|Year : 2016 | Volume
| Issue : 2 | Page : 47-51
Solid pseudopapillary tumors of the pancreas: Is there a role for adjuvant treatment?
Anshuma Bansal, Vikrant Kaushal, Rakesh Kapoor
Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||8-Jun-2016|
Department of Radiation Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Solid pseudopapillary tumors of the pancreas are rare tumors commonly found in females. Surgery is the primary treatment and the role of adjuvant chemotherapy or radiation is not well defined. Although they are mostly benign, they have the potential for late metastasis, thereby defining the need for long-term surveillance for such patients. This review article describes these tumors in detail and in addition, focuses on the management of the resected tumors and the need and indications for adjuvant treatment in selective cases.
Keywords: Chemotherapy, pancreas, radiotherapy, solid pseudopapillary neoplasm, surgery
|How to cite this article:|
Bansal A, Kaushal V, Kapoor R. Solid pseudopapillary tumors of the pancreas: Is there a role for adjuvant treatment?. Saudi Surg J 2016;4:47-51
|How to cite this URL:|
Bansal A, Kaushal V, Kapoor R. Solid pseudopapillary tumors of the pancreas: Is there a role for adjuvant treatment?. Saudi Surg J [serial online] 2016 [cited 2019 May 21];4:47-51. Available from: http://www.saudisurgj.org/text.asp?2016/4/2/47/183672
| Introduction|| |
Solid pseudopapillary tumors of the pancreas constitute 0.13-2.7% of all pancreatic malignancies.  It is one of the histopathological subtypes that demonstrate low malignant potential.  They are typically found in females during their second or fourth decade of life.  The outcome is favorable. Surgery is the mainstay of the treatment. Definitive adjuvant treatment strategy has not been defined yet due to the availability of limited case series or reports only. We carried out a literature search from January 1991 to October 2015, through the PubMed/MEDLINE central database at National Center for Biotechnology Information website (http://www.ncbi.nlm.nih.gov/pmc) using the search terms "solid pseudopapillary neoplasm," "pancreas," "surgery," "chemotherapy," and "radiotherapy." This review article focuses on presentation, diagnostic workup, role of surgery, the indications and the need for adjuvant treatment, and their effects on the disease outcome so that an optimal management can be planned for individual cases.
| Discussion|| |
Solid pseudopapillary tumors of the pancreas also known as Hamoudi tumor or Frantz tumor are one of the rarest histopathological variants of pancreatic cancers, accounting for <2% of the later.  These were first characterized in 1959 by Frantz,  and the World Health Organization in 1996 named it as "solid pseudopapillary neoplasm."  Unlike the aggressive malignant behavior shown by pancreatic carcinomas, these tumors are often benign and have indolent course. Malignant potential is seen only in 10-15% of all cases.  It is seen more frequently in females with male-female ratio of 1:9 and commonly presents in the second to fourth decade of their life.  Pancreatic body and tail are the most common sites of presentation.  The rare extrapancreatic sites of origin can be retroperitoneum, mesentery, and left adrenal gland.  Surgery is the primary treatment.  The role of chemotherapy and radiotherapy has to be individualized depending upon the potential for malignancy.
The cell of origin of these tumors is unknown, but they possibly originate from the multipotent primordial cells and lack definite endocrine and exocrine differentiation.  Other common theories suggest the origin to be from the ductal epithelium, neuroendocrine cells, or possibly extrapancreatic genital ridge angle.  Kosmahl et al.  suggest that the tumor originates from the incorporation of primitive ovarian cells within the pancreatic parenchyma during the 7 th week of embryogenesis though this does not justify the presence of malignancy in males. Sun et al.  reported that 62.5% of these patients are infected with hepatitis B virus (HBV) which can induce overexpression of β-catenin in tumor cells, indicating that HBV infection may be involved in the pathogenesis which, however, has not been confirmed.
Pathology and immunohistochemistry
Macroscopically, these present as well-circumscribed tumor masses usually well demarcated from the pancreas, with large spongy areas of hemorrhage on its cut surface alternating with both solid and cystic degenerative components. Microscopically, the characteristic features are cellular degeneration and pseudopapillary appearance.
These tumors are typically positive for vimentin, a1-antitrypsin, a1-antichymotrypsin, and neuron-specific enolase. Nguyen et al.  showed 100% sensitivity and specificity of beta-catenin in these tumors while positivity for synaptophysin was seen in 36% and for chromogranin in 15%.
The proliferation of these tumors may be affected by sex hormones as 80% of these tumors have progesterone receptor positivity.  Lesions are also known to progress during pregnancy.  The positive rate is variable for estrogen receptor. IHC staining of Ki-67 can help determine malignant potential for these tumors.
The symptoms are mostly nonspecific. Abdominal pain due to mass effect is the common manifestation and palpable mass may be evident in certain cases.  The most common sites of metastasis are liver, regional lymph nodes, mesentery, omentum, and peritoneum. 
Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen combined with age and gender are usually sufficient for the decision to operate, and diagnostic interventions such as preoperative fine needle aspiration cytology, endoscopic ultrasounds, and endoscopic retrograde cholangiopancreatography are seldom performed for the diagnosis. Furthermore, the tumors mostly being benign preclude the use of positron emission tomography scans.
MRI is preferable to CT scan for demonstrating the presence of a capsule, cystic, and solid degeneration, as well as hemorrhage without obvious internal septum, the presence of which is highly suspicious of solid pseudopapillary neoplasms of the pancreas. 
Most of the staging for these tumors in the literature is reported in accordance with the American Joint Committee on Cancer (AJCC) staging used for pancreatic tumors. However, no definite staging system has been approved to date. There are two main reasons. First, the invasion of the portal vein or superior mesenteric artery which constitutes T4 stage and is the criteria for unresectability for pancreatic tumors does not hold true for pancreatic solid pseudopapillary tumors. Further, due to the rare case reporting in the literature, it is impractical to correlate AJCC staging for these tumors with prognosis and survival rates.
Preoperative diagnosis with imaging alone is technically challenging due to difficulties differentiating this tumor from other pancreatic conditions such as a pancreatic cyst or other histological variants such as adenocarcinoma, cystadenoma, cystadenocarcinoma, islet cell tumor, neuroendocrine tumor, or teratoma.
Role of surgery
Surgery is the treatment of choice for pancreatic tumors irrespective of histology. Similarly, for solid pseudopapillary pancreatic neoplasms, whether benign or malignant, surgery is the mainstay even with metastasis or local recurrence. , Local resection or enucleation can be performed for small tumors. Distal pancreatectomy combined with or without splenectomy can be performed for pancreatic body and/or tail tumor, and pancreatoduodenectomy can be performed for pancreatic head tumor. The common sites of local invasion are liver, portal/splenic vein/superior mesenteric vein, spleen, diaphragmatic muscle, omentum or peritoneum, duodenum, stomach, colon, or left kidney.  In contrast to other pancreatic tumors, invasion of the portal vein or superior mesenteric artery does not indicate tumor unresectability. If veins are infiltrated, vascular en-bloc resection and reconstruction with vein grafts have been proposed and the results were encouraging.  Extensive lymphatic dissection is not warranted since lymph node metastasis was found in only 3 patients (0.61%) in one of the studies.  Five-year survival rates range from 94 to 100%. ,,, [Table 1] describes the outcome of such patients following complete surgical resection.
|Table 1: Outcome of solid pseudopapillary tumors of the pancreas with surgery alone|
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For metastatic lesions
In patients who present with metastatic disease, metastasectomy should be considered when possible. Martin et al.  reported that four patients underwent resection of liver metastasis and primary tumor, and two of them survived for at least 6 and 11 years, respectively. Other treatment modalities for liver metastasis, such as alcohol injection, TACE, γ-radiation therapy, and even liver transplantation, have been reported. ,
The most common complications after surgery are pancreatic fistula, pancreatitis, steatorrhea, wound infection, biliary fistula, prolonged gastric emptying, gastrointestinal bleeding, diabetes mellitus, and ileus. 
Rationale and indications for adjuvant therapy
Doubling time of this tumor as described by Kato et al. is 765 days.  Local invasion or hematogenous recurrences are rare.  These tumors displace the surrounding structures instead of invading them.  The use of adjuvant chemotherapy or radiotherapy in the treatment of these tumors is limited to isolated case studies.  Only four deaths caused by tumor metastases have been documented to date. ,, Since the period of recurrences ranges in years ,, and the recurrences (local or metastatic) usually being resectable, the role of adjuvant treatment is uncertain and often redundant.
However, there are certain poor prognostic factors which are associated with its aggressive behavior and may be indicators of its possible metastatic potential. These include the presence of vascular invasion, perineural invasion, tumor size greater than 5 cm, positive Ki-67 staining, and low nuclear grade. , However, the Chinese literature review suggests that clinical factors including sex, age, symptoms, tumor size, and location were not related to its malignant potential.  The decision to consider these patients for any adjuvant treatment is therefore on physician's discretion. In fact, the tumors' high rate of resectability limits the need for adjuvant therapy.
Choice of chemotherapy drugs
Several authors have tried different chemotherapy regimens in these tumors. Available case reports showed variable response rates; however, evidence-based guidelines for the proper use of chemotherapeutic agents in solid pseudopapillary tumors of the pancreas are lacking. Kang et al. performed adenosine triphosphate-based (ATP)-based chemotherapy response assay in five patients of resected solid pseudopapillary pancreatic tumors and evaluated tumor cell viability by measuring intracellular ATP levels of drug treated cells and untreated controls.  Drugs used were cisplatin, oxaliplatin, cyclophosphamide, adriamycin, 5 FU, etoposide, and gemcitabine. The results showed that cisplatin was the most potent drug for these tumors. Further, higher expression of RRM1 in these tumors suggested potential resistance to gemcitabine-based chemotherapy. In contrast to this, Shimizu et al.  showed a case of the same tumor which was highly sensitive to gemcitabine, epirubicin, docetaxel, paclitaxel, and mitomycin C as indicated by collagen gel droplet Y embedded culture drug sensitivity test and had comparatively lesser sensitivity to cisplatin and 5 FU. [Table 2] shows the literature results of the use of various chemotherapy drugs in these tumors and subsequent response to treatment. ,,,
|Table 2: Chemotherapy regimens used in solid pseudopapillary tumors of the pancreas|
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Neoadjuvant chemotherapy or radiotherapy
The role of adjuvant therapy in the treatment of solid pseudopapillary neoplasms of the pancreas is unclear, but the role of neoadjuvant therapy in their treatment is well established.
Studies have demonstrated a role for gemcitabine and radiotherapy either to downsize large tumors or to treat the rare case of unresectable disease. ,, Few authors have reported an increased rate of resectability after chemotherapy.  Intra-arterial chemoembolization in patients with multiple hepatic metastases has also been found to be useful when used in palliative setup. 
Radiation therapy is a viable alternative for the treatment of unresectable tumors and can offer improved quality of life, especially regarding pain relief.  Fried et al. observed substantial shrinkage of an unresectable tumor after 6 weeks of radiotherapy.  There are a few case reports which have shown a survival benefit with radiotherapy.  Krug et al. reported that the selective internal radiotherapy (SIRT) induces long-term remissions of the strongly vascularized liver metastases, and the patient was in a good condition without any evidence for hepatic recurrence 4 years after SIRT. 
Role of neoadjuvant chemoradiation
Only rare case reports are available demonstrating the role of neoadjuvant chemoradiation in these tumors. Ideal patient selection is a key to exploit its use. Tumors with small size that can be well taken into a radiation field can be planned by this technique. Guimarγes et al. treated one patient with unresectable tumor with chemotherapy (5-fluorouracil and leucovorin) and radiotherapy (4.500 Gy), which resulted in reduction of tumor volume from 10.2 cm × 9 cm to 3 cm × 3 cm, making it resectable according to an angiotomographic study. The patient, however, refused the surgical procedure and was kept in the outpatient treatment; still, he remained asymptomatic and without signs of metastatic disease for 11 years. 
Role of hormonal therapy
Tamoxifen has been shown to provide stable disease states in certain case reports with positive estrogen receptor status.  It can be a viable treatment option in metastatic patients who are not the candidates for chemotherapy.
Due to the rarity of solid pseudopapillary neoplasms of the pancreas, evidence-based guidelines regarding postoperative follow-up do not exist. As it is demonstrated by this review article, there can be a significant disease-free interval between resection of the primary tumor and the development of metastases. Therefore, annual imaging studies (CT scans of the thorax and abdomen) may be performed for a minimum of 10 years following definitive tumor resection.
| Conclusions|| |
Pseudopapillary tumor of the pancreas is a distinct histological and biologic disease entity with an indolent clinical course. Surgery is the primary therapeutic modality. The use of adjuvant radiotherapy and chemotherapy is individualized depending upon the risk for local recurrence or metastasis. The prognosis in patients with these tumors is favorable. In metastatic patients, metastasectomy is indicated when possible. There is a definite role of both neoadjuvant chemotherapy and radiotherapy in selected cases. The prognosis of patients even with unresectable metastasis is good.
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Conflicts of interest
There are no conflicts of interest.
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