Anatomic Pathology / PANCREATIC ACINAR CELL CYSTADENOMA
Unilocular Acinar Cell Cystadenoma of the Pancreas
An Unusual Acinar Cell Tumor
Denis Chatelain, MD,1 François Paye, MD,2 Najat Mourra, MD,1 Jean-Yves Scoazec, MD, PhD,3
Marielle Baudrimont, MD,1 Rolland Parc, MD, PhD,2 and Jean-François Flejou, MD, PhD1
Key Words: Pancreatic neoplasm; Acinar cell tumor; Acinar cell cystadenoma; Cystadenoma
Abstract
We report an unusual case of acinar cell
cystadenoma of the pancreas in a 52-year-old man
treated for pulmonary adenocarcinoma. The lesion,
located in the body of the pancreas, was revealed
incidentally by abdominal computed tomography
during follow-up for a pulmonary neoplasm. A left
pancreatectomy was performed. The unilocular cystic
lesion measured 5 cm and was lined by a single layer
of columnar acinar cells with eosinophilic granular
cytoplasm, faintly stained by periodic acid–Schiff.
Immunohistochemical analysis showed the lining cells
were positive for cytokeratin and trypsin, and
electronic microscopy showed that they contained
zymogen granules.
Acinar cell tumors of the pancreas are rare and
include acinar cell carcinomas, acinar cell
cystadenocarcinomas, and acinar cell adenomas. We
report a case of cystic acinar cell tumor of the pancreas
with benign gross and histologic features that could be
added to the list of cystic neoplasms of the pancreas as
acinar cell cystadenoma.
Cystic lesions of the pancreas mostly consist of pseudocysts, which account for 75% to 90% of all pancreatic cysts.1,2
Cystic neoplasms are rare and include a heterogeneous group
of benign and malignant tumors represented mainly by mucinous tumors and serous cystadenomas.2 We report an unusual
case of a benign unilocular cystic tumor of the pancreas lined
by acinar cells in a 52-year-old man. To the best of our knowledge, this tumor has not been reported before.
Case Report
A 52-year-old man treated by radiotherapy and
chemotherapy for pulmonary adenocarcinoma had a unilocular
cystic lesion of the body of the pancreas. It was diagnosed fortuitously in 1999 during the initial follow-up for the pulmonary
neoplasm. At that time, the hypodense cyst measured 16 mm on
computed tomography. For 1 year, the patient complained of
abdominal pain that radiated to the back; the pain was treated
with morphine. In August 2000, the computed tomography scan
showed a hypodense unilocular cystic lesion of the pancreas
measuring 50 mm ❚Image 1❚. The diagnosis of a mucinous cystic
tumor of the pancreas was suspected. A left pancreatectomy was
performed, owing to the symptoms of the patient.
Materials and Methods
The surgical specimen was fixed in 10% neutralbuffered formalin. The whole cyst was entirely submitted
to histologic examination, and the samples were embedded
in paraffin. Consecutive 3-µm sections were cut and
stained with H&E-safran, periodic acid–Shiff (PAS), and
alcian blue, pH 2.5. An immunohistochemical study using
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with small, nodular, whitish, fibrous foci ❚Image 2❚. The
remaining pancreas was apparently normal. The spleen
weighed 200 g and had a normal gross appearance.
Microscopic Findings
The unilocular cyst was lined by a single layer of
columnar cells with eosinophilic granular cytoplasm ❚Image
3❚ . Their nuclei were regular and basally located and
contained small nucleoli without mitosis. There was no solid
tumorous component composed of sheets and ribbons of
acinar cells. The epithelium was eroded focally with fibrous
changes of the cyst wall. It was not connected to pancreatic
ducts or to pancreatic acini. There was no pseudo-ovarian
change in the underlying connective tissue. The rest of the
pancreatic parenchyma and the spleen were normal.
❚Image 1❚ Hypodense unilocular cyst of the body of the pancreas
(arrow) shown by abdominal computed tomography scan.
the avidin-biotin-peroxidase complex was performed with a
panel of antibodies: anticytokeratin (KL1, Immunotech,
Marseille, France; dilution, 1:50), cytokeratin (CK) 7 (clone
OV-TL 12/30, DAKO, Glostrup, Denmark; dilution, 1:50),
CK20 (clone Ks 20.8, DAKO; dilution, 1:25), CK19 (clone
RCK108, DAKO; dilution, 1:50), MUC-1 glycoprotein
(clone Ma695, Novocastra, Newcastle upon Tyne, England;
dilution, 1:200), MUC-2 (clone CCP58, BioGenex, San
Ramon, CA; dilution, 1:100), anti–carcinoembryonic antigen
(polyclonal, DAKO; dilution, 1:400), anti–chromogranin A
(clone LK2H10, Immunotech; prediluted), antisynaptophysin (clone Sy38, Chemicon, Temecula, CA; dilution,
1:10), anti–alpha 1 -antichymotrypsin (clone HA092-5p,
BioGenex; prediluted), and antitrypsin (Bioadvance,
Emerainville, France; dilution, 1:100).
Small slices of formalin-fixed tissue were postfixed in
1% osmium tetroxide in 0.1 L of cacodylate buffer and
embedded in epoxy resin. The sections were stained with 1%
toluidine blue and examined by light microscopy to isolate
appropriate areas for ultramicrotomy. Some ultrathin
sections were stained with uranyl acetate and examined
under an electron microscope (Zeiss EM10, Le Pec, France).
Results
Gross Appearance
The surgical resection comprised the spleen and some
part of the body and the tail of the pancreas and measured 10
cm. It comprised a unilocular cystic lesion localized to the
lower edge of the body of the pancreas. The cyst measured 5
cm and contained a clear fluid. It had a thin translucent wall
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Histochemical and Immunohistochemical Findings
The columnar cells were faintly stained by PAS with a
granular apical pattern and were positive for KL1, alpha1antichymotrypsin, and trypsin immunohistochemical stains
❚Image 4❚. No cell expressed CK7, CK19, CK20, MUC1,
MUC2, chromogranin, synaptophysin, or carcinoembryonic
antigen. No cell was stained with alcian blue.
Electron Microscopic Findings
On semithin sections, there were dark granules at the
apical pole of the cylindrical cells in the lining epithelium of
the cyst. Electron microscopy showed that these cells
contained rough endoplasmic reticulum and mitochondria in
their basal part and round electron-dense granules oriented
toward the apical cytoplasm ❚Image 5❚ . These granules
measured from 200 to 800 nm, and their appearance was
consistent with that of normal pancreatic zymogen granules.
The slides of the lung tumor were reviewed and corresponded to a well-differentiated adenocarcinoma with no acinar
cell component. The postoperative evolution was unremarkable.
No recurrence was observed in 18 months of follow-up.
Discussion
We report an unusual case of a cystic lesion of the
pancreas lined by acinar cells, consistent with the diagnosis
of acinar cell cystadenoma.
The acinar cell tumors of the pancreas are rare and include
acinar cell carcinomas, acinar cell cystadenocarcinomas, and
acinar cell adenomas.3 All acinar cell tumors are composed of
typical round or cylindrical cells with eosinophilic PAS-positive cytoplasmic granules. In immunohistochemical analysis,
these cells express pancreatic enzymes (trypsin, lipase,
chymotrypsin, phospholipase A2, alpha-amylase), and electron
microscopy shows that they contain zymogen granules.3 To
© American Society for Clinical Pathology
Anatomic Pathology / CASE REPORT
❚Image 2❚ Unilocular cyst of the lower edge of the body of
the pancreas with small, whitish, fibrous foci in the cyst wall.
❚Image 3❚ Cyst wall lined by a single layer of columnar cells with
eosinophilic granular cytoplasm (H&E-safran, ×100). Inset: lining
acinar cylindrical cells with basal nuclei (H&E-safran, ×400).
❚Image 4❚ Immunohistochemical analysis revealed the lining
cells are positive for trypsin (antitrypsin antibody) (×100).
❚Image 5❚ Electron microscopy revealed dark granules at the
apical part of the cytoplasm in the cylindrical cells (×11,000).
the best of our knowledge, no unilocular acinar cell cystadenoma of the pancreas has been reported in the literature. Ooi et
al,4 in their series of cystic tumors of the pancreas, reported a
case of a cystic acinar cell tumor treated by distal pancreatectomy, but neither gross nor microscopic description of the
tumor was given.
Acinar cell carcinoma is an uncommon malignant tumor
accounting for 1% to 2% of all exocrine pancreatic
neoplasms.5 Gross examination reveals the tumors to be
usually solid, well-circumscribed, yellowish brown, nodular
masses. The microscopic examination reveals that acinar cell
carcinomas are made up of cords and lobules of acinar cells
with variable nuclear atypia and mitotic activity.5 Cystic
changes in solid acinar cell carcinoma are rare events; only a
few cases are reported in the literature.6,7
Acinar cell cystadenocarcinoma is a rare multicystic
lesion of the pancreas; only 3 cases are reported in the literature.8-11 Gross examination reveals acinar cystadenocarcinomas to be large, multilocular, cystic tumors localized in the
body or the tail of the pancreas. They have a spongy appearance, sometimes with a microcystic pattern.9,10 The cysts are
separated by large fibrous septa and contain clear fluid. There
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are some rare solid areas, and foci of necrosis and hemorrhage also can be present.9,10 Microscopically, the cysts
measure from 1 mm to 7 cm. They can be closely packed, and
there are minimal solid regions between the cystic spaces.
The cysts are lined by a single layer of cuboidal or columnar
cells, the cytoplasm of which displays the characteristic
features of acinar cells.8-11 Nuclear atypia and mitotic activity
are weak. The prognoses of acinar cell cystadenocarcinoma
and usual acinar cell carcinoma seem similar.11
Acinar adenoma is a rare benign tumor of the pancreas.12
Gross examination reveals it to be a solid and well-delimited
tumor without cystic changes. It is difficult to distinguish
acinar adenomas from carcinomas.12 The absence of necrosis,
mitotic activity, angioinvasion, and the encapsulation of the
tumor could be criteria for benignity.12 Some authors have
doubt about the existence of this tumor and consider that it
could be acinar cell carcinoma of low-grade malignancy.3
They suggest that the diagnosis of acinar cell adenoma should
be restricted to cases without morphologic indications of
malignancy after at least a 5-year follow-up.3 Acinar cell
adenomas can appear spontaneously in MRC-Wistar rats, and
this type of neoplasm has been reported in dogs, oxen, and
cats.13 In rats, a fundusectomy inducing hypergastrinemia,
pancreaticobiliary diversion, and some chemical agents, such
as azaserine, 4-hydroxyaminoquinoline 1-oxide, Ndelta-(Nmethyl-nitrosocarbamyl)- L -ornithine, induce pancreatic
neoplasms of the acinar cell type, described as atypical acinar
cell nodules.14 Similar lesions can be found incidentally in
humans.15 The sections of the pancreas show multiple, welldemarcated nodular lesions of acinar cells without capsules
and no compression of the surrounding tissue. They vary in
size from 100 to 1,100 µm and are composed of cells with
eosinophilic or basophilic cytoplasm but without cellular
atypia or mitosis.15 It is difficult to determine whether atypical
acinar cell nodules of the pancreas are a nonneoplastic change,
considered as a degenerative lesion of the pancreas,3 or a
preneoplastic condition involved in the pathogenesis of acinar
cell carcinoma, as the nodules have been noted in rats exposed
to asazerine.15 Those lesions were not present in our case, and
the patient had not been exposed to chemical or toxic agents.
The acinar cystic transformation of the pancreas is a new
entity, consisting of unilocular or multilocular cystic changes of
the pancreas.1 The lesion is composed of cysts measuring from
1 to 10 cm, developed in the whole pancreas. These cysts are
lined by normal or flattened acinar cells with no atypia.1 They
sometimes are connected to normal acini of the pancreatic
parenchyma. The neoplastic or dystrophic nature of this lesion
remains unclear. The cystic lesion we report has some features
in common with a unilocular acinar cystic transformation of the
pancreas. But in our case, the cyst was not connected to normal
pancreatic acini and had grown for several months; therefore,
we prefer to consider it a cystic tumor. This lesion had benign
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gross and histologic features. It was well-demarcated, did not
infiltrate the pancreatic parenchyma, and was lined by regular
acinar cells without atypia or solid component. It could be
considered the cystic counterpart of acinar cell adenoma.
However, the follow-up of the patient is too short to strictly
affirm that it really is a benign cystic tumor of the pancreas.
We report an unusual cystic lesion of the pancreas
consistent with the diagnosis of acinar cell cystadenoma.
This lesion can be added to the list of unilocular cystic
neoplasms of the pancreas.
From the 1Anatomic Pathology Department and 2Digestive Surgery
Department, St Antoine Hospital, Paris; and the 3Anatomic
Pathology Service, Edouard Herriot Hospital, Lyon, France.
Address reprint requests to Dr Flejou: Service d’Anatomie
Pathologique, Hôpital Saint-Antoine, 184 rue du Faubourg SaintAntoine, F-75571 Paris Cedex 12, France.
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© American Society for Clinical Pathology