Solid pseudopapillary tumor of the pancreas: a rare entity in children

Solid pseudopapillary tumors (SPTs) constitute 0.2 to 2.7% of non-endocrine primary tumors of the pancreas and comprise the majority (70%) of pediatric pancreatic neoplasms. These tumors are of unclear pathogenesis, low malignancy and favorable prognosis. Surgical resection offers an excellent chance for longterm survival, even in the presence of distant metastasis. The objective of this study is to review our experience in the management of SPT in a 12 years old girl at the pediatric hospital of the University hospital of Casablanca, in Morocco and provide an update on current management in pediatric population.


Introduction
Solid pseudopapillary tumors (SPTs) are rare neoplasms accounting for 2% to 3% of pancreatic tumors and 0.9% to 2.7% of exocrine pancreatic neoplasms [1]. The first case of SPTs was reported by Virginia Frantz in 1959 [2]. This neoplasm, which has had a variety of names, was designated as SPT by the World Health Organization in 1996 [2]. SPTs primarily affect young females between 20 and 30 years. It is the most frequent pancreatic tumor in the second decade of life [3]. The majority of SPTs are indolent with favorable prognosis and have an excellent long-term outcome after complete surgical resection [3][4][5]. However, SPTs are considered malignant neoplasms due to metastases which are present at the time of diagnosis in 5% to 20% of the cases.

Patient and observation
We present our experience in the management of SPT in a 12 years  Pathologic results, combined with immunohistochemical study were consistent with the diagnosis of SPT ( Figure 3, Table 1). CD 99 which is a particular dot-like intracytoplasmatic marker, was highly expressed ( Figure 4). This last appears to be highly unique for SPTs.
Chromogranin and desmine markers were negative, thereby eliminating an endocrine tumor. The decision of the multi-disciplinary meeting was surgery without preoperative chemotherapy or radiotherapy. The tumor was resected en bloc with a corporo-caudal pancreatectomy without splenectomy. Macroscopically, it demonstrated characteristic areas of hemorrhage and necrosis, that were friable, with tissular portions having a brownish color ( Figure 5).
Histological examination showed a proliferation of tumors arranged in islets, layers, papillae, cords and tubes ( Figure 3). Mitotic activity (Ki-67) was very low (5%). No perineural or vascular invasion was found.
Surgical margins were negative. No postoperative diabetes was developed. Follow-up imaging will include CT at 3 to 6 month intervals and later annually.

Discussion
Epidemiology: SPTs comprise the majority of pediatric pancreatic neoplasms [5]. It is a unique tumor of low malignant potential, most commonly affecting non Caucasian (especially Asian and African) young women, between 20 and 40 years old [6,7]. The female to male ratio is 8-9 to 1 [3]. About 20-25% of the cases are seen in pediatric patients [8]. The origin and histogenesis of SPTs is still unknown, although it is thought to origi¬nate from totipotential stem cells with the capacity for both endocrine and exocrine differentiation [7].

Clinical features: Lee et al. demonstrated that SPTs in children
presented with a palpable mass (60%), followed by abdominal pain (33.3%) [1]. SPTs are also often texturally fairly soft; accounting for the rarity of ductal dilatation and jaundice even for tumors arising in the pancreatic head [7].
Biologic features: pancreatic enzymes and common serum tumor markers (alpha-fetoprotein, carcinoembryonic antigen and betahuman chorionic gonadotrophin) are consistently negative, as was seen in our patient [3,5]. There are no known SPT-specific serum markers [3].
Imaging features: SPTs may appear in any part of the pancreas [1].
Ultrasonographically, SPTs may appear as hypoechoic solid masses, solid masses containing cystic areas or cystic mass [4]. The fibrous capsule may be visualized as an echogenic or less commonly, hypoechoic rim [2]. The most helpful examination is the CT [9]. It helps to configurate the mass, determine the size, define the pancreatic anatomy and recognize the invasion into surrounding structures [4,10]. CT demonstrates a well circumscribed mass, surrounded by a fibrous capsule that may contain calcifications [2]. A delayed enhancement of the thick fibrous capsule can also be seen. approach is mandatory and intensive follow-up is recommended [11].
Preoperative cytologic diagnosis can be confirmed by endoscopic ultrasound scan with fine-needle aspiration biopsy or transabdominal percutaneous biopsy using a trocar needle, with ultrasound or CTguidance but present a risk of tumor dissemination, so his indication remains controversial [3,8,9].
Pathology: SPTs are a rare epithelial solid tumor of the pancreas that invariably develop significant cystic degeneration, acquiring the characteristic solid-cystic appearance.
Gross appearance: macroscopically, SPTs are usually large, well circumscribed and have mixed solid whitish brown areas with foci of necrosis and hemorrhage and cystic areas containing necrotic fragments. As they increase in size, the areas of cystic-hemorrhagic degeneration grow until they get simular to a pseudocyst [3,9].
Histologic appearance: histologically, SPTs have a very characteristic appearance of solid areas composed with of poorly cohesive cells that form pseudopapillae around thin blood vessels.
These polygonal epithelioid cells have medium-size, soft appearance, basophilic cytoplasms, large rounded or ovoid nuclei, with reinforced nuclear membrane and thin chromatin [3,9]. Foaming histiocytes, cholesterol crystals, fibrosis and calcifications can be found. Very rare mitosis are observed; glycogen or mucin are not observed. The tumor cells are PAS and Alcian blue negative [9]. The histological features that lead to aggressive behavior, malignant potential and the worst prognosis are vascular, neural invasion and involvement of the adjacent pancreas, adding in some reports the degree of nuclear atypia, high mitotic index and many apoptotic features. If these criteria are presented, some authors suggest calling them "solid pseudopapillary carcinomas" [9].
Immunohistochemical: immunohistochemical study is very useful, revealing a diffuse positivity for certain histochemical markers like neuron-specific enolase (NSE), vimentin, CD-10 and béta-catenin, which is not specific [9]. α1-antitrypsin and α1-antichymotrypsin are intensely positive, but in a small group of cells [9]. Immunostaining for estrogen receptors, especially progesterone receptors, is sometimes positive; this marking evokes a possible hormonosensitivity of SPTs and could explain the female predominance [6]. Notohara and coworkers found that SPTs exhibited unique immunohistochemical features with expression of CD56, CD10 and local expression of other neuroendocrine markers. These findings suggest that papillary and solid epithelial cells are with predominance of exocrine features but having the capacity for dual (exocrine and endocrine) differentiation [10]. Immunostaining for chromogranin is negative, thereby eliminating an endocrine tumor that is the main differential diagnosis [6]. Cells are consistently negative for mucin (ductal origin), enzymes (acinar origin) and hormones (endocrine origin), which supports the theory that SPTs arise from an embryonal pancreatic pluripotent cell [3]. According to recently published data, a particular dot-like intracytoplasmatic expression of CD99 is highly unique for SPTs [3]. To date, this cytoplasmatic paranuclear "dot-like" pattern has not been described in any other type of endocrine or exocrine pancreatic tumors included in the differential diagnosis of SPTs [3].

Treatment and prognosis: the current recommendations concur
that children with pancreatic SPTs should undergo complete surgical resection that is dictated by tumor location and remains the treatment of choice [5]. Distal pancreatectomy with or without splenic preservation can be performed for tumors in the body or tail and pancreaticoduodenectomy (Whipple or Longmire procedure) for tumors of the head [4,9]. Invasion to the portal vein or superior mesenteric artery should not be included as a criterion for nonresectability. Extensive lymphatic dissection or more radical local approaches are not indicated [4]. Chemotherapy, radiation and hormone therapy are rarely used; their indication is discussed particularly in non-localized forms. Surgery is curative in more than 95% of localized tumors. Survival after complete excision of the tumor is 80-90%; the recurrence rate is 10 to 15%. Malignant forms account for about 15% of cases. The criteria for malignancy are determined Page number not for citation purposes 4 by vascular, ganglionic, perineural invasion of neighboring organs and tumor size greater than 5cm. The prognosis of SPTs is favorable, even in the presence of metastases [10]. Metastases can be hepatic, peritoneal or pulmonary [6]. There is general consensus that surgical debulking (in contrast to other pancreatic malignancies) should be performed for these metastases [4]. Although surgical resection is generally curative, a close follow-up is advised in order to diagnose a local recurrence or distant metastasis and choose the proper therapeutic option for the patient [12].
Differential diagnosis: despite the technological advances, preoperative diagnosis is difficult because of the similarity of findings among other pancreatic tumors [4]. In children, secondary pancreatic involvement of tumors such as neuroblastoma, leukemia, lymphoma and lymphoproliferative disorders is more common than primary neoplasms like pancreatoblastoma [4,6].
It is a rare exocrine pancreatic tumor that typically have the form of

Competing interests
The authors declare no competing interests.

Authors' contributions
All the authors have read and agreed to the final manuscript. Table and figures   Table 1: immunohistochemistry for our case of SPT