Development of the pancreas begins with the formation of 2 anlagen from the embryonic foregut. One arises from the dorsal aspect of the gut and the other from the ventral aspect. The dorsal anlage is initially located opposite to the hepatobiliary diverticulum. The ventral anlage arises from the duodenum at the caudal margin of the hepatobiliary diverticulum. The ventral anlage has right and left buds; the left bud normally regresses. There is progressive rotation of the ventral pancreas around the duodenum until it contacts and fuses with the dorsal segment. The common bile duct migrates with the ventral pancreas. The ventral pancreas forms the uncinate process and a portion of the head of the pancreas; the remainder of the pancreas derives from the dorsal anlage.

The embryonic dorsal pancreas contains the duct of Santorini and the ventral pancreas contains the duct of Wirsung. As the dorsal and ventral components of the developing pancreas come into contact, the 2 pancreatic ducts fuse and the terminal segment of the embryonic dorsal (Santorini) duct atrophies. The dorsal duct loses its communication with the duodenum in most individuals and the remaining segment forms the accessory duct. Persistence of duodenal communication of this duct and failure of appropriate fusion of the dorsal and ventral ducts leads to the developmental anomaly of pancreas divisum. Anomalous communication between the common bile duct and the duct of Wirsung results in the common channel syndrome. Anomalous fusion of the dorsal pancreas and the ventral pancreas around the duodenum due to failure of degeneration of the left bud of the ventral pancreatic anlage causes annular pancreas.

Annular Pancreas

Annular pancreas is a rare developmental lesion in which a band of pancreatic tissue surrounds the second portion of the duodenum. This band is contiguous with the head of the pancreas and may be complete or incomplete. The major significance of this anomaly is the association with duodenal stenosis. Annular pancreas is, after pancreas divisum, the second most common congenital anomaly of the pancreas. This lesion is the most common symptomatic pancreatic anomaly. Annular pancreas occurs in 1 in 12,000 to 15,000 livebirths. Annular pancreas as a concomitant anomaly in 18% to 33% of children with duodenal atresia or stenosis.^1,2

The embryogenesis of annular pancreas involves abnormal duodenal development as well as abnormal pancreatic development. Vacuolation of the duodenum occurs between the 8th and 10th weeks of gestation. Deficiency in this vacuolation process likely accounts for congenital duodenal atresia or stenosis. These duodenal anomalies are sometimes associated with anomalous pancreatic tissue that surrounds and compresses the duodenum, that is, annular pancreas. Although the anomalous pancreatic tissue does compress the duodenum, intrinsic narrowing of the duodenal lumen is typically part of the pathophysiological process and is the major cause of obstructive symptoms. The etiology of annular pancreas likely involves abnormal embryological communication between the ventral and dorsal anlagen of the pancreas. There are 2 predominant hypotheses about the development of annular pancreas: adhesion of the right ventral anlage to the duodenal wall (Lecco’s theory) and persistence on the left ventral anlage (Baldwin’s theory).³

The clinical presentation of patients with annular pancreas largely depends upon the severity of duodenal obstruction. With mild stenosis, the lesion is often completely asymptomatic. Neonates with severe obstruction may present with bilious vomiting and epigastric distension. About half of patients with annular pancreas present with clinical manifestations of a proximal bowel obstruction in the neonatal period. Infants with annular pancreas and significant duodenal obstruction are often premature or small for their gestational ages. Duodenal atresia and stenosis, intestinal malrotation, and trisomy 21 occur in combination with annular pancreas in approximately 10% to 20% of patients. The association between trisomy 21 and annular pancreas is not as strong as with duodenal atresia; the prevalence of trisomy 21 in patients with duodenal atresia is higher than 40%.²

The radiographic diagnosis of annular pancreas is based on findings related to the duodenal obstruction. With significant obstruction, abdominal radiographs demonstrate a double bubble due to dilation of the proximal duodenum. Fluoroscopic contrast studies show a localized area of narrowing in the second portion of the duodenum, usually at or above the level of the ampulla of Vater. The narrowing typically has a circumferential character. The appearance of the mucosa is normal.

Prenatal sonography of the fetus with annular pancreas may show prominence of the duodenal bulb and stomach. Similar findings can often be demonstrated with sonography in the newborn. In some instances, the anomalous pancreatic tissue is visible as an echogenic band that crosses the duodenum in the region of the pancreatic head. This encircling pancreatic tissue can also be visualized in older children with CT or MR (Figure 42-1). With MR, fat-suppressed images often provide optimal differentiation between the anomalous pancreatic tissue and the duodenum.^4–6

Pancreas Divisum

Pancreas divisum is the most common congenital anomaly of the pancreas, although less often symptomatic than annular pancreas. Pancreas divisum occurs in 10% to 14% of the population. Failure of proper fusion between the embryonic ventral and dorsal pancreatic ducts leads to separate drainage of the mature counterparts of these structures. The smaller, ventral pancreas forms a portion of the head of the pancreas (including the uncinate process) and drains through a small duct of Wirsung via the major papilla. The persistent duct of Santorini provides drainage for the majority of the pancreas via the minor papilla. Obstruction at the minor papilla can lead to cystic dilation of the dorsal pancreatic duct near its insertion with the papilla; this is termed a Santorinicele.

There is a weak association between pancreas divisum and pancreatitis in adults and adolescents, apparently due to a propensity for stenosis of the minor papilla. However, a study by Delhaye et al showed this anomaly to occur with the same frequency in patients with pancreatitis as in those without.⁷ Pancreatitis in individuals with pancreas divisum may involve the entire pancreas or be limited to the portion served by the duct of Santorini; isolated involvement of the ventral pancreas is less common.^8–10

MR pancreatography utilizing heavily T2-weighted images allows the noninvasive demonstration of pancreas divisum (Figure 42-2). Duct visualization is optimized by the administration of exogenous secretin. In some patients, the diagnosis can also be established with high-resolution CT or sonography. Important imaging features include a larger caliber of the duct of Santorini than of the duct of Wirsung, and lack of communication between the 2 ducts. On axial images, the duct of Santorini (i.e., the duct that drains the body and tail of the gland) passes anterior and superior to the distal aspect of the common bile duct. In patients with a Santorinicele, there is cystic dilation of the dorsal pancreatic duct near its insertion with the minor papilla. With sonography, the head and uncinate process (the ventral pancreas) sometimes have slightly altered echogenicity relative to the remainder of the gland in patients with pancreas divisum.^6,11–14

Dorsal Pancreas Agenesis

Agenesis of the dorsal pancreas apparently results from failure of development of the dorsal pancreatic anlage. Agenesis of the ventral portion of the pancreas is exceedingly rare; complete agenesis of the pancreas is fatal. Agenesis of the dorsal pancreas is usually asymptomatic. Adults with this anomaly sometimes have manifestations of diabetes mellitus. Dorsal pancreas agenesis can occur in association with polysplenia syndrome. There are rare instances of familial occurrence of this anomaly. Cross-sectional imaging studies show absence of the neck, body, and tail of the pancreas. The pancreatic head has a rounded configuration.^15,16

Pancreas Bifidum

Pancreas bifidum is a rare developmental abnormality in which there are 2 branches of the main pancreatic duct. This is often associated with a bifid configuration of the pancreatic tail (fish tail pancreas). Most patients with this anomaly are asymptomatic.¹⁷

Ectopic Pancreas

Ectopic pancreas (heterotopic pancreas) refers to pancreatic tissue that lacks anatomic and vascular continuity with the main body of the pancreas and has an independent duct. Foci of ectopic pancreatic tissue are present in approximately 2% of individuals. Approximately 70% of ectopic pancreatic rests occur within the wall of the stomach, duodenum, or jejunum. Other potential locations include ileum, spleen, biliary tract, liver, mesentery, umbilicus, Meckel diverticulum, fallopian tube, enteric duplication cyst, and lungs.

Ectopic pancreas is asymptomatic in the great majority of patients. Most lesions that are symptomatic are located in the stomach or duodenum, where they can cause pain, GI hemorrhage, or gastric ulceration. Ectopic pancreas in the prepyloric area can lead to gastric outlet obstruction, usually first becoming symptomatic beyond the first year of life. Inflammation of ectopic pancreatic tissue is a rare complication (i.e., pancreatitis). Pseudocyst formation can also occur.^18,19

Barium contrast studies of gastric and duodenal ectopic pancreas typically show a small rounded elevation of the mucosa with a central umbilication that represents a rudimentary duct. Occasionally, there is sufficient pancreatic tissue to form a small polypoid mass. In the stomach, ectopic pancreas is usually located along the distal portion of the greater curvature. Only rarely is an ectopic pancreas large enough to be identified on cross-sectional imaging studies. Obstruction of the rudimentary duct can cause the lesion to have a cystic character.²⁰

Heterotaxy Syndrome

Various deformities and anomalies of the pancreas can occur in association with heterotaxy syndrome (i.e., asplenia and polysplenia), including annular pancreas, an intraperitoneal location of the pancreas, and a semiannular shape of the gland. There is an association between polysplenia and agenesis of the dorsal pancreas.

Shwachman-Diamond Syndrome

Shwachman-Diamond syndrome is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, metaphyseal dysostosis, bone marrow dysfunction (neutropenia), and a predisposition to leukemic transformation. The cause is a loss-of-function mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene at 7q11.21. The function of the encoded protein is unknown. The pancreatic insufficiency in these children leads to chronic diarrhea and failure to thrive. The skeletal involvement causes short stature. The pancreatic parenchyma in children with Shwachman-Diamond syndrome is completely replaced by fat.²¹

The diagnosis of Shwachman-Diamond syndrome requires the demonstration of pancreatic lipomatosis, that is, fatty replacement of the pancreas. Unlike the diminished size of the pancreas that occurs with cystic fibrosis, the pancreas of the child with Shwachman-Diamond syndrome usually is normal or slightly prominent in size. MR demonstrates a normal-sized or enlarged pancreas, hyperintense signal on T1- and T2-weighted images, and little or no signal on short tau inversion recovery (STIR) images. The pancreas is hyperechoic on sonography and hypoattenuating on CT. Other considerations in the differential diagnosis of fatty replacement are noted in Table 42-1. Skeletal radiographs of patients with Shwachman-Diamond syndrome show an elongated thorax, flared anterior ribs, undertubulated long bones, chondrometaphyseal dysplasia, and clinodactyly.^22–24

Cystic Fibrosis

Cystic fibrosis is the most common cause of exocrine pancreatic insufficiency in children. Approximately 90% of patients with cystic fibrosis have clinical manifestations of pancreatic insufficiency, such as failure to thrive, fat intolerance, steatorrhea, and abdominal pain. Up to half of patients with cystic fibrosis have glucose intolerance; Approximately 2% require insulin therapy. True pancreatitis is uncommon in cystic fibrosis patients since there is usually insufficient pancreatic function for progression to pancreatitis.^25,26

The pathophysiology of pancreatic dysfunction in patients with cystic fibrosis involves defective epithelial chloride ion permeability, leading to secretion of abnormally concentrated pancreatic juice. In addition, impaired activation of pancreatic proteases in the small intestine, leads to continual release of cholecystokinin. The continual hyperstimulation in turn causes intraacinar activation of zymogens and the precipitation of proteins in the pancreatic ducts. Inspissated material obstructs small proximal ducts, leading to acinar atrophy and inflammation. This progresses to fibrosis, ductal ectasia, cyst formation, calcification, atrophy, and fatty infiltration. Greater than 90% of cystic fibrosis patients have some degree of fatty infiltration of the pancreas. The pancreatic cysts that commonly occur in these patients are most often no more than a few millimeters in diameter; many are microscopic. In occasional patients, multiple macroscopic cysts are present. Rarely, epithelial-lined cysts completely replace and enlarge the pancreas; this is termed pancreatic cystosis.^27–29

There are 4 major imaging patterns of pancreatic pathology in patients with cystic fibrosis: partial replacement with fibrofatty tissue, complete fibrofatty replacement, atrophy, and cystosis (rare). Pancreatic calcifications, usually with a punctate character, are occasionally visible on standard radiographs of children with cystic fibrosis. Sonography (echogenic foci) and CT (small high-attenuation foci) are more sensitive for the detection of calcifications (Figure 42-3). The pancreas usually is small, particularly in older patients. Cysts may be present. With sonography, the parenchyma is echogenic (Figure 42-4). CT shows a heterogeneous parenchymal pattern due to intermixed fibrosis and fat replacement. In older patients, fatty replacement tends to predominate (Figure 42-5). With MR, areas of fatty replacement have high signal intensity on T1-weighted images (and hypointensity on fat-suppressed sequences), whereas fibrosis has low signal intensity on both T1- and T2-weighted images. Cysts and ectatic ducts are hyperintense on T2-weighted images (Figure 42-6).^30–33

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is a chronic metabolic syndrome that causes hyperglycemia. The pathophysiology involves the autoimmune destruction of pancreatic islet cells. Although environmental factors contribute to the pathogenesis, individual genetic susceptibility is determined by alleles of the major histocompatability complex class-II genes that express human leukocyte antigens. There is an association with other autoimmune disorders, such as chronic lymphocytic thyroiditis, Addison disease, and celiac disease. The prevalence of type 1 diabetes mellitus in the United States is 20 per 100,000 individuals.

The detection of type 1 diabetes mellitus is often by routine screening for glucosuria. Symptoms are often nonspecific, but can include polyuria, dehydration, and poor weight gain. A random blood glucose level greater than 200 mg/dL in a nonobese child is diagnostic. The long-term treatment consists of multiple daily insulin injections (or the use of insulin analogs) and dietary management.

Cross-sectional imaging studies may show a diminished size of the pancreas in children with type 1 diabetes mellitus. The severity of this finding correlates to some extent with the time course of the disease.³⁴

Von Hippel-Lindau Syndrome

Von Hippel-Lindau syndrome is an autosomal dominant multisystem disorder that is associated with multiple pancreatic cysts in approximately 15% of patients. Pancreatic neuroendocrine tumors can also occur in these patients. The pancreatic cysts are usually simple (epithelial) cysts. Microcystic (serous) adenomas can also occur, however. The pancreatic cysts in patients with von Hippel-Lindau syndrome usually are asymptomatic. One or more large cysts can cause pain due to mass effect on adjacent structures. With extensive cystic replacement of the pancreas, diabetes mellitus can occur.

Imaging studies of cystic pancreatic disease in patients with von Hippel-Lindau syndrome typically show multiple intrinsic pancreatic cysts that have characteristics of clear fluid. There is a propensity for location within the body and tail. Other common clinical manifestations of von Hippel-Lindau syndrome include retinal angiomatosis, central nervous system hemangioblastoma, pheochromocytoma, and cysts of the kidneys, liver, adrenal glands, and epididymis. The identification of multiple pancreatic cysts is occasionally the initial diagnostic manifestation of von Hippel-Lindau syndrome.^35,36

Pancreatic neuroendocrine tumors in patients with von Hippel-Lindau syndrome are solid lesions. Pathological examination demonstrates trabecular and/or glandular architecture, with prominent stromal collagen bands. Many of these tumors have areas of clear-cell cytology. Neurosecretory granules are present on electron microscopic examination. The tumor cells have allelic loss of the second copy of the VHL gene. Pancreatic neuroendocrine tumors in patients with von Hippel-Lindau disease are usually small, located in the pancreatic head, and enhance homogeneously on CT and MR. Larger tumors (>3.0 cm) have greater enhancement. Larger tumors are much more likely to metastasize, usually to liver.^37–39

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome is a multisystem genetic disorder that results in visceromegaly, hemihypertrophy, and a propensity for the development of malignant neoplasms such as Wilms tumor. Nonspecific enlargement of the pancreas occurs in some patients with Beckwith-Wiedemann syndrome. Pancreatoblastoma and nesidioblastosis are rare pancreatic associations with this disorder.

Johanson-Blizzard Syndrome

Johanson-Blizzard syndrome is an inherited disorder predominantly characterized by pancreatic insufficiency, abnormal facies, and psychomotor retardation. Other features include deafness, microcephaly, midline ectodermal scalp defects, hypothyroidism, hypopituitarism, short stature, and aplasia of the alae nasi. Destruction of pancreatic tissue often begins in the fetus. Imaging studies show pancreatic atrophy and fatty infiltration.⁴⁰

Nesidioblastosis

Nesidioblastosis (persistent hyperinsulinemic hypoglycemia of infancy) is a rare disorder of neonates and infants in which there is diffuse islet cell proliferation. This represents a persistent fetal state of the pancreas, with persistence and proliferation of nesidioblasts. Nesidioblasts are cells that differentiate from ductal epithelium and secrete insulin. The clinical manifestations of this disorder are hyperinsulinemia and hypoglycemia. Most infants with nesidioblastosis require a subtotal pancreatectomy for adequate control of the hypoglycemia. There is a relatively high frequency of this disorder in Saudi Arabian and Ashkenazi Jewish populations.^41,42

Cross-sectional imaging studies of the pancreas in children with nesidioblastosis may be normal or show increased size of the gland. With sonography, the pancreas may appear abnormally echogenic. After subtotal pancreatic resection, regeneration of the gland may occur to the point that it develops a relatively normal configuration on imaging studies.

Although most patients with nesidioblastosis have diffuse involvement of the pancreas, focal hyperplasia of pancreatic islet cells can also cause congenital hyperinsulinemia. Accurate differentiation between these forms of hyperinsulinemia is essential for tailoring of appropriate surgical therapy. However, imaging studies are unreliable for detecting focal pancreatic involvement. Selective venous sampling and intraoperative pancreatic biopsies are the usual techniques for the diagnosis and characterization of nesidioblastosis in current practice. Intraoperative sonography is helpful in some patients to detect a focal lesion. Fluorine 18-fluoro-l-DOPA (L-3,4-dihydroxyphenylalanine) positron emission tomography imaging offers promise as a technique for the differentiation of the focal and diffuse forms of nesidioblastosis.^43,44

Pancreatic tumors can be classified according to the tissue of origin into exocrine, endocrine (islet cell), and mesenchymal neoplasms (Table 42-2). Pancreatic neoplasms also are classified as functioning and nonfunctioning lesions. The nonfunctioning tumors typically arise from the exocrine portion of the pancreas. The functioning lesions are islet cell tumors.

Most pancreatic tumors are of epithelial origin. Nonepithelial tumors of the pancreas are quite rare. Benign lesions include hemangioma, dermoid cyst, leiomyoma, lipoma, neurofibroma, and schwannoma. Rhabdomyosarcoma is the most common malignant mesenchymal tumor of the pancreas in children. Primitive neuroectodermal tumor most often occurs in children and adolescents; primary origin within the pancreas or secondary invasion of the pancreas from a retroperitoneal lesion can occur. Other potential malignant nonepithelial pancreatic lesions include lymphoma, fibrosarcoma, leiomyosarcoma, malignant schwannoma, liposarcoma, and malignant fibrous histiocytoma.

Cystadenoma

The cystic epithelial neoplasms of the pancreas are microcystic adenoma (serous adenoma) and mucinous cystadenoma (mucinous cystic neoplasm). Cystadenoma is a mucin-producing neoplasm that is composed of multiple moderate-sized cysts and intervening thick septa. Microcystic adenomas are uniformly benign, and require no treatment if asymptomatic. Mucinous cystadenomas carry the potential for degeneration into a cystadenocarcinoma. Both of these neoplasms are rare in children; microcystic adenoma predominately occurs in elderly women and mucinous cystadenoma occurs in middle-aged women.^45,46

Cross-sectional imaging studies of pancreatic cystadenoma show a mass composed of multiple cysts. The multiple cysts of a microcystic adenoma usually are less than 2 cm in diameter. Mucinous cystadenoma has fewer than 7 cysts, and the individual cysts tend to be larger than those of a microcystic adenoma. Calcifications can occur in both varieties, but are more common with microcystic adenoma. The cysts of a microcystic adenoma usually have imaging characteristics of clear fluid, whereas greater variation between cyst contents is typical with cystadenoma; the character of the cyst fluid is best visualized with MR.^47–49

Intraductal Papillary Mucin-producing Tumor

Intraductal papillary mucin-producing tumor encompasses a spectrum of lesions in which there is abnormal proliferation of the pancreatic ductal epithelium. This is predominantly a tumor of the elderly and is rare in children. The mass arises within the pancreatic ductal system and usually communicates with the duct of origin. Mucin produced by the lesion results in progressive dilation of the main pancreatic duct or cystic dilation of branch ducts. The later form most often occurs in the uncinate process. Imaging studies show diffuse dilation of the main pancreatic duct or a lobulated multicystic pancreatic mass. The dilated ducts or cysts contain mucous plugs. Endoscopic retrograde cholangiopancreatography (ERCP) shows communication of the cysts with the main pancreatic duct.^49–51

Pancreatoblastoma

Pancreatoblastoma (pancreaticoblastoma) is an infantile variety of pancreatic adenocarcinoma. This is a nonfunctioning epithelial tumor of acinar cell origin. Although pancreatoblastoma can arise in the fetus or in patients throughout the childhood years, the peak age range is between 1 and 7 years (mean 4.5 years). Pancreatoblastoma is the most common pancreatic tumor of young children. There is a slight male predominance. Pancreatoblastoma is a low-grade malignancy, with a generally favorable prognosis. Local invasion and local or distant metastasis (lymph nodes, liver, lungs, and brain) can occur. Most patients present with an otherwise asymptomatic palpable abdominal mass; anorexia and vomiting can occur due to local mass effect. An elevated α-fetoprotein level is present in about one-third of patients with this tumor. Pancreatoblastoma can occur in children with Beckwith-Wiedemann syndrome, usually as a cystic lesion.⁵²