a treatable mimicker of cholangiocarcinoma

1Department of Gastroenterology and Hepatology; 2Department of Pathology, Western University, London, Ontario; 3Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia Correspondence: Dr Bandar Al-Judaibi, E2-314, University Hospital, London Health Sciences Centre, 339 Windermere, London, Ontario N6A 5A5. Telephone 519-685-8500, e-mail bandaraljudaibi@gmail.com Received for publication February 3, 2015. Accepted February 8, 2015 CASE PRESENTATION A 68-year-old female nonsmoker, nondrinker with a medical history of hypertension presented with new-onset painless jaundice and pruritus, a three-month history of 9.9 kg weight loss and chronic diarrhea with four to five loose bowel movements per day. Medications included vitamin D, amlodipine and eprosartan. Physical examination was normal except for jaundice and muscle wasting. Recent colonoscopy had been normal. Total and direct bilirubin levels were 6.84 mg/dL (116.96 μmol/L) and 9.18 mg/dL (156.98 μmol/L), respectively. Other results included an international normalized ratio of 1.0, alanine aminotransferase level 247 U/L (normal <33 U/L), aspartate aminotransferase level 139 U/L (normal <32 U/L) and alkaline phosphatase level 524 U/L (normal 35 to 104 U/L). Viral hepatitis serologies, and antimitochondrial antibody and anti-smooth muscle antibody tests were negative. Her alpha-fetoprotein level was 2.4 ng/mL (normal <5 ng/mL), total immunoglobulin (Ig) G was 1880 mg/dL (normal <640 mg/dL), carbohydrate antigen 19-9 was 856 U/mL (normal <33 U/mL) and IgG4 was 890 g/L (normal <3 g/L). Doppler ultrasound, magnetic resonance cholangiopancreatography and magnetic resonance imaging of the liver were suspicious for a subtly enhancing mass (2.8 cm to 4.2 cm in diameter) in the region of the hilum and porta hepatis, obstructing both the right and left hepatic ducts. Endoscopic retrograde cholangiopancreatography identified strictures in the central portions of the right and left hepatic duct, which was concerning for cholangiocarcinoma (Figure 1). Biliary brushings were negative for malignancy.


CASE PRESENTATION
A 68-year-old female nonsmoker, nondrinker with a medical history of hypertension presented with new-onset painless jaundice and pruritus, a three-month history of 9.9 kg weight loss and chronic diarrhea with four to five loose bowel movements per day.Medications included vitamin D, amlodipine and eprosartan.Physical examination was normal except for jaundice and muscle wasting.Recent colonoscopy had been normal.Total and direct bilirubin levels were 6.84 mg/dL (116.96μmol/L) and 9.18 mg/dL (156.98 μmol/L), respectively.Other results included an international normalized ratio of 1.0, alanine aminotransferase level 247 U/L (normal <33 U/L), aspartate aminotransferase level 139 U/L (normal <32 U/L) and alkaline phosphatase level 524 U/L (normal 35 to 104 U/L).Viral hepatitis serologies, and antimitochondrial antibody and anti-smooth muscle antibody tests were negative.Her alpha-fetoprotein level was 2.4 ng/mL (normal <5 ng/mL), total immunoglobulin (Ig) G was 1880 mg/dL (normal <640 mg/dL), carbohydrate antigen 19-9 was 856 U/mL (normal <33 U/mL) and IgG 4 was 890 g/L (normal <3 g/L).Doppler ultrasound, magnetic resonance cholangiopancreatography and magnetic resonance imaging of the liver were suspicious for a subtly enhancing mass (2.8 cm to 4.2 cm in diameter) in the region of the hilum and porta hepatis, obstructing both the right and left hepatic ducts.Endoscopic retrograde cholangiopancreatography identified strictures in the central portions of the right and left hepatic duct, which was concerning for cholangiocarcinoma (Figure 1).Biliary brushings were negative for malignancy.
Esophagogastroduodenoscopy was normal.Biopsies of the ampulla of Vater revealed chronic active duodenitis (Figures 2 and 3); an ancillary test confirmed the diagnosis (Figure 4).Treatment with corticosteroids normalized the patient's biochemical and radiological abnormalities within three months.2), but is invasive and not widely available.Alternatively, positive IgG 4 immunostaining of the major duodenal papilla, as was performed here (Figure 4), is specific and moderately sensitive (3,4), and is less invasive than intraductal manipulation.

DISCUSSION
Treatment is based on case reports and series.Most patients respond to two to four weeks of glucocorticoid steroids.Patients who are glucocorticoid resistant or dependant may respond to azathioprine (2 mg/ kg/day), mycophenolate mofetil (up to 2.5 g/day) or rituximab (5).Potential morbidity and mortality in untreated patients include cirrhosis and portal hypertension, retroperitoneal fibrosis, aortic aneurysms/ dissections, biliary obstruction, diabetes mellitus and lymphoma (5).
Patients with IgG 4 SC progressed to liver transplantation in a significantly shorter time than patients with primary sclerosing cholangitis (1.7 years versus 6.5 years; P=0.0009) (6).Therefore, IgG 4 SC is an under-recognized, highly treatable condition that has high morbidity if misdiagnosed as malignancy, or if undiagnosed and untreated.

KEY POINTS
• IgG 4 is under-recognized by physicians due to the rarity of the disease.Increased medical awareness has an important value in making the diagnosis.• Positive IgG 4 immunostaining of the major duodenal papilla is an extremely specific and moderately sensitive tool for the diagnosis of corticosteroid-responsive IgG 4 -related disease

DISCLOSURES:
The authors have no conflicts of interest to declare.
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