Solid pseudopapillary tumors (SPTs) are epithelial tumors of the exocrine pancreas. They are difficult to diagnose and account for only 1% to 2% of all exocrine pancreatic tumors. The patient in our case underwent open cholecystectomy in 1971, during which a nonresectable pancreatic mass was discovered. The patient remained asymptomatic for 30 years. At age 75, she developed symptoms of early satiety and occasional shooting pains on the right side of her abdomen. During a physical examination, her primary care physician found a palpable abdominal mass and referred her for a computed tomography scan. The images showed a heterogenous mass in the head of the pancreas, and a biopsy specimen was suggestive for neuroendocrine neoplasm. During a pancreatoduodenectomy, a 960-g tumor was removed. The tumor showed no vascular, perineural, or adjacent organ invasions. SPT rarely progresses to malignancy, and the mainstay of treatment—even for very large tumors—is surgical resection, with vascular reconstruction reported to produce favorable results. Patients with SPT have a good long-term prognosis.

A cystic mass of the pancreas can present a diagnostic and surgical dilemma. In recent years, solid pseudopapillary tumors (SPTs) of the pancreas have been identified with greater frequency. An SPT is defined as an epithelial tumor of the exocrine pancreas composed of monomorphous cells, which form solid and pseudopapillary structures, frequently with cystic and hemorrhagic changes.¹ An SPT is sometimes mistaken for a neuroendocrine tumor or a pancreatic pseudocyst. In this paper, we describe a 75-year-old woman who underwent pancreatoduodenectomy for a mass that had been identified 30 years earlier and which was diagnosed preoperatively as a neuroendocrine tumor.

Case report
A 75-year-old woman was evaluated by her primary care physician in 2001 for symptoms of early satiety and occasional episodes of shooting pain on the right side of her abdomen. Her history included an open cholecystectomy for gallstones in 1971, during which surgeons discovered a “3-in mass between her pancreas and liver,” that could not be resected. She remained asymptomatic for 30 years after the cholecystectomy.

During her physical examination, her physician noted a large palpable mass in the right upper quadrant of her abdomen. A computed tomography (CT) scan showed a 12-cm cystic mass. A few groups of malignant-appearing cells were identified in a percutaneous biopsy specimen of the mass, which suggested that it was a neuroendocrine neoplasm. Immunostaining showed strong positivity for neuron-specific enolase; faint reactivity to keratin; and negativity for chromogranin, CD20, and CD3 (Figure 1). The patient was referred to our facility.

Our examination also observed a readily palpable mass in the right upper quadrant of her abdomen. Her alanine aminotransferase level was 41 U/L (normal, 9–29 U/L), and her aspartate aminotransferase level was 38 U/L (normal, 12–31 U/L). Levels of alkaline phosphatase, total bilirubin, and CA 19-9 were within normal limits. The serum and urine markers for neuroendocrine tumors—including pancreatic polypeptide, calcitonin, vasoactive intestinal peptide, gastrin, and 5-hydroxyindoleacetic acid—were also within normal limits.

Magnetic resonance imaging (MRI) of the abdomen showed a 16.3 x 10.2 x 13.9-cm lobulated and well-circumscribed heterogenous mass in the head of the pancreas (Figure 2). The mass contained multiple cystic areas with foci of hemorrhage. The portal vein was displaced medially and the extrahepatic common bile duct laterally, with no evidence of invasion. The inferior vena cava was compressed but patent (Figure 3), and there was mild intrahepatic biliary ductal dilation.

A preoperative evaluation determined that the patient had coronary artery disease and ischemic changes, and she underwent 3-vessel coronary artery bypass grafting in May 2002. After her recovery, a standard pancreatoduodenectomy was performed in July 2002. The tumor was densely adherent to the portal vein and required a segmental resection of the portal vein with primary reconstruction.

The final pathology report described a 15-cm SPT weighing 960 g (Figure 4). There was no vascular invasion or invasion of the common bile duct or duodenum. Mitotic activity was rare (Figure 5), and immunostaining was strongly and diffusively positive for neuron-specific enolase and vimentin. Periodic acid-Schiff staining highlighted globules within the tumor. Focal reactivity was weak to chromogranin and synaptophysin and reacted minimally to carcinoembryonic antigen and CAM 5.2. The keratin stain was strongly negative, and the seven peripancreatic lymph nodes were negative for malignancy. DNA analysis showed 4% aneuploidy with a DNA index of 1.4.

The patient’s postoperative course was uneventful. Imaging with echo Doppler color flow showed normal and appropriate flow within the portal vein and other hepatic vasculature. Tube cholangiography and pancreatography found no biliary or pancreatic anastomotic leaks. Oral intake was resumed on postoperative day 5, and the patient was dismissed from the hospital on postoperative day 7. She has done well postoperatively; her symptoms have resolved and there is no evidence of recurrence after 4 years.  

Discussion
SPT of the pancreas is rare. Although SPT has been identified more frequently in recent years, it still accounts for only 1% to 2% of all exocrine pancreatic tumors.² Since pancreatic SPT was first described in 1959, about 500 cases have been reported.³ More than 90% have occurred in young women between the second and fourth decades of life.⁴ The age of the oldest patient reported to have an SPT was 79 years. An SPT can be quite large at presentation. One study estimated the doubling time at 765 days based on serial CT films.⁵ Unfortunately, our patient had no serial CT scans in the intervening 30 years after identification of her pancreatic mass.

CT, ultrasonography, and MRI are the modalities most commonly used during preoperative evaluation. Imaging findings usually show a large, well-encapsulated mass, which may have areas of hemorrhagic degeneration and calcification. SPT may demonstrate cystic changes and should be considered in the differential diagnosis of any pancreatic cystic mass, particularly if the patient is a young woman. SPT is sometimes misdiagnosed as a pseudocyst or neuroendocrine tumor.⁶ Tumor markers, including CA19-9, are usually undetectable, although an elevated CA19-9 measurement in a patient with SPT has been reported.⁴ 

Percutaneous biopsy specimens of SPTs can be difficult to interpret. A recent study detailed a constellation of cytologic features that may assist in correctly diagnosing SPT.³ These features include high cellularity, branching papillary fronds, small cellular aggregates, single tumor cells, nuclear uniformity, nuclear foldings, giant cells, and foam cells. Immunohistochemical staining may help confirm a diagnosis of SPT.^7-9 SPT consistently demonstrates strong immunoreactivity to vimentin, neuron-specific enolase, and alpha 1—antitrypsin in more than 90% of examined specimens. Progesterone receptors, cytokeratin, and synaptophysin can also be positive to varying degrees. Positive immunostaining to neuron-specific enolase and synaptophysin or chromogranin often leads to a presumptive diagnosis of neuroendocrine tumor, as it did in our patient’s case. The flow cytometric data on SPT are limited. Our patient showed an aneuploid population of 4% with a DNA index of 1.4.³ The importance of diploidy of SPT is not known. Increasing data show that b-catenin mutations are involved in the deregulation of the cell cycle-associated proteins.^10-12 These mutations might participate in the pathogenesis of SPT. SPT may have totipotential stem cells with focal neuroendocrine differentiation.

Tumor size does not predict resectability. These tumors may become quite large before causing symptoms, as was the case with our patient. Symptoms usually arise from compression—not invasion—of surrounding structures by the mass. Approximately two thirds of SPTs are located in the body and tail of the pancreas. In the few recent reports, distribution was estimated to be 43% in the head of the pancreas, 14% in the body, and 43% in the tail.^7,12-16 About one third of patients with SPT will require pancreatoduodenectomy for complete resection of the tumor.

Although our patient experienced no vascular invasion, her tumor was adherent to the portal vein, necessitating segmental portal vein resection with end-to-end primary reconstruction. Vascular resection in pancreatoduodenectomy is safe, although the procedure may increase morbidity and mortality rates. The decision to perform vascular resection usually depends on the ability to peel the tumor from the underlying vessel and on the safe completion of tumor resection.

Many times a definitive diagnosis of SPT cannot be made until all postoperative histologic and immunohistochemical studies have been completed. For tumors located in the body and tail of the pancreas, distal pancreatectomy with or without the spleen en bloc is performed. Recurrence of SPT after complete resection of local disease, even in patients who had large tumors, has never been reported.

Solid pseudopapillary carcinoma (SPC) is morphologically identical to SPT, and the term SPT has been used to include cases of SPC. In contrast, SPC shows clear criteria for malignancy, such as vascular or nerve sheath invasion; or metastasis to lymph nodes, liver, or local peritoneum.^16,17 

Approximately 20 cases of SPC have been reported in the literature. Long-term survival, even with disseminated disease, is quite good. Patients routinely live 7 to 10 years after the initial complete resection. Even patients with unresectable SPC survive for a reasonably long period. However, SPC may recur more than 5 years after the initial complete resection. Two patients whose resected SPTs contained numerous mitotic figures experienced early recurrences and died shortly thereafter. One report describes an SPT misdiagnosed as a nonfunctioning islet cell tumor with a capsular invasion; the failure to diagnose and treat the SPT correctly led to its rapid recurrence and the patient’s subsequent death.¹⁶ In general, no prognostic factors have been established, and experience with chemotherapy and radiotherapy is limited.

Among identified cystic masses of the pancreas, diagnosing SPT is difficult. The mainstay of treatment should be surgical resection, even for very large tumors, with vascular reconstruction reported to have favorable results. SPT rarely progresses to malignancy, and the long-term prognosis for patients with SPT is good.  

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