| Abstract|| |
Background: Solid-pseudopapillary neoplasm (SPPN) of the pancreas is a distinctive tumor of low malignant potential with a predilection for female patients in the second and third decades of life. We studied nine cases of SPPN of the pancreas and reviewed the literature concerning these uncommon tumors. Materials and Methods: A total of 7 cases of SPPN located in the tail of the pancreas and two located in the head of the pancreas were presented. Distal pancreatectomy in three patients and distal pancreatectomy with splenectomy in two patients Whipple's operation in four patients were performed. Histological diagnosis was made by performing hematoxylin-eosin and periodic acid-Schiff staining, immunohistochemical staining. Follow-up of the patients was between 2 months and 12 years. Results: Computed tomography and magnetic resonance imaging were found as equivocal for diagnosis. Mass containing cystic and solid areas were not characteristic but raised suspicion of SPPN. Pathologic examination showed SPPN in all patients. No metastasis or recurrence was detected during follow-up. Conclusions: Solid-pseudopapillary neoplasm is a relatively rare tumor, and patients tend to survive for a long period. Preoperative imaging is not characteristic. Pathologic examination is the mainstay in the diagnosis. Complete surgical removal is the best choice of treatment.
Keywords: Neoplasm, pancreas, pseudopapillary, solid
|How to cite this article:|
Ozguven BY, Tuncel D, Polat N, Sakiz D, Kabukcuoglu F, Koksal H, Kaya H. Solid-pseudopapillary neoplasm of the pancreas: Clinicopathologic and immunohistochemical analysis of nine cases. Indian J Pathol Microbiol 2015;58:292-5
|How to cite this URL:|
Ozguven BY, Tuncel D, Polat N, Sakiz D, Kabukcuoglu F, Koksal H, Kaya H. Solid-pseudopapillary neoplasm of the pancreas: Clinicopathologic and immunohistochemical analysis of nine cases. Indian J Pathol Microbiol [serial online] 2015 [cited 2019 Apr 24];58:292-5. Available from: http://www.ijpmonline.org/text.asp?2015/58/3/292/162833
| Introduction|| |
Solid-pseudopapillary neoplasm (SPPN) is a rare exocrine pancreatic tumor, which occurs in around 1% of pancreatic tumors.  Despite the increasing recognition of the tumor, its pathogenesis, and apparent therapeutic algorithm remain unclear.
They are usually found in young females with nonspecific symptoms including abdominal discomfort, subtle abdominal pain or abdominal mass.  Although the biologic characteristics of these tumors generally indicate a good prognosis, recently, a malignant form has been reported. The presence of extrapancreatic invasion, distant metastases, pancreatic parenchymal invasion, perineural or vascular invasion have been considered to be malignant signs. , SPPN of the pancreas has occasionally been reported in older females, in males, and in extrapancreatic sites. SPPN of the pancreas most commonly arise in the pancreas, while retroperitoneum is the second site of involvement.  Histogenesis remains controversial. Data have been provided for ductal, acinar or pluripotential pancreatic cell origin. The clinicopathological findings and histopathological and immunohistochemical results of nine cases of SPPNs of the pancreas with the clinical course and surgical treatment were analyzed in this study.
| Materials and Methods|| |
Clinical records and follow-up information were reviewed for nine cases of SPPNs of the pancreas between 1998 and 2013. Seven cases of SPPN are located in the tail of the pancreas, and two are located in the head of the pancreas. Distal pancreatectomy in three patients and distal pancreatectomy with splenectomy in two patients were performed. The surgical procedures included Whipple's operation in four patients. The mean age of the patients located in the tail at presentation was 46 years (range: 14-73 years), whereas the mean age of the patients located in the head was 14.5 (range: 12-17). There was a strong female preponderance (89% female, 11% male). The overall size of the tumors ranged from 4 to 9 cm (mean, 5, 8 cm). In all patients, the pancreatic lesions were correctly interpreted by ultrasonography (USG) and computed tomography (CT) scan. Clinical findings are summarized briefly in [Table 1]. Histological diagnosis was made by performing hematoxylin-eosin and periodic acid-Schiff, immunohistochemical staining.
Sections were immunostained by the streptavidin-biotin technique with primary antibodies to epithelial membrane antigen (EMA, DAKO), vimentin (Novocastra), progesterone receptor (Neo Markers), chromogranine A (Neo Markers), Synaptophysin (Neo Markers), cytokeratin (AE1 + AE3, Neo Markers), mouse anti-human p53 (DAKO), rabbit anti-human Ki-67 antigen (DAKO), anti-human EMA (EMA, DAKO), neuron-specific enolase (NSE Ab-1, Neo Markers), carcinoembryonic antigen (CEA) (clone col-1, Neo Markers), S-100 protein (Neo Markers), CD10 (Neo Markers), CD56 (Neo Markers), Beta Catenin (Novacastra, 17C2), E Cadherin (Zymed 4A2C7) and Alpha 1 Antitrypsin (Neo Markers) [Table 2].
Patients were followed-up every 3 months for the 1 st year and 6 monthly then after. During follow-ups, abdominal USG and CT were performed every 6 months. Biochemical analysis included blood glucose, amylase, transaminases, alkaline phosphatase, tumor markers (CA 19-9, CEA).
| Results|| |
The histological findings demonstrated large encapsulated tumors with the sections surrounded by hemorrhagic and necrotic areas [Figure 1]. The solid areas were composed of small and medium size tumor cells, which had no obvious atypia. Pseudopapillary structures were found in the cystic degeneration areas [Figure 2]. Immunohistochemical features are summarized in [Table 2]. All cases were positive for vimentin, CD56, B-Catenin, Alpha-1 Antitrypsin and progesterone receptor, negative for epithelial membran antigen, CEA [Figure 3] and [Figure 4]. Five cases showed immunopositivity for chromogranin or synaptophysin [Figure 5]. In four cases, CD10 immunopositivity have been observed. Ki-67 index ranged from <1% to 2% [Figure 6]. In the follow-up period (2 months-12 years) all patients are alive with no evidence of recurrence.
|Figure 1: Cross-section of specimen, showing a tumor composed of mixed cystic and solid components with hemorrhagic areas|
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|Figure 2: Areas of solid, pseudoglandular and pseudopapillary pattern (H and E, ´200)|
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|Figure 3: Immunohistochemistry revealed strong and diffuse expression of beta-catenin, ´200|
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|Figure 4: Immunohistochemistry revealed strong and diffuse expression of Alpha-1 Antitrypsin, ´200|
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|Figure 5: Immunohistochemistry revealed expression of synaptophysin, ×200|
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| DIscussIon|| |
Solid-pseudopapillary neoplasm of the pancreas is a rare exocrine pancreatic tumor, which comprises only 1-2% of all tumors of the pancreas, first described by Frantz in 1959. ,
Most of these tumors are found in young women in the second or third decade.  Approximately 25% of these tumors may be seen in children.  The most common clinical presentation is a palpable abdominal mass and abdominal pain.  These tumors have a low malignant potential, and their prognosis is extremely good unlike other tumors of the pancreas. 
Solid-pseudopapillary neoplasm of the pancreas was first reported by Frantz in 1959.  It represents a rare tumor that occurs most frequently in young women (90%).  The widespread use of imaging techniques, together with a better knowledge of the disease, has prompted a rapidly increasing number of case reports. Although SPPN is considered an indolent lesion with a low malignant potential and a favorable prognosis after surgical resection, some cases of locally infiltrating and metastatic variety, or recurrences after surgery, have been reported. 
Local recurrence or distant metastases can occur in a significant number of patients. 
They are usually young females with enlarging abdominal masses. These tumors may occur anywhere in the pancreas but have a slight predilection for the tail of the pancreas.  In the presented study, seven were located in the tail of the pancreas, and two were located in the head of the pancreas.
Zhou et al. reported that SPPN was probably the most common pancreatic tumor in the Asian pediatric population.  In the current study, three patients were under age 18, on the other hand two of them were over age 65.
Immunohistochemically, the SPPNs show positive reactivity for keratin, desmoplakin, trypsin, chymotrypsin, amylase and vimentin. In addition, focal positivity has been found for NSE and various islet cell hormones such as insulin and glucagons. This might suggest that SPPN of the pancreas arises from primitive pancreatic epithelial cells with a predominance of exocrine features but having capacity for dual (endocrine and exocrine) differentiation. The presence of progesterone receptors and its well-known predilection for females suggest that it is a hormone-dependent tumor.  Likewise in our study, eight cases were female, and all the cases showed progesterone reseptor positivity.
Based on high rates of positivity for markers of various pancreatic cells (NSE, alfa 1-antitrypsin, vimentin, antichymotrypsin, pancreatic polypeptide, somatostatin, glucagon, insulin) it has been suggested that the tumor originates from pancreatic pluripotential stem cells. The histogenesis of SPPN still remains unsettled because of discrepancies in the immunohistochemical and electron-microscopic findings. Neuroendocrine origin has been suggested by a diffusely positive reaction for neuron-specific enolase, by alleged positivity in a few cases for pancreatic polypeptide, somatostatin, glucagon, insulin. Acinar cell differentiation has been suggested by the reactivity of all SPPNs examined for alpha-1-antitrypsin.  NSE was positive in three cases whereas all our cases showed alpha-1-antitrypsin positivity.
The prognosis of SPPN is generally good with a low prevalence of recurrence after resection and death due to the disease. However, it is also true that there have been reports of cases developing metastasis, invasion, or recurrence. Malignant potential and its marker in SPPNs have not yet been elucidated. It has been reported that although capsule/parenchymal invasion was seen in 13% of SPPN cases, the recurrence rate was not high in such patients compared with that in those without.  In the current study, all patients were alive (1-12 years) in all patients with no evidence of recurrence.
In general, SPPN has an excellent prognosis with a low malignant potential. Malignant appearance is observed in about 10-15% cases.  This kind of tumors can show local aggressiveness. Histologically aggressiveness is generally associated with cellular atypia, mitotic activity, and invasion of vascular spaces, perineural interstitium or neighboring organ. Metastases were seen in regional lymph nodes, liver, and omentum. , In the current study, one of the patients had vascular and perineural invasion, and she was well after 2 years following operation.
Conservative resection with safe margins is the treatment of choice if feasible.  In most cases, distal pancreatectomy would be sufficient. Total pancreatectomy with or without splenectomy would be warranted in some cases. In this study, distal pancreatectomy without splenectomy was performed in two cases. The presence of metastasis does not exclude surgical resection because of the clinical benefits associated with tumor resection.  Tumor related death is uncommon. By virtue of its biologic behavior, SPPN of the pancreas is a highly curable tumor, unlike the more common adenocarcinoma.
Solid-pseudopapillary neoplasms of the pancreas are a distinct clinicopathological entity with a benign clinical course or a very low malignant potential and a high cure rate by surgical resection alone. The results of immunohistochemical and ultrastructural studies indicate that SPPNs of the pancreas must still be regarded as a tumor of uncertain histogenesis and undetermined differentiation.
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Department of Pathology, Sisli Etfal Education and Research Hospital, Istanbul
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]