Diagnosis of SPN is important for the clinical management of patients. Diagnostic modalities including CT and MRI can only suggest a diagnosis of SPN. CT findings include an encapsulated lesion with a well-defined margin and variable central areas with cystic degeneration, necrosis or hemorrhage. Calcifications may occasionally be seen. MRI is helpful for identifying the characteristic internal signal intensities of blood products, which is useful in making a differential diagnosis of SPN from other cystic pancreatic tumors.12
Advances in technology have permitted the performance of FNA biopsy under EUS guidance.13
EUS permits a better evaluation of SPN, but the findings also are not specific. Because SPN occurs almost exclusively in women, with an approximate female-to-male ratio of 9:1, it might be difficult to make a preoperative diagnosis if the case presents with unusual clinical and radiologic findings for which an accurate preoperative diagnosis using EUS-FNA cytology would be highly desirable. This is because a local surgical excision is usually curative in SPN. Since Bondeson et al.14
first made a correct diagnosis of SPN on the preoperative FNA, 57 cases of SPN have been diagnosed based on cytologic findings on the percutaneous FNA.5
Recently, some cases of SPN have also been diagnosed on the EUS-FNA.5
We summarized EUS-FNA cytologic features of SPN () and their immunohistochemical profiles () according to a review of the English literatures. FNA cytomorphologic features are highly characteristic and distinct from those of other cystic or solid tumors of the pancreas. On aspirated materials, the most frequent features are the presence of marked cellularity with pseudopapillary fragments composed of fibrovascular cores lined with one to several layers of tumor cells intermingled with discohesive neoplastic cells.5
As shown in our cases, inter- or intra-cellular pink hyaline globules, mucus-like globules are surrounded by the stromal cells and cellular debris, which is also one of the frequent features.
EUS-FNA cytologic features in 43 cases of SPN described in the English literature
Immunohistochemical findings described in the English literature
Histologic differential diagnosis of SPN from PEN or pancreatic adenocarcinoma is important. This is because SPN have a much better prognosis compared with PEN or pancreatic adenocarcinoma, with only 10% to 15% of cases recurring or metastasizing. More than 95% of SPN are cured by complete surgical resection alone.19
The uniform, bland-appearing, often dispersed epithelial cells of SPN can greatly resemble those of PEN. When the papillary architecture is absent in SPN cytologic specimens, a careful attention to the nuclear details that are commonly seen in many cases of SPN, including the presence of nuclear grooves, indentations, the occasional perinuclear vacuole or intracytoplasmic hyaline droplet, will be useful in making a differential diagnosis between the two disease entities. In an actual clinical setting, however, it would be almost impossible to make a differential diagnosis between the two disease entities without an ancillary test. In case 1, it was particularly difficult to make a diagnosis of SPN because the tumor cells were arranged in solid nests and pseudopapillary architectures were not prominent. The possibility of PEN could not be completely ruled out even in the resected specimens. We could therefore make a diagnosis based on immunohistochemical stains.
The aspirated tissue from any lesion can be prepared in a number of different ways: direct smears, cytospins, liquid-based preparations and cell blocks. Direct smears are the most common, particularly for solid masses, but specimens aspirated as a fluid from cyst are often processed as cytospins or liquid-based specimen. Liquid-based preparations eliminate obscuring blood and inflammation and thereby provide excellent cellular preservation. In case 3, the aspirated prepared in a liquid-based manner, the papillary branching structures were well preserved with a more prominent fine granular chromatin and small nucleoli because the blood was eliminated. In addition, cell block preparation is advantageous given the readily available tissue for immunocytochemistry.
Immunohistochemically, most cases of SPN are immunoreactive for vimentin, α1-antitrypsin and α1-antichymotrypsin; occasionally positive for neuron specific enolase and synaptophysin; and non-reactive for carbohydrate antigen 19.9 and chromogranin A.5
Recently, Kim et al.20
have reported that a loss of E-cadherin and the cytopalsmic-nuclear expression of β-catenin are the immunological profile that is the most useful in making a diagnosis of SPN. Because there was a possibility of case 1 being PEN based on the absence of papillary configuration and an unusual clinical setting, we performed an immunohistochemistry for only two antibodies, thus causing a misdiagnosis. The tumor cells in cell block were immuno-positive for synaptophysin and immuno-negative for chromogranin, based on which case 1 was initially diagnosed with PEN. After the resection of the pancreas mass, the diagnosis was revised to SPN with following immune-profiles: vimentin (+), progesterone receptor (+), CD10 (+), β-catenin (+) and E-cadherin (-). Then, we could make an accurate diagnosis of other two cases on immunohistochemistry of cell blocks. It can therefore be inferred that immunohistochemical stains based on cell block is as important as cytologic features in making an accurate diagnosis of pancreatic neoplasms.
In conclusion, our cases indicate that the cytomorphologic features from EUS-FNA, as well as the clinical correlation and radiological findings, are essential for making an accurate diagnosis of SPN. Therefore, the pathologists should recognize the importance of the characteristic cytologic findings with immunoprofiles of SPN to prevent misdiagnosis of SPN.