Continuing Education Activity

Solid pseudopapillary pancreatic neoplasms are rare pancreatic tumors accounting for 1% to 2% of exocrine pancreatic lesions. Recent surveys report a 7-fold increase in the incidence of SPEN cases since the past two decades. These are low grade with low malignant potential neoplasms commonly seen in young and adolescent females and rarely affects men. This activity reviews the evaluation and management of solid and papillary epithelial neoplasm (SPEN) of the pancreas and highlights the uncommon incidence of these neoplasms, the role of the diagnostic imaging and management of patients with this condition.

Objectives:

• Identify the etiology and epidemiology of SPEN (solid and papillary epithelial neoplasm).
• Describe the clinicopathological of SPEN of the pancreas.
• Review the radiological findings of SPEN of the pancreas.
• Explain the role of the interprofessional team in selecting and implementing management options available for SPENs.

Introduction

Solid pseudopapillary epithelial neoplasms (SPEN), also known Frantz tumors, are rare pancreatic exocrine neoplasms with age and gender predisposition. This pathology was first described by Dr. Virginia Kneeland Frantz in 1959 and hence the name. Other names include solid pseudopapillary tumor (SPT) of the pancreas, solid pseudopapillary neoplasm (SPN), papillary cystic neoplasm of the pancreas, Hamoudi tumor, or Gruber-Frantz tumor. These are low grade with low malignant potential neoplasms commonly seen in young and adolescent females and rarely affects men [1]. Accurate diagnosis of SPEN is of utmost importance since it has a low malignant potential, and with prompt diagnosis and surgery, the patients could have a long life expectancy including possible cure.

Etiology

Solid pseudopapillary pancreatic neoplasms are rare pancreatic tumors accounting for 1% to 2% of exocrine pancreatic lesions. Recent surveys report a 7-fold increase in the incidence of SPEN cases since the past two decades.[2] This increase is likely representative of improved quality and techniques of radiological imaging and increased usage of screening tests.[3] The etiology of this tumor remains unclear. Suggestions are that these neoplasms develop from either pluripotent pancreatic stem cells or cells of female genital epithelial origin due to increased prevalence in younger females.[4]  

Epidemiology

These neoplasms are commonly seen in young women under the third decade of life (90 to 95%)  with only a small minority diagnosed in men. Few studies have reported a slightly higher incidence in patients of African or Asian ethnicities. However, they can occur in patients of all other races. SPEN has a reported incidence of 0.13% to 2.7% of all pancreatic tumors.

Histopathology

Solid and cystic pseudopapillary and epithelial neoplasms of the pancreas are encapsulated and have a variegated and degenerative appearance with solid, cystic, and papillary areas with foci of hemorrhage and necrosis.[5] This variable appearance has been attributed to vascular ischemia. Some reports described pseudopapillary formation with epithelioid cells or trabecular and microcystic pattern with vascularized stroma.[6] These tumors undergo a histopathological evaluation with markers such as alpha-1-antitrypsin, CD10, CD56, neuron-specific enolase, and vimentin.[7] These tumors negatively stain for any endocrine markers.

Rarely these neoplasms are associated with malignant transformation. The criteria for malignancy have not been well defined. Invasive features such as lymphovascular or perineural invasion with or without infiltration into the surrounding organs point towards a malignant neoplasm. Morphologically malignant neoplasms present as lobulated with focal margins and incomplete encapsulations, whereas, benign neoplasms are round with lobulated margins and complete encapsulation. While solid pseudopapillary tumor of the pancreas is considered to have a low Ki-67 proliferation index because of the indolent nature of such tumors, one study highlighted the role of Ki-67 in prognostication of the adverse outcome in patients with SPENs and therefore should be a consideration as part of the routine histological assessment.[8]

History and Physical

Solid pseudopapillary pancreatic neoplasms characteristically have a long asymptomatic period before the development of any signs or symptoms. Majority of the times, due to the indolent nature of these tumors, these are incidentally diagnosed when the patients undergo screening with imaging studies for other medical reasons. Clinical presentation is non-specific and includes vague abdominal pain or discomfort, diarrhea, or nausea. These tumors commonly arise in the tail of pancreas, therefore, rarely present with obstructive symptoms such as jaundice or gastric outlet obstruction. Endocrine symptoms rarely present with these neoplasms. Unlike malignant tumors, weight loss and fatigue are rare. It is most often a benign neoplasm. However, 10% to 15% of the cases are malignant. The liver was reported to be a common site of metastasis, while it could also spread distantly to other organs as well. 

Evaluation

Gross intratumoral or peritumoral hemorrhage strongly suggests solid pseudopapillary pancreatic neoplasm.  Calcification is relatively common in SPENs and may be seen either peripherally or within the center of the lesion. Unenhanced computerized tomography typically shows calcifications in the tumors. The iodinated contrast imaging shows clear enhancement during the arterial phase that persists during the portal and late phases. Hemorrhage contained within a mixed solid and cystic tumor is a characteristic feature of SPENs. These tumors are not associated with elevation of tumor markers such as CA 19-9 or CEA.[9]  Metastatic disease correlates more with large tumor size, and therefore, EUS-guided tumor biopsy can be useful in confirming malignant transformation preoperatively.[10]

Treatment / Management

Treatment is surgery with curative intent and is associated with excellent long term clinical outcomes and overall prognosis — the reported 5-year survival of 90 to 95%. However, SPENs can rarely progress with either local recurrence or distant metastasis, and distant metastasis occurs predominantly in the liver. Early diagnosis of SPEN is crucial to allow for curative resection.

Differential Diagnosis

The clinical presentation at the time of diagnosis is variable and could resemble other pathologic entities. The other tumors that appear as SPEN can be confused with mucinous cystic neoplasm of pancreas, neuroendocrine tumors with cystic features (cystadenoma or cystadenocarcinoma), serous microcystic adenoma, or intraductal papillary mucinous neoplasm (IPMN). The definitive diagnosis has its basis on the combination of typical imaging findings and immunohistological assessments. There are currently no specific or sensitive tumor markers available to diagnose SPENs.

Medical Oncology

The definitive treatment is surgery. At present, there is no role for chemotherapy or radiation for localized tumors as surgery alone is curative. However, for rare malignant presentation or transformation, currently, the evidence is lacking regarding optimal systemic chemotherapeutic regimens. These patients are treated in the lines of pancreatic adenocarcinoma (chemotherapy) or based on actionable mutations detected on next-generation sequencing.

Staging

Currently, there are no specific pathological staging assessments available. However, these tumors can be staged based on the AJCC (American Joint Committee on Cancer) staging system for high grade or malignant tumors defining the extent of disease in patients with malignant neoplasms by utilizing TNM scoring systems. 

Prognosis

The overall prognosis of the SPEN of the pancreas is excellent due to favorable biology and benign presentation in majority of the cases. Surgical resection is very often curative. However, close follow up is recommended to monitor for local or distant recurrence, although rare.

Complications

SPENs rarely develop a malignant transformation. If the malignancy is localized, it could be curable with surgical resection. If the tumor is involved with distant metastasis, then the treatment intent is palliative.

Deterrence and Patient Education

Solid pseudopapillary tumors of the pancreas are rare malignancies that can be curable with surgical resection. There are currently no screening recommendations to identify these tumors earlier. Any symptoms such as abdominal pain, nausea, or vomiting should prompt medical attention for further evaluation.

Pearls and Other Issues

SPEN are uncommon and are often indolent pancreatic tumors of unknown etiology with low malignant potential. These commonly present in young women suggestive of the possible role of hormonal factors. Diagnosis of these tumors is by diagnostic imaging. The definitive treatment is surgery, which is often curative in the majority of cases and associated with excellent long term prognosis. These neoplasms should be a consideration in the differential diagnosis of any cystic pancreatic tumors, specifically in a young woman. Despite the indolent nature of SPENs, most patients require major pancreatic resection. Surgery can be curative regardless of size or location of the tumor and local recurrence or metastasis after complete resection is rare. 

Enhancing Healthcare Team Outcomes

Diagnosis and management of solid pseudopapillary pancreatic neoplasms require an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. Clinicians (MDs, DOs, NPs, PAs) will typically be the ones to diagnose the condition and order the lab tests; given the absence of symptoms earlier in the disease, this step is crucial to prompt treatment initiation.

An interprofessional team, including histopathologists, oncologists, and surgeons, can provide a holistic and integrated approach to achieve the best possible clinical outcomes on the management of the solid pseudopapillary epithelial neoplasms. These clinicians will also determine when and the type of surgical intervention, which nursing will assist. Specialty nursing including operating room, perianesthesia, and medical-surgical nurses will also be responsible for the care and monitoring and communicate their observations to the rest of the team.

While chemotherapy is not presently a part of the treatment picture for solid pseudopapillary epithelial neoplasms, post-operative care will include medication therapy for pain and possible infection prophylaxis. Pharmacists can make medication recommendations based on the patient's current drug profile, comorbid conditions, and also verify dosing, and report recommendations to the nurses or prescribers. In this manner, the entire interprofessional team collaborates to achieve optimal outcomes. [Level V]