Langenbecks Arch Surg (2007) 392:493–496 DOI 10.1007/s00423-007-0193-2
CASE MANAGEMENT AND CLINICAL CONSEQUENCES
Mucinous cystadenocarcinoma of the pancreas diagnosed in postpartum Rene Berindoague & Eduard Targarona & Alfredo Savelli & Juan Pernas & Josep Lloreta
Received: 25 July 2006 / Accepted: 23 February 2007 / Published online: 26 May 2007 # Springer-Verlag 2007
Abstract Background Cystic tumors of the pancreas are uncommon. They account for 10–15% of all pancreatic cystic masses and only 1% of pancreatic malignancies. Mucinous cystadenocarcinoma is the most frequent pancreatic cystadenocarcinoma and it is mainly seen in women, suggesting a sex hormone influence. Its presentation during pregnancy is infrequent and entails difficult diagnostic and therapeutic decisions. We report the case of a 31-year-old woman who presented a pancreatic cystadenocarcinoma 2 months after delivery. Materials and methods A 31-year-old woman was referred to our service because of abdominal pain and mass. She had given birth to her first child 2 months previous. Abdominal ultrasound demonstrated a poorly circumscribed cystic R. Berindoague (*) : E. Targarona : A. Savelli Service of General Surgery, Hospital Sant Pau of Barcelona, Autonomous University of Barcelona, Calle Padre Claret 167, 08025 Barcelona, Spain e-mail:
[email protected] E. Targarona e-mail:
[email protected]
mass in the left upper abdominal quadrant, and the computed tomography scan showed a multilocular cystic lesion located in the body of pancreas. There was no seric alteration of specific pancreatic enzymes or tumor markers. Results Laparoscopic examination showed a large cystic tumor (12×11×5.5 cm) in the pancreas involving the body and the tail. It extended to the spleen and was highly vascularized, precluding a minimal invasive resection. An open body–tail pancreatectomy and splenectomy was performed. The resection margins were free of tumor, and the histological study showed a mucinous pancreatic cystadenocarcinoma with mucin-producing columnar epithelium and associated papillae patterns, reminiscent of ovarian stroma. Immunohistochemical studies were negative for hormonal receptors. The patient had no postsurgical complications and was discharged home in 4 days. Conclusions Cystic tumors of the pancreas are infrequent, and cancer of the pancreas during pregnancy is extremely rare. Insidious symptoms and bodily changes due to pregnancy may mask diagnosis. Aggressive surgery is currently the only chance of cure. Keywords Pancreatic tumor . Pancreatic cysts . Mucinous cystadenocarcinoma . Pregnancy . Postpartum
A. Savelli e-mail:
[email protected] J. Pernas Service of Radiology, Hospital Sant Pau of Barcelona, Autonomous University of Barcelona, Barcelona, Spain e-mail:
[email protected] J. Lloreta Departament of Pathology, Hospital del Mar, Pompeu Fabra University, Barcelona, Spain e-mail:
[email protected]
Introduction Cystic tumors of the pancreas are uncommon and account for only 10–15% of pancreatic masses and 1% of pancreatic malignancies [1]. They are classified as mucinous cystic tumors (MCT), serous cystadenomas, intraductal papillarymucinous tumors, hemangiomas, and lymphangiomas. MCT are large (mean size, 8–10 cm) and usually contain several smaller cysts. They are surrounded by a thick
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Fig. 1 CT scan showing a macrocyst located in the left upper abdomen with septa and pericystic reaction, characteristic of cystadenocarcinoma
fibrous capsule and do not communicate with the pancreatic ductal system. Characterized by mucin-producing columnar epithelium, MCT are sometimes supported by ovarian-like stroma [1, 2]. MCTs of the pancreas are more common in women and are extremely rare during pregnancy. Malignant degeneration is relatively common. Management of these tumors during and after pregnancy presents challenges because tumor growth is rapid, probably as the result of high levels of sex hormones. It has been suggested that these tumors are sex hormone-dependent neoplasms [3]. In this paper, we present the case of a pancreatic cystadenocarcinoma diagnosed in postpartum.
Case report Two months after a non-complicated pregnancy, a 31-yearold woman was referred to our service because of Fig. 2 3D Reconstruction of a large pancreatic tumor: a Anteroposterior, b semi-lateral
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abdominal pain and mass. Physical examination suggested the presence of a soft elastic mass of about 15 cm in diameter in the left hypocondrium. Laboratory data on admission showed normal levels of amylase, lipase, and tumor markers (CEA, CA19.9). Abdominal ultrasound demonstrated a large hypoechoic mass with septa and a speckled sonographic pattern. CT scan and 3D reconstruction (3D-Doctor Able Software) imaging showed a multilocular mass with septa; this was not detected in the pregnancy checkups (Figs. 1 and 2). Initially, a laparoscopic approach was performed. There were no ascites. The tumor was highly vascularized and involved structures on the left hypocondrium. Ovaries, mesenterium, peritoneum, and liver appeared normal, but an open technique was decided due to the size and difficult handling of the tumor. The lesion was localized in the body and tail of the pancreas and was suspected to be a mucinous cystadenocarcinoma. A body–tail pancreatectomy with splenectomy was performed. The surgery time was 160 min, and the bleeding amount was 330 ml. The gross pathological examination showed a 12×11×5.5 cm (721 cm3) multilocular and septated cystic tumor containing a thick viscous secretion. The interior contained several nodular lesions, with a granular and micronodular appearance. Microscopically, the tumor was well circumscribed and had the classic features of a both a papillary and a cystic tumor, with a spindle cell stroma reminiscent of ovarian stroma (Fig. 3). Microscopic infiltration was observed, but the tumor did not extend to the adjacent parenchyma, and there was neither apparent dysplasia nor MCT-columnar epithelial cells. Five lymph nodes were found, all negative for tumor. Signs of chronic pancreatitis with atrophy of the exocrine component and residual nests of islet cells in fibrous tissue were found. Analysis of cystic fluid demonstrated high levels of tumor markers (CEA>50.000 ng/ml; CA19.9>50.000 U/ml; CA 125=1750 U/ml; amilasis=180 U/l).
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Fig. 3 Histologic findings of the pancreatic cystadenocarcinoma showing the classic features of a mucinous cystic tumor
Immunohistochemical studies were negative for hormonal receptors. The definitive pathological diagnosis was mucinous cystadenocarcinoma of the pancreas with foci of ovarian-like stroma. However, in a wider sense, it could be classified as a PanIN III. Seric glucose levels were normal in preoperative and postoperative period. The postoperative course was uneventful.
Discussion Carcinoma of the pancreas is infrequent in women of childbearing age. Donegan [4] found 71 cases (0.6%) of pancreatic cancer in a cohort of 11,606 female cancer patients aged 15–44 years. Mucinous cystadenocarcinoma constitutes 3.3% of all pancreatic lesions [5]. In a recent review, the majority of patients who were found to have a pancreatic mass during pregnancy had a malignant tumor [5]. Olsen et al. [3] and Ganepola et al. [7] analyzed ten patients with pancreatic tumors diagnosed during pregnancy: Four died of the disease due to incomplete resection of the tumor during pregnancy, and five had postpartum resections and survived. The 3- and 5-year survival rates after resection of pancreatic mucinous cystadenocarcinoma are 45 and 27%, respectively [5]. The 5-year survival rate of patients with mucinous cystadenocarcinoma after curative resection appears to be significantly better than for patients with ductal carcinoma [2]. Cystic tumors in the pancreas often grow slowly and can remain indolent for many years. The fact that they tend not
to infiltrate adjacent structures justifies the laparoscopic approach in surgical treatment [6]. Their rapid growth during pregnancy, however, has been related to sex hormone-dependent neoplasms [7, 8]. This case of pancreatic cystadenocarcinoma was classified as a PanIN III, and therefore, has clinical implications beyond the worse stage in the PanIN classification. Analyzing the histological result, we cannot totally exclude that some isolated tumor lesion is still present in any duct section away from the tissue that we were able to examine on microscopy. During the operation, the remained pancreas presents normal aspect, and preoperative computed tomography (CT) scan did not show alterations on pancreatic head. Interestingly, the α-inhibin receptor has been identified in the tumor tissue. The α-inhibin was initially described as an immunohistochemical marker of granulosa cell tumors in the ovary. It has been widely used subsequently as a sensitive diagnostic marker for gonadal sex-cord stromal tumors. Inhibin immunoreactivity in ovarian-type stroma was initially described by Ridder et al. [9] in a case of invasive mucinous cystadenocarcinoma of the pancreas. Subsequently, in a large series of 56 cases, Zamboni et al. [2] observed that α-inhibin was positive in 66% of the mucinous cystic neoplasms. The authors found that tumors presenting ovarian-type stroma were mostly benign mucinous cystic neoplasms, whereas tumors without the ovarian-type stroma were mostly invasive mucinous cystoadecocarcinomas. In this same series, the degree of expression for αinhibin was higher in the benign cystic neoplasm (80%) than in mucinous cystoadecocarcinoma (39%).
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In our patient, the histopathological studies showed ovarian-like stroma, but the immunohistochemical studies for estrogen, progesterone, and α-inhibin were negative. These data, according to previous reports, would favor the malignant nature of our case. However, the rapid increase in tumor size seems to evidence a relationship with the hormonal variations of pregnancy. Zamboni et al. [10] suggested that this situation may simply reflect a lower sensitivity of hormone receptor antibodies that fail to reveal the biochemically detectable hormone receptors. They reported that the nuclei were positive for progesterone receptors in 26 of 56 cases (48%) and for estrogen receptors in 12 cases (22%). Cystic tumors of the pancreas are infrequent, and cancer of the pancreas during pregnancy is extremely rare. Insidious symptoms and bodily changes due to pregnancy may mask the diagnosis. Aggressive surgery is currently the only option for cure.
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