Unusual Pancreatic Neoplasm Research Articles

English

Solid-pseudopapillary tumors are unusual pancreatic neoplasms of low malignant potential that most frequently affect young women. They are histologically, clinically, and prognostically quite distinct from the more common pancreatic ductal adenocarcinomas. Despite their often large size the vast majority of solid-pseudopapillary tumors are indolent neoplasms. They are confined to the pancreas in 85% of patients, and even the 10 to 15% of patients with liver or peritoneal metastases commonly enjoy long-term survival.

Non‐cystic solid‐pseudopapillary tumor of the pancreas showing nuclear accumulation and activating gene mutation of β‐catenin

Solid-pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm that is characterized by a mixture of solid and cystic components and a fibrous capsule. Recently, the tumorigenesis of SPT has been reported to be associated with gene mutations of beta-catenin, which is a molecule participating in the Wnt signaling pathway. Reported herein is the case of a 53-year-old woman with SPT. The tumor, approximately 3 cm in diameter in the pancreas body, had a clear margin and central calcification but had neither a cystic component nor fibrous capsule. Several lines of pathological findings in the surgically resected specimen indicated SPT: (i) pseudopapillary proliferation of eosinophilic polygonal cells with oval nuclei; (ii) positive expression of several marker molecules indicating differentiation into acinar and endocrine cells; and (iii) zymogen granule-like structures in the cytoplasm on electron microscopy. Further, the tumor cells had intense nuclear accumulation of beta-catenin and an activating mutation, (34)Gly(GGA) to Arg(AGA), in exon 3 of the beta-catenin gene, as previously reported in most SPT. These findings suggest that association of the beta-catenin phenotype with development of the rare phenotype of SPT, a non-cystic and unencapsulated tumor, is unlikely.

Histogenesis of solid pseudopapillary tumor of the pancreas: the case for the centroacinar cell of origin

Solid pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm of low malignant potential that most frequently occurs in young women. The tumor is indolent, with long patient survival, even in the presence of extension into adjacent organs and metastases. Histologically, it is a solid and cystic tumor with a prominent vascular network and degenerative pseudopapillae formation. Despite its distinctive morphology and cytological features, its histogenesis is unclear. Herein, we report a case of solid pseudopapillary tumor in a 41-year-old female in which the tumor cells immunohistochemically and ultrastructurally suggest a centroacinar cell origin. The tumor cells and the normal centroacinar cells stained positive for alpha-antitrypsin (α-AT), CD10, cyclin D1 and NSE. Ultrastructural examination shows similarities in nuclear shape, nucleoli location and cytoplasmic contents between neoplastic cells and normal centroacinar cells of the pancreas. Based on both immunohistochemical and ultrastructural features, we propose that the centroacinar cell is the origin of SPT.

Solid-Pseudopapillary Tumors of the Pancreas Are Genetically Distinct from Pancreatic Ductal Adenocarcinomas and Almost Always Harbor β -catenin Mutations

Solid-pseudopapillary tumors (SPTs) are unusual pancreatic neoplasms of low malignant potential that most frequently affect young women. Genetic events contributing to the development of SPTs are unknown. Whereas the more common ductal adenocarcinomas of the pancreas essentially never harbor beta-catenin or APC gene mutations, we have recently identified alterations of the APC/beta-catenin pathway in other nonductal pancreatic neoplasms including pancreatoblastomas and acinar cell carcinomas. We analyzed a series of 20 SPTs for somatic alterations of the APC/beta-catenin pathway using immunohistochemistry for beta-catenin protein accumulation, direct DNA sequencing of beta-catenin exon 3, and direct DNA sequencing of the mutation cluster region in exon 15 of the APC gene in those SPTs that did not harbor beta-catenin mutations. Immunohistochemical labeling for cyclin D1 was performed to evaluate the overexpression of this cell-cycle protein as one of the putative downstream effectors of beta-catenin dysregulation. In addition, we analyzed the SPTs for genetic alterations commonly found in pancreatic ductal adenocarcinomas, including mutations in the K-ras oncogene and p53 and DPC4 tumor suppressor genes, using direct DNA sequencing of K-ras and immunostaining for p53 and Dpc4. Almost all SPTs harbored alterations in the APC/beta-catenin pathway. Nuclear accumulation of beta-catenin protein was present in 95% (19 of 20), and activating beta-catenin oncogene mutations were identified in 90% (18 of 20) of the SPTs. Seventy-four percent (14 of 19) showed overexpression of cyclin D1, ranging from 10 to 70% of tumor nuclei. In contrast, no K-ras mutations were present in any of the 20 SPTs, and Dpc4 expression was intact in all 16 SPTs for which immunohistochemical labeling was successful. Overexpression of p53 was limited to only 3 of 19 (15.8%) SPTs. These results emphasize the two distinct, divergent genetic pathways of neoplastic progression in pancreatic ductal and nonductal neoplasms.

Pancreatic neoplasms: MR imaging and pathologic correlation.

Magnetic resonance (MR) imaging can aid in the detection and characterization of many pancreatic neoplasms. The MR imaging appearances of common pancreatic neoplasms such as ductal adenocarcinoma are well-known. However, MR imaging features of more unusual pancreatic neoplasms are not well understood. Such tumors include mucin-hyper-secreting carcinoma, serous microcystic neoplasm, mucinous macrocystic neoplasm, solid and papillary epithelial neoplasm, multiple cysts associated with von Hippel-Lindau disease, acinar cell carcinoma, pancreaticoblastoma, and endocrine neoplasms (eg, nonfunctioning islet cell tumors, insulinoma, and gastrinoma). In general, pancreatic neoplasms demonstrate high signal intensity on T2-weighted images; the signal intensity on T1-weighted images is more variable but is often intermediate or low. Gadolinium enhancement is often helpful in further characterizing pancreatic neoplasms. The gross and histologic features of pancreatic neoplasms are also not well-known. Correlation with the underlying pathologic features enhances understanding of the MR imaging characteristics of both common and unusual pancreatic neoplasms.

Induction of unusual pancreatic neoplasms, with morphologic similarity to human tumors, and evidence for their ductal/ductular cell origin

A variety of pancreatic neoplasms, including giant cell, poorly differentiated or other unusual types, some morphologically similar to those observed in humans were induced in Syrian hamsters. Unclassified or anaplastic forms were also noted in the hamster. The finding of a blood group A-like antigen, which is produced by normal pancreatic ductal and ductular cells, in all of these induced tumors, but none in acinar, insular, and mesenchymal cells, suggests their ductal/ductular cell origin.