Ductal Adenocarcinoma of the Pancrea

Nobuyuki Ohike
1
, Masashi Sato
1
, Masaaki Kawahara
2
, Sho Ohyama
3
, Toshio Morohoshi
1
Departments of
1
Pathology,
2
Radiology, and
3
General and Gastroenterological Surgery,
Showa University School of Medicine. Tokyo, Japan
ABSTRACT
Context Calcification is extremely rare in
pancreatic ductal adenocarcinomas, but we
may sometimes encounter focal dystrophic
calcification.
Case report We herein report the case of an
83-year-old female with pancreatic ductal
adenocarcinoma associated with diffuse
psammomatous calcification. The calcification
was preoperatively detected by computed
tomography. Numerous psammoma bodies
were scattered throughout the tumor.
Immunohistochemical positivity of osteopontin,
a non-collagenous bone-related protein, was
found in the psammoma bodies.
Conclusions The possibility of pancreatic
ductal adenocarcinoma should therefore be
considered for a localized calcified lesion in
the pancreas. Therefore, osteopontin may play
a significant role in the development of
psammoma bodies. Studies to elucidate the
prognostic significance of psammoma bodies
in pancreatic ductal adenocarcinomas are
therefore recommended.
INTRODUCTION
In pancreatic disease, calcification is not
uncommon in chronic pancreatitis,
pseudocysts, serous cystic neoplasms,
mucinous cystic or non-cystic neoplasms,
solid-pseudopapillary
neoplasms,
and
endocrine tumors, but it is extremely rare in
ductal adenocarcinoma [1, 2].
We herein describe a case of pancreatic ductal
adenocarcinoma (PDAC) with diffuse
psammomatous calcification which was
preoperatively detected by computed
tomography.
CASE REPORT
Clinical Summary
An 83-year-old female was admitted to
Showa University Hospital for a detailed
evaluation of abdominal pain and
hyperamylasemia. She had been suffering
from diabetes and asthma for approximately
40 years. The results of her physical
examination were normal. Her laboratory data
were within the normal limits except for a
mildly elevated amylase level of 376 IU/L
(reference range: 40-160 IU/L). Her serum
calcium level was normal. Computed
tomography (CT) of the abdomen did not
reveal a tumor mass, but it did show a
calcified hyperdense area in the uncinate
process of the pancreas with dilated main
pancreatic and common bile ducts (Figure 1).
Coronal T2-weighted magnetic resonance
imaging showed a filling defect in the main
pancreatic and common bile ducts which was
accompanied by the dilatation of each distal
duct (Figure 2). Magnetic resonance
cholangiopancreatography also showed the
dilatation of the main pancreatic and the
common bile ducts with a filling defect

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336
(Figure 3). Bile juice cytology revealed
malignant cells which were suggestive of
adenocarcinoma. With a diagnosis of cancer
of the head of the pancreas, a pylorus-
preserving pancreaticoduodenectomy was
thus performed. No recurrence has since been
clinically observed during a 5-month
postoperative follow-up.
Pathological Findings
A whitish invasive tumor, measuring 1.5 cm
in diameter, was observed in the head of the
pancreas. The tumor invaded the
intrapancreatic portion of the common bile
duct and caused obstruction of the main
pancreatic duct; each distal duct was dilated.
Histologically, the tumor consisted of a
moderately to poorly differentiated invasive
tubular adenocarcinoma. In addition,
numerous psammoma bodies positive for von
Kossa stain were scattered throughout the
tumor (Figure 4). Some of the psammoma
bodies were found in the lumen of the tumor
glands and others in the stroma. The
localization of the psammoma bodies
appeared to correspond to the distribution of
the infiltrating cancer cells. There were co-
existing intraductal neoplastic changes
(PanINs), but they were not associated with
the psammoma bodies. The calcification was
localized in the tumor, and was not found in
the surrounding pancreatic tissue. The cancer
cells showed scirrhous and ill-demarcated
invasion, as do most PDACs, but no lymph
node metastases were found, and the surgical
margins were free of any tumor.
Immunohistochemically, the tumor cells were
positive for CK7, MUC1, CA 19-9 (weak),
CEA and p53, and negative for MUC2 and
chromogranin A. A strong positivity for
osteopontin was found in the psammoma
bodies, but not in the tumor cells or
macrophages.
Figure 1. Computed tomography shows a calcified
hyperdense area in the uncinate process of the pancreas
with dilated main pancreatic (arrow) and common bile
ducts (arrowhead).
Figure 2. Coronal T2-weighted magnetic resonance
imaging shows a filling defect in the main pancreatic
(right, arrow) and common bile (left, arrow) ducts
which is accompanied by the dilatation of each distal
duct.
Figure 3. Magnetic resonance cholangiopancreatography
shows the dilatation of the main pancreatic and
common bile ducts with a filling defect (arrow).
Figure 4. Histological finding of tubular adenocarcinoma
of the pancreas shows psammoma bodies positive for
von Kossa stain in the lumen of the tumor glands.

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337
DISCUSSION
Calcification is extremely rare in PDACs [1,
2] and, hence, is not typically characteristic of
PDAC. However, we may sometimes
encounter focal amorphous dystrophic
calcification in mucin pools, necrotic areas or
stroma within tumors, and there have also
been some case reports of PDACs with such
calcification [1, 2]. Eelkema et al. reported
calcification to be present in 2% of the
PDACs studied by CT [3]. In the present case,
a unique psammomatous calcification was
observed throughout the tumor. Psammoma
bodies are characterized by the formation of
multiple, discrete, concentrically laminated,
and calcareous bodies, and they are normally
found in various neoplastic and non-
neoplastic lesions. In neoplasms of the
gastrointestinal tract and pancreatobiliary
system, they are observed in small numbers of
gastric, colonic, and cholangiocellular
adenocarcinomas [4, 5, 6] and frequently in
duodenal carcinoids but, to our knowledge,
there have so far been no reports to date on
their occurrence in PDACs.
The mechanism and etiology of psam-
momatous calcification remain controversial,
but one hypothesis is that psammoma bodies
arise due to the secondary accumulation of
hydroxyapatite in cells undergoing degener-
ation. The concentrations of calcium and
phosphate in the extracellular fluid are usually
too low to initiate hydroxyapatite formation.
However, after a crystal nidus is formed, a
large calcified mass with lamination can
develop [4]. In addition, there have been
reports that osteopontin, a non-collagenous
bone-related protein produced by tumor-
associated macrophages, plays a significant
role in the development of the psammoma
bodies [7, 8]. In the present tumor, from the
distribution of the psammoma bodies, they
indeed appeared to originate from the necrotic
or degenerating tumor cells (with somewhat
mucous secretions). In addition, the
immunohistochemical study of osteopontin
showed a strong expression in only
psammoma bodies. These findings indicate
that osteopontin may be produced and then
promptly secreted by macrophages which are
then subsequently translocated to the
degenerated tumor cells, as described in
previous reports [7]. Therefore, the deposited
osteopontin protein may play a critical role in
the following deposition of calcium phosphate
which therefore results in the development of
the psammoma bodies.
In this case, on imaging, the differential
diagnosis included not only other types of
solid tumors with calcification, but also
localized calcifying pancreatitis and
choledocholithiasis. In the present case, a
mass lesion was not detected by CT, although
it was shown by magnetic resonance imaging
as a filling defect in the main pancreatic and
the common bile ducts. Actually, the
definitive diagnosis of PDAC was difficult to
establish without a cytologic examination.
This case, therefore, suggests that the
possibility of a PDAC, and various
approaches for its diagnosis, should be taken
into consideration for a localized calcified
lesion even if a tumor mass is not detected on
imaging findings.
The prognostic significance of psammoma
bodies in PDACs is unclear but, in our case, a
radical cure was expected because of the
T3N0M0R0 status in the TNM classification.
In addition, the more the psammoma bodies
are microscopically noted, the lower the
number of viable tumor cells. In addition,
ovarian serous psammocarcinomas have been
reported to have a more favorable prognosis
than the more common serous carcinomas [9].
In order to clarify and confirm the above
findings, more studies involving similar cases
of PDACs are required.
Received February 21
st
, 2008 - Accepted
March 25
th
, 2008
Keywords Adenocarcinoma; Calcinosis;
Osteopontin; Pancreas; Tomography, X-Ray
Computed
Abbreviations PDAC: pancreatic ductal
adenocarcinoma
Conflict of interest The authors have no
potential conflicts of interest

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JOP. J Pancreas (Online) 2008; 9(3):335-338.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 9, No. 3 - May 2008. [ISSN 1590-8577]
338
Correspondence
Nobuyuki Ohike
First Department of Pathology
Showa University School of Medicine
1-5-8 Hatanodai, Shinagawa-ku
Tokyo 142-8555
Japan
Phone: +81-3.3784.8119
Fax: +81-3.3784.8249
E-mail: ohike@med.showa-u.ac.jp
Document URL: http://www.joplink.net/prev/200805/17.html
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