A previously healthy 65-year-old man of Middle-Eastern origin, with a past medical history of hypertension, was initially referred to our gastroenterology service for evaluation of a suspected gastrointestinal bleed. Upper and lower endoscopies failed to reveal an active source of bleeding at that time, however he did have Helicobacter pylori-associated gastritis, which was treated. On a follow-up appointment our patient described a history of diarrhea with passage of greasy stool of several months duration associated with 13.6 kg weight loss but no associated abdominal pain. On further questioning, our patient described a history of binge alcohol consumption over five years prior to presentation. His physical exam was unremarkable and laboratory investigations revealed mild anemia, with hemoglobin (Hg) 127 g/L, normal liver function tests (LFTs), negative stool cultures, increased fecal fat of 72 g/day, fecal elastase below 15 ug/g of stool, and elevated blood sugar. Ultrasound investigation of his abdomen was unremarkable and computed tomography (CT) of his abdomen revealed an atrophic pancreas with no focal lesions. Our patient was presumed to have chronic alcoholic pancreatitis, although the absence of abdominal pain was puzzling, and was prescribed pancreatic enzyme replacement therapy with significant clinical improvement.
One year later our patient was referred again for an evaluation of malaise and elevated LFTs; again there was no complaint of abdominal pain. His alkaline phosphatase (ALP) level was found to be 265 U/L, gamma- glutamyltransferase (γ-GT) 236 U/L, alanine transaminase (ALT) 138 U/L and aspartate transaminase (AST) 94 U/L in the setting of normal lipase and bilirubin levels. Our patient was not jaundiced on exam; carbohydrate antigen (CA) 19-9 was elevated at 210 U/ml with a normal carcinoembryonic antigen (CEA) level. Abdominal ultrasound revealed right-sided intrahepatic bile duct dilatation suggestive of an obstruction. A subsequent abdominal CT scan showed an irregular soft tissue mass in his right distal hepatic duct proximal to the confluence (Figure ), and a somewhat atrophic pancreas (Figure ). Endoscopic retrograde cholangiopancreatography (ERCP) shortly after identified a long stenotic region within the right intrahepatic biliary tree with mild intermittent left-sided dilatation (Figure ). The overall picture was consistent with a presentation of Klatskin tumor (a representative picture of which, from an unrelated patient, is shown in Figure ), given the elevated CA19-9 level. Our patient then underwent bile duct resection, cholecystectomy and extended right hepatectomy with Roux-en-Y reconstruction. Intraoperatively, a firm mass was palpated at the hilum of his liver extending into the right ductal system. Our patient had an uneventful postoperative recovery with complete normalization of liver enzymes at the time of discharge.
Abdominal CT scan. (A) Arrow pointing to bile duct wall thickening. (B) Arrow outlining atrophic pancreas.
Figure 2 ERCP findings. (A) Stenotic region within right intrahepatic biliary tree. (B) Right and left hepatic ductal dilation (short arrows) above a typical hilar (Klatskin tumor, long arrow) stricture. A guidewire has been passed across the stricture into the (more ...)
Subsequent results of the pathology revealed a fibroinflammatory rather than malignant nature of the resected mass, with predominance of a lymphoplasmacytic infiltrate (Figure ). The liver parenchyma was normal and bile ducts showed proliferation and fibrosis as well as moderate chronic inflammatory infiltrate. Post factum histological staining of the specimen revealed a large IgG4 antibody positive infiltrate, with 55 positive cells per high power field (Figure ). Additional serological tests were ordered during a postoperative patient follow-up appointment. These were negative for serum antinuclear antibody and rheumatoid factor, as well as showing hypergammaglobulinemia with a surprisingly low IgG4 level.
Figure 3 Histopathology of the resected mass. (A) Hematoxylin and eosin staining showing thickened bile duct. (B) Hematoxylin and eosin staining revealing lymphoplasmacytic infiltrate, arrow pointing to plasma cell. (C) IgG4 antibody staining revealing more than (more ...)
The patient returned three months after surgery with malaise, fatigue and a reduced appetite. His laboratory studies revealed abnormal liver enzymes: total/direct bilirubin 21/9 umol/L, ALP 821 U/L, γ-GT 624 U/L, ALT 127 U/L and AST 143 U/L. Abdominal ultrasound revealed the normal appearance of the residual liver with no biliary tract dilatation. Given the histology and positive immunochemical staining for IgG4 positive cells, our patient was then prescribed a trial of a steroid regimen, which led to complete normalization of liver enzymes within three months. After tapering of the steroid therapy three months later our patient developed significant submandibular gland swelling, which again responded to re-introduction of corticosteroids. He now remains well on maintenance azathioprine treatment, 15 months after presenting with unilateral bile duct obstruction.