Premalignant and Malignant Lesions of the Heterotopic Pancreas in the Esophagus

case report
Available from: URL: http://www.jgld.ro/2015/2/19.html
DOI: http://dx.doi.org/10.15403/jgld.2014.1121.242.uly
Premalignant and Malignant Lesions of the Heterotopic Pancreas
in the Esophagus: a Case Report and Review of the Literature
Jan Ulrych1, Vladimir Fryba1, Helena Skalova2, Zdenek Krska1, Tomas Krechler3, David Zogala4
1) 1st Department of Surgery
- Department of Abdominal,
Thoracic Surgery and
Traumatology;
2) Institute of Pathology;
3) 4th Department of
Medicine - Department
of Gastroenterology and
Hepatology;
4) Institute of Nuclear
Medicine;
First Faculty of Medicine,
Charles University in Prague
and General University
Hospital in Prague,
Prague, Czech Republic
Address for correspondence:
Jan Ulrych MD
1st Department of Surgery
First Faculty of Medicine,
Charles University in Prague
General University Hospital
in Prague
U Nemocnice 2, 128 08,
Prague 2, Czech Republic
[email protected],
Received: 06.03.2015
Accepted: 03.04.2015
Abstract
Heterotopic pancreas is a congenital pathology of the gastrointestinal tract, particularly rare in the esophagus.
Both symptomatology and findings during preoperative examinations are non-specific and therefore do not
often lead to an accurate diagnosis, which is usually revealed only by histopathological assessment of a resected
specimen. We report an unusual case of a patient suffering from severe dysphagia caused by heterotopic
pancreas in the distal esophagus with chronic inflammation and foci of premalignant changes. This article
also reviews 14 adult cases of heterotopic pancreas in the esophagus previously reported in the literature,
with the aim of determining the clinical features of this disease and possible complications including rare
premalignant lesions and malignant transformation. Especially with regard to those complications, we suggest
that both symptomatic and incidentally found asymptomatic lesions should be resected.
Key words: heterotopic pancreas – esophagus – pancreatic intraepithelial neoplasia – submucosal esophageal
tumor.
Abbreviations: AFP: alpha-fetoprotein; CA 19.9: cancer antigen 19.9; CEA: carcinoembryonic antigen;
CYFRA: cytokeratin 19 fragment; FDG: fluorodeoxyglucose; GERD: gastroesophageal reflux disease;
GIST: gastrointestinal stromal tumor; IPMN: intraductal papillary mucinous neoplasia; PanIN: pancreatic
intraepithelial neoplasia; PSA: prostate specific antigen; SCCA: squamous cell carcinoma antigen.
Introduction
Heterotopic pancreas is a
rare condition defined as the
occurrence of pancreatic tissue in
an abnormal location without any
anatomic or vascular continuity
with orthotopic pancreas [1].
Heterotopic pancreas can arise
in any part of the gastrointestinal
tract, most frequently in the
stomach, duodenum or jejunum
[2]. Up to now, there have been
only 14 cases of heterotopic
pancreas in the esophagus in
adult patients documented in the
literature [3-16]. Ectopic tissue is
usually discovered incidentally
or may become symptomatic
because of obstruction
caused by enlargement due to
inflammation, bleeding or malignant transformation [3, 6, 7].
A malignant tumor arising in the heterotopic pancreas is an
extremely rare event described in 28 cases in the gastroduodenal
region and in a few cases in other locations [17-20], including
2 in the esophagus [5, 7]. Premalignant lesions, namely in the
form of pancreatic intraepithelial neoplasia (PanIN), are found
not only adjacent to malignant tumors, but also in patients
without invasive carcinoma. We report an unusual case of a
patient suffering from severe dysphagia caused by heterotopic
pancreas in the distal esophagus with chronic inflammation
and foci of premalignant changes.
Case report
An obese 34-year-old man was admitted to the inpatient
department with severe dysphagia. His medical history included
only a cholecystectomy 8 years ago. He confessed to smoking 10
cigarettes per day and occasional alcohol drinking. For several
years, he had suffered from dyspepsia, which had been in the
last 3 months complicated by progressive dysphagia, at first
for solid food, later for liquid, together with odynophagia and
J Gastrointestin Liver Dis, June 2015 Vol. 24 No 2: 235-239
236
Ulrych et al
regurgitation. He complained about weakness and weight loss of
10 kg in the last 2 months. Physical examination, hematological,
biochemical and tumor marker (AFP, CEA, CA19.9, CYFRA,
PSA, beta2-microglobulin, SCCA) tests were within normal
limits. Esophagogastroduodenoscopy showed a narrowing of
the lower esophagus due to a protruding mass lesion covered
by normal mucosa. Endoscopic mucosal biopsy revealed only
mild inflammation without neoplastic or any other pathological
changes. Endoscopic ultrasonography failed because the
endoscope could not pass around the protruding mass. Positron
emission tomography and computed tomography (PET-CT)
revealed a large hypermetabolic tumor mass 100x50x40 mm
in size, located in the dorsal wall of the lower esophagus,
without any distal lymph nodal involvement (Fig. 1). Contrastenhanced CT demonstrated a tumor mass arising from the
lower esophagus without any ingrowth to pericardium or
pleura. Bronchoscopy did not discover any remarkable changes.
Fig. 2. Tissue mass resected from the lower esophagus.
Fig. 3. Heterotopic pancreas with characteristic lobular
structure and hyperplasia of the ducts, surrounded by
esophageal muscular layer (lower right) (H&E x40).
Fig. 1. Axial fused fluorodeoxyglucose PET/CT
image shows a soft tissue mass with high FDG
uptake in the lower posterior mediastinum.
After multi-disciplinary discussion the patient underwent
surgery of this symptomatic, histologically non-verified
mass lesion in the lower esophagus. Left-side posterolateral
thoracotomy was performed. Intraoperative exploration showed
a large tumor arising from the wall of the distal esophagus and
adhesions to the mediastinal pleura, pericardium, pulmonal
ligament and descending aorta. This regionally advanced
but resectable tumor was removed with distal esophagus
resection; afterwards primary anastomosis and partial
fundoplication were carried out. Intraoperative biopsy of the
unevenly shaped specimen 50x40x20 mm in size (Fig. 2) had a
strikingly unexpected outcome: heterotopic pancreatic tissue.
Histopathological examination showed characteristic lobulated
pancreatic tissue encompassing acini, minute Langerhans
islets and many cystically dilated irregular ducts (Fig. 3), that
according to Heinrich’s classification matched type I (Table
I). Pancreatic tissue was partially changed by marked chronic
inflammation (Fig. 4) with suppurative destruction of several
larger ducts. Ductular epithelium focally evidenced marked
reactive changes and papillary proliferation, morphologically
compatible with pancreatic intraepithelial neoplasia of mild and
moderate grade (PanIN 1-2). Bundles of esophageal smooth
muscle layer were seen at the periphery of the specimen.
J Gastrointestin Liver Dis, June 2015 Vol. 24 No 2: 235-239
Fig. 4. Chronic pancreatitis with fibrosis and a dilated
larger duct with reactive epithelial papillary proliferation
that is morphologically compatible with PanIN 1 and 2
(lower left) and hyperplasia of small ducts (H&E x100).
The postoperative course was uneventful, and after three
months, the patient is free from symptoms and remains under
the supervision of a gastroenterologist.
Discussion
Heterotopic pancreas is a congenital anomaly, defined as
the presence of pancreatic tissue outside its normal location
without anatomic, neural and vascular connection with the
orthotopic pancreas [1, 2]. Other terms such as ectopic,
Heterotopic pancreas in the esophagus
237
Table I. Heinrich´s classification of the heterotopic pancreas.
Type
Histopathological characteristics
Type I
ducts, acini and endocrine islets similar to
those seen in normal pancreatic tissue
Type II
large number of acini, a few ducts and no
islets
Type III
numerous ducts, a few acini and no islets
Type IV – modification by
Gaspar-Fuentes
entirely endocrine islets with no exocrine
pancreatic tissue
aberrant or accessory pancreas have been used in the relevant
literature [21]. Presumably, it results from separation of small
parts of pancreatic tissue during the process of foregut rotation
and the fusion of the dorsal and ventral pancreatic buds [2, 22].
The first case of heterotopic pancreas was reported by Schultz
in 1727, but the first histological confirmation was described
by Klob in 1859 [23]. Generally, the prevalence of ectopic
pancreas is low. It is discovered in 0.5 – 13.7% of autopsies and
in approximately 1 of 500 operations of the upper abdomen
[24]. Most frequently, it is found in the stomach (25-38%),
duodenum (17-21%) and jejunum (15-21%), although it can
occur in any part of the gastrointestinal tract and, moreover,
in the abdominal cavity, lung or mediastinum [22, 25-27].
In the gastrointestinal tract, it is most frequently located
only in submucosa (54%), less frequently in submucosa and
muscularis propria together (23%), only muscularis propria
(8%), subserosa (11%) and, rarely, in the whole wall (4%) [28].
Histological structure was originally classified by Heinrich with
later modification by Gaspar-Fuentes et al. (Table I) [29, 30].
Most patients are asymptomatic and heterotopic pancreas
is found incidentally. Some patients may present with various
non-specific symptoms that depend on the site of the lesion and
type of complication. Preoperative diagnostic process is usually
unsuccessful, because all the imaging techniques typically show
a tumor mass in the wall of gastrointestinal tract without any
specific sign and endoscopic biopsy commonly contains only
isolated normal or mildly inflamed mucosa, which covers
the mass. Before surgical resection, the lesion is frequently
misdiagnosed as one of the most common submucosal tumors,
gastrointestinal stromal tumor (GIST) or leiomyoma [2, 6, 31].
In many cases, the correct diagnosis is not determined until
the histopathological examination of the resected specimen
[6, 10-14, 24].
The heterotopic pancreas is susceptible to the same
pathological changes that occur in a normal pancreas, such as
acute or chronic inflammation with fibrosis and pseudocyst
formation [2, 6, 11, 32]. Moreover, premalignant changes
seem to occur with the same incidence in heterotopic and
orthotopic pancreas. In both types of pancreatic tissue, the
most frequent precursor of an invasive carcinoma is PanIN,
a noninvasive flat or papillary epithelial proliferation with
different degree of architectural and cytological atypia [33, 34].
Progression from mild changes (PanIN 1) to higher dysplasia
(PanIN 2, 3) and finally adenocarcinoma is accompanied by
gradual accumulation of genetic abnormalities. Zhang et al.
studied a small group of patients with synchronous ductal
adenocarcinoma of orthotopic pancreas and pancreatic
heterotopia, where they found PanIN of variable grade in all
cases. Interestingly, both adenocarcinomas and PanINs had a
similar pattern of p53, cyclin D1 and p16 expression in all cases
and the same K-ras codon 12 mutation in half of the cases [35].
In heterotopic pancreas, only single cases of another precursor
lesion, intraductal papillary mucinous neoplasia (IPMN) have
been documented, including one in the esophagus [14, 36].
Malignant transformation is an extremely rare event described
in 18 cases in the stomach, 10 cases in the duodenum and in a
few cases in other locations, such as the esophagus, jejunum,
ampulla of Vater, spleen, mesocolon, liver and rectum [20].
Most of them were ductal adenocarcinomas; other types such
as acinar cell carcinoma, mucinous cystadenocarcinoma,
solid pseudopapillary neoplasia, anaplastic carcinoma and
Table II. Previously reported cases of the heterotopic pancreas in the esophagus in adults.
Case
Gender
Age
(years)
Location in
Esophagus
Symptomatology
Associated
anomalies
Neoplasia
Ref.
1.
M
43
Distal third
Hematemesis
None
No
3
2.
M
25
Middle third
Vomiting, epigastric discomfort
Congenital cyst
No
4
3.
M
60
Distal third
Dysphagia, epigastric pain, weight loss
None
Adenoca
5
4.
F
47
Distal third
Dysphagia, epigastric pain, weight loss
None
No
6
5.
M
45
Distal third
Dysphagia
None
Anaplastca
7
6.
F
24
Distal third
Nausea, vomiting, fever
None
No
8
7.
M
52
Distal third
Dysphagia
None
No
9
8.
F
41
Distal third
GERD, dysphagia, epigastric pain,
weight loss
None
No
10
9.
F
26
Distal third
Epigastric pain, nausea
None
No
11
10.
M
63
Middle third
Asymptomatic
None
No
12
11.
F
38
Distal third
GERD, epigastric pain
None
No
13
12.
F
58
Distal third
Dysphagia
None
IPMN
14
13.
M
25
Distal third
Epigastric pain
None
No
15
14.
F
73
Distal third
Epigastric pain, vomiting
None
No
16
F = female, M = male, GERD = gastroesophageal reflux disease, Ref. = references, Adenoca = adenocarcinoma, Anaplastca =
anaplastic carcinoma, IPMN = intraductal papillary mucinous neoplasia
J Gastrointestin Liver Dis, June 2015 Vol. 24 No 2: 235-239
238
neuroendocrine adenocarcinoma appeared in single cases
[20]. An extensive sampling of such tumors is always necessary
to evaluate the origin in the ectopic tissue and exclude the
possibility of coincidental lesions. Up to date, there have been
only 14 cases of esophageal heterotopic pancreas in adults
reported in the literature with equal incidence between males
and females (Table II) [3-16]. Most patients suffered from
dysphagia and epigastric pain, sometimes accompanied
by signs of gastroesophageal reflux, nausea and rarely
hematemesis. In the vast majority of patients including our
case, the heterotopic tissue was located in the distal third of
the esophagus. Related congenital esophageal abnormalities,
sometimes found in children, are exceptional in adults [4]. In
our patient, chronic pancreatitis might be the reason for the
recent enlargement and escalation of symptoms. The described
finding of PanIN alerts to an increased risk of malignant
transformation [33-35], that has been so far reported only in
2 patients with esophageal heterotopic pancreas, once in the
form of ductal adenocarcinoma, once in the form of anaplastic
carcinoma (Table II).
Conclusion
Cases of heterotopic pancreas located in the wall of
the esophagus are extremely rare. Accurate preoperative
diagnosis is difficult and often incorrect and the lesion
is frequently misdiagnosed as a tumor. Treatment differs
according to the clinical course. Symptomatic lesions are
usually resected, which enables histopathological examination
of the specimen. Conservative treatment can be considered
in small asymptomatic lesions but always carries the risk of
underestimation regarding its nature and biological behavior.
The equal incidence of precancerous lesions in heterotopic and
orthotopic pancreas is a warning of the possibility of malignant
transformation, although it seems to be an exceptional event.
Considering all potential complications, we suggest that both
symptomatic and incidentally found asymptomatic lesions
should be resected.
Conflicts of interest: No conflict to declare.
Authors´ contribution: J.U., V.F., H.Sk. designed the report and
collected the patient´s clinical data; Z.K. performed the operation;
T.K. performed the preoperative assessment and diagnosis; D.Z. dealt
with the figures.
References
1. Wlaź J, Mądro A, Kaźmierak W, Celiński K, Słomka M. Pancreatic and
gastric heterotopy in the gastrointestinal tract. Postepy Hig Med Dosw
(Online) 2014; 68: 1069-1075.
2. Trifan A, Târcoveanu E, Danciu M, Huţanaşu C, Cojocariu C, Stanciu
C. Gastric heterotopic pancreas: an unusual case and review of the
literature. J Gastrointestin Liver Dis 2012; 21: 209-212.
3. Razi MD. Ectopic pancreatic tissue of esophagus with massive upper
gastrointestinal bleeding. Arch Surg 1966; 92: 101-104. doi: 10.1001/
archsurg.1966.01320190103024
J Gastrointestin Liver Dis, June 2015 Vol. 24 No 2: 235-239
Ulrych et al
4. Salo JA, Dlouhy M, Virtanen I. Congenital cyst and heterotopic
pancreatic tissue in the oesophagus. Ann Chir Gynaecol 1993; 82:
263-265.
5. Guillou L, Nordback P, Gerber C, Schneider RP. Ductal adenocarcinoma
arising in a heterotopic pancreas situated in a hiatal hernia. Arch Pathol
Lab Med 1994; 118: 568-571.
6. Noffsinger AE, Hyams DM, Fenoglio-Preiser CM. Esophageal
heterotopic pancreas presenting as an inflammatory mass. Dig Dis Sci
1995; 40: 2373-2379. doi: 10.1007/BF02063240
7. Roshe J, Del Buono E, Domenico D, Colturi TJ. Anaplastic carcinoma
arising in ectopic pancreas located in the distal esophagus. J Clin
Gastroenterol 1996; 22: 242-244.
8. Temes RT, Menen MJ, Davis MS, Pett SB Jr, Wernly JA. Heterotopic
pancreas of the esophagus masquerading as Boerhaave’s syndrome. Ann
Thorac Surg 2000; 69: 259-261. doi: 10.1016/S0003-4975(99)01223-0
9. Shalaby M, Kochman ML, Lichtenstein GR. Heterotopic pancreas
presenting as dysphagia. Am J Gastroenterol 2002; 97: 1046-1049. doi:
10.1111/j.1572-0241.2002.05627.x
10. Rodriguez FJ, Abraham SC, Allen MS, Sebo TJ. Fine-needle aspiration
cytology findings from a case of pancreatic heterotopia at the
gastroesophageal junction. Diagn Cytopathol 2004; 31: 175-179. doi:
10.1002/dc.20066
11. Gananadha S, Hunt DR. A unique case of pancreatitis and retention
cyst in esophageal heterotopic pancreas. Surg Laparosc Endosc Percutan
Tech 2005; 15: 345-347.
12. Goto J, Ohashi S, Okamura S, et al. Heterotopic pancreas in the
esophagus diagnosed by EUS-guided FNA. Gastrointest Endosc 2005;
62: 812-814. doi: 10.1016/j.gie.2005.04.031
13. Garn T, Hallenscheidt T, Schumacher B, Krämling HJ. Tumor of the
esophagocardiac junction. Chirurg 2011; 82: 447-449. doi: 10.1007/
s00104-010-1986-3
14. Crighton E, Botha A. Intraductal papillary mucinous neoplasm of the
oesophagus: an unusual case of dysphagia. Ann R Coll Surg Engl 2012;
94: e92-e94. doi: 10.1308/003588412X13171221589090
15. Lowry DM, Mack TE, Partridge BJ, Barbick BC, Marks RM, Kindelan JT.
Thorascopic resection of esophageal heterotopic pancreas. Ann Thorac
Surg 2013; 96: 1850-1851. doi: 10.1016/j.athoracsur.2013.02.061
16. Filip R, Walczak E, Huk J, Radzki RP, Bieńko M. Heterotopic pancreatic
tissue in the gastric cardia: a case report and literature review. World J
Gastroenterol 2014; 20: 16779-16781. doi: 10.3748/wjg.v20.i44.16779
17. St Romain P, Muehlebach G, Damjanov I, Fan F. Adenocarcinoma
arising in an ectopic mediastinal pancreas. Ann Diagn Pathol 2012;
16: 494-497. doi: 10.1016/j.anndiagpath.2011.04.005
18. Yan ML, Wang YD, Tian YF, Lin Y. Adenocarcinoma arising from
intrahepatic heterotopic pancreas: a case report and literature review.
World J Gastroenterol 2012; 18: 2881-2884. doi: 10.3748/wjg.v18.
i22.2881
19. Okasha HH, Al-Bassiouni F, El-Ela MA, Al-Gemeie EH, Ezzat R. A
retroperitoneal neuroendocrine tumor in ectopic pancreatic tissue.
Endosc Ultrasound 2013; 2: 168-170. doi: 10.7178/eus.06.0012
20. Goodarzi M, Rashid A, Maru D. Invasive ductal adenocarcinoma
arising from pancreatic heterotopia in rectum: case report and
review of literature. Hum Pathol 2010; 41: 1809-1813. doi: 10.1016/j.
humpath.2010.06.005
21. Jiang LX, Xu J, Wang XW, et al. Gastric outlet obstruction caused
by heterotopic pancreas: A case report and a quick review. World J
Gastroenterol 2008; 14: 6757-6759. doi: 10.3748/wjg.14.6757