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 © American Society for Clinical Pathology Am J Clin Pathol 2002;118:211-214 211 Chatelain et al / PANCREATIC ACINAR CELL CYSTADENOMA 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 212 Am J Clin Pathol 2002;118:211-214 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 © American Society for Clinical Pathology Am J Clin Pathol 2002;118:211-214 213 Chatelain et al / PANCREATIC ACINAR CELL CYSTADENOMA 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 214 Am J Clin Pathol 2002;118:211-214 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. References 1. Klöppel G. Pseudocysts and other non-neoplastic cysts of the pancreas. Semin Diagn Pathol. 2000;17:7-15. 2. Fernandes-del Castillo C, Warshaw AL. Cystic tumors of the pancreas. Surg Clin North Am. 1995;5:1001-1016. 3. Solcia E, Capella C, Klöppel G. Tumors of the Pancreas. Washington, DC: Armed Forces Institute of Pathology; 1997:103-114. Atlas of Tumor Pathology, 3rd Series, Fascicle 20. 4. Ooi LLPJ, Ho GH, Chew SP, et al. Cystic tumours of the pancreas: a diagnostic dilemma. Aust N Z J Surg. 1998;68:844-846. 5. Klimstra DS, Heffess CS, Oertel JE, et al. Acinar cell carcinoma of the pancreas: a clinicopathologic study of 28 cases. Am J Surg Pathol. 1992;16:815-837. 6. Joubert M, Fiche M, Hamy A, et al. Carcinome à cellules acineuses pancréatique d’allure kystique, envahissant le canal de Wirsung. Gastroenterol Clin Biol. 1998;22:465-468. 7. Ishizaki A, Koito K, Namieno T, et al. Acinar cell carcinoma of the pancreas: a rare case of an alpha-fetoprotein–producing cystic tumor. Eur J Radiol. 1995;21:58-60. 8. Hoorens A, Lemoine NR, McLellan E, et al. Pancreatic acinar cell carcinoma: an analysis of cell lineage markers, p53 expression and Ki-ras mutation. Am J Pathol. 1993;143:685-698. 9. Cantrell BB, Cubilla AL, Erlandson RA, et al. Acinar cell cystadenocarcinoma of human pancreas. Cancer. 1981;47:410-416. 10. Stamm B, Burger H, Hollinger A. Acinar cell cystadenocarcinoma of the pancreas. Cancer. 1987;60:2542-2547. 11. Adsay NV, Klimstra DS. Cystic forms of typically solid pancreatic tumors. Semin Diagn Pathol. 2000;17:81-88. 12. Lack EE, Levey R, Cassady JR, et al. Tumors of the exocrine pancreas in children and adolescents: a clinical and pathologic study of eight cases. Am J Surg Pathol. 1983;7:319-327. 13. Love L, Pelfrene A, Garcia H. Acinar adenomas of the pancreas in MRC-Wistar rats. J Comp Pathol. 1977;87:307-310. 14. Shirai T, Nakamura A, Wada S, et al. Pancreatic acinar cell tumors in rats induced by 3,2'-dimethyl-4-aminobiphenyl. Carcinogenesis. 1989;10:1127-1130. 15. Shinozuka H, Lee RE, Dunn JL, et al. Multiple atypical acinar cell nodules of the pancreas. Hum Pathol. 1980;11:389-391. © American Society for Clinical Pathology
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