Clinical Challenges

Clinical Challenges - January 2017
What’s your diagnosis?

Publish date: January 3, 2017

What’s your diagnosis?

By Victoria Gómez, MD, and Jaime Aranda-Michel, MD. Published previously in Gastroenterology (2012 Dec;143[6]:1441, 1694).

A 65-year-old woman was evaluated for recurrent painless jaundice. Prior investigations at an outside institution included an endoscopic retrograde cholangiopancreatography that showed a stricture in the distal common bile duct with a negative cytology for malignant cells. She underwent laparotomy, during which a pancreatic head mass was found and biopsies revealed no malignancy. A palliative cholecystojejunostomy with gastroenterostomy was performed. Postoperatively, the jaundice improved but she had epigastric pain, persistent nausea, anorexia, and a 20-pound weight loss. Two weeks later she developed recurrent jaundice, and a second endoscopic retrograde cholangiopancreatography demonstrated a hilar stricture. A presumptive diagnosis of multicentric cholangiocarcinoma was made and she was referred to hospice care. She then sought another opinion regarding her condition at our institution.

Enhanced CT of the abdomen with focus on the pancreas (Figure A) showed mild peripancreatic inflammation and glandular enlargement (arrow points to endoscopically placed biliary endoprosthesis).
Percutaneous transhepatic cholangiography (Figure B) showed multiple smooth stenoses in the intrahepatic ducts (arrows). Serum IgG4 levels were normal. She underwent an endoscopic ultrasonography, which showed no evidence of a pancreatic head mass, but the entire pancreas was diffusely inhomogeneous and abnormal. The parenchyma presented alternating hypoechogenic and hyperechogenic areas with strands and lobulations. The outer border of the gland was lobular and the main pancreatic duct was normal. Biopsies of the pancreas showed changes consistent with chronic pancreatitis with loss of the acinar parenchyma and residual islets and ducts seen with fibrosis and infiltration composed of mononuclear cells. Immunostain for CD138 was performed and very high numbers of plasma cells were observed infiltrating the tissue. Immunostain for IgG4 demonstrated approximately 10-15 positive cells per high-power field.


 

The diagnosis

The radiographic and pathologic findings and the patient’s clinical presentation were most consistent with autoimmune pancreatitis and IgG4-related sclerosing cholangitis, which are manifestations of IgG4-related disease. IgG4-related disease is a fibroinflammatory condition that has been described in almost every organ system. Elevated serum IgG4 levels suggest this diagnosis, but many times remain normal.1,2 Therefore, a strong clinical suspicion should prompt a biopsy of the affected tissue, which will show a dense lymphoplasmacytic infiltrate organized in a matted and irregularly whorled pattern.2,3 Making a diagnosis requires immunohistochemical confirmation with IgG4 immunostaining of plasma cells.

First-line therapy is corticosteroids, followed by immunomodulators such as azathioprine, mycophenolate mofetil, and methotrexate.3 Many patients show a dramatic response with therapy. In the setting of suspected malignant tumors of the pancreatobiliary system, IgG4-related disease should be considered in the differential diagnosis to avoid unnecessary surgery and unfavorable as well as incorrect prognosis.

The patient was started on prednisone followed by azathioprine and experienced a rapid and sustained clinical and biochemical response even after stopping immunosuppressive therapy. After treatment, repeat imaging studies were performed, which showed dramatic improvement in the above-mentioned abnormalities. Abdominal CT showed a decrease in size of the pancreatic head (Figure C) and repeat cholangiogram showed resolution of biliary stenoses (Figure D).

References

1. Oseini, A.M., Chaiteerakij, R., Shire, A.M., et al. Utility of serum immunoglobulin G4 in distinguishing immunoglobulin G4-associated cholangitis from cholangiocarcinoma. Hepatology. 2011;54:940-8.

2. Takuma, K., Kamisawa, T., Gopalakrishna, R., et al. Strategy to differentiate autoimmune pancreatitis from pancreas cancer. World J Gastroenterol. 2012;18:1015-20.

3. Stone, J.H., Zen, Y., Deshpande, V. IgG4-related disease. N Engl J Med. 2012;366:539-51.

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