Rethinking Ormond's disease: "idiopathic" retroperitoneal fibrosis in the era of IgG4-related disease

Abstract

Idiopathic retroperitoneal fibrosis (RPF) is a periaortic sclerotic disease that encases adjacent retroperitoneal structures, particularly the ureters. A subset of idiopathic RPF cases can be associated with IgG4-related disease, but the frequency of this association is not clear. We selected 23 cases of idiopathic RPF and identified IgG4-related RPF cases based on the presence of IgG4+ plasma cells in the tissue, using an IgG4/IgG ratio cutoff of >40%. We then compared the IgG4-related RPF patients and the non-IgG4-related RPF patients in terms of both the presence of histopathologic features typical of IgG4-related disease and the simultaneous occurrence (or history) of other organ manifestations typical of IgG4-related disease. The IgG4-related RPF and non-IgG4-related RPF groups were also analyzed in terms of clinical, laboratory, and radiologic features and treatment review. We identified 13 cases of IgG4-related RPF (57% of the total cohort). The distinguishing features of IgG4-related RPF were histopathologic and extra-organ manifestations of IgG4-related disease. The IgG4-related RPF patients were statistically more likely than non-IgG4-related RPF patients to have retroperitoneal biopsies showing lymphoplasmacytic infiltrate (p = 0.006), storiform fibrosis (p = 0.006), or tissue eosinophilia (p = 0.0002). Demographics of the 2 groups, including a middle-aged, male predominance (mean age, 58 yr; 73% male), were similar. IgG4-related disease accounts for a substantial percentage of patients with "idiopathic" RPF. Histopathologic features such as storiform fibrosis, obliterative phlebitis, and tissue eosinophilia are critical to identifying this disease association. Extraretroperitoneal manifestations of IgG4-related disease are also often present among patients with IgG4-related RPF. Elevated IgG4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic.

FIGURE 1

IgG4/IgG ratios of IgG4-related RPF and non-IgG4-related RPF groups. The mean IgG4/IgG ratios, designated by the horizontal lines, are 78% for the IgG4-related RPF group and 8.2% for the non-IgG4-related RPF group.

FIGURE 2

IgG4-related RPF showing storiform type of fibrosis (A & B). The inflammatory infiltrate is composed of lymphocytes, plasma cell, and eosinophils (B). The inflammatory infiltrate frequently extends into the adipose tissue (C). Non-IgG4-related RPF cases typically showed acellular fibrosis with entrapped necrotic fat cell (arrow head). A lymphoid aggregate is also seen (arrow) (D). Immunohistochemical stain for IgG4. IgG4-related RPF showing elevated numbers of IgG4+ plasma cells (E). Immunohistochemical stain for IgG (F). The IgG4/IgG ratio was close to 100%. [This figure can be viewed in color online at http://www.md-journal.com].

FIGURE 3

A, Abdominal and pelvic CT scan of a patient with known IgG4-related RPF displaying a soft tissue periaortic mantle. B, Abdominal and pelvic CT scan of a patient with IgG4-related RPF showing a periaortic soft tissue and left hydronephrosis with asymmetric nephrogram on the left side.

FIGURE 4

Histopathology of Cases 1 and 2. Case 1. Cellular fibroinflammatory infiltrate arranged in a storiform pattern (A). The infiltrate was also rich in eosinophils (arrows) (B). Case 2. The biopsy is dominated by fibrosis with only a few lymphocytes and plasma cells (C). Immunohistochemical stain for IgG4 (D): 13 IgG4+ plasma cells were identified per hpf. [This figure can be viewed in color online at http://www.md-journal.com].