Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

and are surrounded by lymphoid tissue. They occur throughout the pancreas and some are even exophytic in location. Their etiology is not known.

The imaging findings of these nonneoplastic cystic tumors are similar to those seen with a mucinous cystic pancreatic neoplasm. Imaging of a pancreatic lymphoepithelial cyst reveals a heterogeneous water-density tumor, often containing septa. Endoscopic US is useful to confirm the presence of septa, a somewhat nonspecific finding. In two lymphoepithelial cysts a lipid component was detected by CT and MRI (59). Some have multiple cystic regions and rim calcifications. With most of these cysts a diagnosis is established only after resection.

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Papilloma/Papillomatosis

Not all solid pancreatic tumors are malignant. A papilloma can be quite large. The diagnosis is established by fine-needle aspiration cytology. Diffuse papillomatosis may involve both the pancreatic ducts and bile ducts.

Adenoma

An intraductal adenoma is rare. These are premalignant tumors and some already contain a carcinoma in situ. Even small adenomas in the main pancreatic duct can be associated with acute pancreatitis.

Lymphangioma

Pancreatic lymphangiomas are rare. These usually multilocular cystic nonepithelial tumors are lined by endothelial cells and are filled with serous fluid or chyle. Ten of these tumors, in patients ranging in age from 2 to 61 years at initial presentation, were collected by the Endocrine Pathology Registry of the Armed Forces Institute of Pathology (60); six were in the tail of the pancreas.

Computed tomography of two lymphangiomas revealed complex cysts containing septa and thin and regular walls, some calcified (61).

Other Tumors

A rare intrapancreatic accessory spleen has been described. These are hypervascular on CT and isointense to the spleen on MRI. At times scintigraphy is useful to confirm activity.

An inflammatory pseudotumor is more common in the liver than in the pancreas. Imaging of these solid tumors reveals findings similar to a malignancy (62); a histopathologic study is necessary for diagnosis.

Benign Neoplasms

Other benign pancreatic neoplasms are discussed in a later sections (see Cystic Neoplasms, and Neuroendocrine (Islet Cell) Tumors).

Benign Stromal Tumors

Stromal (mesenchymal) tumors are very rare in the pancreas. Benign varieties include fibroma, fibromyoma, lipoma, lymphangioma, hemangioma, schwannoma, and leiomyoma. They range from solid to cystic in appearance.

Fat-containing pancreatic tumors consist of focal fatty deposits, lipoma, liposarcoma, and a mixed mesenchymal tumor such as a fibrolipoma or cystic teratoma. Although fatty infiltration of the pancreas is common, a lipoma is rare. A lipoma is identified by CT as a welldefined, focal, homogeneous tumor ranging in density from -80 to -120HU and no contrast enhancement. An MRI reveals similar findings. Ultrasonography shows a solid hypoechoic tumor. Favoring a lipoma is a homogeneous tumor containing a well-defined margin. Lipomatosis is more diffuse in extent. Focal lipomatosis lacks a surrounding capsule but otherwise is similar to a lipoma.

Malignant Neoplasms

Adenocarcinoma

Clinical

General

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in the United States and the incidence continues to increase in the Western world. It is more common in males. Typically, the cancer is discovered when it has already spread extensively.

PANCREAS

About two thirds of pancreatic carcinomas originate in the head of the pancreas. Jaundice is typically the initial presentation, and an enlarged, nontender gallbladder is often palpable (Courvoisier gallbladder). Occasionally, however, even a large pancreatic head tumor will not obstruct bile ducts. Duodenal obstruction initially is uncommon with a pancreatic head carcinoma, the exception being with a cancer developing in an annular pancreas, where duodenal obstruction is due directly to the cancer or, if the cancer develops in the adjacent pancreatic head, the obstruction is due to the surrounding pancreatitis. Pancreatic body and tail carcinomas present with pain and weight loss and generally extensive local invasion and metastases are already present when the tumor is first discovered.

Dull, almost constant visceral pain due to neural invasion is characteristic for these tumors. Malabsorption, steatorrhea, and weight loss ensue. Diabetes mellitus is quite common, but its etiology is puzzling. Pancreatic cancer patients show increased peripheral tissue resistance to insulin. Diabetes is an early manifestation, and long-standing diabetics are also at increased risk for pancreatic cancer.

Surrounding focal pancreatitis is common, possibly a result of duct obstruction and rupture. An occasional patient presents with pancreatitis, even with acute recurrent pancreatitis.

An association exists between deep venous thrombosis, pulmonary emboli, and pancreatic cancer. Date from the Danish Cancer Registry yields a cancer incidence ratio of 1.3 in these patients, but the risk is elevated only during the first 6 months and then declines to slightly above 1.0 at 1 year after thrombosis (63); of note is that distant metastases were already present in 40% of patients with a cancer detected within 1 year of thromboembolism.

Various paraneoplastic syndromes are more common with an acinar cell origin carcinoma. An occasional pancreatic carcinoma is preceded by seborrheic keratosis (Leser-Trelat sign); skin lesions tend to diminish after resection, but progress with tumor recurrence.

Etiology

Several risk factors are identified for pancreatic carcinoma. The relative risk of developing pan-

creatic cancer is about six times greater in patients who have had previous pancreatitis, with this risk beginning to increase 5 or more years after a diagnosis of pancreatitis is established. This risk appears to be independent of sex, country, and type of pancreatitis.

The initial data pointed to an association with cigarette smoking and coffee, but a Health Professionals Follow-Up Study and the Nurses’ Health Study, consisting of nearly two million person-years of follow-up and 288 pancreatic cancers, concluded that neither coffee nor alcohol increases the risk for pancreatic cancer (64). Likewise, if an association with a previous cholecystectomy exists, it is a modest one at best. An increased prevalence of gallstones, however, is found in those with pancreatic cancer.

In rare families an autosomal-dominant predilection for pancreatic cancer appears to exist.

With an increase in life expectancy in patients with Hodgkin’s disease after chemotherapy and radiation, the development of a second malignancy is a well-recognized entity. Among these are reports of pancreatic cancer.

An increased risk of pancreatic cancer appears to exist in patients with cystic fibrosis.

Patients with von Recklinghausen’s disease are more prone to developing neuroendocrine pancreatic neoplasms than the average population, but not those of ductal origin.

Screening

Screening for pancreatic cancer is not widely practiced, and most tumors are not detected at an early tumor stage. Nevertheless, an abdominal US screening program in Japan achieved impressive results for detecting pancreatic cancer, reaching a sensitivity and specificity of 98% and 96%, respectively (65).

Ideally, screening should detect a potentially curable cancer. A definition of high-risk groups is still evolving. Detection of K-ras mutations in endoscopically obtained pancreatic juice is applicable only to a high-risk group. Current technology suggests CT or US as a screening tool and, if either modality suggests a pancreatic carcinoma, then endoscopic US or MRCP should be done.

Serum Markers

A number of tumor markers are available. Their current major diagnostic limitation is a lack of tumor specificity and, to a lesser extent, low sensitivity in detecting a pancreatic carcinoma.

Serum levels of CA 19-9 appear useful in discriminating pancreatic cancer from benign disease, predicting resectability, survival rate after surgery, and as a marker for recurrence. The sensitivity of CA 19-9 levels in discriminating between benign and malignant disease was 85% (66); patients with a resectable tumor had CA 19-9 levels significantly lower than those with an unresectable tumor. After tumor resection, survival for those with CA 19-9 levels returning to normal was significantly longer than for those with CA 19-9 levels not normalizing. A majority of postoperative patients developing a recurrence have increased CA 19- 9 levels. Nevertheless, false-positive CA 19-9 levels occur in pancreatitis, and the specificity of this test is low.

Pathology

Pancreatic adenocarcinomas are very aggressive tumors, and at the initial diagnosis either intrapancreatic metastases or multicentric tumor origin is common. A capsule is not evident. Often a desmoplastic reaction surrounds a tumor, making it appear larger. Either the main pancreatic duct or one of its secondary branches becomes obstructed early in the course, leading to duct dilation. A prominent histologic finding is early and extensive perineural invasion, believed to account for the persistent and severe pain associated with these tumors. Vascular invasion and spread to adjacent lymph nodes is also an early finding.

Most pancreatic adenocarcinomas arise from pancreatic duct epithelium. A spectrum of changes ranging from ductal hyperplasia to carcinoma in situ are identified. Cancer variants include giant cell carcinoma, acinar cell adenocarcinoma, adenosquamous carcinoma, mucinous-type carcinoma, and probably some of the cystadenocarcinomas.A need for histopathologic diagnosis exists because about 10% of suspected pancreatic carcinomas are either not of ductal origin or not even malignant. Thus either a needle biopsy (or even cytology) or surgical biopsy is necessary.

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Instead of ductal origin, an occasional neoplasm originates from pancreatic acinar cells; these include acinar cell adenocarcinomas and cystadenocarcinomas. An acinar cell adenocarcinoma is more common in elderly men and has an even worse prognosis than ductal ones. At initial presentation these tumors tend to be large and partly necrotic. For unknown reasons an occasional one is associated with subcutaneous fat necrosis. A rare carcinoma has both acinar and endocrine components.

Pancreatic adenocarcinoma in children is either ductal or acinar in origin. Early metastasis is common.

These carcinomas involve activation of the Ki-ras oncogene, inactivation or mutation of the p53 tumor-suppressor gene, and dysregulation of growth factors. Additional tumorsuppression genes have been identified. Mutations in the p53 tumor-suppressor gene are present in up to 60% of solid pancreatic carcinomas. Pancreatic adenocarcinomas DNA also yield Ki-ras mutations in most patients (67). Ki- ras and p53 mutations are also identified in pancreatic juice from these patients, and such study may have a future role in early pancreatic cancer detection.

Early Cancer

No consensus exists for defining an early pancreatic cancer. Ideally, these should be cancers limited to duct epithelium. Follow-up of patients with tumor limited to the duct epithelium reveals a high 5-year survival rate (68), but these tumors are rarely detected.

A review of small pancreatic cancers <2cm or stage I cancers (pooled from 15 publications) found 42% to be stage I and 58% to have no lymph node metastasis, and in almost all reports the 5-year postoperative survival rate was <50% (69); among pancreatic cancers 1cm or less (pooled from three publications), 85% to 100% were stage I and the 5-year postoperative survival rate was 78% to 100%. Patients with 12 carcinoma-in-situ and intraductal carcinomas (pooled from four publications) were all stage I and were alive with no evidence of tumor recurrence for varying lengths of time. Based on these results, the authors propose that either pancreatic cancers <1cm or in-situ and intraductal cancers with minimal invasion be defined as early pancreatic cancers.

PANCREAS

The problem of defining early cancer is illustrated by a 63-year-old man who had a CT for follow-up of rectal cancer, which revealed a pancreatic cyst in the head of the pancreas; ERP showed a narrowed main pancreatic duct in the body, and MRCP identified dilated ducts draining this region (70). Cancer cells were obtained by brushing cytology, and a total pancreatectomy was performed. Two sites of invasive carcinoma were identified in the neck and body, and there were multiple foci of severe dysplasia in the body of the pancreas, with some foci containing carcinoma in situ. The cystic tumor was an intraductal papillary adenoma.

Detection

Some pancreatic cancers are associated with pancreatic stones. In most of these patients pancreatic calcifications precede the cancer and are findings of superimposed chronic pancreatitis, while in a minority stones form in dilated pancreatic ducts and cysts upstream from a cancer.

Comparison Studies

In most hands a CT diagnosis of pancreatic carcinoma is more reliable than its transabdominal sonographic counterpart. Earlier studies showed endoscopic US superior to nonhelical CT, but comparing CT with endoscopic US in detecting pancreatic carcinomas, both techniques identified a pancreatic tumor equally well, although in the diagnosis of malignancy CT appears superior. No consensus exists between the relative accuracies of CT and ERP. Most publications agree that for pancreatic cancer detection, intraductal US, a technically difficult and not readily available study, is currently superior to other imaging, especially for cancers smaller than 2cm in diameter.

In consecutive patients suspected of having a focal pancreatic lesion (mostly adenocarcinomas), triphasic CT detected 88%, precontrast MRI 91%, and post-mangafodipir MRI 93% (71); use of mangafodipir did not significantly improve detection. Another study of thinsection CT and MRI (precontrast and post-oral and IV contrast) revealed no statistically significant differences in detecting pancreatic neoplasms (72).

General Imaging Findings

A majority of pancreatic cancers present as focal tumors and thus only a portion of the pancreas is enlarged. It is the less common infiltrative variety that is difficult to identify. At times the only imaging finding is a subtle alteration in pancreatic gland outline. Especially when a tumor originates from the uncinate process, this finding is difficult to differentiate from normal, keeping in mind that a pancreatic gland contour abnormality may be a normal variant, especially in the elderly. Distortion due to associated atrophy or pancreatitis is common.

Pancreatic head cancers tend to obstruct both the pancreatic and common bile ducts (Fig. 9.14). If obstructed, the pancreatic duct dilates; duct dilation upstream of the tumor is occasionally the only finding detected by imaging, a finding also seen in chronic pancreatitis (Fig. 9.15). An abrupt duct obstruction should raise suspicion for an underlying neoplasm; this finding is more common with a neoplasm than with chronic pancreatitis, where the entire pancreatic duct tends to be dilated. Even detection of a focal tumor is not pathognomonic; focal pancreatitis may have similar imaging findings.

Most pancreatic cancers develop in a setting of a grossly normal pancreas, but with growth, surrounding pancreatitis is common and tends

Figure 9.14. An adenocarcinoma, probably of pancreatic origin, obstructs the common bile duct (arrowhead). The cystic duct is also infiltrated (arrow).

Figure 9.15. The pancreatic duct is obstructed (arrow) by a carcinoma in the pancreatic body.

to obscure a tumor. The overall appearance is often also complicated by superimposed gland atrophy. At times a carcinoma in the body or tail is sufficiently large at initial presentation that it appears as an obvious necrotic tumor (Fig. 9.16).

Computed Tomography

Computed tomography became a primary modality for pancreatic carcinoma detection early in its development. Throughout this era it was plagued by both false-negative and falsepositive studies, although with equipment and software improvements both have decreased considerably. Thin-section CT, bowel distention by oral tap water, and individually determined time-to-peak contrast are some of the technical refinements applied. Current multislice CT use in pancreatic cancer detection consists primarily of arterial and portal venous images, keeping in mind that various MR techniques are making strong inroads.

Precontrast, a majority of pancreatic adenocarcinomas are detected by CT as hypoto isodense tumors, with only about half being recognized as a discrete tumor. At times only pancreatic duct dilation is evident.

The literature is undecided about whether arterial-, parenchymal-, and venous-phase

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scans are necessary for tumor detection. Some investigators suggest that venous-phase scans suffice. Although some studies found no difference in tumor attenuation between arterialphase and venous-phase CT others suggest mean tumor-to-pancreas contrast differences to be significantly greater at 40 to 70 seconds (pancreatic phase) (57–67HU) than at 70 to 100 seconds (portal vein phase) (35–39HU) (73). Both greater pancreatic tissue enhancement and lower tumor enhancement were evident during the earlier time frames. Surrounding vascular structures are also better opacified during earlier phase. Tumor CT density does vary, however, with delayed enhancement seen in some small lesions (Fig. 9.17). Isodense regions on both earlyand late-phase postcontrast CT contain either increased tumor cellularity or a mix of acinar tissue and tumor cells; hypodense regions on early-phase images and isoor hyperdense on late-phase images consist mostly of dense fibrosis. Hypodense regions on both earlyand late-phase images and unenhanced regions represent mostly mucin or necrosis.

Postcontrast multidetector row CT shows that maximal tumor-to-parenchyma attenuation differences are equivalent during the parenchymal phase and portal venous phase, but in both phases are greater than during the arterial phase (74); subjectively, tumor conspicuity is similar during parenchymal and portal venous phases. It is this marked enhancement of normal pancreatic parenchyma during the parenchymal

Figure 9.16. Carcinoma body of pancreas. Computed tomography reveals a large necrotic tumor (arrow).

phase that provides increased detection of these hypovascular neoplasms (compared with conventional CT).

Thin-section CT outlines peripancreatic venous anatomy and detects major variations. Helical CT visualizes normal inferior pancreaticoduodenal veins in up to half of studies (75); these vessels dilate when a tumor invades the superior mesenteric vein or portal vein. Inferior pancreaticoduodenal vein invasion leads to dilation of other peripancreatic veins, such as superior pancreaticoduodenal veins and gastrocolic vein, and generally signifies tumor invasion of the third duodenal segment.

Computed tomography arteriography in 36 patients with pancreaticoduodenal tumors concluded that tumor conspicuity was not superior to that obtained with conventional IV contrast injection, except in patients with cystic tumors (76).

Ultrasonography

Based on data from the Swedish Death and Cancer Registries, a clinical diagnosis of tumor in the pancreatic region confirmed within 1 year after a US study in 140 of patients achieved an US sensitivity of tumor detection of 89% and specificity of 99%, and the authors concluded that US is a viable primary diagnostic study in patients with suspected pancreatic tumors (77).

Gray-scale US shows most pancreatic carcinomas to be hypoechoic or heterogeneous to

adjacent normal parenchyma. In the aged, part of the pancreas is often hypoechoic, especially the uncinate process, making differentiation between normal and carcinoma difficult. The use of bowel hypotonia combined with gastroduodenal distention with water aids both tumor detection and in assessing resectability. Calcifications, if present, are limited to the periphery of the hypoechoic masses and most often are sequelae of prior chronic pancreatitis.

Color Doppler aids in establishing unresectability by detecting vascular occlusion and circumferential vessel encasement.

Endoscopic and intraductal US detect considerably more tumors than conventional US.

Magnetic Resonance Imaging

On T1-weighted fat-suppressed MRI, carcinomas appear as hypointense tumors having an intensity similar to the spleen. If a pancreatic head carcinoma is associated with atrophy of the body and tail, the latter also are hypointense on T1-weighted images. Signal intensity varies on T2-weighted images and these images are of limited use.

Optimal MR sequences to detect a subtle tumor are still evolving. Dynamic MR and fatsuppression are more useful than conventional SE imaging. Due to their relative hypovascularity, most pancreatic carcinomas are hypointense to normal pancreatic tissue on immediate postcontrast images and variable in appearance on