Case 3 -

Solid-Pseudopapillary Tumor Ritu Nayar Northwestern University Feinberg School of Medicine Chicago, IL

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Terminology: Franz tumor (originally described by Virginia Franz in 1959), solid and papillary tumor, solid-cystic tumor, solid, cystic and papillary neoplasm, benign or malignant papillary tumor of the pancreas, cystic acinar tumor, papillary epithelial neoplasm of the pancreas, have all been used. The term "solid-pseudopapillary tumor" was proposed by WHO in 1996. This term encompasses the two most conspicuous gross features: solid and pseudopapillary areas. Incidence: Solid pseudopapillary tumors account for approximately 1-2% of all exocrine pancreatic tumors and 3% of pancreatic cystic lesions. These tumors occur predominantly in adolescent girls and young women (mean age 22, range 2-81 years); the female to male ratio is 10:1 Case 3 - Figure 1 Diff-Quik, medium power Case 3 - Figure 2 Diff-Quik, high power Case 3 - Figure 3 Papanicolaou, medium power Case 3 - Figure 4 Cell block, Chromogranin Histogenesis: Origin is not ascertained. Many investigators favor that SPT originate from multipotent primordial germ cells, while others suggest an extra pancreatic origin from genital ridge angle related cells. Recently, Geers et al suggest that the presence of galectin-3 in both SPT and pancreatic ducts raises the hypothesis of a possible ductal origin of these tumors. SPT's are classified as epithelial neoplasms but immunohistochemical patterns suggest that they cannot be regarded as purely epithelial since epithelial, mesenchymal, exocrine and endocrine markers may be expressed. While the theory that SPT may derive from a pluripotent stem cell is attractive, there is no clear cut terminal differentiation to either acinar or endocrine cells, the cytologic features and low proliferative index do not favor a stem cell origin and the strong sex-linked occurrence is also not in keeping with a stem cell origin. There is no definite association with use of hormonal contraceptives. Radiologic Findings: Endoscopic ultrasound (EUS) shows a heterogeneous solid or mixed solid/cystic hypoechoic lesion. On CT scan, findings include an encapsulated lesion with well defined borders, and variable areas of cystic degeneration, necrosis, hemorrhage and occasional calcifications. With contrast there is solid enhancement peripherally. In general a well defined, heterogeneous mass in the tail or body of the pancreas in a young woman is highly suggestive of SPT Gross Findings: Large solid or solid-cystic mass, frequently having necrotic and hemorrhagic zones. The most common locations are the body and tail of the pancreas (about 65% of all tumors). Rarely the tumor can have an extrapancreatic location Size can be variable, ranging from a few cm to 30 cm, mean is 10.5 cm. Histology and Cytomorphology Histologically a fibrous capsule is usually present, within which solid areas are interspersed by cystic and pseudopapillary foci. The cystic areas are a result of gradual degenerative changes in the solid component. The solid areas are formed by cords of small to medium sized, polygonal, monomorphous cells, separated by small vessels which exhibit varying degrees of perivascular collagen deposition. Tumor cells have eosinophilic to vacuolated cytoplasm, the nucleus has fine evenly distributed chromatin, with 1-2 distinct, small nucleoli. The nuclear membrane is often grooved and the coffee bean shape of the nucleus is reminiscent of granulosa cell tumor nuclei. Occasionally there may be cytoplasmic or extracellular hyaline globules that are PAS positive, diastase resistant. Preoperative diagnosis of SPT can be provided by EUS or percutaneous FNA biopsy. Aspirated smears are generally cellular, with prominent vascular structures with attached monotonous cuboidal neoplastic cells in papillary like arrangements. The nuclear features of the tumor cells are bland, with nuclear grooves, and cytoplasm is granular or finely vacuolated with ill defined borders. Usually mitosis and nuclear atypia are not observed. Myxoid stroma in background or papillary cores, hyaline globules (red on Diff Quik, pink on H&E ), necrosis, foamy histiocytes or histiocytic giant cells may be seen. The globules may be surrounded by tumor cells, similar to that seen in adenoid cystic carcinoma. Immunohistochemistry: Beta catenin positive Vimentin positive CD 10 +/-ve CD 56 +/-ve, Progesterone and estrogen ER[beta] +/- Focal positivity reported in some cases with: keratins, EMA, alpha-1-antitrypsin, alpha-1 antichymotrypsin, NSE, synaptophysin, S100 and melan A Chromogranin- negative Genetics Differs from ductal adenocarcinoma, in not being associated with abnormalities in K-ras, p53, or DPC4 genes. Alteration of the adenomatous polyposis coli (APC)/ beta catenin pathway and deregulated expression of cell cycle associated protein is seen as overexpression of cyclin D-1 and cyclin D 3 Presentation and clinical behavior The tumors are often asymptomatic and found incidentally. If present, symptoms include nausea, vomiting, abdominal pain or vague abdominal pain due to compression of adjacent organs. Jaundice is rare. Tumor markers are usually normal. SPT is regarded as a low grade malignant tumor. Despite its low malignant potential, up to 10% to 15% of the cases have aggressive behavior with metastatic dissemination possibly leading to death. Surgery is the treatment of choice, with a cure rate > 95%. Pancreaticoduodenectomy is performed for tumors in the head and distal pancreatectomy for lesions in the body or tail of the pancreas. To date, no pathological factor can reliably predict the outcome of these tumors, although angioinvasion, perineural invasion and deep invasion of the surrounding pancreatic parenchyma are suggested as markers of malignant potential. Extensive necrosis, nuclear atypia, high mitotic rate and sarcomatoid areas are suggested to be associated with aggressive behavior. Recently, Geers et al have suggested that galectin-3 may be a useful marker to distinguish SPT from neuroendocrine tumor, and also be an indicator of behavior because its low expression is associated with metastatic spread. Differential diagnosis: Acinar tumors- wide age range, no specific location in pancreas, only has acinar cells, papillary/ductal structures not observed. Pancreaticoblastoma - childhood malignant tumor, male predilection, presence of squamoid corpuscles surrounded by solid and tubular structures is most diagnostic. Neuroendocrine tumors - older patients, clinical syndromes +/-. There are some common morphologic features with SPT. Immunohistochemistry helpful Adenocarcinoma- presentation, morphology and immunohistochemistry Serous cystadenoma: elderly women, more common in head, watery aspirate, paucicellular with cuboidal to columnar cells, immunohistochemistry Papillary mucinous tumor: mucin extra and intracellular, immunohistochemistry References Geers C; Pierre, M; Jean-Francois, G; Birgit, W; Pierre, D; Jacques, R; Christine, S. Solid and pseudopapillary t umor of the pancreas-Review and New Insights Into Pathogenesis. Am J of Surg Pathol. 2006; 30(10):1243-1249. Santini D, et al. Solid papillary tumors of the pancreas: histopathology. J Pancreas 2006; 7(1): 131-136 Klimstra Ds, et al. Solid pseudopapillary tumor of the pancreas: a typically cystic neoplasm of low malignant potential. Sem Diagn Pathol 2000; 17: 66-80 Koppel G, et al. WHO Classification of Tumors: Pathology and genetics of tumors of the digestive system. Lyon, France. IARC Press 2000; 436: 473-480 Stommer, et al. Solid and cystic pancreatic tumors: clinical Immunohistochemical and electron microscopic features in 10 cases. Cancer 1991; 67: 1635-1641 Papavramidis T, et al. Solid pseudopapillary tumors of the pancreas: a review of 718 patients reported in the English literature. J Am Coll Surg 2005; 200: 965-972. Bhanot P, et al. Clinical, imaging, cytopathologic features of solid pseudopapillary tumor of the pancreas: a clinicopathologic study of 3 cases and review of the literature. Diagn Cytopathol 2005; 33: 421-428. Pettinato G, et al. Solid pseudopapillary tumor of the pancreas: a neoplasm with distinct and highly characteristic cytologic features. Diagn Cytopathol 2002; 27(6): 325-334. Liu X, et al. Solid-pseudopapillary neoplasm of the pancreas. Appl Immuno Mol Morpho 2006; 14: 445-453. Nishimori I, et al. Non cystic solid pseudopapillary tumor of pancreas showing nuclear accumulation and activating gene mutation of beta catenin. Pathol Int 2006; 56: 707-711