Serous oligocystic adenoma of the pancreas

Case Report Pancreatology 2003;3:482–486 DOI: 10.1159/000075579 Published online: December 11, 2003 Serous Oligocystic Adenoma of the Pancreas José Eduardo M. Cunha a Marcos Vinicius Perini a Sheila Aparecida C. Siqueira b José Jukemura a Sonia Penteado a Marcel C.C. Machado c Emilio E. Abdo a André Luis Montagnini a Departments of a Gastroenterology, Surgical Division, b Pathology and c Surgery, São Paulo University Medical School, São Paulo, Brazil Key Words Pancreatic cystic tumors W Oligocystic pancreatic adenoma W Serous macrocystic adenoma W Immunohistochemistry W Pancreatoduodenectomy Abstract Cystic neoplasms of the pancreas are uncommon lesions but are becoming increasingly prevalent. Herein we report a case of an oligolocular cystic lesion in the head of the pancreas in a young female that had undergone a cystenteroanastomosis 10 years ago. She underwent a duodenopancreatectomy with an uneventful recovery. The histology showed a serous oligocystic adenoma of the pancreas and the immunohistochemistry study confirmed the diagnosis. There is no sign of recurrence after the surgery. The role of pre-operative diagnosis based on tomographic, echoendoscopy and fine needle aspiration are discussed. Copyright © 2003 S. Karger AG, Basel Introduction While pancreatic pseudocyst is the most common pancreatic cystic lesion, cystic neoplasms are responsible for only 10% of the cystic lesions of the pancreas [1]. ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2003 S. Karger AG, Basel 1424–3903/03/0036–0482$19.50/0 Accessible online at: www.karger.com/pan Primary pancreatic cysts are rare and classified as serous and mucinous [2, 3]. The real incidence of the serous and mucinous cystadenomas of the pancreas is still a matter of debate. Reported incidences of mucinous cystic lesions vary among authors [1, 4–6]. Serous cystic adenomas are usually benign whereas mucinous cystadenomas are considered malignant or with the potentiality of malignant transformation [2–4]. A newly recognized entity, the intraductal papillary mucinous neoplasm (IPMN), also classified as a cystic neoplasm, is characterized by intraductal proliferation of mucin-producing cells, which are arranged in a papillary pattern [6]. The main characteristic of IPMN, which differentiates this tumor from both serous and mucinous cystic tumors, is its evident communication with the main pancreatic duct not found in the other two neoplasms. The serous cystadenoma (SCA) is a rare benign pancreatic neoplasm. The most common variety of SCA is the serous microcystic adenoma (SMA) which is formed by small cysts filled with a clear watery fluid rich in glycogen and lined by cuboid epithelial cells disposed in a single layer. The other, much less common variant of SCA is the serous oligocystic adenoma (SOA) which has fewer but much larger cysts histologically similar to SMA [7, 8]. We report herein the clinicophatological imaging and immunohistochemical findings of a patient with oligocyst serous pancreatic adenomas in the head of the pancreas. José Eduardo Monteiro Cunha Department of Gastroenterology, Surgical Division São Paulo University Medical School, Rua Oquirá 116 05467-030 São Paulo S.P. (Brazil) Tel. +55 11 3082 8832, Fax +55 11 3083 7720, E-Mail jemcunha@yahoo.com Fig. 1. Preoperative computed tomography scan demonstrates a large cyst at the head of the pancreas and two smaller adjacent cysts (black arrow). Case Report A 36-year-old female was admitted to our surgical unit with a history of episodes of abdominal pain and vomiting for the last 8 years and a palpable abdominal mass. On no occasion an episode of acute pancreatitis could be characterized. She had been submitted, 10 years before at another institution, to a cystenterostomy with the diagnosis of a pancreatic pseudocyst but, apparently, without a biopsy of the cyst wall. The records of that hospital admission could not be recovered but, according to the patient, she had had an uneventful postoperative course. Symptoms recurred 2 years after this procedure. She denied weight loss or familiar history of gastro-intestinal malignancy. Physical examination revealed a painless and soft abdominal mass measuring 20 ! 20 cm in the mesogastrium. No signs of Von Hippel-Lindau disease were found. Helical CT scan showed a cystic mass at the head of the pancreas with 20 cm in diameter and two other adjacent cysts sized 8 cm each (fig. 1). The larger cyst compressed the gastric wall; there was no radiological evidence of lymph node enlargement. Because of the size of the tumor and the intensity of symptoms, surgical intervention was indicated. At operation a large cystic tumor and two smaller adjacent cysts were found at the head of the pancreas. The site of the cystenterostomy performed at the first operation could be identified on the cystic tumor wall (fig. 2). A pyloruspreserving pancreatoduodenectomy was performed associated with the resection of the previously done cystojejunostomy. The reconstruction of the alimentary tract was accomplished by using two separate jejunal limbs, one for the pancreato-jejunostomy and another for the biliary jejunostomy [9]. The pathological specimen showed a large cyst of the pancreatic head, measuring 13 ! 12 cm; the cut surface revealed few cysts filled with serous fluid (fig. 3A). Histopathological studies demonstrated cysts lined by a single layer of cuboid or flattened epithelial cells, Oligocystic Adenoma of the Pancreas Fig. 2. Intraoperative findings: cystic neoplasia (arrow) with pre- viously performed cystojejunostomy (arrowhead). characteristic of a SOA. The cell cytoplasm was pale to clear and the nucleus was round to oval, centrally located. Occasionally the tumor cells formed intracystic papillary projections. The stroma separating the cysts was thin with occasional hyaline areas. The tumor tissue was well demarcated and adjacent pancreatic parenchyma showed acinar atrophy and fibrosis (fig. 3B). The immunohistochemical study was positive for the expression of cytokeratin 7, CA 19-9 and Ki67 (index ! 1%) and negative for cytokeratin 20, polyclonal CEA, chromogranin, synaptophysin, Ca125 and p53. Discussion Macrocystic serous adenoma of the pancreas is a rare neoplasm. Its preoperative diagnosis by physical examination and imaging studies is challenging, if not impossible. Some cases of pancreatic cysts do not fit in the traditional classification of Compagno and Oertel [2, 3]. Lewandrowski et al. [10] proposed the term SCA instead of microcystic adenoma, to define all benign cystic lesions of the pancreas and not just the cysts !2 cm in diameter as proposed by Compagno. According to the World Health Organization Classification of Tumors [7] the term SOA includes the macrocystic serous cystadenoma, the serous oligocystic, the illdefined oligocystic adenoma (SOIA) [10–12] and some cystadenomas observed in children [13]. The solid variant of SCA that shows cytology and immune histochemical Pancreatology 2003;3:482–486 483 Fig. 3. A Gross photograph of the surgical specimen, cut surface reveals cysts filled with serous fluid material. B Microphotograph of the cyst wall showing a well demarcated adjacent pancreatic parenchyma with acinar atrophy and fibrosis. studies equal to cystic lesions has been described but remains to be established as a separate disease entity [14]. Microcystic adenomas and the SOA are composed of the same cell type, characterized by glycogen-rich cytoplasm and a ductal immunoprofile [2, 11]. In fact they represent macroscopic morphologic variants of the same benign pancreatic neoplasm as the SCA [10]. To date there are about 43 cases of SOA reported in the English literature [7, 8, 10–12, 15–29]. Although some authors refer no sex predilection [7, 8] other reports show it is more common in women and the pancreatic head its principal location [10–12, 15–29]. The cephalic location of the cysts in our patient is in accordance with this observation. The potential malignant degeneration of the serous cystic pancreatic lesion is low. Therefore some authors advise that patients not clinically suitable for surgical treatment can be closely followed [5]. The tomographic appearance can give clues regarding the nature of the cyst. The starburst appearance and a central calcified scar (honeycomb appearance) are found in 30% of the SMA [5, 6]. Peripheral calcification, vascular involvement and hypervascular pattern are suggestive of a mucinous cyst. There is not a definitive pattern in the vascular appearance of the cystic lesion of the pancreas [1, 4, 5]. Association of tomographic imaging and the clinical manifestations may help the diagnosis. Observation of 484 Pancreatology 2003;3:482–486 hypervascularity of the lesion and the stroma with some small cystic lesions without signs of metastasis or local invasion may provide a diagnostic accuracy of 95% [5]. Cyst fine needle aspiration guided by EUS may help determine the nature of the cyst [5, 30, 31]. This was not done in the present case since surgical treatment was imperative regarding the cyst size. Some reports have shown that determination of CEA levels in cyst fluid has a sensitivity and specificity of 87.5 and 44%, respectively, and that high levels of this marker (1250 ng/ml) reliably identify a mucinous neoplasm, whereas values lower than 5 ng/ml are sensitive for excluding a mucinous neoplasm [30]. High CA 19-9 levels in cyst fluid have been shown to be indicative of mucinous tumors [30, 31]. Values for CA 125 in the cyst fluid are usually variable in mucinous cystic neoplasms and in SCA. Furthermore, this marker may be found both in benign and in malignant cysts with wide value overlap [31]. Combined measurement of CA 72-4 and CEA in the pancreatic cyst fluid may be used to distinguish accurately mucinous cystadenomas and cystadenocarcinoma from SCA and pseudocysts [32, 33]. Positive mucin staining in the fluid identifies the mucin secretor lesion from the serous lesion. Expression of mucin-like carcinoma associated antigen in the fluid can also be used to differentiate cystadenomas from cystadenocarcinomas and pseudocysts [34]. According to several studies mucin staining in conjunction with CEA levels in the cyst fluid appears to be the best discriminating Cunha/Perini/Siqueira/Jukemura/ Penteado/Machado/Abdo/Montagnini approach for the differential diagnosis of pancreatic cystic lesions [35]. An adequate preoperative diagnostic work-up is of utmost importance for the differentiation between a pseudocyst and a cystic tumor. Misdiagnosing a cystic tumor for a pancreatic pseudocyst, as occurred in the first operation performed on this patient, may result in inadequate treatment of these neoplasms. It is important to stress that intraoperative biopsy of the cystic lesion may not help the differential diagnosis as it is well known that the epithelium lining of the cystic neoplasm is partially denuded of epithelium in over 40% of the cases [4]. Immunohistochemical study of SOA shows the expression of the cytokeratins 7, 8, 18 and 19, with the predominance of cytokeratin 7 and 19 [11, 29, 32, 36], lack of p53 [37] and K-ras mutations [34, 36, 38]. There is a negative staining for CEA, trypsin, desmin, actin and factor XIII [29]. In about 40% of the cases the cells are positive for neuron-specific enolase (NSE), but immunostaining for neuroendocrine or islet cell differentiation, such as chro- mogranin, synaptophysin, insulin, glucagon and somatostatin, VIP are negatives [29, 32]. In the patient of the present report only cytokeratin 7 and CA 19 were expressed. Ki67 index was !1%, indicating a low proliferative cell activity. Most pancreatic serous cystadenomas may be treated conservatively [5]. Surgical treatment should probably be reserved for patients with mass-related symptoms such as pain and marked abdominal discomfort. When operative treatment is indicated, nonradical resections should be used. 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