Elevated serum IgG4 and eosinophilia in a persistent indeterminate biliary stricture with high-risk features: a case report.

Background: Indeterminate biliary strictures remain diagnostically challenging because inflammatory biliary disease, premalignant epithelial change, and cholangiocarcinoma may share overlapping clinical, radiologic, serologic, and histologic features. Eosinophilic cholangitis is a rare benign inflammatory entity that can mimic malignancy, whereas elevated serum IgG4 and eosinophilia may coexist with other biliary disorders. Case presentation: A 68-year-old man presented with progressive jaundice, cholestatic liver injury, marked eosinophilia, elevated CA19-9, elevated IgE, and elevated serum IgG4. Baseline MRCP, ultrasound, and contrast-enhanced CT showed an indeterminate common bile duct stricture/occupying lesion with upstream biliary dilatation. Exploratory laparotomy with bile duct exploration revealed distal common bile duct stenosis, flocculent material, and multiple intrabiliary polypoid lesions. Pathology from the polypoid biliary lesion showed chronic inflammatory change with lymphoplasmacytic infiltration and scattered eosinophils, negative IgG4 staining, Ki-67 hot spot of approximately 10%, and wild-type p53. The distal common bile duct biopsy showed moderate chronic inflammation, compressed glands, mild cytologic atypia, negative tissue IgG4, and an epithelial Ki-67 hot spot of approximately 50%, but the sampled tissue was insufficient for a diagnosis of carcinoma. During reassessment, MRI showed a hilar nodule and lymphadenopathy, and dual-phase FDG PET/CT showed hilar/biliary uptake with an early SUVmax of 3.9 and delayed SUVmax of 5.0. Methylprednisolone 40 mg/day was started on December 28, 2019. Peripheral eosinophilia, liver biochemistry, serum IgG4, and CA19-9 improved over time, but T-tube cholangiography on January 13, 2020 still showed persistent segmental common bile duct stenosis with upstream ductal dilatation. Later family follow-up indicated clinical deterioration and an outside-hospital diagnosis of advanced biliary malignancy, but outside pathology and cause-of-death documentation were unavailable. Conclusion: This case is best interpreted as a persistent indeterminate biliary stricture with high-risk features rather than as proven eosinophilic cholangitis, IgG4-related sclerosing cholangitis, or pathologically confirmed cholangiocarcinoma. Improvement in eosinophils, serum IgG4, liver tests, or CA19-9 did not establish a benign diagnosis. Persistent anatomical stenosis after corticosteroid exposure should prompt renewed hepatobiliary malignancy assessment and repeat targeted tissue acquisition.