On gross examination, there was a well-circumscribed and totally encapsulated mass measuring 55x50x45 mm located in the tail of the pancreas. On the cut surface, it was heterogenous and predominantly a cystic tumor. Focal solid areas were also present (Figure 2). The cystic parts were mainly filled with dark brown hemorrhagic debris. Normal pancreatic tissue was identified at the periphery. The spleen weighed 150 gm and was in normal limits.
On microscopic examination, we observed a tumor mainly composed of cystic cavities lined by friable tissue and cholesterol clefts (Figure 3a). The solid parts grossly described were showing diffuse growth pattern with minimal supporting fibrovascular stroma. They were composed of papillary, pseudopapillary and microcystic structures with dyscohesive neoplastic cells (Figure 3b). The neoplastic cells in these areas had polygonal, uniform, centrally located grooved nuclei and vacuolated or eosinophilic large cytoplasm (Figure 3c). There were rare mitotic figures in solid areas. No atypical cells were found. The tumor was separated from the normal pancreatic tissue with a thick fibrous capsule in which there was infiltration of the tumor cells in some areas (Figure 3d). Surgical margins were free of tumor. Immunohistochemistry evaluation was performed. The tumor cells showed strong cytoplasmic positivity for vimentin (Figure 4a) and both nuclear and cytoplasmic positivity for β catenin (Figure 4b). Weak or moderate staining for p53, pancytokeratin (PanCK), cyclinD1, CD10, synaptophysin, estrogen (ER) and progesterone receptors (PR) were observed. No immunostaining was seen for chromogranine A, CD34, CD117, cytokeratin 7 (CK7) and cytokeratin 20 (CK20). The proliferative index assessed by Ki-67 immunoreactivity was 1-2% in solid areas of the tumor (Figure 4c). With the histopathological and immunohistochemical findings, we signed out the case as “solid pseudopapillary neoplasm of the pancreas”. The patient did not undergo any adjuvant therapy and has been doing well in the year after her operation.
Grossly, the tumor is well circumscribed and may reach a huge size in some instances[2,8]. Invasion into the capsule, peritumoral tissues or adjacent pancreatic parenchyme[3] as well as distant metastasis to adjacent organs such as liver[2,5], spleen[8] and regional lymph nodes[2] are reported in some series.
Immunohistochemically, SPN cells strongly and diffusely express vimentin, α-1 antitrypsin, α-1 antichymotrypsin (AACT), neuron specific enolase, PR and β form of ER[1,7]. CD10, CD56, CD 117, FLI-1, and also epithelial markers such as CK, AE1/AE3, CAM 5.2 can be focally positive[1]. Chromogranine A, a specific endocrine marker, is typically negative or only very focally positive[1].
Abnormal nuclear localization of β catenin gene results in nuclear staining[1,3,6] and also this genetic abberation activates the Wnt-signaling pathway resulting in overexpression of cyclinD1, but not in overt malignancy of this tumor[9]. In our case, we observed strong immunoreactivity for vimentin, β catenin and weak staining for synaptophysin, PR and ER. Moderate expression of cyclinD1 was observed. There was no immunoreactivity for CD117, CD34, Chromogranine A, CK20 and CK7. Our immunohistochemistry results were consistent with the literature findings and supported our diagnosis of SPN.
The pathogenesis and the cell of origin of SPN remain unknown, since it lacks evidence of ductal, acinar or frank endocrine differentiation[1-5]. The strong preponderance in young women and the common expression of PR suggests that during early embryogenesis, especially the left genital ridge cells come into contact with the pancreas and follow a different line of differentiation[10].
On the other hand, genetic changes involved in SPNs are different from the genetic changes involved in conventional ductal adenocarcinomas. Mutation in exon 3 of the β-catenin gene is a well-known genetic abberation in SPN[1].
Clinical behavior of SPN is still unclear. The long-term follow up of the patients showed that distant metastasis or invasion of the peritumoral tissues itself does not indicate aggressive clinical behavior of this tumor[2,8]. High-grade malignant transformation into undifferentiated carcinoma has been reported to be the only reliable predictor of clinical aggressiveness of this tumor till now[2]. In our case, we noticed capsular invasion in focal areas and the tumor cells were very close to the adjacent pancreatic tissue. Our patient is well and free of any sign of disease on her second follow up one year after her operation.
In conclusion, SPT is a rare tumor of low malignant potential with uncertain origin. Capsular invasion or invasion of the tumor to the adjacent pancreas does not correlate with aggressive behavior. Radical resection of the lesion, where technically feasible, should be considered as the treatment of choice since it is safe and effective in controlling the disease.
ACKNOWLEDGEMENT
We would like to thank to Prof Dr Volkan Adsay of Emory
University, Department of Pathology, Atlanta, USA for his
diagnostic assistance.
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