|Year : 2015 | Volume
| Issue : 3 | Page : 439-442
Solid pseudopapillary tumor of the pancreas: A retrospective analysis of 36 cases from a single institution in India
P Singh1, K Patel2, B Ramakrishna1
1 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Pathology, Bharat Cancer Hospital and Research Institute and Nirali Memorial Radiation Centre, Saroli, Surat, Gujarat, India
|Date of Web Publication||18-Feb-2016|
Department of Pathology, Christian Medical College, Vellore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Solid pseudopapillary tumor (SPT) of the pancreas is uncommon, occurring predominantly in young women. We analyzed the clinicopathological features of SPT diagnosed in our institution. Materials And Methods: A retrospective analysis of all cases of SPT diagnosed in the Department of Pathology from January 2001 to September 2012, utilizing an electronic database search, was carried out. In all, 36 cases (35 resections and 1 fine needle aspiration cytology with cell block material) were found. All these cases were then analyzed for clinical presentation, duration and histopathological features, including immunohistochemistry and correlated with the clinical outcome. Results: The mean age of patients (31 females) was 24.1 years. The SPT was suspected preoperatively in 25% of cases. Tumor location was equally common in head (15), body (9), tail (8), distal body and tail (3), and neck (1). Thirty five patients underwent resection. The mean tumor size was 7.16 cm. Grossly, the tumors were solid and cystic (22), predominantly solid (11) or entirely cystic (2). Histologically, pseudopapillary structures, cholesterol clefts, hemorrhage, necrosis, and foam cells were commonly seen. Infiltration into the adjacent pancreas or capsule and perineural invasion were seen in some cases. Immunostaining for CD 10, CD56, and vimentin were positive. Chromogranin and cytokeratin were negative. Follow up in 20 patients from 2-82 months did not show evidence of recurrence or metastasis, even in those with limited surgery or minimal parenchymal or focal perineural infiltration. Conclusion: This study suggests that a management approach with only limited complete tumor resection would be adequate in these tumors.
Keywords: Immunohistochemistry, pancreas, pancreatic neoplasm, solid pseudopapillary tumor
|How to cite this article:|
Singh P, Patel K, Ramakrishna B. Solid pseudopapillary tumor of the pancreas: A retrospective analysis of 36 cases from a single institution in India. Indian J Cancer 2015;52:439-42
|How to cite this URL:|
Singh P, Patel K, Ramakrishna B. Solid pseudopapillary tumor of the pancreas: A retrospective analysis of 36 cases from a single institution in India. Indian J Cancer [serial online] 2015 [cited 2020 Jul 16];52:439-42. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/439/176727
| » Introduction|| |
Solid pseudopapillary tumor (SPT) is an uncommon exocrine pancreatic neoplasm, with low malignant potential, first described in 1959 by Frantz. These tumors predominantly occur in young women, usually follow a benign course, and are curable with excision., They continue to pose a diagnostic challenge both clinically and radiologically due to their vague clinical presentation and varying degree of cystic degeneration, hemorrhage, and necrosis mimicking malignancy or even pseudocyst., Even histopathologically they pose difficulty, especially on fine needle aspiration cytology (FNAC) smear or core biopsy, as the morphology is variable and limited immunostains are available to support their diagnosis. Here we present a single institution large series of SPT cases, discussing their clinicopathological features.
| » Materials and Methods|| |
A retrospective analysis of all cases of SPT diagnosed in the Department of Pathology from January 2001 to September 2012 was carried out utilizing electronic database search. In all, 36 cases (35 resections and 1 FNAC with cell block material) were found. The slides were reviewed and the diagnosis of SPT was reconfirmed. All these cases were then analyzed for clinical presentation, duration, histopathological features and immunohistochemistry, and correlated with the clinical outcome.
| » Results|| |
Thirty one (86.1%) patients were female. The mean age at presentation was 24.1 years (ranging from 10-50 years). The presenting symptoms included abdominal pain (13), abdominal pain and vomiting (6), abdominal mass (6) and less commonly intermittent fever, vomiting or jaundice with vomiting only. Four cases were incidentally detected on abdominal ultrasonography. The clinical details were not available in six cases. The mean duration of symptoms was 6 months (range 1 day–4 years). Preoperative diagnoses suggested in these cases were SPT in 9, benign pancreatic tumor in 7, malignancy in 6, and no diagnosis was given in the remaining 12 cases. Imaging results were not available in two cases. Preoperative FNAC done in five cases, two of which were endoscopic ultrasound (EUS) guided, and Trucut biopsy in two cases, were suggestive of SPT. In one case FNAC done elsewhere was misdiagnosed as lymphoproliferative disorder and the patient had received three cycles of chemotherapy before coming to our hospital. The resection specimen revealed SPT. The tumor was located in the head (15), body (9), tail (8), and distal body and tail (3) of pancreas. In one case of EUS-guided FNAC diagnosed as SPT, the patient did not undergo surgery. The lesion in this case was located in the neck of pancreas and radiologically suggested as pseudocyst. Thirty five patients underwent surgery that varied depending on the location of the tumor in the pancreas: Pancreaticoduodenectomy (11), distal pancreatectomy with and without splenectomy in 12 and 3 cases, respectively, excision of the tumor (7) and subtotal pancreatectomy with splenectomy (2). The tumors ranged in size from 2.5-16 cm (mean 7.16 cm).
The histopathological features seen in 35 resected tumors are described. Grossly, all tumors were well circumscribed and/or encapsulated, solid and cystic in 22 cases, predominantly solid in 11 [Figure 1]a or entirely cystic in 2 [Figure 1]b. Areas of hemorrhage (27) and necrosis (14) were present. Histological examination showed bland cuboidal to polygonal tumor cells with round to oval nuclei exhibiting nuclear grooving and arranged in loosely cohesive sheets, nests and/or pseudopapillae [Figure 2]a with hyalinized cores in foci. Nuclear grooving was observed in 19 cases and was present focally in better preserved areas. Microfollicles [Figure 2]b, pseudo rosettes, trabeculae, and cystic spaces were also seen in some cases. Varying degree of hemorrhage, necrosis, aggregates of foam cells, myxoid change, and hyalinization were also present. Six cases showed extensive infarction and two with marked cystic degeneration. One of the latter showed curvilinear calcification in the wall [Figure 2]c. Other features were the presence of clear cells (14), hyaline globules (12), cholesterol clefts (13), and small foci of calcification (9). Perineural invasion (3), focal capsular infiltration but no penetration (11), and minimal (<1 mm) parenchymal infiltration (8) at the pancreatic interface [Figure 2]d were also noted. The mitotic activity was inconspicuous and in 2 cases seen as 1-2/10 high power fields (HPF). A few tumor cells with bizarre dark staining nuclei were noted in one case, which was regarded as probably a degenerative change and this was not associated with increased mitosis. One case with FNA smear and cell block material showed sheets, singly lying and papillaroid clusters of similar tumor cells and few foam cells. Immunostaining, done in 25 cases (including one cell block section), included CD10, CD56, beta-catenin, vimentin, pancytokeratin, chromogranin, synaptophysin, neuron specific enolase, and progesterone receptors. Positive immunostaining was observed for CD10 (14/15 cases) [Figure 3]a, CD56 11/11 cases), vimentin (14/17 cases), NSE (8/10 cases), beta-catenin (nuclear staining in 6/6 cases and one was only focal) [Figure 3]b and progesterone receptors (3/3 cases, but focal in one case). Chromogranin was consistently negative (19/19 cases). Weak focal immunoreactivity was seen for synaptophysin (6/15 cases) and pancytokeratin (3/8 cases).
|Figure 1: Macroscopic appearance of SPT. (a) Cut section of a solid and encapsulated tumor. (b) Cystic degeneration of SPT|
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|Figure 2: Microscopic features of SPT. (a) Hemotoxylin and eosin stain section showing tumor cells arranged in pseudopapillary pattern (×200). (b) As microfollicles (×100). (c) Cyst wall with curvelinear calcification (×100), and (d) Tumor infiltration into adjacent pancreas (×100)|
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|Figure 3: Immunohistochemical features of SPT. (a) Positive staining for CD10 (×400) and. (b) nuclear staining for beta catenin (×200)|
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There were other incidental pathological lesions in two patients that included benign fibrous polyp in the ileum and adrenal cortical adenoma in 1, and intestinal tuberculosis in another patient.
Follow up was available in 20 patients ranging from 2 months to 82 months. There was no tumor recurrence or metastasis.
| » Discussion|| |
Solid pseudopapillary tumor (SPT) is rare and constitutes 0.2% to 2.7% of the primary nonendocrine tumors of the pancreas., We have reported in this study the largest series of SPT cases from a single institution in India.
It has distinctive pathologic features and preferentially affects young women.,, The mean age at presentation in our series was 24.1 years with a female predominance (86.1%). The female to male ratio may vary from 5:1.9 and up to 10:1. It has been reported that in males these tumors tend to occur in a slightly older age group (average age 31 years). However, in this study the mean age of the five male patients was 23.4 years, which was similar to that of the entire group.
The presenting symptoms and signs are seldom specific that, together with the rarity of this tumor, leads to clinical misdiagnosis.,, Preoperatively, SPT was suspected only in 25% of our cases, which is similar to the report on recent review of SPT cases in the Chinese literature. Most of our patients presented with upper abdominal pain, associated with nonbilious vomiting or abdominal mass in a few cases. These tumors may even be incidentally detected as seen in four cases in this study. On CT imaging, most tumors in this series were well defined, hypodense and variably contrast enhancing. These features can closely mimic malignant processes like pancreatic ductal carcinoma; however, there is usually a preserved fat plane appreciable around the tumor that supports a benign lesion. The radiologic appearance and clinical features overlap with pancreatic pseudocyst  and with other pancreatic neoplasms, including acinar cell carcinoma, mucinous neoplasms, and pancreatic endocrine tumor (PET).,, Massive degeneration, giving rise to cystic appearances on radiological imaging, mimics a pancreatic pseudocyst. However, the presence of a pseudocapsule and intratumoral hemorrhage are important clues to the diagnosis because these features are rarely found in other pancreatic neoplasms.
These neoplasms are reported to more commonly arise from the tail, but can also arise from any other portion of the pancreas. In our series, tumors were almost equally distributed in the head, body and tail of pancreas.
Grossly, a variable combination of solid and cystic areas with much hemorrhage and secondary degenerative changes are seen, which can be extensive leading to an entirely cystic hemorrhagic or infarcted tumor as seen in a few cases in this study. Histologically, even in such tumors, one could find scanty viable foci and tell-tale pseudopapillae at the periphery, hence, the importance of extensive tissue sampling. Peripheral curvilinear calcification, as found in one of our cases, is rare in SPT, but may be detected on radiographs and CT scans. Central and stippled calcifications have been reported. The smaller tumors are primarily organized in solid sheets and nests of cells with rich microvasculature. In most of our cases, the tumor cells were present in loosely cohesive sheets or pseudopapillae, many with hyalinized cores. Distinction of SPT pseudopapillae from true papillae can be made by looking at the surface of papillae where the cells appear to be falling off. Individual tumor cells appear fairly uniform, cuboidal to polygonal or epithelioid, with moderate to abundant pale eosinophilic cytoplasm, round to oval sometimes grooved nuclei, dispersed granular chromatin and inconspicuous nucleoli. Mitoses were inconspicuous to absent. Nuclear grooving has been described as a feature that is often present. We observed it in 19 of 36 cases but this was seen only focally in better preserved areas. Clear cell change, seen as solid sheets in large areas, has recently been described  and was conspicuous in two of our cases. The prognostic significance of this morphological feature is not known and we did not find any adverse significance on follow-up in our cases. These histologic features make SPT distinctive from other neoplasms of the pancreas  and therefore morphological diagnosis is usually not difficult in resection specimen if viable tumor areas are adequately sampled. Fibrous pseudocapsule was present in all the cases but was not uniform in thickness all around the tumor and in some cases it was focally absent at the pancreatic interface. Some cases even showed capsular and minimal (<1 mm) parenchymal infiltration by tumor at the pancreatic interface.
On the cut surface, hemorrhagic and cystic areas are much more common in SPT than in pancreatic endocrine tumors (PET). Histologically, tumor cells in both SPT and PET could be arranged as solid areas, and the size and shape of the tumor cells are relatively uniform with round or oval nuclei and vacuolated or eosinophilic cytoplasm. It can be difficult to distinguish these two types of tumor if only such histological pattern is seen in tissue section. However, the unique morphological characteristics of SPT, with large areas composed of pseudopapillary structures indicating evidence of cellular dyscohesiveness, degeneration, cholesterol clefts, aggregates of foamy histiocytes, and the absence of stippled nuclear chromatin help in differentiating it from PET. FNAC has been used for the preoperative cytological diagnosis of SPT.,, The aspirate smear is usually highly cellular with the presence of epithelioid cells that present singly or in aggregates containing fibrovascular cores. A conclusive identification of SPT is the pseudopapillary arrangement with bland appearing tumor cells. EUS-guided FNAC has been reported, and this can help in diagnosing SPT preoperatively. Some overlapping features are noted between PET and SPT in FNA samples  or on limited material in core biopsy like the solid or clear cell patterns in SPT that can mimic pancreatic neuroendocrine tumors. Immunohistochemistry is important and useful in such cases to reach the correct diagnosis, but the antibodies need to be chosen judiciously to best use limited cytologic material to distinguish among these morphologic mimickers.
Several antibodies have been used in the immunohistochemical evaluation of SPT. As with most tumors, no one marker is specific, but rather a panel of markers is suggested., Recently, both beta-catenin and E-cadherin have been shown to be of diagnostic use in the immunohistochemical work-up of SPT. Aberrant beta-catenin and E-cadherin protein expression occurs in 100% of SPT and is probably linked mechanistically to beta-catenin nuclear localization. Two distinct patterns of E-cadherin immunoreactivity are seen in SPT: Nuclear (with the antibody against the cytoplasmic domain), or immunonegativity (complete loss) when stained with the antibody for the E-cadherin extracellular fragment.
Immunohistochemistry was done to a limited extent in our cases, as all except one were resection specimens and the diagnosis was possible in all cases on histological features. With the availability of various antibodies in recent years, IHC was carried out to confirm the histological diagnosis. However, it can be useful in needle biopsies or FNA samples, especially to differentiate from neuroendocrine tumors, acinar cell carcinoma, and pancreatoblastoma. Tumor cells of SPT are characteristically positive for vimentin, CD10, CD56, beta-catenin, E-cadherin, trypsin, chymotrypsin, galectin 3, claudins 2, 5, and 7; sometimes focal faint positivity can be seen for cytokeratin and focal positivity for NSE,, but are negative for chromogranin. Progesterone receptor may be positive which, together with female predilection, indicate this to be a hormone-dependent tumor, thus potentially amenable to hormone treatment. Beta-catenin was done only in six cases in this study that were from the recent years, and showed positive nuclear staining in all cases which ranged from focal to diffuse.
The histogenesis of SPT still remains only partly resolved. The only known, almost consistent, genetic aberration is a mutation in exon 3 of the β-catenin gene., This aberration results in nuclear β-catenin staining. Functionally, this gene mutation may be responsible for the peculiar morphological growth pattern of SPT, which is characterized by pseudopapillary formation owing to the loss of cell adhesion.
Rarely atypical histological features, which correlate with aggressive presentation and adverse outcome, may be seen in these tumors. These include a diffuse growth pattern in the solid areas of the tumor, with minimal supporting fibrovascular stroma; the presence of true tumor necrosis in either a diffuse geographic or a punctate pattern; an increased nucleus to cytoplasm ratio with hyperchromatic nuclei and irregular nuclear borders; a high mitotic rate. None of these adverse features were seen in our case series. Mitosis up to 1-2/10 HPF were present in two cases but was insignificant compared to very high mitotic rate (>35/50 HPF) in the aggressive cases with atypical histological features described by Tang et al.
Overall, these neoplasms are thought to have low malignant potential with about 10% to 15% of cases recurring or metastasizing. In contrast to conventional ductal adenocarcinomas, most SPTs, although often large in size, are usually well circumscribed and complete surgical resection has been reported to provide a 95% cure rate. In our series, we found good outcome in all the cases that were followed up. Clear cell change in solid areas of the tumor, minimal capsular, and parenchymal pseudoinfiltration at the tumor-pancreatic interface can be present but were not found to have any adverse prognostic significance in our study. One of the three patients, who had evidence of perineural infiltration, also was doing well on follow-up at 21 months. This suggests that a management approach with only limited tumor resection would be adequate in these tumors. Surgery as the only curative treatment for SPTs has also been recommended in other studies.,,, On the basis of a low recurrence rate and prolonged survival after complete local resection, aggressive attempts at complete resection seem to be warranted, even if accompanied by metastases , but neither extensive lymphatic dissection nor adjacent structure resection is needed.
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[Figure 1], [Figure 2], [Figure 3]
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