Summary: 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.
Summary: 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
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 pancreatic
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 cholangiography 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
progression 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 cholangiopancreatography (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 beginning 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,
peritonitis, 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.
- Stephens DH, Sheedy PF, James ME: Neoplastic
lesions. In: Margulis AR, Burhenne JH, (eds): Alimentary Tract
Radiology, ed 3, pp 1331-1332. St Louis, CV Mosby, 1983.
- Vilgrain V, Edinger S, Belghiti J, et al:
Cholangiographic appearance simulating sclerosing cholangitis in
metastatic adenocarcinoma of the liver. Gastroenterology
99:850-853, 1990.
- MacCarty RL, LaRusso NF, Weisner RH, Ludwig J:
Primary sclerosing cholangitis: Findings on cholangiography and
pancreatography. Radiology 149:39-44, 1983.
- Rohrmann CA, Ansel HJ, Feeny PC, et al:
Cholangiographic abnormalities in patients with inflammatory bowel
disease. Radiology 127:635-641, 1978.
- Taylor AJ, Bohorfoush AG: Inflammation of the
biliary tract. In: Taylor AJ, Bohorfoush AG, (eds): Interpretation
of ERCP with associated digital imaging correlation, pp 77
- Philadelphia: Lippincott Raven, 1997.
- Porayko MK, Wiesner RH, LaRusso NF, et al:
Patients with asymptomatic primary sclerosing cholangitis
frequently have progressive disease. Gastroenterology 98:1594-1604,
1990.
- Chapman RW: Aetiology and natural history of
primary sclerosing cholangitis-a decade of progress? Gut
32:1433-1435, 1991.
- MacCarty RL, LaRusso NF, May GR et al:
Cholangiocarcinoma complicating primary sclerosing cholangitis:
Cholangiographic appearances. Radiology 156:43-46, 1985.
- Lillimoe KD, Pitt HA, Cameron JL:Primary
sclerosing cholangitis. Surg Clin North Am 79:1381-1402, 1980.