Pathlet 002
Michelle Winston KCUMB '15

These pathlets are edutainment. This site collects no information about visitors, and cannot substitute for your own doctor's care. It has some questions without clear right-or-wrong answers. Scripting by Ed Friedlander MD.

Van Gogh, "An Old Woman of Arles"
Upstate New York, 2005. Winter.

An 83 year old grandmother of five presents to the ER complaining of a yellowish tint to her skin and sclera, and mild, intermittent, colicky pain in the right upper quadrant of the abdomen. She reports slight weight loss over the last couple of months, and notes that her urine has been quite dark since the jaundice began.

The grandmother reports that she is currently being treated for hypertension and hyperlipidemia. She controls her hypertension with Atenolol, and treats her hyperlipemia via diet.

Her past surgical history is positive for a tonsillectomy and appendectomy in young adulthood. Other than her Atenolol, she takes no other medications. She does take a Once A Day Multi-Vitamin. She happily tells the medical student doing her H&P that she vaginally delivered five children in the comfort of her own home. She reports that she does not use alcohol or tobacco, because she is trying to set a good example for her grandchildren.

Apart from her presenting jaundice and abdominal pain, the grandmother seems to be in good spirts. However, she does report feeling more tired than usual. She also states that her stools have been more pale than usual, and describes them as clay colored.

Physical exam reveals an elderly woman of small stature. Her skin and sclera are jaundiced. She is alert and oriented. She has normal bowel, lung and heart sounds. Temperature is 98.6 F, pulse 60, respiratory rate 12, blood pressure 120/80. The liver is slightly enlarged to palpation. There are no other pertinent physical findings.

Based on the history and physical exam, what likelihood would you assign each of the following?

BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS Very Unlikely                   Very Likely
BILE DUCT CYSTADENOCARCINOMA Very Unlikely                   Very Likely
BILE DUCT CYSTADENOMA Very Unlikely                   Very Likely
BYLER SYNDROME Very Unlikely                   Very Likely
CAROLI SYNDROME Very Unlikely                   Very Likely
CHOLANGIOCARCINOMA Very Unlikely                   Very Likely
CHOLANGITIS Very Unlikely                   Very Likely
CHOLECYSTITIS Very Unlikely                   Very Likely
CHOLEDOCHOLITHIASIS (COMMON BILE DUCT STONE) Very Unlikely                   Very Likely
DUBIN-JOHNSON SYNDROME Very Unlikely                   Very Likely
HEPATOCELLULAR CARCINOMA Very Unlikely                   Very Likely
METASTATIC CARCINOMA Very Unlikely                   Very Likely
PRIMARY BILIARY CIRRHOSIS Very Unlikely                   Very Likely
SARCOIDOSIS Very Unlikely                   Very Likely
SCLEROSING CHOLANGITIS Very Unlikely                   Very Likely

We thought that most of the above are good ideas. We would favor a common duct stone, or any of the tumors. Especially because she's elderly, we think that biliary cirrhosis, primary sclerosing cholangitis, and sarcoidosis are unlikely to present this suddenly. Dubin-Johnson and the hereditary cholestasis syndromes (Byler's, Caroli's, benign intermittent cholstasis) do not present initially in later adulthood. Cholecystitis should not produce an obstructive jaundice unless there is also a common duct stone ("choledocholithiasis"). Cholangitis should be accompanied by more discomfort and by a fever, and she has no known underlying disease to put her at risk.

Now, assume that you have ordered a complete blood count and that the results are normal. Assume you have ordered a chemical profile and the results have been returned with high-normal transaminases (SGOT/AST and SGPT/ALT), that the alkaline phosphatase is three times the upper limit of normal for an adult, that the serum total bilirubin is 5.2 mg/dL with direct 4.3 mg/dL, and that the serum iron and iron binding capacity are normal. Assume that urinalysis is normal except for heavy direct bilirubinemia. And assume that the patient is not in any discomfort and does not want any medication.

What diagnostic studies do you want?

Abdominal ultrasound
Alpha-1 antitrypsin levels
Alpha-1 antitrypsin genotype
Angiotensin converting enzyme
Computer tomography (CT) scan
Hepatitis A antibody
Hepatitis B panel
Hepatitis C antibody
Magnetic resonance cholangiopancreatography (MRCP)
Serum ferritin
Wilson's testing (serum copper, serum ceruloplasmin, urinary Cu/creatinine ratio)

Upstate New York -- "Morning Looking East", by Frederic Church

Since this is an obstructive "surgeon's" jaundice, imaging is most likely to give useful information. Of the bloodwork, the iron and the hepatitis B and C checks are perhaps the most reasonable. The normal transminases rule out acute hepatitis, but it would be good to know whether she carries the virus(es) or is iron-overloaded in case this is hepatocellular carcinoma.

Abdominal ultrasound and CT revealed a dilated intrahepatic biliary tree due to a intrahepatic mass. She has a normal gallbladder and pancreas. The contrast-enhanced CT and MRCP provided more precise details of the mass. It was located at the junction of the hepatic ducts with the common bile duct. There was no sign of metastatic disease.

The attending physicians decided to biopsy the mass by laparoscopy.


What is the diagnosis?

Bile duct cystadenocarcinoma
Bile duct cystadenoma
Hepatocellular carcinoma
Malignant lymphoma
Papillary cholangiocarcinoma
Portal vein smooth-muscle tumor

This is a papillary cholangiocarcinoma of the bile ducts. At this location, it is called a "Klatskin tumor." This often occurs at the the bile duct bifurcation and accounts for 60-80% of cholangiocarcinomas.

The anaplastic low-columnar epithelium covers a tree-like stroma. The papillary adenocarcinoma pattern is familiar from basic pathology. In this setting, there is no reasonable question that the tumor is of bile duct epithelial origin.

The molecular pathways of this tumor are not well-defined yet. Ongoing damage and healing in the bile duct epithelium increasses the risk. Consequently, primary sclerosing cholangitis, congenital biliary cystic disease ("Caroli's"), parasitic infections of the ducts (famously the Chinese and South East Asian liver flukes), hepatolithiasis, and choledocholithiasis have been associated with Klatskin Tumors. The role of industrial exposures in these tumors has been discussed.

Klatskin tumors are equally common in men and women and tend to appear in people over the age of 65. There is a tenfold increase in people over the age of 80. If staging is low and the tumor has yet to invade the surrounding tissue, surgical resurrection is usually successful. However, if this relatively uncommon malignancy goes untreated patients will suffer death due to progressive jaundice and liver failure.

Upon receiving the biopsy, the attending physicians decided to perform a cholecystectomy, resection of the extrahepatic ductal system, portal lymphadenectomy, and biliary enteric anastomoses.

The octogenarian grandmother of five is doing well without any recurrence of jaundice two years following surgery.


Resources: http://www.ncbi.nlm.nih.gov/books/NBK6906/ WHO Classification of Tumors: Tumors of the Digestive System

Michelle Winston KCUMB '15

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