Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

Nesidioblastosis

Nesidioblastosis, also called noninsulinoma pancreatogenous hypoglycemic syndrome and other similar names, is a rare condition consisting of islet hyperplasia and b-cell hyperfunction. This is a nonneoplastic condition but is discussed here because it is in the differential of a suspected insulinoma. Also, occasionally nesidioblastosis coexists with an insulinoma (131).

Nesidioblastosis is a well-recognized entity in neonates but also occasionally develops in adults. It may be part of MEN-I syndrome. Familial nesidioblastosis occurs in neonates.

These patients present with hyperinsulinemic hypoglycemia, but a prolonged fast tends to be normal. An insulinoma is usually suspected, but preoperative localization, operative exploration, and intraoperative US do not detect a tumor. At times a blind distal pancreatectomy is performed. The diagnosis is made by the pathologist finding nesidioblasts and islet cell hyperplasia in a resected specimen. Also, the islets are structurally abnormal. A defect in insulin gene regulation appears involved in these patients.

Portal venous sampling in some of these patients shows a gradient in insulin concentration, and a misdiagnosis of insulinoma is thus made. These patients have a positive selective arterial calcium stimulation test indicative of pancreatic b-cell hyperfunction (there is an increase in plasma insulin level when calcium is injected into the arteries supplying the pancreas) (134).

In neonates, a >95% pancreatectomy is performed for persistent hyperinsulinemic hypoglycemia due to nesidioblastosis and failed medical management. At times only that portion of the gland lying between the common bile duct and duodenum and a small rim of pancreas along the duodenal sweep are not resected; still, in about one third of children with such a resection, hyperinsulinemia and hypoglycemia recur and a near-total pancreatic resection is then necessary. Of interest is that partial pancreatic regrowth develops in some of these ueouates. On a long-term basis, over two

Gastrinoma

Clinical

The Zollinger-Ellison syndrome is caused by a gastrin-secreting tumor. Most gastrinomas are malignant. About 25% of gastrinomas occur in a setting of MEN-I syndrome and a patient presenting with a gastrinoma probably should be investigated for this syndrome. Gastrinomas tend to be multiple when part of MEN-I syndrome. The risk of gastrinoma malignancy, growth rates, and high prevalence in the duodenum seen in MEN-I patients cannot be extrapolated to patients with isolated gastrinomas. Even with liver metastases these tumors grow slowly, and prolonged survival is feasible.

Some of these tumors are extrapancreatic in location (duodenal gastrinomas are discussed in Chapter 3). Occasionally a small gastrinoma is discovered in a lymph node; most of these are metastatic foci, although a rare one is believed to represent a primary tumor and excision of that lymph node should be curative. With such a scenario a search for a primary gastrinomas should, of course, be performed.

A review of patients with gastrinoma/ Zollinger-Ellison syndrome found that a correct preoperative diagnosis is made in about half of these patients, and about half of these tumors are <20 mm in diameter (135); although about 40% had metastases, the 10-year survival rate was 64%.

These patients develop recurrent, multiple ulcers in atypical locations. They have basal gastric acid hypersecretion and a markedly elevated fasting serum gastrin level, with values considerably greater than seen after a truncal vagotomy or proximal gastric vagotomy.

In the absence of metastases, unless surgery is contraindicated, even with negative preoperative imaging studies these patients probably should undergo exploratory laparotomy, with the aim of a curative resection. Previously, if excision was not feasible, a total gastrectomy was performed for symptom control; today total gastrectomy is rarely performed and in most patients gastric acid hypersecretion is managed with H2 receptor antagonists. Thus with suspected liver metastases a biopsy establishes the

PANCREAS

diagnosis and these patients are then treated medically.

Many of these tumors contain somatostatin receptors, and somatostatin analogues are potential therapeutic agents. Using an autoradiography technique, both pancreatic carcinomas and gastrinomas expressed specific somatostatin receptors (136); in gastrinomas, octreotide inhibited iodine-125–somatostatin- 28 binding similar to somatostatin-28, but little competitive binding of I-125–somatostatin-28 was evident in carcinomas, suggesting that somatostatin receptors in gastrinomas differ from those in carcinomas.

Imaging

A barium study detects gastritis, often severe, and peptic ulcer disease, especially in postbulbar regions. Hyperacidity is also associated with reflux esophagitis in many of these patients.

The imaging procedures useful in detecting a gastrinoma include CT, endoscopic US, MRI, indium-111–octreotide scintigraphy, and selective arterial secretin injection, with the initial study of choice often being octreotide scintigraphy. Still, only approximately half of gastrinomas are detected with these studies (Fig. 9.31).

Figure 9.31. Gastrinoma in a 75-year-old man. Transverse precontrast CT identifies enlargement of the pancreatic head (arrow). Initially believed to represent a pancreatic carcinoma, biopsy suggested a gastrinoma. (Courtesy of Patrick Fultz, M.D., University of Rochester.)

In patients with Zollinger-Ellison syndrome, duodenal, lymph node, and pancreatic gastrinomas were eventually found in 42%, 38%, and 17% of patients, respectively (137). Of these tumors, endoscopic US detected 50% of duodenal wall tumors while conventional endoscopy detected 40%. Endoscopic US detected 75% of pancreatic tumors while CT detected 25%; endoscopic US detected 62% of lymph node tumors while CT detected none. The authors concluded that endoscopic US is the imaging technique of choice for preoperative imaging of gastrinomas. At times intraoperative US is necessary in locating small gastrinomas.

Similar to other solid pancreatic tumors, gastrinomas are hypointense on T1and hyperintense on T2-weighted fat-suppressed MRI. In distinction to most other neuroendocrine tumors, gastrinomas enhance postcontrast in a ring pattern (129). Such ring-like enhancement is also seen in liver metastases; this finding is not specific for gastrinomas but is also occasionally found with other neuroendocrine tumors. An occasional cystic component is detected in a gastrinoma.

Indium-111–pentetreotide scintigraphy is probably superior to CT in localizing gastrinomas; scintigraphy can detect duodenal tumors several millimeters in size. Nevertheless, In-111–pentetreotide is not foolproof. In a patient with a previous partial pancreatectomy and splenectomy and now presenting with Zollinger-Ellison syndrome, In-111– pentetreotide scintigraphy revealed nodular increased uptake in an accessory spleen (138).

Glucagonoma

Pancreatic glucagonomas are uncommon. These are slow-growing tumors, most are malignant, and metastases are often present at initial detection.

Glucagonomas result in elevated serum glucagon levels. These are complex tumors, however, and patients often have increased gastrin levels, VIP, serotonin, insulin, human pancreatic polypeptide, calcitonin, and adrenocorticotropic hormone; metastases are common at initial presentation.

The glucagonoma syndrome consists of weight loss, necrolytic migratory erythema, dia-

betes mellitus, stomatitis, and diarrhea. In a number of patients a specific erythematous rash suggests the diagnosis.

Contrast-enhanced CT should detect larger tumors. Similar to other solid pancreatic tumors, glucagonoma are hypointense on T1and hyperintense on T2-weighted MRI. Postcontrast, most reveal early diffuse, heterogeneous enhancement.

Glucagonomas metastasize readily. Still, in spite of liver metastases, prolonged survival is possible through judicious surgery, hepatic artery tumor embolization, and somatostatin analogue therapy.

Somatostatinoma

Most somatostatinomas occur in the pancreas or duodenum and most are malignant. High plasma somatostatin levels are found in some patients. Metastases are common at initial presentation. These patients have elevation of fasting plasma somatostatin levels. Any clinical hormonal effect depends on other peptides being secreted in addition to somatostatin, although somatostatin does tend to inhibit the release of other hormones.

No specific imaging findings exist for smaller tumors. Larger somatostatinomas are hypointense on T1and hyperintense on T2weighted MRI. Postcontrast, most exhibit early diffuse, heterogeneous enhancement.

Abnormal In-111–pentetreotide uptake occurs with some somatostatinomas.

Vasoactive Intestinal Peptide Tumors

Vasoactive intestine polypeptide–secreting tumors (VIPomas, Verner-Morrison syndrome) are associated with increased plasma vasoactive intestinal polypeptide levels, although elevation can be episodic. These tumors tend to be solitary and have a predilection for the pancreatic tail.

A review yielded 241 patients with VIPomas, with 74% being intrapancreatic and 26% extrapancreatic in origin (139); among extrapancreatic ones, 23% were nonneurogenic in origin. About two thirds of pancreatic VIPomas were malignant versus one third of extrapancreatic tumors. Of necessity, the definition of a VIPoma overlaps with some other tumors, and the above review includes such extrapancreatic

ADVANCED IMAGING OF THE ABDOMEN

neurogenic tumors as ganglioneuromas, ganglioneuroblastomas, and neuroblastomas. An occasional VIPoma contains large amounts of amyloid.

The classic clinical findings are secretory diarrhea, hypokalemia, hypochlorhydria, and metabolic acidosis. Metastasis is not uncommon at first presentation.

VIPomas are hypointense on T1and hyperintense on T2-weighted MRI. Postcontrast, most have early diffuse, heterogeneous enhancement. Some metastases show intense peripheral enhancement on immediate postcontrast SGE images.

One tumor, not detected by other imaging or by radiolabeled octreotide, was localized in the pancreatic tail by I-123–VIP (140).

Carcinoid’

Pancreatic carcinoids are rare; most are malignant, and metastasis at time of diagnosis is common. In the literature, the terms serotoninproducing tumor of the pancreas and pancreatic serotoninoma are also used to designate these tumors.

The carcinoid syndrome is absent unless liver metastasis is present. A diagnosis of pancreatic carcinoid is made if a pancreatic tumor is associated with elevated serum 5- hydroxytryptamine (serotonin) levels or elevated urine 5-hydroxyindole acetic acid (5- HIAA) levels. Ideally, serotonin is isolated in tumor tissue, and no other dominant hormone is detected. Positive silver staining in tumor cells is suggestive of a carcinoid but is not as specific as a serotonin assay. Some pancreatic neuroendocrine tumors labeled as being nonfunctioning (discussed below) probably represent carcinoids with low levels of serotonin production.

Carcinoids are hypointense on T1and hyperintense on T2-weighted images. A heterogeneous enhancement is evident on immediate postcontrast images.

Paraganglioma

Pancreatic paragangliomas are rare. Some secrete somatostatin and other hormones. An occasional one is discovered only after it has metastasized.

PANCREAS

Schwannoma

Pancreatic schwannomas range from benign to malignant, solid to cystic. Most are solitary, except in a setting of von Recklinghausen’s disease. A schwannoma originating close to the celiac axis can be misdiagnosed as an intrapancreatic neoplasm.

Schwannomas tend to be sharply marginated. Some mimic a pseudocyst. Computed tomography reveals an inhomogeneous appearance and some contain septa. They have a variable CT appearance, ranging from isoto hypodense (61); they enhance with contrast. Some contain a necrotic center. They are hypointense on T1and hyperintense on T2-weighted MR sequences.

Neurofibroma

Computed tomography of a plexiform neurofibroma revealed a near-water homogeneous density, mild contrast enhancement, and an infiltrating appearance (61).

Nonfunctioning Islet Cell Tumor

Islet cell tumors not associated with clinically detectable hormone production are called nonfunctioning. Some do secrete a polypeptide, but are still considered nonfunctioning if the patient is asymptomatic. Differentiation between functioning and nonfunctioning is not straightforward. At times a primary islet cell carcinoma is nonfunctioning and is resected, but later metastases develop a de novo capacity to secrete hormones.

The controversy in differentiating these tumors from papillary cystic neoplasms has already been mentioned. Focal lymphoma is also in the differential of an occasional solid nonfunctioning neuroendocrine tumor.

Most of these tumors are slow-growing. Smaller tumors tend to be benign, but most tumors >5cm are malignant (141). Aside from incidentally discovered ones, these tumors tend to be large when first detected and metastases are often evident. Incidentally, malignancy cannot be established by histology,and evidence of either metastases or local invasion is the criterion used.

A rare nonfunctioning malignant islet cell tumor contains eggshell calcifications.

Postcontrast CT shows better tumor conspicuity during the arterial phase than portal venous phase (142); the arterial phase also detects more liver metastases than the portal phase. On the other hand, venous encasement by tumor is better identified during the portal venous phase.

Computed tomography typically shows a large, hypervascular tumor (141). Some tumors contain cystic regions and punctate calcifications, an appearance that distinguishes them from ductal adenocarcinomas. The larger ones tend toward necrosis. A heterogeneous CT contrast enhancement pattern is common.

A correct preoperative diagnosis is not common. Both a primary tumor and metastases tend to respond to chemotherapy. Their better prognosis makes it important to distinguish these tumors from the more common pancreatic ductal adenocarcinomas.

Pancreas in Diabetes Mellitus

Postmortem pancreatic angiography in non– insulin-dependent diabetics revealed that 58% of diabetics and 20% of controls showed one or more of the following (143): >50% celiac or splenic artery stenosis, two or more irregular intrapancreatic branches, or decreased vascularity in the body and tail—segments responsible for most insulin secretion.

Insulin-dependent type 1 diabetes is caused by autoimmune destruction of insulinproducing b-cells. If diabetes is identified early enough, some of these patients still have functioning residual b-cells and benefit from adjuvant immunotherapy to protect remaining b-cell function.

Technetium-99m–human polyclonal immunoglobulin (HIG) scintigraphy in nearly half of newly diagnosed type 1 diabetics shows a significant accumulation of radiolabeled HIG in the pancreas (144); thus HIG scintigraphy, performed at the time of diabetes onset identifies a subset of patients who appear to benefit from adjuvant immunotherapy.

Some diabetics also have an abnormal exocrine pancreas. Endoscopic retrograde pancreatography reveals pancreatic duct abnormalities consisting of dilation, stenosis, tortuosity, obstruction, or calculi.