Intrahepatic Inflammatory Pseudotumor With Elevated Serum CA 19-9 Showing Overlapping Features of ALK Negative Myofibroblastic Tumor & IgG4-Related Disease: A Diagnostic Challenge

IgG4-related disease (IgG4RD) usually involves multiple organs and often presents tumefactive lesions. Inflammatory myofibroblastic tumor (IMT) and IgG4-related inflammatory pseudotumors (IPT) share common clinicopathological features, but differentiating between them is important for a pathologist since their treatment modalities can differ. A 46-year-old woman presented with upper abdominal pain for 3 weeks and markedly elevated serum CA 19-9 levels (>1000 u/mL). Imaging studies revealed pericholecystic oedema/collection/lesion involving segment 4 of the liver and calculous cholecystitis, prompting suspicion of malignancy. She underwent cholecystectomy and segmental liver resection. The specimen was received for histopathological examination. Histopathological and immunohistochemical analyses of the specimen identified a spindle cell lesion with focal nuclear atypia. Immunohistochemical study revealed the spindle cell to be positive for smooth muscle actin and calponin, and negative for ALK. The spindle cells were surrounded by dense aggregates lymphocytes and plasma cells, with plasma cells showing IgG4 (∼40 per high power field) and IgG (∼100 per high power field) positivity in hotspot regions. Additionally, areas of fibrosis, phlebitis, and xanthogranulomatous reaction with bile ductular proliferation were observed. The final diagnosis was an “inflammatory pseudotumor with overlapping features of ALK-negative inflammatory myofibroblastic tumor and IgG4-related disease.” The patient was doing well 8 months postsurgery, with no relapse. While both IgG4RD and IMT share immunomorphological features, they can often be distinguished through strict criteria. Yet, there are lesions, like ours, where distinguishing between the two becomes challenging due to overlapping characteristics. Most IMT tumors show ALK expression; however, ours is among the 40% lacking ALK immunopositivity. A xanthogranulomatous reaction might initiate IMT/IPT development. High CA 19-9 levels do not always indicate carcinoma.