Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

PANCREAS

Some of these tumors are positive for p53 protein and K-ras mutations. p53 overexpression increases with tumor grade, which is in distinction to solid pancreatic cancers, which exhibit no change for tumor grade. Alterations of these two genes occur in hyperplasia, dysplasia, and carcinomas, and presumably represent early changes in tumor evolution.

The benign variety tend to communicate with secondary branches, while malignant ones more often involve the main pancreatic duct, but a distinction between benign and malignant tumors is difficult at best. Most of these tumors are small, grow slowly, and produce exuberant mucus. Serum tumor markers do not aid in differentiating benign from malignant tumors.

Imaging

The hallmark of these tumors is a dilated pancreatic duct and increased amounts of intraluminal mucin; the tumor either fills the duct lumen or, less often, lines the lumen. A location in the head of the pancreas is most common (117). With tumors originating in the main pancreatic duct, this duct is considerably more dilated with malignant tumors (119); segmental dilation is common with benign tumors. Even with a tumor located in a secondary duct, the main pancreatic duct often dilates due to excess mucus and resultant obstruction, although dilation generally is less than with main duct tumors. With some, endoscopy reveals viscid mucin draining from a patulous ampulla in a bulging papilla of Vater (Fig. 9.28). During ERCP an intraductal tumor is often too small to be visualized directly or is obscured by adjacent thick mucus, although fixed filling defects should suggest a malignant tumor.

Computed tomography signs of malignancy are the presence of a solid tumor, a main pancreatic duct diameter >10 mm, a diffuse or multifocal tumor, and calcified intraluminal contents (120); of note is that in some of these patients, the CT-histopathologic correlation of duct involvement, lesion location, and presence of malignancy is poor. Computed tomography reveals frond-like projections in an occasional tumor. Larger tumors are detected with both thin-section CT (121) and MRCP (122). At times intraductal content contains calcifications.

Intraductal US, using a frequency of 20 or 30mHz, aids in outlining tumor extent and

Figure 9.28. Pancreatitis, pseudocyst (arrows) and probable mucinous cystic pancreatic head tumor (arrowheads) in an 83- year-old woman. Calcifications are present within the tumor.The pancreatic duct is dilated and the tumor prolapses into the duodenum. ERCP also identified a prolapsing papilla. No biopsy or resection were performed. (Courtesy of Patrick Fultz, M.D., University of Rochester.)

parenchymal invasion. In branch duct tumors intraductal US appears superior to endoscopic US in identifying mural nodules.

Magnetic resonance cholangiopancreatography is evolving as the imaging procedure of choice to evaluate these tumors, at times providing more information than does ERCP (Fig. 9.29). An MRCP detects dilated main and secondary ducts better than ERCP (123); intraluminal nodules, on the other hand, are often better defined by ERCP. Pancreatography reveals duct dilation, often with numerous noncalcified intraluminal filling defects or obstruction and excess mucus. The ducts tend to be blocked to retrograde flow of contrast.

Imaging differential diagnosis includes chronic pancreatitis, other cystic neoplasms, or even pancreatic duct obstruction and secondary dilation due to a stone or adenocarcinoma. Likewise, although CT, US, and pancreatography can suggest a diagnosis of an intraductal tumor, imaging cannot reliably differentiate malignant from benign tumors.A large tumor and involvement of pancreatic parenchyma suggest a malignancy. Also, excrescent nodules are more common with a malignancy.

Oncocytic Tumors

A pancreatic intraductal oncocytic papillary neoplasm consists of mucin-filled cysts con-

taining nodular papillary outpouchings. Some of these tumors communicate with dilated pancreatic ducts. The cysts probably represent dilated ducts. The papillary component consists of a fibrovascular core lined by stratified oncocytic cells. Although these tumors are intraductal, some become invasive.

Whether these tumors represent a separate entity, are part of the spectrum of intraductal mucinous tumors, or are papillary cystic neoplasms is conjecture.

Papillary Cystic Neoplasms

(Embryonic Tumor)

The classification and terminology of papillary cystic neoplasms of the pancreas is still evolving. These tumors are also called solid and papillary epithelial neoplasms, solid and cystic tumors of the pancreas, and Frantz’s tumors in some European literature. In the older literature a number of these tumors were labeled as nonfunctioning islet cell tumors, and the differences between these two entities are not clear. Some postulate that these papillary cystic neoplasms originate from pleuropotential embryonic stem cells, and thus the term pancreatic embryonic tumor is preferred by some.

Most papillary cystic tumors of the pancreas occur in young women, with an occasional one encountered in a teenager. Most of these tumors are large, well circumscribed, and locally inva-

sive. They are considered either benign or lowgrade malignant. Aggressive ones tend to be larger and have a thicker capsule. Of interest is that a number of these patients developing metastases, including peritoneal carcinomatosis, had prior trauma (124).

In 53 women and three men (mean age at diagnosis, 25 years) with proven papillary cystic neoplasms of the pancreas, the mean tumor diameter was 9.0cm; they were located in the tail (n = 30), head (n = 18), and body (n = 8); and all tumors contained either hemorrhage or cystic degeneration, ranging from solid friable tumor to gelatinous or cystic regions (125). All tumors were encapsulated, and a minority contained calcifications or fluid-debris levels.

Pathologists have difficulty in discriminating between papillary cystic tumors and nonfunctioning endocrine tumors. Histology of a papillary cystic tumor reveals small, eosinophilic tumor cells often arranged in rosettes; these tumor cells tend to be immunohistochemically positive for somatostatin, a-1 antitrypsin, neuron-specific enolase and synaptophysin. Some contain immature neurosecretory granules.

The most common imaging appearance is a mixture of solid and cystic components in a tumor surrounded by a thick capsule. An occasional one appears solid. The cystic component ranges from barely identifiable to the tumor resembling a pseudocyst. Hemorrhage and necrosis are common and blood and debris in

PANCREAS

the cystic component increase CT density levels. Computed tomography reveals the capsule as a hypodense structure enhancing with contrast. Calcifications develop within a fibrous capsule or solid tumor component in some. Extracapsular spread is unusual.

Magnetic resonance imaging reveals the solid component to be isointense or even hypointense on T1and hyperintense on T2-weighted images. Hemorrhage is common and results in a hyperintense T1-weighted image. The solid component enhances postcontrast.

Angiography identifies either a hypovascular or avascular tumor, thus differentiating these tumors from nonfunctioning islet cell tumors, which tend to be hypervascular.

Imaging can distinguish these tumors from ductal pancreatic adenocarcinomas; the latter typically are more invasive. Serous and mucinous cystadenomas and carcinomas usually do not have a solid tumor component to the extent seen with papillary cystic neoplasms.

A percutaneous biopsy is usually superfluous because most of these tumors are resected. In fact, it has been stated that “tumor biopsies . . .

should never be performed” because of possible spread by trauma (124).

Other Tumors

A hemangiopericytoma is rare in any location. Its malignant propensity varies considerably and, in general, malignancy is established by detecting metastases. Intraabdominal hemangiopericytomas tend to be very aggressive.

Ultrasonography and CT typically reveal a cystic tumor.

A cystic teratoma of the pancreas contained multiple calcifications, mucin, and lipid components (61).

Neuroendocrine (Islet Cell) Tumors

Clinical

Pancreatic neuroendocrine tumors are often also called islet of Langerhans tumors, although a number originate at other sites. Most share certain cytochemical characteristics and have been labeled as APUDomas (amine precursor uptake and decarboxylation), although currently most authors prefer the term neuroendocrine tumors. These tumors are not

confined to the pancreas but also include pituitary gland adenomas, adrenal gland pheochromocytomas and neuroblastomas, medullary thyroid carcinomas,and carcinoid tumors in the gastrointestinal tract and lung.

About half of these tumors produce a number of hormones and occasionally even switch secretion to a different hormone. Rare functioning endocrine tumors include calcitoninoma (126), ACTHoma (adrenocorticotropic hormone), and neurotensinoma. The activity of one hormone generally predominates, and these tumors are classified based on the predominant hormone detected. Some are clinically silent and are discovered incidentally, and some are associated with hypercalcemia. In general, with the exception of insulinomas, most are malignant and are highly vascular.

The presence of calcitonin secretion does not necessarily imply a calcitoninoma and is occasionally found in a nonfunctioning endocrine tumor. Calcitonin secretion often implies malignancy, and many such tumors already have metastasized; calcitonin secretion should be suspected in patients with a neuroendocrine tumor and diarrhea that cannot be otherwise explained.

Although uncommon, the first evidence of an islet cell tumor can be acute pancreatitis, either associated with duct obstruction or due to other reasons.

A carcinoid, pheochromocytoma, islet cell tumor, Merkel cell carcinoma, and other neuroendocrine tumors often contain vasoactive intestine polypeptide (VIP), somatostatin, and other receptors. Therapy with somatostatin analogues in these patients reduces hormonal hypersecretion. This in turn helps control flushing attacks, diarrhea, hypoglycemia, and electrolyte abnormalities that patients with carcinoid tumors and other islet cell tumors are prone to developing.

Detection of a neuroendocrine pancreatic tumor in association with another tumor, especially a neural one, should suggest von HippelLindau disease.

Imaging

Depending on the type of neuroendocrine tumor suspected, preoperative localization may include CT, MRI, radionuclide scanning, angiography, and venous blood sampling. During

surgical exploration, intraoperative US is useful in detecting occult tumors and in defining underlying anatomy. Whether enucleation is performed or resection is required often depends on the tumor’s proximity to the pancreatic duct; intraoperative US can provide this information. A high-frequency transducer is essential for detecting and evaluating these small tumors.

Most of these tumors are hypervascular. Larger tumors are more prone to calcify (Fig. 9.30). Insulinomas tend to be more homogeneous in appearance, while non–insulin- producing tumors are more cystic or necrotic. Only an occasional one obstructs the pancreatic duct, results in vascular encasement, or leads to portal vein thrombosis, findings common with ductal carcinomas.

More islet cell tumors are detected with biphase CT than conventional CT. Tumors several millimeters in diameter can be detected. Most are detected during the arterial phase, although some are identified only during the venous phase. Computed tomographic arteriography with contrast injected through a celiac artery catheter is occasionally helpful when searching for these small hypervascular tumors.

Gray-scale US shows most islet cell tumors to be well-marginated and hypoto isoechoic.

Figure 9.30. Metastatic islet cell carcinoma. Computed tomography reveals a calcified tumor in the pancreatic tail (arrows) and a liver metastasis (arrowhead). The patient has had a previous left hepatectomy. (Courtesy of Patrick Fultz, M.D., University of Rochester.)

ADVANCED IMAGING OF THE ABDOMEN

Some are detected only with intraoperative or endoscopic US. An intraductal high-frequency transducer is useful in detecting tumors adjacent to the duct.

Contrary to some earlier studies suggesting that MR is superior to CT, a later study found biphasic CT and MRI similar in detecting these tumors (127). Another study of 28 patients with clinically suspected functional islet cell tumors achieved even better MRI results, reaching a sensitivity of 85% and specificity of 100% in tumor detection (128). Most of these tumors are hypointense on T1and hyperintense on fatsuppressed T2-weighted images. They enhance more than surrounding normal pancreatic parenchyma early after contrast injection and gradually become isointense (129). Except for gastrinomas, enhancement is either uniformly homogeneous or heterogeneous. Magnetic resonance features distinguishing these tumors from pancreatic ductal adenocarcinomas are their hyperintense signal on T2-weighted images, early postcontrast enhancement, and, for many of the malignant ones, hypervascular liver metastases. A number exhibit a ring-like enhancement immediately postcontrast. Nevertheless, the occasional poorly differentiated ones and those inciting a desmoplastic reaction tend to be isointense on T2-weighted images, show little postcontrast enhancement, and mimic ductal adenocarcinomas.

An occasional islet cell tumor results in a main pancreatic duct stricture.

Portal venous sampling is performed using a transhepatic approach. The technique is insensitive when multiple tumors are present.

Except for insulinomas, most neuroendocrine tumors contain varying amounts of somatostatin receptors, which bind somatostatin analogues. Whole-body imaging using a somatostatin analogue (indium-111–diethylen- etriamine pentaacetic acid (DTPA)–octreotide, Octreoscan), also known as somatostatin receptor scintigraphy, is useful in localizing these tumors. Results in primary tumor detection are variable, but in a setting of positive laboratory tests but negative imaging this test appears worthwhile. It has a role in detecting tumor recurrence and metastases. Also, tumors found to be somatostatin receptor positive respond to somatostatin analogue therapy.

An ectopic thyroid mimicked a pancreatic tumor (130).

PANCREAS

Numerous endocrine tumors have been biopsied without complication. Nevertheless, a functioning endocrine tumor should be approached with caution because of possible excess hormone release.

Hyperinsulinoma Conditions

The most common but not the only etiology of recurrent severe hypoglycemia in an adult is an insulinoma. Less common is nesidioblastosis and neoplasms producing insulin-like growth factor. Thus an occasional patient with a hemangiopericytoma presents with hypoglycemia; a history of a hemangiopericytoma resected previously is not uncommon. Generally not appreciated is that a large nonpancreatic leiomyosarcoma may mimic clinical findings of an insulinoma, including severe hypoglycemia. Even a bowel adenocarcinoma with liver metastases can have hypoglycemia induced by tumor insulin-like growth factor production. Occasionally encountered is hypoglycemia developing in a patient with renal failure or fulminant hepatic failure.

Insulinoma

The most common islet cell endocrine tumor is an insulinoma. A Japanese literature search of over 1000 patients with insulinoma or hypoglycemic syndrome revealed that 81% of these tumors were 20 mm or smaller (131).About 90% are benign and most tend to be solitary, solid, and homogeneous. Multiple insulinomas should suggest MEN-I syndrome. Primary extrapancreatic insulinomas are rare. Cystic insulinomas are uncommon. Histologically, an insulinoma mimics normal islet cells. It is difficult to tell with some whether indeed it is a neoplasm or simply represents hyperplasia.

Autonomous insulin synthesis and secretion are the hallmark of an insulinoma even in a setting of low blood glucose levels, leading to further hypoglycemia and resultant clinical findings.

Most insulinomas are small and are difficult to detect with imaging. Conventional CT, grayscale US, and MRI are of limited value. In one study, combined dual-phase thin-section multidetector CT and endoscopic US achieved a diagnostic sensitivity of 100% in detecting these tumors (132). Endoscopic US appears to be

somewhat more sensitive in detecting insulinomas in the pancreatic head and less sensitive in the pancreatic tail. Nevertheless, some tumors are found only by the surgeon or by intraoperative US; some surgeons opine that detection of an insulinoma does not require extensive preoperative localization.

A rare insulinoma is hyperdense to normal pancreatic parenchyma on precontrast CT. An early arterial phase and pancreatic phase appears best in detecting these tumors (133). Postcontrast CT ring-like enhancement progressing into homogeneous tumor enhancement is seen in about half of these tumors.

The uncommon malignant insulinoma is a highly vascular tumor in the pancreatic tail often detected from liver metastases; liver venous sampling after arterial stimulation with calcium confirms insulin secretion. In some, serum levels of a-fetoprotein and trypsin are markedly elevated.

Intraoperative US is very helpful in localizing these tumors and in defining adjacent structures.

Magnetic resonance imaging localizes some pancreatic insulinomas. They are hypointense on T1and hyperintense on T2-weighted sequences and are homogeneously hyperintense on postcontrast images.

While not usually performed, indium- 111–octreotide scintigraphy does, at times, localize an insulinoma.

Insulin venous sampling is useful in detecting insulinomas not detected by other imaging modalities. Calcium gluconate is injected directly into the gastroduodenal, splenic, and superior mesenteric arteries, followed by venous sampling. Injection into an artery supplying an insulinoma results in a marked increase in the draining vein insulin level. An insulin increase post–calcium infusion of at least 100% above basal levels is considered abnormal. Such an approach obviates the need for transhepatic portal venous sampling and is simpler. This test is also useful for suspected hepatic metastases; no increase in insulin concentration in hepatic venous blood after intraarterial calcium stimulation makes insulinoma liver metastases unlikely. Nevertheless, this test should be interpreted with caution, because an injection into an artery not supplying a tumor may also increase venous insulin levels, possibly by the influx of