—  SPECIALTY CONFERENCE  —

Pediatric Pathology

Case 4 - Solid Pseudopapillary Tumor of the Pancreas

Ana M. Gomez
Children's Medical Center
Dallas, TX


Click on each slide thumbnail image for an enlarged view
Clinical History
The patient, a previously healthy 16 year old Hispanic female, presented to the Emergency Department with a three-day history of abdominal pain. The pain awoke her from sleep and became progressively severe. The pain was centered in the left upper quadrant, and was associated with nausea and vomiting. Physical examination revealed an obese teenager in moderate distress. The abdomen was soft, non-distended, with moderate discomfort to deep palpation of the left upper quadrant. She had normally active bowel sounds. Laboratory examination revealed a white count of 15.7 with 86% neutrophils. Amylase and lipase were within normal limits. An abdominal CT scan revealed a cystic mass in the pancreatic body, diagnosed radiologicaly as a pancreatic pseudocyst versus a duplication cyst.

The patient underwent distal pancreatectomy and splenectomy on hospital day 3. She did well postoperatively. A CT scan of the chest was performed and was normal. She was discharged on hospital day 10, postoperative day 7. The patient received no further therapy and remains well with no evidence of disease 6 months after her diagnosis.


Case 4 - Figure 1 - Distal pancreas, peripancreatic tissue and spleen (gross)
Case 4 - Figure 2 - Pancreas with well-circumscribed partially cystic mass (gross)
Case 4 - Figure 3 - Pancreas mass exhibiting a variable growth pattern with solid and papillary areas (H & E stain)



Case 4 - Figure 4 - Pancreas mass solid areas composed of small uniform cells with eosinophilic cytoplasm, ovoid uniform nuclei with finely dispersed chromatin and inconspicuous nucleoli (H & E stain)
Case 4 - Figure 5 - Pancreas mass with papillary-appearing areas (H & E stain)



Case 4 - Figure 6 - Pancreas tumor cells strongly and uniform positive (Vimentin immunoperoxidase stain)
Case 4 - Figure 7 - Pancreas tumor cells exhibit positive nuclear staining (beta-catenin immunoperoxidase stain)

Gross Features
Gross examination revealed an 11.5 x 11 x 2.5 cm/331 gm surgical specimen consisting of an 8 x 8 x 6 cm segment of distal pancreas, attached peripancreatic tissue, and an 11 x 5.8 x 5 cm/150 gm spleen (Figure 1). Serial sectioning through the pancreas demonstrated a 7 x 6.5 x 2.5 cm well circumscribed partially cystic mass with a yellow-tan to pink-tan variegated cut surface, and multiple areas of necrosis and hemorrhage (Figure 2). The peripancreatic fibroadipose tissue appeared soften and necrotic, but no extrapancreatic extension of the tumor or involvement of the spleen was demonstrated.

Histologic Features
Histologic sections through the tumor revealed a well circumscribed lesion with a variable growth pattern with solid and papillary areas (Figure 3). Extensive areas of hemorrhage and necrosis were scattered throughout. The solid areas were composed of small uniform cells with eosinophilic cytoplasm, ovoid uniform nuclei with finely dispersed chromatin, and inconspicuous nucleoli (Figure 4). Occasional nuclear grooves were observed and mitoses were rare. In some areas, the tumor appeared papillary, with the cells furthest from the vessels undergoing degeneration and death, causing the remaining cells to form pseudorossettes or papillae (Figure 5). The cystic areas were the result of more extensive necrosis and hemorrhage. The peripancreatic tissue revealed fat necrosis, but no extrapancreatic extension of the tumor was identified. The spleen was histologically unremarkable. Immunohistochemical staining demonstrated that tumor cells were strongly and uniformly positive for Vimentin (Figure 6) and CD10, but only focally for synaptophysin. In addition, tumor cells also demonstrated positive nuclear staining for beta catenin (Figure 6). Cytogentic analysis of the tumor revealed a 46-XX karyotype.

Differential Diagnosis
Pancreatoblastoma
Islet cell tumors

Diagnosis: Solid pseudopapillary tumor of the pancreas

Discussion
Solid pseudopapillary tumor (SPT) of the pancreas is a tumor of uncertain malignant potential and accounts for about 1-2% of all pancreatic tumors [1]. More than 90% of patients are young women in their 20s. Patients commonly present with abdominal discomfort, distention or mass in the upper abdomen. Physical examination is often normal, other than the presence of an upper abdominal mass [2]. A CT scan of the abdomen usually shows a well-encapsulated mass with both solid and cystic components. There may be calcification at the periphery of the mass and also peripheral contrast enhancement [3]. The accuracy of radiologic diagnosis is about 60% [4]. Preoperative diagnosis may be aided by CT-guided fine needle aspiration [5]. The diagnostic cytological features are pseudopapillary arrangement and cytoplasmic granules that are acidophilic, PAS-positive and diastase-resistant [1].

Macroscopically SPT are generally well circumscribed encapsulated spherical masses with an average diameter ranging from 8 to cm. The growth pattern is variable with cystic areas and areas of hemorrhage and necrosis. The tumor microscopically has solid, cystic and papillary components. The solid areas are composed of nests and sheets of small, uniform cells with eosinophilic cytoplasm which may contain PAS-positive eosinophilic hyaline globules. Nuclei are uniform, round to ovoid, with finely dispersed chromatin and inconspicuous nucleoli. The nuclei frequently display a groove or indentation. Mitoses are few. The solid areas are also characterized by a rich and delicate vascular network. The most characteristic feature of this tumor is the formation of pseudpapillary areas where many of the cells farthest from the vessels undergo degeneration and death, causing the remaining cells to form pseudorosettes or pseudopapillary patterns; this organoid pattern may mimic an endocrine tumor. The cystic areas result from more extensive degenerative changes and there may be conspicuous necrosis and hemorrhage. Foamy macrophages may be numerous, and cholesterol clefts may be present [1, 2].

Electron microscopy demonstrates cell junctions in the majority of cells, supporting epithelial differentiation. Most cells are rich in mitochondria and resemble those of normal ducts or acini. Some SPT cells contain rare neurosecretory or zygmogen granules [1].

By immunohistochemical staining, tumor cells are usually positive for CD10 and beta catenin (nuclear pattern) [6, 7] . Tumor cells are generally negative for chromogranin and weakly positive for synaptophysin. Positivity for α1-anti-rypsin, neuron specific enolase and vimentin has been reported. In general, these tumors do not express CEA or CA19-9. Immunohistochemical staining for progesterone receptors has been demonstrated, but estrogen receptors have not been found [8].

Limited studies about the molecular changes in SPT are available. Genetically, SPPTs are different from ordinary ductal adenocarcinomas and almost always exhibit beta-catenin mutations [6]. One case has been shown to have a distinctive unbalanced translocation between chromosomes 13 and 17 [9].

The origin of this tumor remains unknown. Due to the prevalence of this tumor in females, the presence of progesterone receptors, and the close relationship of the pancreas to the genital ridges during embryogenesis, it has been postulated that SPT might be derived from pluripotent stem cells from the genital ridge [10]. These stem cells may become attached to the pancreatic tissue during embryogenesis. The ultrastructural and immunohistochemical studies suggest SPT originate from pluripotent embryonal cells that are not yet differentiated into either endocrine or exocrine and thus have the capability to show acinar, ductal and in some instances, neuroendocrine differentiation [10].

The differential diagnosis includes islet cell tumors. The nuclei of both tumors may be similar, but papillae, hyaline globules, and the presence of foamy cell histiocytes suggest the diagnosis of SPT, while strong expression of chromogranin favors the diagnosis of islet cell tumor [1]. In addition, expression of CD10 and nuclear staining for beta-catenin, also favor the diagnosis of SPT [6-7]

The overall prognosis of this tumor is excellent with surgical resection. However, the clinical behavior may be unpredictable and histologically benign tumors can show local aggressiveness. The incidence of malignancy is thought to be about 15% [10]. Common sites of metastasis include liver (42%) and lymph nodes (25%) [3]. Interestingly, this tumor has a high propensity for peritoneal spread, similar to those of ovarian tumors. Invasion into the surrounding organs is not uncommon with spleen, portal vein, and duodenum being the most common structures affected [1]. Several features like old age, invasion into adjacent normal pancreatic parenchyma, cellular atypia, vascular and perineural invasion, are associated with increased malignant potential [11]. Surgery is the mainstay of treatment. Patients with localized disease are usually cured by surgery. Even in cases considered malignant, the survival of patients is prolonged after adequate surgical resection [12]. Prolonged survival of patients with residual disease after surgery, and in patients with unressectable tumors is well reported in the literature [12]. Surgical debulking may help to reduce the tumor load, thus prolonging survival. Due to this prolonged survival of patients with SPT, surgical resection is usually restricted to the tumor affected part of of the pancreas, with maximal preservation of normal pancreatic tissue. An intraoperative frozen section is usually used to assure an adequate resection margin. The use of adjuvant chemotherapy is frequently restricted to locally advanced and metastatic disease, and thus information is scant. The use of radiotherapy has only been reported in a few cases [13].

References

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  2. Mao C, Guvendi M, Domenico DR, et al. Papillary cystic and solid tumors of the pancreas: a pancreatic embryonic tumor? Studies of three cases and cummulative review of the world's literature. Surgery 1995;118:821-28.
  3. Dong PR, Lu DS, Degregario F, et al. Solid and papillary neoplasm of the pancreas: radiological-pathological study of five cases and review of the literature. Clin Radiol 1996;21:702-5.
  4. Procacci C, Graziani R, Bicego E, et al. Papillary cystic neoplasm of the pancreas: radiological findings. Abdom Imaging 1996;20:554-8.
  5. Pelosi G, Iannucci A, Zamboni G, et al. Solid and cystic papillary neoplasm of the pancreas: a clinicopathologic and immunochemical study of five new cases diagnosed by fine-needle aspiration cytology and a review of the literature. Diagnosti Cytopathol 1995;13:233-46.
  6. Abraham SC, Klimstra DS, Wilentz RE, et al. Solid pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations. Am J Surg Pathol 2002;160:1361-9.
  7. Notohara K, Hamazaki S, Tsukayama C, et al. Solid-pseudopapillary tumor of the pancreas: Immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol 2000;24:1361-71.
  8. Zamboni G, Bonetti F, Scarpa A, et al. Expression of progesterone receptors in solid-cystic tumors of the pancreas: a clinicopathological and immunohistochemical study of ten cases. Virchows Arch A Pathol Anat Histopathol 1993;423:425-31.
  9. Grant LD, Laweres GY, Meloni AM, et al. Unbalanced chromosomal translocation, der(17)t(13;17)(q14;p11) in a solid and cystic papillary epithelial neoplasm of the pancreas. Am J Surg Pathol 1996;20:339-345.
  10. Canzonieri V, Beretta M, Buonadonna A, et al. Solid pseudopapillary tumor of the pancreas, Lancet Oncology 2003;4:255-56.
  11. Ng KH, Tan PH, Thng CH, et al. Solid pseudopapillary tumor of the pancreas. ANZ J Surg 2003;73:410-415.
  12. Martin RC, Klimstra DS, Brennan MF, et al. Solid pseudopapillary tumor of the pancreas: a surgical enigma? Ann Surg Oncol 2002;9:35-40.
  13. Rebhandl W, Felberbauer FX, Puig S, et al. Solid-pseudopapillary tumor of the pancreas (Frantz tumor) in children: report of four cases and review of the literature. J Surg Oncol 2001;76:289-96.