Applied Radiology

Prepared by Daniel B. Brown, MD; Craig B. Glaiberman, MD; Anthony W. Allen, MD; Harjit Singh, MD; and Peter N. Waybill, MD, of the Department of Radiology, Pennsylvania University Hospital, Hershey, PA.

CASE SUMMARY

A 51-year-old woman presented with jaundice, pruritus, incessant abdominal pain that radiated to the back, and postprandial nonbilious vomiting. She had undergone 8 months of chemotherapy for pancreatic carcinoma. Her past medical history was significant for ulcerative colitis (UC) diagnosed in 1974. She had a total proctocolectomy with construction of a Koch pouch in 1981.

She was admitted for liver failure. Admission lab work revealed a total bilirubin of 20.4 mg/dL (normal 0.1-1.2 mg/dL) and an alkaline phosphatase of 2620 U/L (normal 40-130 U/L). A CT scan (figure 1) showed gross ascites, a 4 * 4 cm pancreatic mass which invaded the lesser sac and occluded the portal vein, massive abdominal varices, extensive retro-peritoneal adenopathy, and a common bile duct that was 2.1 cm in diameter. Suspected bilateral deep venous thromboses were confirmed by ultrasound.

The patient was referred for percutaneous trans-hepatic cholangiography (PTHC) and possible percutaneous biliary drainage. At PTHC, the intrahepatic biliary system was noted to be irregular and had a beaded appearance (figure 2). The patient's condition deteriorated quickly over the next few days and she died shortly thereafter.

DIAGNOSIS

Metastatic adenocarcinoma of the pancreas

AUTOPSY FINDINGS

At autopsy, a large hemorrhagic and necrotic mass in the head of the pancreas was present, consistent with pancreatic adenocarcinoma. There was extensive infiltration of the porta hepatis. Intrahepatically, microscopic foci of pancreatic carcinoma diffusely surrounded and encased the portal triads including the periductal regions. There was no evidence of periductal fibrosis, inflam-mation, or duct obliteration typical of primary sclerosing cholangitis (PSC). The final diagnosis was metastatic adenocarcinorna of the pancreas infiltrating the intrahepatic biliary system, mimicking PSC.

DISCUSSION

Approximately 80% of pancreatic adenocar-cinomas occur in the head of the gland. ¹ The mean age of onset is 55 years and the disease has approximately a 2:1 male:female incidence. Patients typically present late in the course of the disease with weight loss and abdominal pain that radiates to the back. At the time of diagnosis, up to 90% of cases show local invasion and/or metastases to the liver and/or lung. Spread along the biliary tree producing diffuse narrowing of the intrahepatic biliary radicals is rare. ²

Less than 2% of patients diagnosed with pan-creatic adenocarcinoma survive 5 years after diagnosis. ¹ Even if "curative" resection (pancreaticoduodenectomy) is performed, 5-year survival only approaches 10%. Multiple combinations of chemotherapy and radiation have been tried with little improvement in survival. Metal stents may be placed to palliate non-operative disease. Splanchnic blocks can also be used to control intractable pain.

Metastatic adenocarcinoma of the pancreas simulating sclerosing cholangitis at cholan-giography has been described. ² As in our patient, the extrahepatic ducts were dilated, a finding not typical of PSC. Pancreatic cancer most often causes diffuse biliary dilation proximal to a distal obstruction. Although most patients with sclerosing cholangitis have involvement of the extrahepatic ducts, the diagnosis cannot be excluded if they do not appear affected at cholangiography. ² This suggests disease progres-sion from within the liver distally to involve the extrahepatic ducts. ³

PSC is a cholestatic syndrome of unknown etiology involving both the intra- and extrahepatic ducts. ^3-5 PSC is most common in young men and presents insidiously with pruritus, jaundice, and hepatosplenomegaly. Pathologic hallmarks include periductal fibrosis and inflammation resulting in scarring of the biliary tree. Approximately 50% to 75% of patients have one or more signs of liver disease at the time of diagnosis of PSC. ⁶ Elevation of alkaline phosphatase, aspartate transaminase, and bilirubin levels are variable. Cirrhosis, portal hypertension, varices, and ascites result as PSC progresses to overt liver failure. Up to 10% to 15% of cases of PSC progress to cholangiocarcinoma. Differentiation of PSC and cholangiocarcinoma is difficult and stricture progression, polyp formation, or ductal dilation identified during interval cholangiography must be considered suspicious for malignant change. ⁸ Definitive diagnosis can be made with biopsy via percutaneous access or endoscopic retrograde cho-langiopancreatography (ERCP). Today, PSC continues to be one of the leading indications for liver transplantation.

Toxins, certain viruses (CMV and Reovirus type III), ischemia, AIDS, and presence of HLA-B8 and HLA-DR3 have all been suspected of causing PSC. ^2-3,6-7 A patient expressing both HLA-B8 and HLA-DR3 has an estimated 10-fold increased relative risk of developing PSC, suggesting genetic and immunologic mediation of disease abnormality. ⁷ Disease processes associated with PSC include UC, pancreatitis, and diabetes mellitus. ⁹

Patients diagnosed with UC have a 10% chance of developing PSC. In contrast, up to 70% of people with PSC have UC as well. ^5,7 PSC may present a number of years before or after the diagnosis of the bowel disease. PSC may remain undetected until liver failure becomes fulminant. However, coexistent PSC in UC patients is becoming recognized more frequently because of better diagnostic procedures (ERCP and PTHC), screening blood work, and physician awareness of the association of PSC with UC. ⁶

UC is bimodal, presenting in patients between the ages of 15 to 30 and 50 to 70 years. The colitis is a submucosal inflammatory infiltration begin-ning in the rectosigmoid colon and extending proximally in a continuous fashion. Crypt abscesses and mucosal ulcerations are common and can involve the entire colon. Typically, the ulcerations do not extend through all layers of the bowel wall like the lesions of Crohn's disease. The stuttering clinical course is fraught with attacks of varying intensity that are characterized by crampy abdominal pain, frequent loose stools containing blood and mucus, fever, and anorexia. Toxic megacolon, the most serious complication, can lead to anemia, hypotension, perforation, peri-tonitis, and septicemia. ¹ Proctocolectomy is the definitive treatment for UC but does not slow the progression of PSC. ⁵ Extra-colonic manifestations of UC include arthritis, ankylosing spondylitis, sacroiliitis, uveitis, and aphthous ulcers, which can wax and wane with flare-ups.

PSC can present clinically either before or after UC. Although the findings at cholangiography are typical, they are not pathognomonic. Subtle differences, such as the lack of extrahepatic biliary stricture in this case should lead to the consideration of other diagnoses. Review of physical findings can suggest the diagnosis in most cases. Knowledge of all other pathologic processes is essential to arrive at the correct diagnosis.

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