Case Presentation: A 39-year-old woman presented with one year of epigastric abdominal pain, progressive weakness and a 50-lb weight loss. Labs showed pancytopenia, most notably a Hgb of 5.0 g/dL. Abdominal CT scan revealed portal hypertension, possible cirrhosis and hepatic biliary dilation. EGD showed small esophageal varices. MRCP revealed a large soft tissue mass centered at the SMA. Endoscopic ultrasound (EUS) did not show a discrete mass. Liver biopsy demonstrated non-cirrhotic portal hypertension. The patient was discharged with outpatient follow-up. She was re-hospitalized for melena and hematemesis and found to have non-bleeding esophageal varices and erosive gastritis. Two weeks later, her pain worsened with associated abdominal bloating prompting a 3rd hospitalization. Paracentesis demonstrated benign ascitic fluid. Further imaging again showed obstructing retroperitoneal mass. She was transferred to our hospital. Exam revealed diffuse tenderness to palpation worse in the epigastric region without any masses palpated. She had persistent pancytopenia on labs. Repeat EUS was now able to visualize the mass which was biopsied. Pathology showed benign lymphoid infiltrate without evidence of lymphoma. Scattered IgG4-staining plasma cells were noted (up to 7 per hpf). Rheumatology reviewed her case but the low IgG4 cellularity not meet criteria for IgG4 related disease (IgG4-RD). Additionally, fibrosis was not seen and IgG subclasses were normal.We had a strong “gut feeling” that the patient had IgG4 related retroperitoneal fibrosis. Experts on IgG4-RD at our institution concurred that IgG4-RD was the likely diagnosis but malignancy, specifically lymphoma, was quite possible. Thus, all involved felt uncomfortable committing to treatment without convincing pathology. Bone marrow was unremarkable. PET scan showed FDG avid tissue at the mesenteric root, consistent with a metabolically active mass. Repeat biopsy via EUS showed benign soft tissue. Ultimately to make a diagnosis, general surgery agreed to perform an exploratory laparotomy. Pathology revealed fibrosclerosing lesion with morphologic features clearly consistent with IgG4-RD. Systemic corticosteroid therapy was started.
Discussion: IgG4-RD is a relatively recently recognized immune-mediated fibroinflammatory condition that can affect multiple organs. It typically presents sub-acutely, either with systemic symptoms or isolated organ involvement. It is characterized as (1) tumor-like swelling of involved organ(s), (2) lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, and (3) variable degree of fibrosis with a characteristic storiform pattern. IgG4-RD often mimics other disease states such as lymphoma or other autoimmune diseases. Serum IgG4 concentrations are normal in 1/3 of patients. Tissue biopsy is gold standard for diagnosis but IgG4 staining plasma cells alone is inadequate; diagnosis requires other key features such as storiform fibrosis or obliterative phlebitis. This case demonstrates the clinical diligence that is often needed to make this difficult diagnosis. Treatment generally includes a long course of systemic corticosteroids (2 months), or if no response, other immune modulating therapies such as azathioprine or rituximab.
Conclusions: IgG4-RD can have a wide range of presentation and can mimic other diseases such as lymphoma. Adequate tissue sampling is key to making the diagnosis and deciding on treatment course.