HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) CME Test (opens in a new window) Appendix E1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chung, E. M. Articles by Conran, R. M. Search for Related Content PubMed PubMed Citation Articles by Chung, E. M. Articles by Conran, R. M. Related Collections Pediatric Radiology Gastrointestinal Radiology

From the Archives of the AFIP

Pancreatic Tumors in Children: Radiologic-Pathologic Correlation¹

¹ From the Department of Radiologic Pathology, Armed Forces Institute of Pathology, Alaska and Fern streets NW, Washington, DC 20306-6000 (E.M.C.); the National Capitol Radiology Consortium, National Naval Medical Center, Bethesda, Md, and Walter Reed Army Medical Center, Washington, DC (M.D.T.); the Institute for Pediatric Medical Education, Uniformed Services University of the Health Sciences, Bethesda, Md (R.M.C.); and the Department of Pathology, Georgetown University School of Medicine, Washington, DC (R.M.C.). Received February 2, 2006; revision requested March 13 and received April 21; accepted April 21. All authors have no financial relationships to disclose. Address correspondence to E.M.C. (e-mail: chunge{at}afip.osd.mil).

	Abstract

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
Pancreatic neoplasms are rare in children and have a different histologic spectrum and prognosis than those in adults. In general, these tumors are well demarcated with expansile rather than infiltrating growth patterns. They may be quite large at diagnosis, and central cystic necrosis is common. They infrequently cause biliary duct obstruction. The imaging appearance of each neoplasm reflects its pathologic features. Pancreatoblastoma is the most common pancreatic neoplasm in young children. At imaging, pancreatoblastomas are heterogeneous and often multilocular with hyperechoic and enhancing septa. Solid-pseudopapillary tumor occurs in adolescent girls. It is heterogeneous in internal architecture, with a mixture of solid and cystic hemorrhagic and necrotic elements. This tumor is distinguished by its fibrous capsule and hemorrhagic nature, which are best shown at magnetic resonance imaging as a dark rim on T1- or T2-weighted images and hyper-intense foci on T1-weighted images, respectively. Islet cell tumors in children are insulinomas or gastrinomas. These tumors manifest early due to hormonal syndromes and are distinguished by their small size, homogeneous appearance, and intense enhancement with intravenous contrast material. All pancreatic neoplasms in children are capable of producing metastases, usually to the liver and lymph nodes; however, on the whole, these tumors have a better clinical outcome than most pancreatic tumors in adults. Knowledge of the differential diagnosis of pancreatic masses in children and their relatively good prognosis may promote correct preoperative diagnosis and appropriate treatment.

	LEARNING OBJECTIVES FOR TEST 6

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
After reading this article and taking the test, the reader will be able to:

• Describe the imaging features of pancreatic tumors in children and the pathologic bases of these features.
  
• Identify the features of each of these tumors that may allow differentiation from other pancreatic masses in children.
  
• Discuss the differential diagnosis and management of pancreatic masses in pediatric patients.
  

	Introduction

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
Pancreatic tumors are quite rare in children, causing less than 0.2% of malignant pediatric deaths (1). The scarcity of cases limits our ability to study these tumors. Even authors from large referral centers, reporting their experience over 20–35 years, have encountered only small numbers of cases (2–5). In a surgical review of 92 pancreatic disorders in children over a period of 10 years, only 10 cases were tumors (6). In addition, confusing and evolving nomenclature makes it difficult to compare current cases to more remote cases in the literature. In general, pancreatic tumors in children have a different histologic spectrum and better clinical outcome compared to those in adults.

Pancreatic neoplasms are divided into epithelial and nonepithelial types (Table). Epithelial tumors may be further classified as exocrine or endocrine. Exocrine tumors may be of acinar, ductal, or undetermined cell origin. Only a small subset of the described neoplasms occurs in the pediatric population. The acinar cell tumor that occurs almost exclusively in children is pancreatoblastoma. Although rare, pancreatoblastoma is the most common pancreatic tumor of young children. Carcinoma of acinar cell origin has rarely been reported in older children. Ductal adenocarcinoma and its many variants are the most common pancreatic tumors in adults, but these are exceedingly rare in children. No convincing cases of the cystic neoplasms (serous cystadenoma and mucinous cystic neoplasm) have been reported in children (7). Solid-pseudopapillary neoplasm, currently classified as an epithelial neoplasm of uncertain cellular origin, is most commonly diagnosed in adolescent girls and young women. Endocrine cell tumors are uncommonly encountered in older children, and focal or diffuse neuroendocrine adenomatosis of the gland can cause neonatal hypoglycemia. Nonepithelial neoplasms arising primarily in the pancreas are quite rare in children. These include lymphoma, primitive neuroectodermal tumor, and mesenchymal tumors. Secondary involvement of the pancreas by adjacent tumor, especially neuroblastoma, may be difficult to distinguish from a primary pancreatic tumor and is much more common than the latter. Congenital and acquired cystic lesions can occur in children and mimic cystic neoplasms.

	Pancreatoblastoma

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
Pancreatoblastoma, also called pancreaticoblastoma or infantile-type carcinoma of the pancreas, is the most common pancreatic tumor of young children (8). Like all pancreatic tumors in children, pancreatoblastoma is rare, accounting for only 0.2% of 645 pancreatic tumors reviewed by Cubilla and Fitzgerald (9). The tumor was first described in a 15-month-old boy as "infantile adenocarcinoma of the pancreas" by Becker (10) in 1957. In subsequent case reports, Horie et al (11) in 1977 observed histologic similarities to the normal embryonic appearance of the pancreas at 8 weeks gestation, analogous to other embryomas, and proposed the name pancreatoblastoma. Since then, fewer than 75 cases have been reported in the literature.

Clinical Features
Pancreatoblastoma most commonly occurs in the first decade of life. The age range is fetus to 9 years (mean, 4.5 years), although rare cases in adults have been reported (11–16). There is a male predominance ranging from 1.3:1 to 2.7:1 (8,14,17). More than half of reported cases are in Asians (8,17). Patients most commonly present with an asymptomatic, large abdominal mass (15,18–20). Those with symptoms usually have nonspecific complaints such as abdominal pain, fatigue, lethargy, weight loss, anorexia, diarrhea, or vomiting (13–15,18). Jaundice is uncommon (8,13,14). There are reports of associated elevated -fetoprotein level in up to one-third of patients (8), as seen in other embryonal tumors such as hepatoblastoma and embryonal carcinoma.

Congenital cases of pancreatoblastoma have been described in association with Beckwith-Wiedemann syndrome, and these are predominantly cystic in nature (16,21). Beckwith-Wiedemann syndrome is a genetic, systemic disorder characterized by macrosomia, macroglossia, omphalocele, and visceromegaly. Patients are at increased risk of developing embryonal tumors, including nephroblastoma, hepatoblastoma, rhabdomyosarcoma, and pancreatoblastoma (16,21,22). The risk of malignancy is estimated to be about 4% (23).

For information on the molecular genetics of pancreatoblastoma, see Appendix E1 at radiographics.rsnajnls.org/cgi/content/full/26/4/1211/DC1.

Pathologic Features
Gross Features.— Pancreatoblastomas are usually large, solitary masses (Fig 1). The size range is 1.5–20 cm with a mean of 10.6 cm (14). Approximately half arise in the head of the pancreas (8,13,15). The tumor is a well-defined or partially circumscribed, solid mass with lobulated margins (Fig 1) (8,14,24). The cut surface is yellowish to tan with lobulations separated by fibrous bands (13–15). The mass may contain cystic spaces due to hemorrhagic necrosis and cystic degeneration (8,9,24) (Fig 1). They may be grossly cystic, as reported in most cases associated with Beckwith-Wiedemann syndrome (21).

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Pancreatoblastoma in an 11-year-old girl who presented with abdominal pain, vomiting, and syncope after minor trauma. (a) Computed tomographic (CT) scan enhanced with intravenous contrast material shows a large, well-circumscribed, heterogeneous mass growing exophytically from the body and tail of the pancreas. Round, unenhancing cystic areas (arrow) and foci of intense enhancement (arrowheads) are noted within the mass. (b) Photograph of the cut surface of the resected gross specimen shows the encapsulated heterogeneous mass with cystic components filled with serous fluid (arrows). (c) Photomicrograph (original magnification, x16; hematoxylineosin [H-E] stain) shows small, rosette-like glandular structures (arrows) intermixed with solid sheets of uniform epithelial cells (arrowheads).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Pancreatoblastoma in an 11-year-old girl who presented with abdominal pain, vomiting, and syncope after minor trauma. (a) Computed tomographic (CT) scan enhanced with intravenous contrast material shows a large, well-circumscribed, heterogeneous mass growing exophytically from the body and tail of the pancreas. Round, unenhancing cystic areas (arrow) and foci of intense enhancement (arrowheads) are noted within the mass. (b) Photograph of the cut surface of the resected gross specimen shows the encapsulated heterogeneous mass with cystic components filled with serous fluid (arrows). (c) Photomicrograph (original magnification, x16; hematoxylineosin [H-E] stain) shows small, rosette-like glandular structures (arrows) intermixed with solid sheets of uniform epithelial cells (arrowheads).

View larger version (199K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  Pancreatoblastoma in an 11-year-old girl who presented with abdominal pain, vomiting, and syncope after minor trauma. (a) Computed tomographic (CT) scan enhanced with intravenous contrast material shows a large, well-circumscribed, heterogeneous mass growing exophytically from the body and tail of the pancreas. Round, unenhancing cystic areas (arrow) and foci of intense enhancement (arrowheads) are noted within the mass. (b) Photograph of the cut surface of the resected gross specimen shows the encapsulated heterogeneous mass with cystic components filled with serous fluid (arrows). (c) Photomicrograph (original magnification, x16; hematoxylineosin [H-E] stain) shows small, rosette-like glandular structures (arrows) intermixed with solid sheets of uniform epithelial cells (arrowheads).

Imaging Features
Although the pathologic features of pancreatoblastoma are well described in the literature, few series describe the radiologic features of pancreatoblastoma. Often the mass is so large at presentation as to make determination of the organ of origin quite difficult. In the series of Montemarano et al (15), in only half of the cases did the imaging appearance suggest the pancreas as the organ of origin. These large tumors typically compress surrounding structures without appearing to invade them, although local invasion may be evident at surgical resection (11,13,15,18). Dilatation of the biliary tree is uncommon, although half arise in the pancreatic head and most are quite large at presentation. This is likely due to the soft consistency of the tumor (15). Identification of local adenopathy at imaging is difficult (15). Encasement of large arteries has been reported (17,18).

At sonography, the majority of pancreatoblastomas appear as well-circumscribed heterogeneous masses with solid and cystic components (15,17). Cystic structures are hypoechoic with hyperechoic internal septa (15,18,19,25). Occasionally, a hypoechoic, solid mass is seen (25).

At CT, the mass is most commonly well or partially circumscribed, although an infiltrative margin is uncommonly encountered (13,15). The tumor is often smooth and may be multilobulated (25). Although lobulation is typically identified at gross pathologic inspection, it is an inconstant finding at CT (15). In the majority of cases, the mass is heterogeneous due to internal cystic areas, reflecting areas of necrosis seen at pathologic inspection (Fig 1). Frequently, the tumor appears multiloculated with enhancing septa (15,18,25). Small punctate, clustered, or curvilinear calcifications may be identified (15,25). Although there are few reports of cases with imaging before and after administration of intravenous contrast material, attenuation similar to that of enhancing vessels is common at CT (15) (Fig 1). Hepatic metastases are typically hypoattenuating at CT.

Few reports or series describing the magnetic resonance (MR) imaging appearance of pancreatoblastoma exist, and those available involve small numbers of cases. Typically, pancreatoblastomas are well marginated with low to intermediate signal intensity on T1-weighted images and heterogeneous high signal intensity on T2-weighted images (13,15,20). Low signal intensity on T1-weighted images corresponds to foci of necrosis (26). One reported case demonstrated intense enhancement on MR images obtained with intravenous contrast material (15). One report of MR imaging of hepatic metastases demonstrated signal intensity characteristics paralleling those of the pancreatic primary tumor (15).

Invasion of adjacent organs and distant metastases may occur with pancreatoblastoma. If locally advanced, the tumor is poorly marginated and invades the surrounding pancreas, as well as peripancreatic tissue and adjacent organs (5,9, 14). Biliary invasion has been reported (15). Vascular invasion is rare, although portal and mesenteric vein invasion has been reported. Metastases to the liver and abdominal lymph nodes are found in 35% at presentation (13–15,18). Less commonly, metastases are seen in the lung and brain (15,24). Rare cases of metastasis to the omentum, pelvic cul-de-sac, colon, spleen, kidney, and adrenal glands have been reported (14,15).

Differential Diagnosis
When the mass is large and not clearly arising from the pancreas, common tumors of adjacent organs occurring in young children must be considered. These include neuroblastoma, Wilms tumor, hepatoblastoma, and other primary liver tumors. Non-Hodgkin lymphoma occurs in children in this age group and may involve the pancreas, especially Burkitt lymphoma. Predominantly cystic pancreatoblastomas can appear radiologically similar to solid-pseudopapillary tumor, but the epidemiologic characteristics of these two tumors are dissimilar. Cystic pancreatoblastomas tend to occur in newborn patients with Beckwith-Wiedemann syndrome, more commonly boys (27), whereas solid-pseudopapillary tumor tends to arise in adolescent girls and young women. Acinar cell carcinoma is pathologically similar to pancreatoblastoma, so there is overlap in their radiologic appearances. The two can be distinguished based on the age of the patient. Pancreatoblastoma occurs in children less than 10 years of age, whereas acinar carcinoma is almost exclusively seen in older patients. Endocrine neoplasms are very rare in this age group and commonly manifest while quite small due to hormonally mediated clinical syndromes, whereas pancreatoblastomas are typically rather large at presentation.

Treatment and Prognosis
Pancreatoblastomas are best treated with complete surgical resection. The benefit of adjuvant chemotherapy has not been fully elucidated, but chemotherapy is commonly used empirically (5). The long-term prognosis is good in the absence of metastatic disease with complete surgical resection (2,5,8,13,14,21,24), but recurrence is common, so long-term follow-up is compulsory.

	Solid-Pseudopapillary Tumor

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
Solid-pseudopapillary tumor is a unique tumor of low malignant potential most commonly affecting females of reproductive age. This unusual tumor of unclear cellular origin was first described by Frantz (28) in 1959 in a report of three cases. The tumor was further characterized in a case involving a 12-year-old girl by Hamoudi et al (29) in 1970 and then proposed as a distinct tumor entity in 1981 by Klöppel et al (30). In 1996, the World Health Organization recognized the designation "solid pseudopapillary tumor" as a distinct tumor of the exocrine pancreas (31). The nomenclature has evolved over time but remains confusing. This tumor has been variously known as solid and papillary tumor, solid-cystic tumor, papillary cystic tumor, papillary epithelial neoplasm, papillary and solid neoplasm, solid and pseudopapillary epithelial neoplasm, solid and cystic acinar cell neoplasm, and Frantz tumor.

In the past, solid-pseudopapillary tumors were commonly misdiagnosed as nonfunctioning islet cell tumors, adenocarcinomas, cystadenomas, or pseudocysts (9,28,32,33). Recently, solid-pseudopapillary tumor has been recognized with increasing frequency, as its pathologic features have become better characterized. As of 2004, more than 700 well-documented cases had been reported in the English literature (34).

Clinical Features
Solid-pseudopapillary tumor is most commonly diagnosed in adolescent girls and young women, and a predilection for blacks and East Asians has been suggested. The age range is 2–85 years with a mean age of 21.97 years (33–37). Published reviews of the literature that separate patients by age have found that 22%–52.6% of patients are children (32,33,37,38). Most children with solid-pseudopapillary tumor present to medical attention in the second decade of life. Female patients account for 83%–98.5% of the reported cases (33–42). Zhou et al (42) reported a similar finding in children. There is no known genetic or hormonal factor to explain the strong female predilection. Several studies have suggested a racial predilection for blacks (9,35,41) and East Asians. In fact, Zhou et al (42) have suggested that solid-pseudopapillary tumor may represent the most common pancreatic tumor of Asian children.

Presenting symptoms are usually subtle and commonly include abdominal discomfort or pain and a mass. Jaundice is rare, even in patients with lesions involving the head of the pancreas (4,32, 33,42,43). Occasionally, solid-pseudopapillary tumors are asymptomatic and are discovered at abdominal imaging, physical examination, or laparotomy performed for other reasons, including health screening, abdominal trauma, and pregnancy (32,44–46). Tumor rupture and hemoperitoneum related to abdominal trauma have been reported (33,36,37,47–49).

For information on the molecular genetics of solid-pseudopapillary tumor, see Appendix E1 at radiographics.rsnajnls.org/cgi/content/full/26/4/1211/DC1.

Pathologic Features
Gross Features.— Solid-pseudopapillary tumor is a slow-growing tumor. It is commonly large and circumscribed or encapsulated, with marked degenerative and hemorrhagic change (Fig 2). The tumors are usually round to ovoid and solitary and occur throughout the pancreas (8,33,40,42,50), although some investigators have observed a predilection for the tail (35, 36,48). In the largest review of the literature, Papavramidis and Papavramidis (34) reported that 247 of 688 tumors (35.9%) arose in the pancreatic tail and 234 (34%) in the pancreatic head. The tumors may be quite exophytic, and occasionally their pancreatic origin may not be apparent, even at surgery (48).

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Solid-pseudopapillary tumor in a 12-year-old girl with a 2-week history of mild abdominal pain, nausea, vomiting, and pruritus. Laboratory examination revealed elevated results of liver function tests in an obstructive pattern. (a) CT scan enhanced with intravenous and oral contrast material shows a well-demarcated, predominantly hypoattenuating mass in the head of the pancreas. The mass deflects the superior mesenteric vein medially (curved arrow) and the common bile duct laterally (straight arrow). Note the dilated intrahepatic ducts (arrowheads). (b) Coronal CT image shows upward displacement of the main portal vein (arrow) by the mass. (c) Transverse color Doppler sonogram of the upper abdomen shows the heterogeneous mass with prominent peripheral vessels. (d) Photograph of the cut surface of the en bloc resected specimen shows the mass surrounding but not invading the opened common bile duct (arrow). Arrowhead = gallbladder, * = duodenum. (e) Photomicrograph (original magnification, x 16; H-E stain) shows the characteristic pseudopapillary formations of solid-pseudopapillary tumor (*).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Solid-pseudopapillary tumor in a 12-year-old girl with a 2-week history of mild abdominal pain, nausea, vomiting, and pruritus. Laboratory examination revealed elevated results of liver function tests in an obstructive pattern. (a) CT scan enhanced with intravenous and oral contrast material shows a well-demarcated, predominantly hypoattenuating mass in the head of the pancreas. The mass deflects the superior mesenteric vein medially (curved arrow) and the common bile duct laterally (straight arrow). Note the dilated intrahepatic ducts (arrowheads). (b) Coronal CT image shows upward displacement of the main portal vein (arrow) by the mass. (c) Transverse color Doppler sonogram of the upper abdomen shows the heterogeneous mass with prominent peripheral vessels. (d) Photograph of the cut surface of the en bloc resected specimen shows the mass surrounding but not invading the opened common bile duct (arrow). Arrowhead = gallbladder, * = duodenum. (e) Photomicrograph (original magnification, x 16; H-E stain) shows the characteristic pseudopapillary formations of solid-pseudopapillary tumor (*).

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 2c.  Solid-pseudopapillary tumor in a 12-year-old girl with a 2-week history of mild abdominal pain, nausea, vomiting, and pruritus. Laboratory examination revealed elevated results of liver function tests in an obstructive pattern. (a) CT scan enhanced with intravenous and oral contrast material shows a well-demarcated, predominantly hypoattenuating mass in the head of the pancreas. The mass deflects the superior mesenteric vein medially (curved arrow) and the common bile duct laterally (straight arrow). Note the dilated intrahepatic ducts (arrowheads). (b) Coronal CT image shows upward displacement of the main portal vein (arrow) by the mass. (c) Transverse color Doppler sonogram of the upper abdomen shows the heterogeneous mass with prominent peripheral vessels. (d) Photograph of the cut surface of the en bloc resected specimen shows the mass surrounding but not invading the opened common bile duct (arrow). Arrowhead = gallbladder, * = duodenum. (e) Photomicrograph (original magnification, x 16; H-E stain) shows the characteristic pseudopapillary formations of solid-pseudopapillary tumor (*).

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 2d.  Solid-pseudopapillary tumor in a 12-year-old girl with a 2-week history of mild abdominal pain, nausea, vomiting, and pruritus. Laboratory examination revealed elevated results of liver function tests in an obstructive pattern. (a) CT scan enhanced with intravenous and oral contrast material shows a well-demarcated, predominantly hypoattenuating mass in the head of the pancreas. The mass deflects the superior mesenteric vein medially (curved arrow) and the common bile duct laterally (straight arrow). Note the dilated intrahepatic ducts (arrowheads). (b) Coronal CT image shows upward displacement of the main portal vein (arrow) by the mass. (c) Transverse color Doppler sonogram of the upper abdomen shows the heterogeneous mass with prominent peripheral vessels. (d) Photograph of the cut surface of the en bloc resected specimen shows the mass surrounding but not invading the opened common bile duct (arrow). Arrowhead = gallbladder, * = duodenum. (e) Photomicrograph (original magnification, x 16; H-E stain) shows the characteristic pseudopapillary formations of solid-pseudopapillary tumor (*).

View larger version (217K): [in this window] [in a new window] [Download PPT slide]   Figure 2e.  Solid-pseudopapillary tumor in a 12-year-old girl with a 2-week history of mild abdominal pain, nausea, vomiting, and pruritus. Laboratory examination revealed elevated results of liver function tests in an obstructive pattern. (a) CT scan enhanced with intravenous and oral contrast material shows a well-demarcated, predominantly hypoattenuating mass in the head of the pancreas. The mass deflects the superior mesenteric vein medially (curved arrow) and the common bile duct laterally (straight arrow). Note the dilated intrahepatic ducts (arrowheads). (b) Coronal CT image shows upward displacement of the main portal vein (arrow) by the mass. (c) Transverse color Doppler sonogram of the upper abdomen shows the heterogeneous mass with prominent peripheral vessels. (d) Photograph of the cut surface of the en bloc resected specimen shows the mass surrounding but not invading the opened common bile duct (arrow). Arrowhead = gallbladder, * = duodenum. (e) Photomicrograph (original magnification, x 16; H-E stain) shows the characteristic pseudopapillary formations of solid-pseudopapillary tumor (*).

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Solid-pseudopapillary tumor in a 14-year-old girl who developed abdominal pain after sledding. (a) CT scan enhanced with intravenous contrast material shows a well-defined, fairly homogeneous, cystic mass arising in the tail of the pancreas (arrow). The mass enhances less than the adjacent normal pancreatic tissue. Arrowhead = splenic vein. (b) Axial T2-weighted MR image shows that the mass has heterogeneous internal signal intensity (arrow), which indicates that the mass is more complex than suggested by the CT findings. (c) Axial T1-weighted out-of-phase MR image shows that the mass has peripheral high signal intensity (arrow), a finding consistent with hemorrhage. (d) Axial gadolinium-enhanced MR image shows enhancement of only the capsule of the mass (arrow). (e) Photograph of the cut surface of the resected gross specimen shows the thick capsule (arrow) and predominantly gelatinous-appearing contents.

View larger version (88K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Solid-pseudopapillary tumor in a 14-year-old girl who developed abdominal pain after sledding. (a) CT scan enhanced with intravenous contrast material shows a well-defined, fairly homogeneous, cystic mass arising in the tail of the pancreas (arrow). The mass enhances less than the adjacent normal pancreatic tissue. Arrowhead = splenic vein. (b) Axial T2-weighted MR image shows that the mass has heterogeneous internal signal intensity (arrow), which indicates that the mass is more complex than suggested by the CT findings. (c) Axial T1-weighted out-of-phase MR image shows that the mass has peripheral high signal intensity (arrow), a finding consistent with hemorrhage. (d) Axial gadolinium-enhanced MR image shows enhancement of only the capsule of the mass (arrow). (e) Photograph of the cut surface of the resected gross specimen shows the thick capsule (arrow) and predominantly gelatinous-appearing contents.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 3c.  Solid-pseudopapillary tumor in a 14-year-old girl who developed abdominal pain after sledding. (a) CT scan enhanced with intravenous contrast material shows a well-defined, fairly homogeneous, cystic mass arising in the tail of the pancreas (arrow). The mass enhances less than the adjacent normal pancreatic tissue. Arrowhead = splenic vein. (b) Axial T2-weighted MR image shows that the mass has heterogeneous internal signal intensity (arrow), which indicates that the mass is more complex than suggested by the CT findings. (c) Axial T1-weighted out-of-phase MR image shows that the mass has peripheral high signal intensity (arrow), a finding consistent with hemorrhage. (d) Axial gadolinium-enhanced MR image shows enhancement of only the capsule of the mass (arrow). (e) Photograph of the cut surface of the resected gross specimen shows the thick capsule (arrow) and predominantly gelatinous-appearing contents.

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 3d.  Solid-pseudopapillary tumor in a 14-year-old girl who developed abdominal pain after sledding. (a) CT scan enhanced with intravenous contrast material shows a well-defined, fairly homogeneous, cystic mass arising in the tail of the pancreas (arrow). The mass enhances less than the adjacent normal pancreatic tissue. Arrowhead = splenic vein. (b) Axial T2-weighted MR image shows that the mass has heterogeneous internal signal intensity (arrow), which indicates that the mass is more complex than suggested by the CT findings. (c) Axial T1-weighted out-of-phase MR image shows that the mass has peripheral high signal intensity (arrow), a finding consistent with hemorrhage. (d) Axial gadolinium-enhanced MR image shows enhancement of only the capsule of the mass (arrow). (e) Photograph of the cut surface of the resected gross specimen shows the thick capsule (arrow) and predominantly gelatinous-appearing contents.

View larger version (153K): [in this window] [in a new window] [Download PPT slide]   Figure 3e.  Solid-pseudopapillary tumor in a 14-year-old girl who developed abdominal pain after sledding. (a) CT scan enhanced with intravenous contrast material shows a well-defined, fairly homogeneous, cystic mass arising in the tail of the pancreas (arrow). The mass enhances less than the adjacent normal pancreatic tissue. Arrowhead = splenic vein. (b) Axial T2-weighted MR image shows that the mass has heterogeneous internal signal intensity (arrow), which indicates that the mass is more complex than suggested by the CT findings. (c) Axial T1-weighted out-of-phase MR image shows that the mass has peripheral high signal intensity (arrow), a finding consistent with hemorrhage. (d) Axial gadolinium-enhanced MR image shows enhancement of only the capsule of the mass (arrow). (e) Photograph of the cut surface of the resected gross specimen shows the thick capsule (arrow) and predominantly gelatinous-appearing contents.

Imaging Features
The imaging features of solid-pseudopapillary tumor reflect the pathologic findings of cystic and solid components, intratumoral hemorrhage, a fibrous capsule, and, less commonly, calcification. When present, the fibrous capsule and internal hemorrhage are the features that distinguish solid-pseudopapillary tumor from other pancreatic tumors.

Occasionally, solid-pseudopapillary tumors are discovered incidentally on abdominal radiographs due to rim-like calcifications within the tumor capsule or chunky calcifications inside the tumor (35,47,53).

At ultrasonography (US) and CT, the tumor is usually large, well circumscribed, and quite variable in appearance depending on its composition. The mass almost always appears well demarcated, even in cases with pathologic findings of adjacent organ invasion (35,47) (Figs 2, 3). The fibrous capsule may be visualized as an echogenic or, less commonly, hypoechoic rim at US (50). The capsule is typically hypoattenuating at CT (51). The tumors are usually large at presentation and often compress adjacent structures rather than invading them (26,51) (Fig 2). Associated duct dilatation is uncommon even with large masses in the head of the pancreas (47,49). Solid-pseudopapillary tumors are frequently exophytic, and the origin from the pancreas may not be apparent.

The internal architecture varies from a solid mass to a thick-walled cyst, with most tumors appearing as a mixture of solid and cystic elements (49,54). Very small tumors may be completely solid and are usually homogeneous. Larger tumors tend to be centrally cystic with enhanced through transmission. Occasionally, the tumors are nearly completely cystic with a small amount of residual solid tumor at the periphery. Most commonly, solid-pseudopapillary tumors appear complex in internal architecture, with echogenic, solid components and variable amounts of hypo-echoic, cystic areas corresponding to hemorrhagic necrosis (50,51,55). They usually display no through transmission (56). Occasionally, the mass can be echogenic with enhanced through transmission corresponding to friable tumor with massive hemorrhagic necrosis (50). At CT, the solid portions of the mass are isoattenuating to the pancreas. The attenuation of the cystic components is slightly higher than that of fluid in the gallbladder, with attenuation coefficients of 20–50 HU, likely due to the presence of blood products and debris (41,47,49,54,56). Fluid-debris levels are seen in up to 20% of tumors (35). Less than one-third demonstrate internal septations (47,50). Calcifications were previously thought uncommon but may be seen in up to one-third of cases, usually in the periphery of the tumor (35,47,50,55).

Enhancement with intravenous contrast material increases the conspicuity of the tumor but is usually slight (47,56). Enhancement is limited to the solid portions of the tumor, most often at the periphery, with unenhancing fluid and debris centrally (35,47,54). A peripheral rim of enhancement can also be seen with a thick fibrous capsule (41,51) (Fig 3).

At MR imaging, a surrounding hypointense fibrous capsule and internal hemorrhage, seen as high signal intensity on T1-weighted images, are distinguishing features of solid-pseudopapillary tumor (26,35,49,54). Ohtomo et al (49) reported that four of five tumors studied had fibrous capsules and also exhibited dark rims around the tumors on T1-weighted images (51). Similar dark rims on T2-weighted images were described in all nine cases with MR imaging reported by Buetow et al (35) (Fig 3). The solid portions of the tumor are iso- to hypointense to pancreas on T1-weighted images and slightly hyperintense to pancreas on T2-weighted images (40,49,51). The presence of hemorrhage is a distinctive feature, which is present, at least focally, in most tumors and best shown on MR images (35,49,51,54) (Fig 3). On T1-weighted images, most tumors have foci that are hyperintense to normal gland and correspond to areas of hemorrhagic necrosis or debris. The signal intensity of these foci on T2-weighted images is variable, due to the presence of multiple degradation products of hemoglobin (35,49,54). The appearance of hyperintense foci on T1-weighted images was noted in six of six cases reported by Ohtomo et al (49), 22 of 22 cases reported by Sun et al (54), and 14 of 19 cases reported by Cantisani et al (40).

Few reports describe the appearance of solid-pseudopapillary tumor on gadolinium-enhanced MR images, but the enhancement pattern is similar to that seen at CT. Cantisani et al (40) describe early peripheral, heterogeneous enhancement or ring enhancement greater than that of the adjacent pancreas (Fig 3). They also observed progressive fill-in on dynamic enhanced images. On delayed postgadolinium images, almost all enhanced less than the adjacent normal pancreas overall. In seven of 10 cases, capsular enhancement was early and more intense than that of the rest of the tumor (40). Peripheral enhancement was seen in two of three cases reported by Buetow et al (35) and in nine of 11 cases reported by Sun et al (54).

At angiography, solid-pseudopapillary tumor is typically avascular to hypovascular and displaces vessels. Some blush is seen in the solid portions, usually at the periphery (41,47,51). This appearance distinguishes solid-pseudopapillary tumor from the hypervascular islet cell tumor.

Differential Diagnosis
The imaging appearance of solid-pseudopapillary tumor can overlap with that of other tumors and benign disease, such as pseudocyst, but its characteristic clinical presentation and encapsulated and hemorrhagic nature help distinguish solid-pseudopapillary tumor from other pancreatic lesions.

Treatment and Prognosis
Solid-pseudopapillary tumor is a slow-growing tumor usually with a benign clinical course but with the potential for aggressive behavior, so that it is treated with complete surgical resection. About 85% of tumors are limited to the pancreas, and these patients have an excellent prognosis (36,37,48). More than 95% of patients with local disease are cured by complete resection (8,36, 44,48). In the past, some children were treated with limited or incomplete surgical resection due to misdiagnosis of an adenocarcinoma, the complete fibrous capsule making enucleation technically feasible, or reluctance to subject a child to a radical surgery. Unfortunately, some of these children went on to develop tumor recurrence and/or metastases, and a few eventually succumbed to the disease (34,42). Consequently, most authors recommend an attempt at curative resection for all patients with solid-pseudopapillary tumor (3,32,33,48).

Metastatic disease was initially thought to be rare, but, as the frequency of diagnosis of solid-pseudopapillary tumor increases, so do reports of aggressive behavior. Metastases develop in 7%–16% of patients, usually older women. Reports of metastases in children are rare (33,37,38,42,46). Liver metastases are usually solitary and may be amenable to surgical resection (48). Even if complete surgical resection of metastases or the primary tumor is not possible, patients with solid-pseudopapillary tumor still benefit from surgical debulking (8,32–34,36–38,44).

	Islet Cell Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
Islet cell or neuroendocrine tumors are endocrine cell–derived tumors of the pancreas. Those that are benign are termed adenomas, while those that metastasize are called carcinomas. These tumors are most commonly discovered in middle age but may be encountered in older children. The age range is 7–83 years (8). The mean age at diagnosis of insulinoma is 47 years for all patients and 25 years for patients with multiple endocrine neoplasia type 1 (MEN 1) (57). Of symptomatic insulinomas diagnosed during a 60-year period at the Mayo Clinic, 4.9% occurred in children over 10 years of age (57). There is no significant sex predilection.

Given their endocrine nature, islet cell tumors may or may not elaborate a hormonally active polypeptide, and this peptide product may or may not be capable of producing a clinical syndrome. It is not uncommon for tumors to produce more than one hormonal peptide, but clinical symptoms, if present, are related to one predominant hormone (8). Tumors that produce clinical syndromes are designated functioning or hyperfunctioning islet cell tumors. All others, even if they can be shown histologically to produce a peptide product, are called nonfunctioning or clinically silent islet cell tumors. The most common type of functioning islet cell tumor is the insulinoma (47% of functioning islet cell tumors), followed by gastrinoma (30%) (8). Other types of functioning and nonfunctioning islet cell tumors are exceedingly rare or have never been reported in children.

Clinical Features
The clinical presentation varies depending on whether the tumor produces a hormone-related syndrome and on the nature of the hormonal product.

Insulinoma.— Insulinoma is composed of B or ß cells and causes fasting hyperinsulinemic hypoglycemia. Most patients have the Whipple triad of fasting hypoglycemia, symptoms of hypoglycemia, and immediate resolution of symptoms with intravenous administration of glucose. In young children, hypoglycemia commonly manifests as behavioral problems, seizures, or coma. These symptoms may be attributed to other causes, and diagnosis may be delayed. Untreated, recurrent hypoglycemia can lead to permanent neurologic sequelae (8).

Gastrinoma.— Gastrinoma is composed of G cells and causes the Zollinger-Ellison syndrome. Patients frequently have multiple or recurrent peptic ulcers, classically in uncommon locations, such as the postbulbar duodenum and proximal jejunum (8,27). Gastroesophageal reflux and heartburn are also common symptoms. Gastric hypersecretion may cause diarrhea.

Other Functioning Islet Cell Tumors.— All other functioning islet cell tumors are much less common in children. Adrenal corticotropic hormone–secreting islet cell tumor (ACTHoma) is a rare cause of Cushing syndrome. VIPoma is composed of D1 cells, secretes vasoactive intestinal peptide (VIP), and causes the Verner-Morrison or WDHA syndrome of massive watery diarrhea, hypokalemia, and achlorhydria. Most cases of VIP-producing tumors in children are not of pancreatic origin, as opposed to those in adults. According to Grosfeld et al (2), only two of 56 reported cases of pediatric VIP-producing tumors were pancreatic islet cell tumors. The rest were neurogenic tumors. Somatostatinoma is composed of D cells and causes a syndrome of diabetes mellitus, gallbladder disease, and steatorrhea. Glucagonoma is composed of A or cells and rarely causes a syndrome of diabetes mellitus, painful stomatitis, and a characteristic skin rash, necrolytic migratory erythema. To our knowledge, the last two have never been reported in a child (27).

Nonfunctioning Islet Cell Tumors.— Nonfunctioning tumors commonly manifest late with symptoms due to mass effect, local invasion, or metastatic disease. The mean age at presentation is 70 years, except when associated with MEN 1, in which they occur in younger patients (8).

Pathologic Features
Tumor Size.— Overall, neuroendocrine tumors vary widely in size, from 0.5 mm to 20 cm, but the size of a particular tumor at presentation reflects its tendency to produce clinical symptoms and the severity and specificity of those symptoms. Nonfunctioning islet cell tumors manifest late due to mass effect and are significantly larger than functioning islet cell tumors. Most patients with insulinoma have striking clinical symptoms and present with relatively small tumors, with mean diameter in the range of 2–2.2 cm (58,59) (Fig 4). Insulinomas are usually less than 3 cm in size unless malignant (8). In contrast, very few glucagon-producing tumors are associated with a clinical syndrome, and these are much larger at presentation, with a mean diameter of 7.6 cm (8).

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Insulinoma in a 9-year-old girl with unexplained seizure disorder who had hypoglycemia immediately after a recent seizure. (a) Contrast-enhanced CT scan shows a small, homogeneous, intensely enhancing mass (arrow) in the body and tail of the pancreas. (b) Photograph of the resected specimen shows the well-circumscribed tumor, which has protuberant red and yellow areas on the cut surface but no cystic spaces. (c) Photomicrograph (original magnification, x16; H-E stain) shows sheets of small uniform cells (arrows), which are separated into lobules by intervening fibrovascular stroma (arrowheads). (d) Photomicrograph (original magnification, x40; insulin stain) shows brown-staining insulin-producing cells in a trabecular pattern. (e) Photomicrograph (original magnification, x40; Congo red stain) obtained under polarized light shows apple-green birefringence (arrows), which is indicative of amyloid in the stroma, thus allowing a specific diagnosis of insulinoma.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Insulinoma in a 9-year-old girl with unexplained seizure disorder who had hypoglycemia immediately after a recent seizure. (a) Contrast-enhanced CT scan shows a small, homogeneous, intensely enhancing mass (arrow) in the body and tail of the pancreas. (b) Photograph of the resected specimen shows the well-circumscribed tumor, which has protuberant red and yellow areas on the cut surface but no cystic spaces. (c) Photomicrograph (original magnification, x16; H-E stain) shows sheets of small uniform cells (arrows), which are separated into lobules by intervening fibrovascular stroma (arrowheads). (d) Photomicrograph (original magnification, x40; insulin stain) shows brown-staining insulin-producing cells in a trabecular pattern. (e) Photomicrograph (original magnification, x40; Congo red stain) obtained under polarized light shows apple-green birefringence (arrows), which is indicative of amyloid in the stroma, thus allowing a specific diagnosis of insulinoma.

View larger version (195K): [in this window] [in a new window] [Download PPT slide]   Figure 4c.  Insulinoma in a 9-year-old girl with unexplained seizure disorder who had hypoglycemia immediately after a recent seizure. (a) Contrast-enhanced CT scan shows a small, homogeneous, intensely enhancing mass (arrow) in the body and tail of the pancreas. (b) Photograph of the resected specimen shows the well-circumscribed tumor, which has protuberant red and yellow areas on the cut surface but no cystic spaces. (c) Photomicrograph (original magnification, x16; H-E stain) shows sheets of small uniform cells (arrows), which are separated into lobules by intervening fibrovascular stroma (arrowheads). (d) Photomicrograph (original magnification, x40; insulin stain) shows brown-staining insulin-producing cells in a trabecular pattern. (e) Photomicrograph (original magnification, x40; Congo red stain) obtained under polarized light shows apple-green birefringence (arrows), which is indicative of amyloid in the stroma, thus allowing a specific diagnosis of insulinoma.

View larger version (167K): [in this window] [in a new window] [Download PPT slide]   Figure 4d.  Insulinoma in a 9-year-old girl with unexplained seizure disorder who had hypoglycemia immediately after a recent seizure. (a) Contrast-enhanced CT scan shows a small, homogeneous, intensely enhancing mass (arrow) in the body and tail of the pancreas. (b) Photograph of the resected specimen shows the well-circumscribed tumor, which has protuberant red and yellow areas on the cut surface but no cystic spaces. (c) Photomicrograph (original magnification, x16; H-E stain) shows sheets of small uniform cells (arrows), which are separated into lobules by intervening fibrovascular stroma (arrowheads). (d) Photomicrograph (original magnification, x40; insulin stain) shows brown-staining insulin-producing cells in a trabecular pattern. (e) Photomicrograph (original magnification, x40; Congo red stain) obtained under polarized light shows apple-green birefringence (arrows), which is indicative of amyloid in the stroma, thus allowing a specific diagnosis of insulinoma.

View larger version (184K): [in this window] [in a new window] [Download PPT slide]   Figure 4e.  Insulinoma in a 9-year-old girl with unexplained seizure disorder who had hypoglycemia immediately after a recent seizure. (a) Contrast-enhanced CT scan shows a small, homogeneous, intensely enhancing mass (arrow) in the body and tail of the pancreas. (b) Photograph of the resected specimen shows the well-circumscribed tumor, which has protuberant red and yellow areas on the cut surface but no cystic spaces. (c) Photomicrograph (original magnification, x16; H-E stain) shows sheets of small uniform cells (arrows), which are separated into lobules by intervening fibrovascular stroma (arrowheads). (d) Photomicrograph (original magnification, x40; insulin stain) shows brown-staining insulin-producing cells in a trabecular pattern. (e) Photomicrograph (original magnification, x40; Congo red stain) obtained under polarized light shows apple-green birefringence (arrows), which is indicative of amyloid in the stroma, thus allowing a specific diagnosis of insulinoma.

Tumor Location.— Particular cell types of islet cell tumors vary in anatomic location. Sixty-five percent of insulinomas involve the body and tail of the pancreas (8,59). The vast majority of insulinomas occur in the pancreas, with less than 1% arising in extrapancreatic sites (8,57). On the other hand, gastrinomas and symptomatic nonfunctioning islet cell tumors have a predilection for the head of the pancreas, with the head involved in 71% of reported tumors (8).

Although gastrinomas most commonly arise in the pancreas, about 30% of gastrin-secreting tumors arise in extrapancreatic locations, including the duodenum, proximal jejunum, and stomach (8). Those involving the duodenum are often microadenomas, in the range of 1–2 mm in size (8). Despite their small size, duodenal gastrin-cell microadenomas may metastasize early to regional lymph nodes. The lymph node metastasis may be much larger than the duodenal primary, and the lymph node may be mistaken for the primary tumor (8). Unlike their pancreatic counterparts, gastrin-secreting tumors of the duodenum and proximal jejunum are mostly nonfunctioning (8), although those that do cause Zollinger-Ellison syndrome occur in younger patients.

In general, gastrinomas are found in the so-called gastrinoma triangle, bounded by the porta hepatis and the second and third portions of the duodenum. This triangle contains the head of the pancreas, the duodenum, peripancreatic soft tissues, and regional lymph nodes (8,27,61) (Fig 5).

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Metastatic gastrinoma in an 8-year-old girl who presented with a several-month history of abdominal discomfort, chronic diarrhea, episodic vomiting, and black stools. Esophagogastroduodenoscopy revealed erosions and an ulcer in the gastric fundus and nodularity and two ulcers in the duodenum. Laboratory studies revealed no Helicobacter pylori and an elevated serum gastrin level. (a) Reformatted coronal image from CT arteriography shows an irregular but homogeneously enhancing mass in the region of the pancreatic head (straight arrow), a small enhancing mass in the left lobe of the liver (arrowhead), and thickening of gastric rugal folds (curved arrow). (b, c) Coronal single-photon-emission CT (SPECT) images from somatostatin receptor scintigraphy performed with indium 111–pentetreotide show localization of the radiopharmaceutical in the regions of the pancreatic head (straight solid arrow) and the left lobe of the liver (curved arrow in c), which correspond to the foci of abnormality on the CT image. The activity in the gallbladder (arrowhead in b) and kidney (open arrow in c) is physiologic.

View larger version (78K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Metastatic gastrinoma in an 8-year-old girl who presented with a several-month history of abdominal discomfort, chronic diarrhea, episodic vomiting, and black stools. Esophagogastroduodenoscopy revealed erosions and an ulcer in the gastric fundus and nodularity and two ulcers in the duodenum. Laboratory studies revealed no Helicobacter pylori and an elevated serum gastrin level. (a) Reformatted coronal image from CT arteriography shows an irregular but homogeneously enhancing mass in the region of the pancreatic head (straight arrow), a small enhancing mass in the left lobe of the liver (arrowhead), and thickening of gastric rugal folds (curved arrow). (b, c) Coronal single-photon-emission CT (SPECT) images from somatostatin receptor scintigraphy performed with indium 111–pentetreotide show localization of the radiopharmaceutical in the regions of the pancreatic head (straight solid arrow) and the left lobe of the liver (curved arrow in c), which correspond to the foci of abnormality on the CT image. The activity in the gallbladder (arrowhead in b) and kidney (open arrow in c) is physiologic.

View larger version (94K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Metastatic gastrinoma in an 8-year-old girl who presented with a several-month history of abdominal discomfort, chronic diarrhea, episodic vomiting, and black stools. Esophagogastroduodenoscopy revealed erosions and an ulcer in the gastric fundus and nodularity and two ulcers in the duodenum. Laboratory studies revealed no Helicobacter pylori and an elevated serum gastrin level. (a) Reformatted coronal image from CT arteriography shows an irregular but homogeneously enhancing mass in the region of the pancreatic head (straight arrow), a small enhancing mass in the left lobe of the liver (arrowhead), and thickening of gastric rugal folds (curved arrow). (b, c) Coronal single-photon-emission CT (SPECT) images from somatostatin receptor scintigraphy performed with indium 111–pentetreotide show localization of the radiopharmaceutical in the regions of the pancreatic head (straight solid arrow) and the left lobe of the liver (curved arrow in c), which correspond to the foci of abnormality on the CT image. The activity in the gallbladder (arrowhead in b) and kidney (open arrow in c) is physiologic.

Gross Features.— Islet cell tumors are round or ovoid, well-demarcated tumors with expansile growth patterns. Most small tumors are homogeneous, and many larger tumors are cystic, necrotic, or hemorrhagic. Occasionally, small calcifications are found in larger tumors (8,60). Smaller tumors are unencapsulated and larger tumors have a fibrous pseudocapsule. The pseudocapsule is often incomplete, and this finding should not be mistaken for invasive behavior. Consistency varies from soft to firm or rubbery, depending on the relative content of fibrous stroma.

Histologic Features.— Generally, islet cell tumors are composed of sheets or nests of monomorphic medium-sized cells (Fig 4). These may be arranged in three different patterns as follows: (a) trabecular with or without gyriform arrangement; (b) acinar or glandular pattern, often surrounding a lumen; and (c) medullary or solid pattern. One pattern may predominate in one cell type of tumor or in benign versus malignant tumors, but the cellular pattern does not reliably predict the cell type or the biologic behavior of the tumor. Mitoses are unusual, even in tumors that behave aggressively (58).

The amount of intervening stroma is variable and affects the gross appearance of the tumor as well as the imaging findings. The stroma may be quite dense or appear hyalinized. Numerous blood vessels in the stroma impart the hypervascular nature characteristic of islet cell tumors. The finding of amyloid, which shows green birefringence under polarized light and stains for Congo red, is highly suggestive of insulinoma.

The biologic behavior of islet cell tumors is difficult to predict. Approximately 10% of insulinomas, 60% of gastrinomas, and most other functional islet cell tumors are malignant (2). In general, primary tumors that display malignant behavior are larger than benign tumors (mean diameter, 6.4–7.4 cm for malignant vs 1.7–2.9 cm for benign tumors) (58). Although almost all tumors 2 cm or less in size exhibit benign behavior, and tumors over 3 cm are usually malignant, there is significant overlap. Thus, tumor size cannot be used as the sole determinant of biologic behavior (8).

Imaging Features
The imaging appearance of islet cell tumors reflects their size and pathologic nature. Most small tumors are insulinomas and are characteristically homogeneous and well defined (Fig 4). Gastrinomas are generally larger than insulinomas, and some may have a heterogeneous appearance even if relatively small (58,60) (Fig 5). The other functioning and nonfunctioning islet cell tumors are significantly larger than insulinomas at presentation (27). They are more likely to have cystic changes, necrosis, hemorrhage, and small calcifications, conferring a heterogeneous appearance at imaging (58).

Insulinomas are typically round or ovoid and hypoechoic at US (58) (Fig 6). They may display a hyperechoic rim. At CT enhanced with intravenous contrast material, insulinomas and small gastrinomas enhance homogeneously and more than normal pancreas (58,59) (Fig 4). Liver metastases similarly enhance more than adjacent liver (Fig 5). Dual-phase CT studies demonstrate that enhancement of both the pancreas and insulinomas is significantly higher in the arterial phase than the portal venous phase. The conspicuity of the tumor is much higher in the arterial phase (59,63). At angiography, small islet cell tumors produce an intense vascular stain in the late arterial and capillary phases (60) (Fig 4).

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Insulinoma in the tail of the pancreas in a 27-year-old man. (a) CT scan enhanced with intravenous contrast material shows irregular contour and enlargement of the pancreatic tail (arrow) but no well-defined mass. (b) Endoscopic US scan shows a slightly heterogeneous but well-defined, hypoechoic mass within the pancreatic tail.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Insulinoma in the tail of the pancreas in a 27-year-old man. (a) CT scan enhanced with intravenous contrast material shows irregular contour and enlargement of the pancreatic tail (arrow) but no well-defined mass. (b) Endoscopic US scan shows a slightly heterogeneous but well-defined, hypoechoic mass within the pancreatic tail.

Larger islet cell tumors are usually malignant insulinomas, gastrinomas, or other functioning and nonfunctioning islet cell tumors (8,58,59). These are more commonly heterogeneous with foci of cystic change, hemorrhage, necrosis, and even calcification (58). They may display cystic areas or small, shadowing calcifications at US. A heterogeneous appearance is noted at CT with enhancing solid portions, usually at the periphery, and unenhancing cystic portions (58,61). Larger tumors demonstrate a vascular stain at the periphery of the tumor (60). Larger tumors are more likely to be associated with liver metastases, which are well demonstrated at CT and MR imaging.

The role of the radiologist in the evaluation of patients with functioning islet cell tumor is not to diagnose the tumor, but to localize the tumor already diagnosed on the basis of clinical and laboratory findings (58,65). Ninety percent to 98.6% of insulinomas are palpable at surgery (58,59,65), and the addition of intraoperative US yields a combined sensitivity of 96%–100% (59,66). Still, there is a small risk of negative laparotomy results, and preoperative localization is desirable (59,65). Insulinomas are the smallest islet cell tumors and the most challenging intrapancreatic tumors to localize. Studies comparing the ability to localize islet cell tumors with different imaging modalities have been performed in adults, mostly with insulinomas. These have compared transabdominal US, angiography, transhepatic portal venous sampling, single-phase CT, dual-phase CT, MR imaging, and endoscopic US (Fig 6) (59,63–71). Overall, MR imaging and dual-phase thin-collimation multidetector CT show the highest sensitivities (85%–100%) with relatively low risk.

Somatostatin receptor scintigraphy is useful for the localization of neuroendocrine tumors, especially intra- and extrapancreatic gastrinomas and their metastases, particularly in light of recent technological advances (Fig 5). Somatostatin receptor scintigraphy is limited by the fact that not all neuroendocrine tumors express enough somatostatin receptors to be detected. Only 60%–70% of insulinomas express somatostatin receptors and may go undetected (60). The sensitivity for gastrinomas is 58%–75% for regional disease with a high false-negative rate, although lesions as small as 3 mm have been detected in the duodenum (72,73). The sensitivity for gastrinoma metastases is nearly 100%. The small size of the primary tumors and poor anatomic detail have limited the utility of conventional scintigraphy, but use of SPECT-CT hybrid imaging will likely decrease the magnitude of these limitations (74).

Differential Diagnosis
In patients with functional syndromes, the differential diagnosis is of no consequence. Without a recognized functional syndrome, a differential diagnosis is necessary.

Large islet cell tumors with central necrosis may be difficult to distinguish from solid-pseudo-papillary tumors and pseudocyst. Both tumors can occur in older children or adolescents; however, solid-pseudopapillary tumor does not tend to demonstrate the hypervascularity of the tumor periphery that characterizes islet cell tumors. A clinical history of pancreatitis distinguishes pseudocyst from tumor.

Treatment and Prognosis
Patients with nonmetastatic islet cell tumors can be cured of the tumor and any associated clinical syndrome with surgical resection. Resection may entail partial pancreatic resection or enucleation of the tumor. Intraoperative US is particularly helpful in surgical planning because the relationship of the tumor to the main pancreatic duct is shown.

In patients in whom the tumor cannot be localized, surgery may still be beneficial. Insulinomas are almost always intrapancreatic and are more frequently localized to the body and tail, so resection of the distal pancreas can cure the patient. On the other hand, distal pancreatectomy is unlikely to cure a patient with gastrinoma. Most gastrinomas occur in the so-called gastrinoma triangle around the head of the pancreas, and resection of its contents often cures the patient (8,65).

Patients who remain symptomatic after resection may be treated medically. Medical treatment for insulinoma syndrome is often unrewarding, but medical treatment for Zollinger-Ellison syndrome is usually successful.

The long-term prognosis for insulinoma is very good as most are benign, but more than half of gastrinomas are malignant. Metastasizing gastrinomas arising in the duodenum have a better prognosis than those arising in the pancreas (8). The presence of regional lymph node metastases does not portend a worse prognosis, but the presence of metastatic disease to the liver does. Even with liver metastases, gastrinomas are slow-growing tumors with long survival (8).

	Multiple Endocrine Neoplasia Type 1

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
MEN 1, or Wermer syndrome, is an inherited condition characterized by synchronous or metachronous tumors of the parathyroid glands, anterior pituitary, pancreas, and gastrointestinal tract. Other organs are less commonly involved, including the thymus, lung, thyroid, and adrenal gland. The disease is usually autosomal dominant with high penetrance (75) but may occur sporadically. The causative genetic defect was recently localized to a new tumor suppressor gene called mu at the 11q13 locus (76). Patients commonly present in the third or fourth decade, but, with suggestive family history, patients may be discovered in childhood. Trump et al (75) showed in a study of 220 gene carriers that 43% had findings by the age of 20 years. The same study found that in MEN 1 patients, gastrinomas are more common over the age of 40 years and insulinomas are more common under the age of 40 years (75).

Thirty percent to 80% of MEN 1 patients have clinical evidence of pancreatic endocrine tumors, although 100% of patients have pancreatic tumors at autopsy (8). The most common syndrome is Zollinger-Ellison syndrome, which occurs in more than 50% of MEN 1 patients (8,60,77). This is followed by hyperinsulinism, which is found in 10%–30% (75). Occasionally, glucagonoma syndrome or acromegaly, due to secretion of growth hormone–releasing factor, is encountered.

Pathologically, multiplicity of pancreatic islet cell tumors is the rule. Most are small, benign, clinically insignificant microadenomas (62). Most of these produce hormonally active peptides but do not cause clinical symptoms. Clinical symptoms are caused by the relatively few macroadenomas (>0.5 cm), which most commonly secrete insulin. These insulinomas are most commonly found in the body and tail of the pancreas (65). In general, the tumors consistently secrete more than one hormonal product, but one predominates. The most commonly elaborated peptides are pancreatic peptide and glucagon, followed by insulin (62), vasoactive intestinal peptide, and growth hormone–releasing hormone. Gastrin-producing pancreatic tumors are uncommon (62,78–80).

It has recently been discovered that most cases of Zollinger-Ellison syndrome in MEN 1 are caused by gastrin-producing microadenomas of the duodenum, in contrast to cases of sporadic Zollinger-Ellison syndrome, which is most often caused by pancreatic macroadenomas (78,80). Unlike the pancreatic tumors, these stain almost exclusively for gastrin (77).

The outcome for patients with pancreatic islet cell tumors and MEN 1 differs from that of patients with sporadic tumors. Gastrinoma in patients with MEN 1 is associated with a lower risk of metastasis and longer 10-year survival compared to those with sporadic gastrinoma (93% and 74%, respectively) (8,62,79). For duodenal microgastrinomas, 60%–80% of these metastasize to regional lymph nodes (78,80). Liver metastases are rare and occur late in the course of the disease (78,79). The high recurrence rate previously reported for patients with insulinoma and MEN 1 is likely due to metachronous lesions rather than true recurrence of the original tumor (8). Despite these findings suggesting good outcome, actuarial studies of large numbers of MEN 1 patients reveal that they die prematurely of neoplasia, often originating in the pancreas, perhaps reflecting the multiplicity of these tumors (79).

	Nesidioblastosis or Persistent Hyperinsulinemic Hypoglycemia of Infancy

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
The infantile form of nesidioblastosis is now more precisely called persistent hyperinsulinemic hypoglycemia of infancy, persistent neonatal hyperinsulinemic hypoglycemia, or congenital hyperinsulinism. It is a tumorlike disorder characterized by a proliferation of hyperfunctioning ß cells, distributed diffusely throughout the pancreas or forming a focal mass, and causing unregulated release of insulin. The overall incidence is 1 in 30,000–50,000 births (81), with a much higher incidence in Saudi Arabian and Ashkenazi Jewish populations. The condition has been known by a myriad of designations including adenomatous hyperplasia, islet cell hyperplasia, nesidiodysplasia, and microadenomatosis. The ambiguity of nomenclature reflects the heterogeneous nature of the disorder, which is now known to encompass at least two clinically similar but pathologically distinct entities. The differentiation of the two forms has important implications for treatment and prognosis.

Clinical Features
Symptoms usually become apparent in the first few hours to days of life, although presentation is occasionally delayed up to a year or more (82,83). Persistent hyperinsulinemic hypoglycemia of infancy is clinically distinguished from transient causes of hyperinsulinemic hypoglycemia, including maternal diabetes and Beckwith-Wiedemann syndrome. The diagnosis is recognized when laboratory tests reveal elevated serum insulin levels in the presence of hypoglycemia. The hypoglycemia is usually severe and persistent, often requiring constant high-rate intravenous infusion of glucose to maintain acceptable serum glucose levels. A large majority are resistant to diazoxide and even somatostatin analog therapy (83,84). Secondary cardiac abnormalities occur, including heart failure. Prompt diagnosis and treatment are imperative to prevent permanent neurologic sequelae (83).

The clinical syndrome of persistent neonatal or infantile hyperinsulinemic hypoglycemia is now recognized to be due to at least two pathologically distinguishable entities with heterogeneous genetic causes. In general, the diffuse or nontumoral form, accounting for two-thirds to three-fourths of the cases, is characterized by pathologic changes throughout the pancreas and a constitutional genetic abnormality. In the focal form, on the other hand, the pathologic and genetic anomaly is somatic and limited to a focal pancreatic lesion.

For information on the molecular genetics of persistent hyperinsulinemic hypoglycemia of infancy, see Appendix E1 at radiographics.rsnajnls.org/cgi/content/full/26/4/1211/DC1.

Pathologic Features
At pathologic examination, the diffuse form of persistent hyperinsulinemic hypoglycemia of infancy shows a widespread increase in islet cells in a pattern previously called diffuse nesidioblastosis and now called diffuse adenomatosis. The diffuse form is challenging to differentiate histologically from the normal infant pancreas, as exocrine pancreatic development continues postnatally throughout the first year. Compared to a set of aged-matched controls, these pancreases show varying-sized islets, often ill defined and encroaching on adjacent acinar tissues, and abundant individual neuroendocrine cells or clusters of cells with characteristic ductuloinsular complexes.

The pathologic appearance of the focal form was first described by Laidlaw (85), who coined the term "nesidioblastoma," but is now termed focal adenomatous hyperplasia (Fig 7). Most commonly, the lesion is solitary and consists of a focal proliferation of islet cells within the pancreatic lobules, pushing aside acinar elements or randomly incorporating them while preserving the lobular architecture. The most characteristic feature is the recapitulation of normal islet structure, with ß cells oriented centrally and A and D cells at the periphery (7,8).

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Focal endocrine adenomatosis of the pancreas in a 1-month-old, 34-week gestation premature baby girl with persistent hypoglycemia and hyperinsulinism. Diazoxide therapy was unsuccessful, and the patient underwent 95% pancreatectomy. (a) Transverse sonogram of the upper abdomen shows heterogeneous enlargement of the neck and body of the pancreas (arrows) with cystic areas. (b) CT scan enhanced with intravenous contrast material shows a heterogeneous mass (arrow) in the neck and body of the pancreas. Arrowhead = splenic vein. (c) Photograph of the cut surface of the resected gross specimen shows the large, solid mass involving the head and body of the pancreas.

View larger version (98K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Focal endocrine adenomatosis of the pancreas in a 1-month-old, 34-week gestation premature baby girl with persistent hypoglycemia and hyperinsulinism. Diazoxide therapy was unsuccessful, and the patient underwent 95% pancreatectomy. (a) Transverse sonogram of the upper abdomen shows heterogeneous enlargement of the neck and body of the pancreas (arrows) with cystic areas. (b) CT scan enhanced with intravenous contrast material shows a heterogeneous mass (arrow) in the neck and body of the pancreas. Arrowhead = splenic vein. (c) Photograph of the cut surface of the resected gross specimen shows the large, solid mass involving the head and body of the pancreas.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 7c.  Focal endocrine adenomatosis of the pancreas in a 1-month-old, 34-week gestation premature baby girl with persistent hypoglycemia and hyperinsulinism. Diazoxide therapy was unsuccessful, and the patient underwent 95% pancreatectomy. (a) Transverse sonogram of the upper abdomen shows heterogeneous enlargement of the neck and body of the pancreas (arrows) with cystic areas. (b) CT scan enhanced with intravenous contrast material shows a heterogeneous mass (arrow) in the neck and body of the pancreas. Arrowhead = splenic vein. (c) Photograph of the cut surface of the resected gross specimen shows the large, solid mass involving the head and body of the pancreas.

Treatment and Prognosis
The importance of discriminating between the diffuse and focal forms of persistent hyperinsulinemic hypoglycemia of infancy is due to the marked difference in treatment and prognosis. The diffuse form requires near-total (95%) pancreatectomy to prevent recurrence of severe hypoglycemia and permanent neurologic sequelae. Those treated with subtotal pancreatectomy frequently require repeat surgery (6,83). Persistent hypoglycemia following near-total pancreatectomy may be controlled with medical therapy. Surgery is often complicated by diabetes mellitus and pancreatic exocrine insufficiency (8,83,84, 87). On the contrary, the focal form is cured by resection of the lesion with very little risk of complications (83,84,87).

	Other Pancreatic Tumors and Tumorlike Lesions

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 
Acinar Cell Carcinoma
Acinar cell carcinoma represents 1%–2% of pancreatic exocrine tumors (9,90) and usually affects older men, but a small number of cases have been reported in children (4,91–94). Although quite rare in children, carcinoma of acinar cell origin is more common than ductal cell adenocarcinoma in the pediatric age group (93). Acinar cell carcinoma is pathologically divergent from ductal adenocarcinoma but similar to pancreatoblastoma, which is considered by some authors to be the embryonic counterpart to acinar cell carcinoma (93).

The presenting symptoms are most often non-specific and related to local tumor growth or metastases. The most common complaint is abdominal pain.

An unusual paraneoplastic syndrome called lipase hypersecretion syndrome has been reported to occur in 4%–16% of adult patients (92,93), but no case has been reported in a child. This syndrome of diffuse fat necrosis, due to systemic release of tumor-elaborated lipase, commonly manifests as peripheral polyarthropathy and painful, erythematous subcutaneous nodules (93,95, 96).

For information on the molecular genetics of acinar cell carcinoma, see Appendix E1 at radiographics.rsnajnls.org/cgi/content/full/26/4/1211/DC1.

Acinar cell carcinoma occurs throughout the pancreas with no preferential location (8,92,97). The tumor is most often a large, well-demarcated, soft, round to lobular mass. The size ranges from 2 to 30 cm with a mean of 10 cm (92,93,95). They are almost always well circumscribed and may be partially or completely encapsulated. The cut surface reveals a tan to reddish mass separated into large lobules by thin, fibrous strands. Necrotic foci are frequent (8,92,93).

In children, the histologic differentiation between acinar cell carcinoma and pancreatoblastoma may be particularly difficult. Macro- and microscopically, these tumors are very similar in appearance owing to their common acinar differentiation. The distinguishing histologic features are the squamoid corpuscles and mesenchymal differentiation that are seen in pancreatoblastoma but not in acinar cell carcinoma.

Few reports describe the imaging appearance of this rare tumor. At US, a well-defined, predominantly hypoechoic mass has been described (98). At CT, the tumor is almost always well demarcated and most show a well-defined, partial or complete capsule. The masses are frequently exophytic. The internal architecture is usually heterogeneous in attenuation. Most tumors show a central hypoattenuating area, often large, which represents tumoral necrosis. Calcification is present in one-third to half of cases and may be visible on plain radiographs. These calcifications may be punctate or chunky and may be peripheral or central within the tumor. Although intratumoral hemorrhage may be a prominent pathologic feature, hemorrhage may not be observed at CT (96,99).

Acinar cell carcinoma demonstrates more enhancement with intravenous contrast material than ductal adenocarcinoma but less than islet cell tumors. The tumor usually enhances but less than normal pancreas. Smaller tumors tend to show a homogeneous enhancement pattern, while larger tumors generally exhibit enhancement of the peripheral, solid portion of the mass (96,99).

Little information about the MR imaging appearance of acinar cell carcinoma is available in the literature. Tatli et al (96) describe one acinar cell carcinoma as homogeneous and slightly hypointense on T1-weighted images and hyperintense on T2-weighted images relative to the normal pancreas. Enhancement of this mass was homogeneous and less than that of the surrounding parenchyma. Another acinar cell carcinoma was well marginated with a central area of mixed signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The central focus correlated pathologically with necrosis.

CT and MR imaging can demonstrate associated enlarged regional lymph nodes, invasion of adjacent organs, venous encasement, and venous tumor thrombus and are useful for preoperative tumor staging (96,99).

The imaging appearance of acinar cell carcinoma is reminiscent of that of solid-pseudopapillary tumor and pancreatoblastoma, which are also often quite large with central necrosis. Calcifications may also be seen in all. The age of the patient may help differentiate these. Acinar cell carcinomas are quite rare in children, while one-third of solid-pseudopapillary tumors occur in adolescents and pancreatoblastoma occurs in children under the age of 10 years.

The overall prognosis for patients with acinar cell carcinoma is slightly better than for patients with ductal adenocarcinoma, particularly for those whose disease is amenable to surgical resection. Klimstra et al (93) reported 1-year survival of 57%, 3-year survival of 26%, and 5-year survival of 5.9% compared to 11.9% 1-year survival and 2%–4% 5-year survival for ductal adenocarcinoma (100). Thus, the short-term survival is better for acinar cell carcinoma, but long-term survival is poor for both tumors.

Ductal Adenocarcinoma
Ductal adenocarcinoma with its variants is the most common neoplasm of the pancreas, accounting for 85%–95% of pancreatic tumors; however, the tumor is rare under the age of 40 years (100–102). Reports of convincing cases in children are extraordinarily rare. Lüttges et al (102), in a review of the literature from 1818 to 2001, found 71 cases diagnosed as ductal adeno-carcinoma in patients under 40 years of age. On the basis of the World Health Organization classification system of 1996 and data available in the reports, only 20 of these were thought by the authors to represent true ductal adenocarcinomas. They also noted that, similar to breast and colon cancer, young patients with ductal adenocarcinoma of the pancreas tend to have special circumstances or familial predisposition. Genetic conditions associated with increased risk of pancreatic carcinoma include hereditary pancreatitis, hereditary pancreatic cancer syndrome, hereditary non-polyposis colon carcinoma, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, and BRCA2, the second identified breast cancer gene (4,101–104).

Clinical, imaging, and pathologic findings of ductal adenocarcinoma in patients under 40 years of age are similar to cases in older adults, although one study (100) indicated poorer differentiation and high prevalence of metastatic disease in younger patients, perhaps due to delayed diagnosis related to lack of suspicion of malignancy in younger patients (2,100). Also, the relative frequency of variants, especially those with mucinous components, is greater in younger patients (90). The pathologic features are similar to those of tumors in older patients (26,101). At imaging, ductal adenocarcinomas are small, echogenic and inhomogeneous at US, hypoattenuating at CT, hypointense to normal pancreas on T1-weighted images due to sclerosis, and variable in signal intensity on T2-weighted images. They enhance less than normal pancreas.

The prognosis is as dismal in younger patients as it is in older patients, with a 5-year survival rate of 2%–4% (100–102). Previous reports of better prognosis for "adenocarcinoma" in children, in light of the current body of knowledge, are thought to actually represent examples of other tumors known to have better prognosis, including solid-pseudopapillary tumor and pancreatoblastoma (4,9,91,100,102).

Other Rare Cystic Neoplasms
Cystic pancreatic neoplasms account for less than 1% of pancreatic neoplasms in adults and are even less common in children. Rare reports of cystadenomas in children exist but no cases of cystadenocarcinomas (5). Other authors have questioned these diagnoses of "cystadenoma" (5,7).

Cystic pancreatic neoplasms are divided into two distinct types. Microcystic serous adenomas contain many small cysts (<2 cm in diameter), display a honeycomb appearance at imaging, and have no malignant potential. Mucinous cystic neoplasms contain six or fewer larger cysts, exhibit a multilocular appearance at imaging, and represent a continuum of benign to malignant disease. Calcifications are more common in the serous form (27,49).

Nonepithelial Neoplasms or Tumorlike Lesions
Lymphoma.— Although lymphoma is more likely to involve peripancreatic nodes, lymphomatous masses may extend into the pancreas or may arise primarily within the pancreas (Fig 8). Intrinsic involvement of the pancreas is difficult to distinguish from peripancreatic nodal disease even at surgery. Non-Hodgkin lymphoma may be the most common nonepithelial childhood pancreatic tumor (105). Pancreatic and peripancreatic involvement is more common with large cell lymphoma and sporadic Burkitt lymphoma than with other non-Hodgkin lymphomas. In Burkitt lymphoma, pancreatic involvement may appear as a solitary lesion, multiple lesions, or diffuse infiltration of the gland (Fig 8). Diffuse enlargement of the gland may also be due to secondary pancreatitis or pancreatitis related to tumor lysis syndrome (7,55).

View larger version (158K): [in this window] [in a new window] [Download PPT slide]   Figure 8.  Lymphoblastic lymphoma in a 17-year-old boy with epigastric pain for 3 days who was found to have elevated results of liver function tests and an elevated amylase level. CT scan enhanced with intravenous and oral contrast material shows diffuse, homogeneous enlargement of the pancreas. There is dilatation of the common bile duct (arrow) and intrahepatic ducts (arrowheads).

Lymphangioma.— Lymphangioma, or lymphatic malformation, a congenital mass believed due to fetal lymphatic obstruction, rarely involves the pancreas. They are typically multicystic with micro- and macrocystic portions, surrounded by a thin fibrous capsule (Fig 9). The cystic spaces contain serosanguineous or chylous fluid. At CT, the mass is uni- or multilocular with an enhancing capsule and septa. Microcystic portions appear solid and enhancing (106).

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Lymphangioma of the pancreas in a 5-year-old boy with a 1-week history of abdominal pain and vomiting. (a) CT scan enhanced with intravenous and oral contrast material shows a predominantly cystic mass (straight arrows) in the pancreatic body and tail. The mass has an enhancing wall and multiple thin, enhancing septa (curved arrows). No solid components or surrounding inflammatory changes are evident. Arrowhead = splenic vein. (b) Photograph of the cut surface of the resected specimen shows the reddish mass with large cystic spaces (arrows), which are now drained of fluid.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Lymphangioma of the pancreas in a 5-year-old boy with a 1-week history of abdominal pain and vomiting. (a) CT scan enhanced with intravenous and oral contrast material shows a predominantly cystic mass (straight arrows) in the pancreatic body and tail. The mass has an enhancing wall and multiple thin, enhancing septa (curved arrows). No solid components or surrounding inflammatory changes are evident. Arrowhead = splenic vein. (b) Photograph of the cut surface of the resected specimen shows the reddish mass with large cystic spaces (arrows), which are now drained of fluid.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Mature teratoma of the pancreas in a 21-year-old woman who presented with a long history of nonspecific abdominal pain. CT scans enhanced with intravenous and oral contrast material show a complex mass arising in the body of the pancreas with foci of fat attenuation (* in a), very bright foci of calcific attenuation or intense enhancement (arrows in a), and a large cystic component (arrowheads in b).

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Mature teratoma of the pancreas in a 21-year-old woman who presented with a long history of nonspecific abdominal pain. CT scans enhanced with intravenous and oral contrast material show a complex mass arising in the body of the pancreas with foci of fat attenuation (* in a), very bright foci of calcific attenuation or intense enhancement (arrows in a), and a large cystic component (arrowheads in b).

Other Mesenchymal Tumors.— Benign and malignant mesenchymal tumors very rarely involve the pancreas. Reported benign lesions include hemangioendothelioma in children, leiomyoma, lipoma, neurofibroma, and schwannoma. The most common malignant mesenchymal tumor of the pancreas in children is rhabdomyosarcoma (Fig 11). Secondary involvement of the pancreas by retroperitoneal sarcoma is much more common than primary sarcoma of the pancreas. Sarcomas are highly malignant, frequently showing early metastatic spread, especially to the liver (8,105,106,112). Other rare malignant mesenchymal tumors include leiomyosarcoma, malignant schwannoma, fibrosarcoma, liposarcoma, and malignant fibrous histiocytoma (105,113).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  High-grade sarcoma of the head of the pancreas in a 10-year-old boy who presented with jaundice, nausea, and vomiting. (a) US scan shows an ill-defined, predominantly hypoechoic mass (arrows) in the pancreatic head and a dilated main pancreatic duct (arrowhead). (b) CT scan enhanced with intravenous contrast material shows the very heterogeneous mass with ill-defined borders in the region of the pancreatic head. There is mass effect on the gallbladder (arrow). Some small areas within the mass enhance intensely (arrowheads).

View larger version (139K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  High-grade sarcoma of the head of the pancreas in a 10-year-old boy who presented with jaundice, nausea, and vomiting. (a) US scan shows an ill-defined, predominantly hypoechoic mass (arrows) in the pancreatic head and a dilated main pancreatic duct (arrowhead). (b) CT scan enhanced with intravenous contrast material shows the very heterogeneous mass with ill-defined borders in the region of the pancreatic head. There is mass effect on the gallbladder (arrow). Some small areas within the mass enhance intensely (arrowheads).

Pancreatic Cysts
Pancreatic Pseudocyst.— The most common cystic lesion of the pancreas in children is pancreatic pseudocyst, accounting for 75% of cystic lesions (6,8) (Fig 12). In children, pseudocysts most commonly occur after blunt abdominal trauma and following pancreatitis. Blunt abdominal trauma is most commonly due to motor vehicle collisions, handlebar injuries, and inflicted trauma. The causes of pancreatitis in children are much more varied than in adults and include gallstones, usually related to hematologic diseases, choledochal cysts, pancreas divisum, drug toxicity, multisystem disease, metabolic disorders, hemolytic uremic syndrome, viral infection (mumps, coxsackie), and hereditary pancreatitis (6,114).

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Pancreatitis complicated by pseudocyst formation in an 11-year-old girl with a history of cholelithiasis and acute epigastric pain and a markedly elevated serum amylase level. (a) CT scan enhanced with intravenous and oral contrast material and obtained in the acute setting shows an area of fluid attenuation (*) with an ill-defined enhancing margin and surrounding inflammatory change (arrows) adjacent to the pancreatic body and tail. (b) CT scan enhanced with intravenous contrast material and obtained weeks later shows a cyst with central fluid attenuation (*) and a well-defined, enhancing wall (arrows) adjacent to the pancreatic body and tail (arrowhead).

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Pancreatitis complicated by pseudocyst formation in an 11-year-old girl with a history of cholelithiasis and acute epigastric pain and a markedly elevated serum amylase level. (a) CT scan enhanced with intravenous and oral contrast material and obtained in the acute setting shows an area of fluid attenuation (*) with an ill-defined enhancing margin and surrounding inflammatory change (arrows) adjacent to the pancreatic body and tail. (b) CT scan enhanced with intravenous contrast material and obtained weeks later shows a cyst with central fluid attenuation (*) and a well-defined, enhancing wall (arrows) adjacent to the pancreatic body and tail (arrowhead).

Congenital Cysts and Cysts Associated with Systemic Disease or a Syndrome.— True congenital epithelium-lined cysts of the pancreas are rare, usually asymptomatic lesions found incidentally. Rarely, they manifest in infancy due to mass effect. These may be solitary without an associated syndrome or may be multiple in a patient with a malformative syndrome.

Solitary cysts may be caused by abnormal development of the embryonic duct system. These are usually small, do not communicate with the duct system, and are lined with flat epithelium. At CT, the internal contents have an attenuation coefficient in the range of water and do not enhance (Fig 13). They may be uni- or multilocular (7,8,109).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  Congenital pancreatic cyst in a term newborn girl in whom a large abdominal cyst was diagnosed antenatally and who was found to have jaundice and elevated results of liver function tests. (a) Transverse sonogram of the fetal abdomen from a prenatal examination shows a round, anechoic cyst (arrow) on the opposite side of the J-shaped stomach (arrowhead). The smaller cystic structure between the two is a dilated biliary duct in cross section. (b) Postnatal contrast-enhanced CT scan shows the large simple cyst (*) on the right side with the stomach (arrowhead) on the left. Also note the multiple dilated biliary ducts (arrows).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  Congenital pancreatic cyst in a term newborn girl in whom a large abdominal cyst was diagnosed antenatally and who was found to have jaundice and elevated results of liver function tests. (a) Transverse sonogram of the fetal abdomen from a prenatal examination shows a round, anechoic cyst (arrow) on the opposite side of the J-shaped stomach (arrowhead). The smaller cystic structure between the two is a dilated biliary duct in cross section. (b) Postnatal contrast-enhanced CT scan shows the large simple cyst (*) on the right side with the stomach (arrowhead) on the left. Also note the multiple dilated biliary ducts (arrows).

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 14.  Pancreatic retention cysts in a 17-year-old patient with cystic fibrosis who presented with renal colic and hematuria due to nephrolithiasis. CT scan enhanced with intravenous and oral contrast material shows multiple cysts in the pancreas (arrows) adjacent to the splenic vein (arrowhead).

	Conclusions

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

Pancreatoblastoma is the most common pancreatic neoplasm of young children. At imaging, these are heterogeneous with central cystic change and often multiloculated in appearance. Solid-pseudopapillary tumor occurs in adolescent girls. This tumor is also usually large with a prominent fibrous capsule visible at imaging. The internal architecture is quite heterogeneous with a mixture of solid and cystic hemorrhagic and necrotic elements. Islet cell tumors occasionally occur in older children and are either insulinomas or gastrinomas. These manifest early as hormonal syndromes, so that they are distinguished from the other neoplasms in children by their small size, homogeneous appearance at imaging, and hypervascular nature.

Awareness of the relatively good prognosis of pancreatic tumors in children and an understanding of their malignant potential are important in optimizing surgical treatment. Children with pancreatic tumors benefit from curative resection when possible, debulking of advanced local disease, and, in select cases, resection of metastases. An appreciation of the malignant nature of these lesions is also necessary to prevent inadequate treatment.

	Acknowledgments

 
The authors acknowledge Angela Levy, LTC, MC, USA, for her critical review of the manuscript.

	Footnotes

 

Abbreviations: H-E = hematoxylin-eosin, MEN 1 = multiple endocrine neoplasia type 1

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views of the Departments of the Army, Navy, or Defense.

SUPPLEMENTAL MATERIAL

An appendix on molecular genetics is available online at radiographics.rsnajnls.org/cgi/content/full/26/4/1211/DC1.

	References

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Pancreatoblastoma Solid-Pseudopapillary Tumor Islet Cell Tumors Multiple Endocrine Neoplasia... Nesidioblastosis or Persistent... Other Pancreatic Tumors and... Conclusions References

 

1. Tsukimoto I, Watanabe K, Lin JB, Nakajima T. Pancreatic carcinoma in children in Japan. Cancer 1973;31(5):1203–1207.[CrossRef][Medline]
2. Grosfeld JL, Vane DW, Rescorla FJ, McGuire W, West KW. Pancreatic tumors in childhood: analysis of 13 cases. J Pediatr Surg 1990;25(10): 1057–1062.[CrossRef][Medline]
3. Jaksic T, Yaman M, Thorner P, Wesson DK, Filler RM, Shandling B. A 20-year review of pediatric pancreatic tumors. J Pediatr Surg 1992; 27(10):1315–1317.[CrossRef][Medline]
4. Lack EE, Cassady JR, Levey R, Vawter GF. Tumors of the exocrine pancreas in children and adolescents: a clinical and pathologic study of eight cases. Am J Surg Pathol 1983;7(4):319–327.[Medline]
5. Shorter NA, Glick RD, Klimstra DS, Brennan MF, Laquaglia MP. Malignant pancreatic tumors in childhood and adolescence: the Memorial Sloan-Kettering experience, 1967 to present. J Pediatr Surg 2002;37(6):887–892.[CrossRef][Medline]
6. Vane DW, Grosfeld JL, West KW, Rescorla FJ. Pancreatic disorders in infancy and childhood: experience with 92 cases. J Pediatr Surg 1989; 24(8):771–776.[CrossRef][Medline]
7. Jaffe R. The pancreas. In: Stocker J, Dehner L, eds. Pediatric pathology. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2002; 797–834.
8. Solcia E, Capella C, Klöppel G. Atlas of tumor pathology: tumors of the pancreas. Washington, DC: Armed Forces Institute of Pathology, 1997.
9. Cubilla A, Fitzgerald P. Tumors of the exocrine pancreas. In: Hartmann W, Sobin L, eds. Atlas of tumor pathology: tumors of the pancreas. Washington, DC: Armed Forces Institute of Pathology, 1984; 208–219.
10. Becker WF. Pancreatoduodenectomy for carcinoma of the pancreas in an infant: report of a case. Ann Surg 1957;145(6):864–870; discussions, 870–872.[Medline]
11. Horie A, Yano Y, Kotoo Y, Miwa A. Morphogenesis of pancreatoblastoma, infantile carcinoma of the pancreas: report of two cases. Cancer 1977;39(1):247–254.[CrossRef][Medline]
12. Du E, Katz M, Weidner N, Yoder S, Moossa AR, Shabaik A. Ampullary pancreatoblastoma in an elderly patient: a case report and review of the literature. Arch Pathol Lab Med 2003;127(11): 1501–1505.[Medline]
13. Imamura A, Nakagawa A, Okuno M, et al. Pancreatoblastoma in an adolescent girl: case report and review of 26 Japanese cases. Eur J Surg 1998; 164(4):309–312.[CrossRef][Medline]
14. Klimstra DS, Wenig BM, Adair CF, Heffess CS. Pancreatoblastoma: a clinicopathologic study and review of the literature. Am J Surg Pathol 1995; 19(12):1371–1389.[Medline]
15. Montemarano H, Lonergan GJ, Bulas DI, Selby DM. Pancreatoblastoma: imaging findings in 10 patients and review of the literature. Radiology 2000;214(2):476–482.[Abstract/Free Full Text]
16. Pelizzo G, Conoscenti G, Kalache KD, Vesce F, Guerrini P, Cavazzini L. Antenatal manifestation of congenital pancreatoblastoma in a fetus with Beckwith-Wiedemann syndrome. Prenat Diagn 2003;23(4):292–294.[CrossRef][Medline]
17. Roebuck DJ, Yuen MK, Wong YC, Shing MK, Lee CW, Li CK. Imaging features of pancreatoblastoma. Pediatr Radiol 2001;31(7):501–506.[CrossRef][Medline]
18. Gupta AK, Mitra DK, Berry M, Dinda AK, Bhatnagar V. Sonography and CT of pancreatoblastoma in children. AJR Am J Roentgenol 2000;174(6):1639–1641.[Abstract/Free Full Text]
19. Passmore SJ, Berry PJ, Oakhill A. Recurrent pancreatoblastoma with inappropriate adrenocorticotrophic hormone secretion. Arch Dis Child 1988;63(12):1494–1496.[Abstract/Free Full Text]
20. Stephenson CA, Kletzel M, Seibert JJ, Glasier CM. Pancreatoblastoma: MR appearance. J Comput Assist Tomogr 1990;14(3):492–493.[Medline]
21. Drut R, Jones MC. Congenital pancreatoblastoma in Beckwith-Wiedemann syndrome: an emerging association. Pediatr Pathol 1988;8(3): 331–339.[Medline]
22. Abraham SC, Wu TT, Hruban RH, et al. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/ beta-catenin pathway. Am J Pathol 2002;160(3): 953–962.[Abstract/Free Full Text]
23. Elliott M, Bayly R, Cole T, Temple IK, Maher ER. Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases. Clin Genet 1994;46(2):168–174.[Medline]
24. Klimstra D, Longnecker D. Pancreatoblastoma. In: Hamilton S, Aaltonen L, eds. WHO classification of tumours: pathology and genetics of tumours of the digestive system. Lyon, France: IARC Press, 1996; 244–245.
25. Lee JY, Kim IO, Kim WS, Kim CW, Yeon KM. CT and US findings of pancreatoblastoma. J Comput Assist Tomogr 1996;20(3):370–374.[CrossRef][Medline]
26. Mergo PJ, Helmberger TK, Buetow PC, Helmberger RC, Ros PR. Pancreatic neoplasms: MR imaging and pathologic correlation. RadioGraphics 1997;17(2):281–301.[Abstract]
27. Williams T, Babyn P. The pancreas. In: Stringer D, Babyn P, eds. Pediatric gastrointestinal imaging and intervention. 2nd ed. Hamilton, Ontario, Canada: Decker, 2000.
28. Frantz V. Tumors of the pancreas. In: Atlas of tumor pathology. Section 7, fascicles 27 and 28. Washington, DC: Armed Forces Institute of Pathology, 1959; 32–33.
29. Hamoudi AB, Misugi K, Grosfeld JL, Reiner CB. Papillary epithelial neoplasm of pancreas in a child: report of a case with electron microscopy. Cancer 1970;26(5):1126–1134.[CrossRef][Medline]
30. Klöppel G, Morohoshi T, John HD, et al. Solid and cystic acinar cell tumour of the pancreas: a tumour in young women with favourable prognosis. Virchows Arch A Pathol Anat Histol 1981; 392(2):171–183.[CrossRef][Medline]
31. Group WHOW. WHO histological classification of tumours of the exocrine pancreas. In: Hamilton S, Aaltonen L, eds. WHO classification of tumours: pathology and genetics of tumours of the digestive system. Lyon, France: IARC Press, 1996; 220.
32. Sclafani LM, Reuter VE, Coit DG, Brennan MF. The malignant nature of papillary and cystic neoplasm of the pancreas. Cancer 1991;68(1):153–158.[CrossRef][Medline]
33. Todani T, Shimada K, Watanabe Y, Toki A, Fujii T, Urushihara N. Frantz’s tumor: a papillary and cystic tumor of the pancreas in girls. J Pediatr Surg 1988;23(2):116–121.[CrossRef][Medline]
34. Papavramidis T, Papavramidis S. Solid pseudopapillary tumors of the pancreas: review of 718 patients reported in English literature. J Am Coll Surg 2005;200(6):965–972.[CrossRef][Medline]
35. Buetow PC, Buck JL, Pantongrag-Brown L, Beck KG, Ros PR, Adair CF. Solid and papillary epithelial neoplasm of the pancreas: imaging-pathologic correlation in 56 cases. Radiology 1996;199(3):707–711.[Abstract/Free Full Text]
36. Mao C, Guvendi M, Domenico DR, Kim K, Thomford NR, Howard JM. Papillary cystic and solid tumors of the pancreas: a pancreatic embryonic tumor? Studies of three cases and cumulative review of the world’s literature. Surgery 1995;118(5):821–828.[CrossRef][Medline]
37. Wang KS, Albanese C, Dada F, Skarsgard ED. Papillary cystic neoplasm of the pancreas: a report of three pediatric cases and literature review. J Pediatr Surg 1998;33(6):842–845.[CrossRef][Medline]
38. Nishihara K, Nagoshi M, Tsuneyoshi M, Yamaguchi K, Hayashi I. Papillary cystic tumors of the pancreas: assessment of their malignant potential. Cancer 1993;71(1):82–92.[CrossRef][Medline]
39. 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 Pathol 2002;160(4):1361–1369.[Abstract/Free Full Text]
40. Cantisani V, Mortele KJ, Levy A, et al. MR imaging features of solid pseudopapillary tumor of the pancreas in adult and pediatric patients. AJR Am J Roentgenol 2003;181(2):395–401.[Abstract/Free Full Text]
41. Friedman AC, Lichtenstein JE, Fishman EK, Oertel JE, Dachman AH, Siegelman SS. Solid and papillary epithelial neoplasm of the pancreas. Radiology 1985;154(2):333–337.[Abstract/Free Full Text]
42. Zhou H, Cheng W, Lam KY, Chan GC, Khong PL, Tam PK. Solid-cystic papillary tumor of the pancreas in children. Pediatr Surg Int 2001;17(8): 614–620.[CrossRef][Medline]
43. Orlando CA, Bowman RL, Loose JH. Multicentric papillary-cystic neoplasm of the pancreas. Arch Pathol Lab Med 1991;115(9):958–960.[Medline]
44. Klöppel G, Lüttges J, Klimstra DS, Hruban RH, Kern SE, Adler G. Solid-pseudopapillary neoplasm. In: Hamilton S, Aaltonen L, eds. WHO classification of tumours: pathology and genetics of tumours of the digestive system. Lyon, France: IARC Press, 1996; 246–248.
45. Kosmahl M, Seada LS, Janig U, Harms D, Klöppel G. Solid-pseudopapillary tumor of the pancreas: its origin revisited. Virchows Arch 2000; 436(5):473–480.[CrossRef][Medline]
46. Matsunou H, Konishi F. Papillary-cystic neoplasm of the pancreas: a clinicopathologic study concerning the tumor aging and malignancy of nine cases. Cancer 1990;65(2):283–291.[CrossRef][Medline]
47. Choi BI, Kim KW, Han MC, Kim YI, Kim CW. Solid and papillary epithelial neoplasms of the pancreas: CT findings. Radiology 1988;166(2): 413–416.[Abstract/Free Full Text]
48. Klimstra DS, Wenig BM, Heffess CS. Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. Semin Diagn Pathol 2000;17(1):66–80.[Medline]
49. Ohtomo K, Furui S, Onoue M, et al. Solid and papillary epithelial neoplasm of the pancreas: MR imaging and pathologic correlation. Radiology 1992;184(2):567–570.[Abstract/Free Full Text]
50. Lee DH, Yi BH, Lim JW, Ko YT. Sonographic findings of solid and papillary epithelial neoplasm of the pancreas. J Ultrasound Med 2001;20(11): 1229–1232.[Abstract/Free Full Text]
51. Procacci C, Graziani R, Bicego E, et al. Papillary cystic neoplasm of the pancreas: radiological findings. Abdom Imaging 1995;20(6):554–558.[CrossRef][Medline]
52. 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(4):289–296.[CrossRef][Medline]
53. Ishikawa O, Ishiguro S, Ohhigashi H, et al. Solid and papillary neoplasm arising from an ectopic pancreas in the mesocolon. Am J Gastroenterol 1990;85(5):597–601.[Medline]
54. Sun CD, Lee WJ, Choi JS, Oh JT, Choi SH. Solid-pseudopapillary tumours of the pancreas: 14 years experience. ANZ J Surg 2005;75(8): 684–689.[CrossRef][Medline]
55. Friedman AC, Edmonds PR. Rare pancreatic malignancies. Radiol Clin North Am 1989;27(1): 177–190.[Medline]
56. Balthazar EJ, Subramanyam BR, Lefleur RS, Barone CM. Solid and papillary epithelial neoplasm of the pancreas: radiographic, CT, sonographic, and angiographic features. Radiology 1984;150(1):39–40.[Abstract/Free Full Text]
57. Service FJ, McMahon MM, O’Brien PC, Ballard DJ. Functioning insulinoma: incidence, recurrence, and long-term survival of patients—a 60-year study. Mayo Clin Proc 1991;66(7):711–719.[Medline]
58. Buetow PC, Parrino TV, Buck JL, et al. Islet cell tumors of the pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status. AJR Am J Roentgenol 1995;165(5):1175–1179.[Abstract/Free Full Text]
59. Gouya H, Vignaux O, Augui J, et al. CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol 2003;181(4):987–992.[Abstract/Free Full Text]
60. Buetow PC, Miller DL, Parrino TV, Buck JL. Islet cell tumors of the pancreas: clinical, radiologic, and pathologic correlation in diagnosis and localization. RadioGraphics 1997;17(2):453–472.[Abstract]
61. Semelka RC, Ascher SM. MR imaging of the pancreas. Radiology 1993;188(3):593–602.[Abstract/Free Full Text]
62. Klöppel G, Willemer S, Stamm B, Hacki WH, Heitz PU. Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I: an immunocytochemical study of nine patients. Cancer 1986;57(9):1824–1832.[CrossRef][Medline]
63. King AD, Ko GT, Yeung VT, Chow CC, Griffith J, Cockram CS. Dual phase spiral CT in the detection of small insulinomas of the pancreas. Br J Radiol 1998;71(841):20–23.[Abstract]
64. Thoeni RF, Mueller-Lisse UG, Chan R, Do NK, Shyn PB. Detection of small, functional islet cell tumors in the pancreas: selection of MR imaging sequences for optimal sensitivity. Radiology 2000;214(2):483–490.[Abstract/Free Full Text]
65. Machado MC, da Cunha JE, Jukemura J, et al. Insulinoma: diagnostic strategies and surgical treatment—a 22-year experience. Hepatogastroenterology 2001;48(39):854–858.[Medline]
66. Doherty GM, Doppman JL, Shawker TH, et al. Results of a prospective strategy to diagnose, localize, and resect insulinomas. Surgery 1991; 110(6):989–996; discussion 996–997.[Medline]
67. Aspestrand F, Kolmannskog F, Jacobsen M. CT, MR imaging and angiography in pancreatic apudomas. Acta Radiol 1993;34(5):468–473.[Medline]
68. Chung MJ, Choi BI, Han JK, Chung JW, Han MC, Bae SH. Functioning islet cell tumor of the pancreas: localization with dynamic spiral CT. Acta Radiol 1997;38(1):135–138.[Medline]
69. Pavone P, Mitchell DG, Leonetti F, et al. Pancreatic beta-cell tumors: MRI. J Comput Assist Tomogr 1993;17(3):403–407.[Medline]
70. Pisegna JR, Doppman JL, Norton JA, Metz DC, Jensen RT. Prospective comparative study of ability of MR imaging and other imaging modalities to localize tumors in patients with Zollinger-Ellison syndrome. Dig Dis Sci 1993;38(7):1318–1328.[CrossRef][Medline]
71. Schumacher B, Lubke HJ, Frieling T, Strohmeyer G, Starke AA. Prospective study on the detection of insulinomas by endoscopic ultrasonography. Endoscopy 1996;28(3):273–276.[Medline]
72. Cadiot G, Lebtahi R, Sarda L, et al. Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D’etude Du Syndrome De Zollinger-Ellison. Gastroenterology 1996;111(4): 845–854.[CrossRef][Medline]
73. Meko JB, Doherty GM, Siegel BA, Norton JA. Evaluation of somatostatin-receptor scintigraphy for detecting neuroendocrine tumors. Surgery 1996;120(6):975–983; discussion 983–984.[CrossRef][Medline]
74. Krausz Y, Keidar Z, Kogan I, et al. SPECT/CT hybrid imaging with 111 Inpentetreotide in assessment of neuroendocrine tumours. Clin Endocrinol (Oxf) 2003;59(5):565–573.[CrossRef][Medline]
75. Trump D, Farren B, Wooding C, et al. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 1996;89(9):653–669.[Abstract]
76. Chandrasekharappa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997; 276(5311):404–407.[Abstract/Free Full Text]
77. Komminoth P, Heitz PU, Klöppel G. Pathology of MEN-1: morphology, clinicopathologic correlations and tumour development. J Intern Med 1998;243(6):455–464.[CrossRef][Medline]
78. Donow C, Pipeleers-Marichal M, Schroder S, Stamm B, Heitz PU, Klöppel G. Surgical pathology of gastrinoma: site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer 1991;68(6):1329–1334.[CrossRef][Medline]
79. Oberg K, Skogseid B, Eriksson B. Multiple endocrine neoplasia type 1 (MEN-1): clinical, biochemical and genetical investigations. Acta Oncol 1989;28(3):383–387.[Medline]
80. Pipeleers-Marichal M, Somers G, Willems G, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 1990; 322(11):723–727.[Abstract]
81. Glaser B, Thornton P, Otonkoski T, Junien C. Genetics of neonatal hyperinsulinism. Arch Dis Child Fetal Neonatal Ed 2000;82(2):F79–F86.[Abstract/Free Full Text]
82. de Lonlay P, Fournet JC, Touati G, et al. Heterogeneity of persistent hyperinsulinaemic hypoglycaemia: a series of 175 cases. Eur J Pediatr 2002;161(1):37–48.[Medline]
83. Fekete CN, de Lonlay P, Jaubert F, Rahier J, Brunelle F, Saudubray JM. The surgical management of congenital hyperinsulinemic hypoglycemia in infancy. J Pediatr Surg 2004;39(3):267–269.[CrossRef][Medline]
84. de Lonlay-Debeney P, Poggi-Travert F, Fournet JC, et al. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med 1999;340(15): 1169–1175.[Abstract/Free Full Text]
85. Laidlaw G. Nesidioblastoma, the islet tumor of the pancreas. Am J Pathol 1938;14:125–134.
86. Berrocal T, Prieto C, Pastor I, Gutierrez J, al-Assir I. Sonography of pancreatic disease in infants and children. RadioGraphics 1995;15(2): 301–313.[Abstract]
87. Rahier J, Sempoux C, Fournet JC, et al. Partial or near-total pancreatectomy for persistent neonatal hyperinsulinaemic hypoglycaemia: the pathologist’s role. Histopathology 1998;32(1):15–19.[CrossRef][Medline]
88. Ribeiro MJ, De Lonlay P, Delzescaux T, et al. Characterization of hyperinsulinism in infancy assessed with PET and 18F-fluoro-L-DOPA. J Nucl Med 2005;46(4):560–566.[Abstract/Free Full Text]
89. Telander RL, Charboneau JW, Haymond MW. Intraoperative ultrasonography of the pancreas in children. J Pediatr Surg 1986;21(3):262–266.[Medline]
90. Morohoshi T, Held G, Klöppel G. Exocrine pancreatic tumours and their histological classification: a study based on 167 autopsy and 97 surgical cases. Histopathology 1983;7(5):645–661.[Medline]
91. Grosfeld JL, Clatworthy HW Jr, Hamoudi AB. Pancreatic malignancy in children. Arch Surg 1970;101(3):370–375.[Abstract/Free Full Text]
92. Hoorens A, Lemoine NR, McLellan E, et al. Pancreatic acinar cell carcinoma: an analysis of cell lineage markers, p53 expression, and Ki-ras mutation. Am J Pathol 1993;143(3):685–698.[Abstract]
93. Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas: a clinicopathologic study of 28 cases. Am J Surg Pathol 1992;16(9):815–837.[CrossRef][Medline]
94. Osborne BM, Culbert SJ, Cangir A, MacKay B. Acinar cell carcinoma of the pancreas in a 9-year-old child: case report with electron microscopic observations. South Med J 1977;70(3):370–372.[Medline]
95. Morohoshi T, Kanda M, Horie A, et al. Immunocytochemical markers of uncommon pancreatic tumors: acinar cell carcinoma, pancreatoblastoma, and solid cystic (papillary-cystic) tumor. Cancer 1987;59(4):739–747.[CrossRef][Medline]
96. Tatli S, Mortele KJ, Levy AD, et al. CT and MRI features of pure acinar cell carcinoma of the pancreas in adults. AJR Am J Roentgenol 2005; 184(2):511–519.[Abstract/Free Full Text]
97. Holen KD, Klimstra DS, Hummer A, et al. Clinical characteristics and outcomes from an institutional series of acinar cell carcinoma of the pancreas and related tumors. J Clin Oncol 2002; 20(24):4673–4678.[Abstract/Free Full Text]
98. Radin DR, Colletti PM, Forrester DM, Tang WW. Pancreatic acinar cell carcinoma with subcutaneous and intraosseous fat necrosis. Radiology 1986;158(1):67–68.[Abstract/Free Full Text]
99. Chiou YY, Chiang JH, Hwang JI, Yen CH, Tsay SH, Chang CY. Acinar cell carcinoma of the pancreas: clinical and computed tomography manifestations. J Comput Assist Tomogr 2004; 28(2):180–186.[CrossRef][Medline]
100. Ivy EJ, Sarr MG, Reiman HM. Nonendocrine cancer of the pancreas in patients under age forty years. Surgery 1990;108(3):481–487.[Medline]
101. Klöppel G, Hruban R, Longnecker D, Adler G, Kern S, Partanen T. Ductal adenocarcinoma of the pancreas. In: Hamilton S, Aaltonen L, eds. WHO classification of tumours: pathology and genetics of tumours of the digestive system. Lyon, France: IARC Press, 1996; 222–230.
102. Lüttges J, Stigge C, Pacena M, Klöppel G. Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years. Cancer 2004; 100(1):173–182.[CrossRef][Medline]
103. Hruban RH, Petersen GM, Goggins M, et al. Familial pancreatic cancer. Ann Oncol 1999; 10(suppl 4):69–73.
104. Tersmette AC, Petersen GM, Offerhaus GJ, et al. Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 2001; 7(3):738–744.[Abstract/Free Full Text]
105. Vaughn DD, Jabra AA, Fishman EK. Pancreatic disease in children and young adults: evaluation with CT. RadioGraphics 1998;18(5):1171–1187.[Abstract]
106. Ferrozzi F, Zuccoli G, Bova D, Calculli L. Mesenchymal tumors of the pancreas: CT findings. J Comput Assist Tomogr 2000;24(4):622–627.[CrossRef][Medline]
107. Jacobs JE, Dinsmore BJ. Mature cystic teratoma of the pancreas: sonographic and CT findings. AJR Am J Roentgenol 1993;160(3):523–524.[Free Full Text]
108. Mester M, Trajber HJ, Compton CC, de Camargo Junior HS, de Almeida PC, Hoover HC Jr. Cystic teratomas of the pancreas. Arch Surg 1990;125(9):1215–1218.[Abstract/Free Full Text]
109. Ros PR, Hamrick-Turner JE, Chiechi MV, Ros LH, Gallego P, Burton SS. Cystic masses of the pancreas. RadioGraphics 1992;12(4):673–686.[Abstract]
110. Danner DB, Hruban RH, Pitt HA, Hayashi R, Griffin CA, Perlman EJ. Primitive neuroectodermal tumor arising in the pancreas. Mod Pathol 1994;7(2):200–204.[Medline]
111. Movahedi-Lankarani S, Hruban RH, Westra WH, Klimstra DS. Primitive neuroectodermal tumors of the pancreas: a report of seven cases of a rare neoplasm. Am J Surg Pathol 2002;26(8): 1040–1047.[CrossRef][Medline]
112. Yasuda I, Adachi S, Kasahara S, et al. Pancreatic rhabdomyosarcoma. Gastrointest Endosc 2004; 60(3):433–434.[CrossRef][Medline]
113. Tunell WP. Hemangioendothelioma of the pancreas obstructing the common bile duct and duodenum. J Pediatr Surg 1976;11(5):827–830.[CrossRef][Medline]
114. Weizman Z, Durie PR. Acute pancreatitis in childhood. J Pediatr 1988;113(1 pt 1):24–29.[CrossRef][Medline]
115. Hernanz-Schulman M, Teele RL, Perez-Atayde A, et al. Pancreatic cystosis in cystic fibrosis. Radiology 1986;158(3):629–631.[Abstract/Free Full Text]

This Article Abstract Figures Only Full Text (PDF) CME Test (opens in a new window) Appendix E1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chung, E. M. Articles by Conran, R. M. Search for Related Content PubMed PubMed Citation Articles by Chung, E. M. Articles by Conran, R. M. Related Collections Pediatric Radiology Gastrointestinal Radiology