Background: In contrast to mucinous cystic neoplasms of the pancreas, which are known to have considerable malignant potential, the serous variant is generally thought to be benign. There are, however, several reports of malignancy in serous cystic neoplasms of the pancreas. Aims: To assess the risk of malignancy of serous cystic tumors of the pancreas and to investigate specific clinical and histological features. Methods: Clinical and pathological characteristics of benign and malignant serous cystic neoplasms of the pancreas were investigated by a review of the literature and documented by a case of a serous cystadenocarcinoma and immunohistochemical analysis of a series of serous cystadenomas. Reviewing the literature prevalence, age and sex distribution of serous cystic neoplasms were analyzed. Results: The prevalence of cancer among serous cystic neoplasms reported since 1989 was 3%. Serous cystadenoma of the pancreas present at an earlier age (61 years) than serous cystadenocarcinoma (66 years; p = 0.056) and are symptomatic in the majority of patients.Pathological examination of the primary tumor was not able to distinguish cystadenoma from cystadenocarcinoma in 38% of cases. In 25% the diagnosis of cancer was established only after growth of metachronous metastases. In the present case, nuclear atypia, papillary structures, proliferation marker Ki-67 and p53 protein were increased in the primary tumor and/or metachronous metastasis. Conclusion: Serous cystic neoplasms of the pancreas do have malignant potential with a risk of malignancy of 3% and should be surgically treated if the operative risk is acceptable. Routine analysis of genetic and proliferation markers may improve diagnosis of malignancy in these tumors.

Keywords:
Pancreas, Serous cystadenoma, Serous cystadenocarcinoma
1.
Becker WF, Welsh A, Pratt HS: Cystadenoma and cystadenocarcinoma of the pancreas. Ann Surg 1965;161:845–860.
2.
ReMine SG, Frey D, Rossi RL: Cystic neoplasms of the pancreas. Arch Surg 1987;122:443–446.
3.
Klöppel G, Solcia E, Longnecker DS, Capella C, Sobin LH: Histological Typing of Tumors of the Exocrine Pancreas, ed 2. WHO International Histological Classification of Tumors. Berlin, Springer, 1996, pp 11–20.
4.
Solcia E, Capella C, Klöppel G: Tumors of the Pancreas; in Rosai J, Sobin LH (eds): Atlas of Tumor Pathology, 3rd series, fasc 20. Washington, Armed Forces Institute of Pathology, 1995.
5.
Zirinsky K, Abiri M, Baer JW: Computed tomography demonstration of pancreatic microcystic adenoma. Am J Gastroenterol 1984;79:139–142.
6.
George DH, Murphy F, Michalski R, Ulmer BG: Serous cystadenocarcinoma of the pancreas: A new entity? Am J Surg Pathol 1989;13:61–66.
7.
Schneider C, Reck T, Greskötter KR, Köckerling F, Gall FP: Cystic tumors of the pancreas. Langenbecks Arch Surg 1993;379:281–287.
8.
Grieshop NA, Wiebke EA, Kratzer SS, Madura JA: Cystic neoplasms of the pancreas. Am Surg 1994;60:509–515.
9.
Sarr MG, Kendrick ML, Nagorney DM, Thompson GB, Farley DR, Farnell MB: Cystic neoplasms of the pancreas: Benign to malignant epithelial neoplasms. Surg Clin North Am 2001;81:497–509.
10.
Le Borgne J, de Calan L, Partensky C: Cystadenomas and cystadenocarcinomas of the pancreas: A multi-institutional retrospective study of 398 cases. French Surgical Association. Ann Surg 1999;230:152–161.
11.
Strasberg SM, Belghiti J, Clavien PA, Gadzijev E, Garden JO, Lau WY, Makuuchi M, Strong RW: The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000;2:333–339.
12.
Lewandrowski KB, Southern JF, Pins MR, Compton CC, Warshaw AL: Cyst fluid analysis in the differential diagnosis of pancreatic cysts – A comparison of pseudo cysts, serous cystadenoma, mucinous cystic neoplasms and mucinous cystadenocarcinoma. Ann Surg 1993;217:41–47.
13.
Wagner M, Z`graggen K, Vagianos CE, Redaelli CA, Holzinger F, Sadowski C, Kulli C, Baer HU, Büchler MW: Pylorus-preserving total pancreatectomy. Dig Surg 2001;18:188–195.
14.
Friedmann HD: Nonmucinous, glycogen-poor cystadenocarcinoma of the pancreas. Arch Pathol Lab Med 1990;114:888–891.
15.
Kamei K, Funabiki T, Ochiai M, Amano H, Kasahara M, Sakamoto T: Multifocal pancreatic serous cystadenoma with atypical cells and focal perineural invasion. Int J Pancreatol 1991;10:161–172.
16.
Kamei K, Funabiki T, Ochiai M, Amano H, Marugami Y, Kasahara M, Sakamoto T: Some considerations on the biology of pancreatic serous cystadenoma. Int J Pancreatol 1992;11:97–104.
17.
Okada T, Nonami T, Miwa T, Yamada F, Ando K, Tatematsu A, Sugie S, Kondo T: Hepatic metastasis of serous cystadenocarcinoma resected 4 years after operation of the primary tumor: A case report (in Japanese). Jpn J Gastroenterol 1991;88:2719–2723.
18.
Yoshimi N, Sugie S, Tanaka T, Aijin W, Bunai Y, Tatematsu O, Mori H: A rare case of cystadenocarcinoma of the pancreas. Cancer 1992;69:2449–2453.
19.
Ohta T, Nagakawa T, Itho H, Fonseca L, Miyazaki I, Terada T: A case of serous cystadenoma of the pancreas with focal malignant changes. Int J Pancreatol 1993;14:283–289.
20.
Widmaier U, Mattfeldt T, Siech M, Beger HG: Serous cystadenocarcinoma of the pancreas. Int J Pancreatol 1996;20:135–139.
21.
Ishikawa T, Nakao A, Nomoto S, Hosono J, Harada A, Nonami T, Takagi H: Immunohistochemical and molecular biological studies of serous cystadenoma of the pancreas. Pancreas 1998;16:40–44.
22.
Siech M, Tripp K, Schmidt-Rohlfing B, Mattfeldt T, Widmaier U, Gansauge F, Görich J, Beger HG: Cystic tumors of the pancreas: Diagnostic accuracy, pathologic observations and surgical consequences. Langenbecks Arch Surg 1998;383:56–61.
23.
Eriguchi N, Aoyagi S, Nakayama T, Hara M, Miyazaki T, Kutami R, Jimi A: Serous cystadenocarcinoma of the pancreas with liver metastases. J Hepatobiliary Pancreat Surg 1998;5:467–470.
24.
Abe H, Kubota K, Mori M, Miki K, Minagawa M, Noie T, Kimura W, Makuuchi M: Serous cystadenoma of the pancreas with invasive growth: Benign or malignant? Am J Gastroenterol 1998;93:1963–1966.
25.
Schmidt-Rohlfing B, Siech M, Mattfeldt T, Schoenberg MH, Beger HG: Cystic neoplasms of the pancreas: Surgical treatment and outcome (in German). Z Gastroenterol 1998;36:939–945.
26.
Kimura W, Makuuchi M: Operative indications for cystic lesions of the pancreas with malignant potential – Our experience. Hepatogastroenterology 1999;46:483–491.
27.
Horvath K, Charbot JA: An aggressive resectional approach to cystic neoplasms of the pancreas. Am J Surg 1999;178:269–274.
28.
Wu CM, Fishman EK, Hruban RK, Schlott WD, Cameron JL: Serous cystic neoplasm involving the pancreas and liver: An unusual clinical entity. Abdom Imaging 1999;24:75–77.
29.
Warshaw AL, Compton CC, Lewandrowski KB, Cardenosa G, Mueller PR: Cystic tumors of the pancreas. New clinical, radiologic and pathologic observations in 67 patients. Ann Surg 1990;212:432–443.
30.
Yamaguchi K, Hirakata R, Kitamura K: Serous cystadenoma of the pancreas: Radiologic and clinicopathologic features in seven cases. Gastroenterol Jpn 1990;25:607–612.
31.
Pyke CM, van Heerden JA, Colby TV, Sarr MG, Weaver AL: The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic and surgical aspects. Ann Surg 1992;215:132–139.
32.
Egawa N, Maillet B, Schroder S, Mukai K, Klöppel G: Serous oligocystic and ill-demarcated adenoma of the pancreas: A variant of serous cystic adenoma. Virchows Arch 1994;424:13–17.
33.
Saint-Marseille S, Lapointe R, Roy A, Dagenais M, Gagnon J, Lavoie P: Cystic tumors of the pancreas: A propos of 36 cases (in French). Ann Chir 1994;48:697–702.
34.
Soyer P, Rabenandrasana A, Van Beers B, Barge J, Sibert A, Laissy JP, Achour E, Leyesque M: Cystic tumors of the pancreas: Dynamic CT studies. J Comput Assist Tomogr 1994;18:420–426.
35.
Levy M, Levy P, Hammel P, Zins M, Vilgrain V, Amouyal G, Amouyal P, Molas G, Flejou JF, Voitot H, et al: Diagnosis of cystadenomas and cystadenocarcinomas of the pancreas. Study of 35 cases. Gastroenterol Clin Biol 1995;19:189–196.
36.
Brenin DR, Talamonti MS, Yang EY, Sener SF, Haines GK, Joehl RJ, Nahrwold DL: Cystic neoplasms of the pancreas. A clinicopathologic study, including DNA flow cytometry. Arch Surg 1995;130:1048–1054.
37.
Zanow J, Gellert K, Benhidjeb T, Müller JM: Cystic tumors of the pancreas. Chirurg 1996;67:719–724.
38.
Fabiani A, Delia GJ, De Rosa R, Pombo MT, Molfino O, Ferraina P, Laffaye HA: Pancreatic serous cystadenomas. Report of 8 cases with a mean follow-up of 7 years. HPB Surg 1996;9:215–217.
39.
Procacci C, Graziani R, Bicego E, Bergamo-Andreis IA, Guarise A, Valdo M, Bogina G, Solarino U, Pistolesi GF: Serous cystadenoma of the pancreas: Report of 30 cases with emphasis on the imaging findings. J Comput Assist Tomogr 1997;21:373–382.
40.
Spitale LS, de la Fuente JL, Perez Gimenez PA, Saliba JA, Montenegro RB: Microcystic serous cystadenoma of pancreas. Clinicopathological and surgical features. Acta Gastroenterol Latinoam 1997;27:39–42.
41.
Bartsch D, Bastian D, Barth P, Schudy A, Nies C, Kisker O, Wagner HJ, Rothmund M: K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas. Ann Surg 1998;228:79–86.
42.
Carlson SK, Johnson CD, Brandt KR, Batts KP, Salomao DR: Pancreatic cystic neoplasms: The role and sensitivity of needle aspiration and biopsy. Abdom Imaging 1998;23:387–393.
43.
Martin I, Hammond P, Scott J, Redhead D, Carter DC, Garden OJ: Cystic tumours of the pancreas. Br J Surg 1998;85:1484–1486.
44.
Hashimoto L, Walsh RM, Vogt D, Henderson JM, Mayes J, Hermann R: Presentation and management of cystic neoplasms of the pancreas. J Gastrointest Surg 1998;2:504–508.
45.
Ooi LL, Ho GH, Chew SP, Low CH, Soo KC: Cystic tumours of the pancreas: A diagnostic dilemma. Aust NZ J Surg 1998;68:844–846.
46.
Nagel M, Dobrowolski F, Bunk A, Saeger HD: Serous cystadenoma of the pancreas. Chirurg 2000;71:424–428.
47.
Curry CA, Eng J, Horton KM, Urban B, Siegelman S, Kuszyk BS, Fishman EK: CT of primary cystic pancreatic neoplasms: Can CT be used for patient triage and treatment? AJR Am J Roentgenol 2000;175:99–103.
48.
Colovic R, Bilanovic D, Milicevic M, Barisic G: Cystadenomas of the pancreas. Acta Chir Iugosl 1999;46:39–42.
49.
Sperti C, Pasquali C, Perasole A, Liessi G, Pedrazzoli S: Macrocystic serous cystadenoma of the pancreas: Clinicopathologic features in seven cases. Int J Pancreatol 2000;28:1–7.
50.
Compton CC: Serous cystic tumors of the pancreas. Semin Diagn Pathol 2000;17:43–55.
51.
Klöppel G, Kosmahl M: Cystic lesions and neoplasms of the pancreas. Pancreatology 2001;1:648–655.
52.
Büchler MW, Friess H, Wagner M, Kulli C, Wagener V, Z’graggen K: Pancreatic fistula after pancreatic head resection. Br J Surg 2000;87:950–956.
53.
Scott J, Martin I, Redhead D, Hammond P, Garden OJ: Mucinous cystic neoplasms of the pancreas: Imaging features and diagnostic difficulties. Clin Radiol 2000;55:187–192.
54.
Sand JA, Hyoty MK, Mattila J, Dragorn JC, Nordback IH: Clinical assessment compared with cyst fluid analysis in the differential diagnosis of cystic lesions of the pancreas. Surgery 1996;119:275–280.
55.
Talamini MA, Pitt HA, Hruban RH, Boitnott JK, Coleman J, Cameron JL: Spectrum of cystic tumors of the pancreas. Am J Surg 1992;163:117–124.
56.
Brandwein SL, Farrell JJ, Centeno BA, Brugge WR: Detection and tumor staging of malignancy in cystic, intraductal and solid tumors of the pancreas by EUS. Gastrointest Endosc 2001;53:722–727.
57.
Jimenez RE, Warshaw AL, Z`graggen K, Hartwig W, Taylor DZ, Compton CC, Fernandez-del Castillo C: Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy. Ann Surg 1999;230:501–511.
58.
Z’graggen K, Rivera JA, Compton CC, Pins M, Werner J, Fernandez-del Castillo C, Rustgi AK, Warshaw AL: Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Ann Surg 1997;226:491–500.
59.
Kawahira H, Kobayashi S, Kaneko K, Asano T, Ochiai T: p53 protein expression in intraductal papillary mucinous tumors of the pancreas as an indicator of tumor malignancy. Hepatogastroenterology 2000;47:973–977.
60.
Iacobuzio-Donahue CA, Wilentz RE, Argani P, Yeo CJ, Cameron JL, Kern SE, Hruban RH: DPC4 protein in mucinous cystic neoplasms of the pancreas: Frequent loss of expression in invasive carcinomas suggests a role in genetic progression. Am J Surg Pathol 2000;24:1544–1549.
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