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A 23-year-old woman presented with vague abdominal discomfort and mild pain. A CT scan revealed a well-demarcated heterogeneous mass in the tail of her pancreas. The resection specimen was comprised of an 18.0 x 16.0 x 12.0 cm, 1698 g, well-circumscribed mass in the pancreatic tail. The mass was multinodular with yellow-tan areas mixed with small, hemorrhagic, purple-tan foci. On cut surface, the mass was partially cystic. The cystic areas contain serosanguinous fluid and were surrounded by yellow necrotic-appearing tissue.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 27, and is solid-pseudopapillary neoplasm.
Criteria for Diagnosis and Comments:
The diagnosis is solid-pseudopapillary neoplasm (SPPN). SPPN is usually a tumor of low malignant potential. The tumor is composed of monomorphic cells forming solid and pseudopapillary structures. Frequently there are hemorrhagic and cystic changes. The origin of the tumor cells is unknown, and they variably express epithelial, mesenchymal and neuroendocrine markers.
SPPN is a rare tumor, accounting for approximately 2% of all exocrine pancreatic tumors. It occurs predominantly in young women, mostly in the early to mid-20s. Clinically, the patients often present with abdominal pain/discomfort or a mass. A significant proportion of patients are asymptomatic, and the mass is an incidental finding on abdominal imaging studies for other reasons. Jaundice is rare, and usually a functional endocrine syndrome is not appreciated nor are abnormal tumor markers documented. The pancreatic tail is a common location, though the tumor also occurs in the head and body.
Ultrasonography and CT reveal a sharply demarcated, variably solid and cystic mass with areas of hemorrhage. The tumor margin may be calcified. Contrast administration may show peripheral enhancing of the solid areas. MRI usually shows heterogeneous signal intensity on T1- and T2-weighted images. Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has been increasingly used to diagnose such pancreatic tumors preoperatively. Cytological smears from SPPN tend to be cellular with delicate, branching papillary fronds. The cells are bland and monomorphic, with round to oval nuclei and finely granular chromatin. These cytological features are similar to endocrine neoplasms, thus often causing misinterpretation.
Histologically, the tumor cells are small and fairly uniform. They have moderate eosinophilic or clear cytoplasm. The nuclei are round or oval shaped, with frequent nuclear grooves. The chromatin is finely granular, and the nucleoli are small or inconspicuous. Generally there is no significant nuclear atypia. Mitotic figures are rare to absent. The solid and cystic features on gross appearance are also reflected on the histological sections. In the solid areas, the tumor cells form tight nests or pseudopapillae. The pseudopapillae appear to be attached to edematous or hyalinizing fibrovascular stroma, which may show focal myxoid changes. The tumor cells in the pseudopapillae are very discohesive. Areas of cystic spaces are present. It is believed that the pseudopapillae are formed secondary to degeneration. Hemorrhage is often a salient feature, and in some areas, the pseudopapillae with blood-containing cystic spaces may have an angiosarcoma-like appearance. Small clusters of foamy macrophages are often noted in the tumor. In addition, areas of necrosis with cholesterol clefts are usually present. The presence of hyaline globule clusters, both intracellular and extracellular, are also a characteristic feature of this tumor. These hyaline globules stain positive with Periodic acid-Schiff (PAS) and are resistant to diastase digestion (PAS-D).
Immunohistochemically, the tumor cells show consistent expression with antibodies directed against vimentin, alpha-1-antitrypsin, CD56, CD10, and progesterone receptor. Expression of cytokeratin, chymotrypsin, neuron-specific enolase, and synaptophysin are variably positive. Staining for chromogranin A is generally negative. The majority of SPPN harbor beta-catenin mutations, though similar changes are also reported in other pancreatic tumors with the exception of ductal adenocarcinoma.
In line with its low malignant potential, the prognosis of SPPN is generally good. Although local invasion or even metastasis has been reported, 95% of patients with SPPN can be surgically cured. The five-year survival rate is about 95%.
The main differential diagnosis is pancreatic endocrine neoplasm (PEN). Similar to SPPN, PEN tumor cells are often small and uniform, with finely granular chromatin. The tumor cells usually show a nested or trabecular architecture, and a papillary configuration is unusual. Although PEN can rarely have cystic spaces, hyaline globules and cholesterol clefts are not characteristic. PEN often shows strong expression of cytokeratin and chromogranin A, and are variably positive for vimentin. Of note, both tumors can express CD56 and synaptophysin; thus these two markers are less useful in differentiating one from the other.
Acinar cell carcinoma (ACC) of the pancreas is also a rare tumor. In contrary to SPPN, ACC shows a slightly male predominance and mostly occurs in late adulthood with a mean age of 62 years. The pancreatic head is the more common location. Grossly, ACC is generally a bulky, well-circumscribed, multinodular solid mass. Areas of necrosis and cystic changes may be present. Architecturally, the tumor is arranged in an acinar, solid, or trabecular pattern. The tumor cells are uniform, with amphophilic to eosinophilic granular cytoplasm which contains PAS-positive, diastase-resistant (PAS-D) zymogen granules. The nucleus is irregularly sized and contains a single central nucleolus. A papillary architecture is not a feature of ACC, and it does not contain the extracellular hyaline globules or foci of cholesterol-clefts. Immunohistochemically, ACC cells are often strongly positive for cytokeratin and pancreatic enzymes including trypsin, chymotrypsin, lipase and elastase. They also show variable staining for vimentin and neuroendocrine markers. The prognosis is poor.
Pancreatoblastoma is essentially a pediatric tumor with a mean age of 4 years. It often occurs in the pancreatic head. Grossly, most tumors are well-defined, solid lobulated masses. Uncommonly they may be cystic. Histologically, the tumor consists of cellular epithelium arranged in well-defined solid nests or acini, separately by stromal bands. The tumor cells are fairly uniform, with small nuclei and a single central nucleolus. The characteristic feature is the squamoid corpuscle, which is not present in SPPN. The stroma can be highly cellular, and may have heterologous components.
Pancreatic ductal adenocarcinoma is the most common tumor of the pancreas. In the poorly differentiated form, the tumor may consist of solid nests, with areas of squamoid, spindle cell, or anaplastic foci. In most cases, it does not pose a problem in the differential diagnosis of SPPN since ductal structure are often focally present, and the tumor cells are markedly pleomorphic and atypical, consistent with its aggressive clinical course.