First Report of Immunoglobulin G4-related Hepatic Inflammatory Pseudotumor in Transplanted Liver.

Abstract

Immunoglobulin (Ig)G4–related hepatic inflammatory pseudotumor (IgG4-HIPT) is a rare subset of IgG4-related disease characterized by IgG4-positive plasma cell infiltration and fibrosis.1 Only 28 cases have been reported, all occurring in native livers.1-3 We report herein the first case of IgG4-HIPT developing in a transplanted liver. All ethical approval and consent procedures were approved by the Medical Ethical Committee of Icahn School of Medicine at Mount Sinai. According to the institutional guidelines, the patient’s signed privacy consent is not necessary for a single case report with deidentified patient-specific information. Our patient, who is a 62-y-old women who underwent liver transplantation for primary biliary cholangitis 14 y prior, presented with bacteremia. Laboratory tests showed normal white blood cell count, elevated gamma-glutamyl transferase 101 U/L (normal, 8–35), normal alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin. Blood culture was positive for methicillin-resistant Staphylococcus aureus and Klebsiella oxytoca. Serological tests for hepatitis A, B, C, and E; cytomegalovirus; and Epstein-Barr virus were negative. Serum total IgG 1654 mg/dL (normal, 586–1602) and IgG4 171 mg/dL (normal, 2–96) were elevated. Computed tomography (Figure 1A) and magnetic resonance imaging (Figure 1C–E) of the abdomen revealed a 6-cm infiltrative mass in segment 8 of the liver. A biopsy of the lesion demonstrated parenchymal collapse replaced with fibrosis and sheets of plasma cells (Figure 1F). Immunohistochemical stains showed up to 150 IgG4-positive plasma cells per high power field and an IgG4:IgG ratio of 60% (Figure 1G and H). There was no evidence of malignancy, recurrent primary biliary cholangitis, acute cellular rejection, or chronic rejection, and a diagnosis of IgG4-HIPT was rendered. Given the patient’s bacteremia, she was started on intravenous daptomycin and ertapenem. Prednisone was deferred because she was asymptomatic from the lesion. The patient was restarted on mycophenolate mofetil 1 mo postdischarge. Repeat computed tomography of the abdomen 7 mo later demonstrated the decreased size of the lesion to 2.3 cm (Figure 1B).FIGURE 1.: Radiology features (A–E). A, Contrast-enhanced computed tomography images demonstrate an infiltrative enhancing mass in segment 8 measuring 6 cm (arrow). B, Follow-up postcontrast computed tomography after 7 mo demonstrates the decreased conspicuity and size of the lesion (measuring 2.3 cm, arrow). Contrast-enhanced MRI obtained during the (C) arterial, (D) portal venous, and (E) delayed venous phases demonstrates an ill-defined lobulated infiltrative progressively enhancing mass (arrow). Microscopic and immunohistochemical features (F–H). F, The inflammatory cells consist predominantly of lymphocytes and plasma cells (arrow) (hematoxylin and eosin stain ×200). The inflammatory cells demonstrated diffuse reactivity for (G) cluster of differentiation 138 and (H) immunoglobulin G4. MRI, magnetic resonance imaging.IgG4-related disease is generally described as an autoimmune disease because the oligoclonal expansions of both activated B cells and cytotoxic CD4+ T cells were considered central to the process.4 In our case, the IgG4-HIPT developed in a liver allograft in a patient on immunosuppression (tacrolimus target trough level 2–6 ng/dL, mycophenolate mofetil 500 mg twice daily). It may seem counterintuitive that an autoimmune process may develop in such a setting. On the other hand, infections such as Escherichia coli and Klebsiella may also incite an IgG4-predominant inflammatory response.3 In our case, the patient developed bacteremia with methicillin-resistant Staphylococcus aureus and Klebsiella at the time the liver mass was noted. Bacterial translocation from the gut to the portal circulation may have provoked an intrahepatic inflammatory response. This theory was further supported by partial or complete treatment response observed in the current and prior reported cases2 upon administration of antibiotics. Diagnosing IgG4-HIPT is challenging because of its rarity and overlapping clinical and radiological features with malignancy. Because IgG4-HIPT is clinically benign, the recognition of this entity is important to avoid unnecessary treatment.