Solid pseudopapillary tumors (SPTs) of the pancreas are rare neoplasms with low malignant potential and were first described in 1959.10 Historically, several other names have been associated with this tumor, including Frantz tumors, Hamoudi tumors, and papillary cystic neoplasm. It is estimated that SPTs represent up to 3% of all pancreatic tumors and 6% to 12% of pancreatic cystic neoplasms.11 SPTs are notable for their high prevalence among women, most commonly occurring in the third decade of life and earlier.12,13 The largest review of the literature included 718 patients over a 70-year time period.14 The authors observed that the prevalence of SPT is 10-fold higher in women than in men and affected predominantly younger individuals (mean age, 22 years; range, 2 to 85 years). More than 70% to 90% of patients with SPT present with symptoms, the most common being pain (45%) and/or an abdominal mass (34%).14 In the asymptomatic patient, tumors may also be discovered as a palpable mass on routine physical examination, as a mass seen on casual view of the abdomen (by a mother or father of an affected daughter), or as an incidental finding on imaging for an unrelated complaint. Serologic tests are often of little value with CA 19-9 elevated in 4.3%, amylase in 22.6%, and lipase in 29.3%.
On CT imaging, SPTs are characteristically large, heterogeneously enhancing lesions with solid and cystic components, and they frequently demonstrate peripheral enhancement and central calcification (Fig. 149-3). These lesions can range from being completely cystic to completely solid.15 The cystic portion of SPTs is not a true cyst, but rather it has a cystic appearance which is secondary to necrotic degeneration of the primary tumor. As the solid papillary vascular stalks within the tumor slough and hemorrhage, central necrosis can occur resulting in cystic degeneration. Although SPTs can occur throughout the pancreas, they are perhaps slightly more common in the pancreatic tail and, when discovered, are generally large in size (mean diameter, 5.4 cm).15 Whether the clinical and radiographic features are prognostic of aggressive biologic behavior is controversial, largely because malignant behavior is so uncommon. In a recent review of 51 patients with SPT, no demographic, clinical, or CT imaging features were found to correlate with aggressive biology.15 In contrast, another series of 64 SPTs identified larger size (mean 10.5 vs. 5.2, p <0.001) as the sole prognostic factor for predicting disease recurrence.16 The radiographic differential diagnosis of a predominantly cystic SPT should include other cystic neoplasms including mucinous neoplasms or serous cystadenomas, and intraductal papillary mucinous neoplasms, as well as cystic degeneration of a typically solid neoplasm, such as a pancreatic neuroendocrine tumor or acinar cell cancer. In a young woman under the age of 30 (for example), SPT and pancreatic neuroendocrine tumor would be most likely; in a young woman under the age of 20, SPT would clearly be the most likely diagnosis. FNA biopsy may be useful when routine imaging is inconclusive and diagnostic uncertainty exists; however, because of the tumor's largely necrotic composition, FNA biopsy can be nondiagnostic.
Axial image of a contrast-enhanced CT scan from a patient with a solid pseudopapillary tumor of the pancreas with solid and cystic characteristics (long arrows) and central calcification (short arrow and arrowheads).
Solid pseudopapillary tumors have a characteristic microscopic appearance which include solid cellular hypervascular regions without gland formation, and the presence of branching papillary fronds with sheets and degenerative pseudopapillae.17 Cells have eosinophilic granules within the nuclei which are typically grooved. The immunophenotype demonstrates positive staining for neuron-specific enolase, CD10, and particularly atypical nuclear staining for beta-catenin, which is generally a cytoplasmic protein.17,18 Keratins, chromogranin, synaptophysin, and endocrine pancreatic enzymes are generally not expressed. SPTs are often stain positive for progesterone receptors, while estrogen receptor positivity is more variable.19 SPTs have also been reported to positively stain for α-methylacyl-coenzyme A racemase (AMCAR) in contrast to acinar and neuroendocrine tumors of the pancreas which do not.20 In 1996, the World Health Organization (WHO) further defined malignant SPTs as tumors with histologic characteristics of angioinvasion, perineural invasion, or extension into the surrounding pancreatic parenchyma.21 Loss of CD10 expression and high Ki-67 proliferative index has been associated with malignant SPTs.22,23
The molecular changes associated with the development of SPT have been well described and are distinct from the pattern of mutations seen in pancreatic ductal adenocarcinoma. As with ACC, the genetic profile associated with SPT is different from adenocarcinoma, most notably for an absence of KRAS and SMAD4 mutations. Almost all SPTs harbor alterations in the APC/beta-catenin pathway due to a mutation involving CTNNB1 (exon 3). Nuclear accumulation of beta-catenin has been described in 95% of SPTs and 74% of tumors overexpress cyclin D1, a downstream effector of beta-catenin.24 In addition, genes involved in the hedgehog and androgen receptor signaling pathways as well as genes involved in epithelial mesenchymal transition have been shown to be activated in SPT.25
Given the unpredictable but real metastatic potential of these tumors, surgical resection is recommended for all patients with localized SPT. Although these tumors may be extremely large and can invade critical vasculature, most lesions are usually amenable to complete resection. Pancreaticoduodenectomy or distal pancreatectomy can be performed with en bloc resection of involved adjacent organs when indicated. Complete margin-negative resection (R0) is associated with a 5-year survival rate of 95%.26 In a single-institution series of 24 patients, 17 of 19 patients underwent complete R0 resection. At a median follow-up of 8 years, no evidence of recurrent disease was observed in all patients who received an R0 resection.26 In another single-institution study of 37 patients with SPT, only 1 patient (3%) had a recurrence at median follow-up of 4.8 years.27
Given the excellent survival rates following surgical resection alone, adjuvant systemic therapy is not routinely utilized. If metastatic disease occurs, the most common sites include liver, mesentery, and peritoneum. Several series have reported long-term survival following metastasectomy.26 For unresectable metastatic disease, anecdotal case reports have suggested that gemcitabine-based chemotherapy may be successful in some patients.28,29