similar to polypoid
lesions or as yellow-colored nodules, varying in
dimension from a few millimeters to 4 cm. Fifty
percent of heterotopic pancreatic tissue arises in the
neck of the gallbladder [2, 3, 7, 8, 9, 14]. In our case,
the heterotopic pancreas was subserosal. It is less
common and is found in only 10% of cases. The
submucosal presentation is most common and is found
in 73% of cases [16].
Our histopathological examination revealed a
heterotopic pancreas made up of exocrine acinar and
ductal components without islet cells, corresponding to
incomplete heterotopia. Islets of Langerhans are
identified in only one-third of cases [16].
An immunohistochemical study was carried out to
identify and characterize the endocrine and exocrine
activity in the ectopic pancreas situated in the
gallbladder. The literature contains only a few reports
concerning the immunohistochemical profile [7, 9]. We
used an ample variety of immunologic markers.
Vimentin is a marker of pancreatic precursor cells and
has been used by Ko et al. [17] as expression in
proliferative duct cells. However, Beltran and Barria
[7], and Pilloni et al. [9], reported the negative
immunoreactivity in pancreatic duct cells to vimentin
as happened in our case. Tubular and epithelial
structures were immunoreactive to cytokeratins 7, 8,
18, and 19, and to CA 19-9. Exocrine activity was
identified by immunoreactivity to alpha-1-antitrypsin
and alpha-1-chymotrypsin but endocrine activity was
Most patients with heterotopic pancreas are
asymptomatic, and the heterotopic tissue is found
incidentally at histological exam following a
cholecystectomy. Heterotopic pancreas in the
gallbladder is rarely symptomatic. The manifestation of
symptoms is largely associated with acute or chronic
cholecystopathy, with or without gallstones [5, 6, 7, 13,
14, 16]. Qizilbash [12], reported a case in which the
Figure 2. Ectopic pancreas in the gallbladder. Pancreatic ducts,
acinar component and gallbladder epithelium (H&E; original
magnification x25).
Figure 3. Pancreatic tissue was reactive to alpha-1-chymotrypsin,
demonstrating exocrine activity (alpha-1-chymotrypsin; original
magnification x100).

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JOP. J Pancreas (Online) 2011 Sep 9; 12(5):458-460.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 5 - September 2011. [ISSN 1590-8577]
cause of acute symptoms was the inflammation of the
heterotopic pancreatic tissue, resembling acute
Inceoglu et al. [11] reported a case of heterotopic
pancreas in the cystic duct with hydrops of the
gallbladder and chronic pancreatitis due to ectopic
tissue. In three cases similar to our case, heterotopic
pancreas has been found to stimulate cholecystopathy
with all symptoms disappearing after a
cholecystectomy. Malignant transformation of an
ectopic pancreas may occasionally occur [10].
The mechanism whereby this aberrant tissue may
produce various symptoms is unclear. Previous studies
[18] have suggested that active pancreatic enzymes,
such as amylase and trypsin, refluxing into the biliary
tract and gallbladder lumen might produce
inflammation, spasm and biliary symptoms in patients
without gallstones, and acute cholecystitis in patients
with gallstones [6, 7, 13, 16, 18].
In our case, we could hypothesize that the cause of
gallbladder symptomatology may have been due to the
continuous secretion of active pancreatic enzymes,
mainly amylase, directly into the gallbladder lumen,
causing damage to the epithelium and producing
symptoms associated with chronic inflammation.
The preoperative diagnosis of an aberrant pancreas in
the gallbladder is impossible using the imaging exams
currently available. Ultrasonography and computed
tomography cannot distinguish an aberrant pancreas in
the gallbladder from other lesions, such as cholesterol
polyps, adenoma and carcinoma [14].
However, an ectopic pancreas in the gallbladder,
despite its rarity, should be considered in the
differential diagnosis of acalculous lesions, such as
polypoid formations, isolated parietal thickenings or
nodulations, especially when these coexist with
hyperamylasuria of unknown origin.
Conflict of interest The authors have no potential
conflicts of interest
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