Retroperitoneal fibrosis (RPF) is characterized by the replacement of the normal retroperitoneal tissue with fibrosis and/or chronic nonspecific inflammation.¹ Pelvic retroperitoneal fibrosis is a rare location for the primary presentation of this disease, with only a few documented cases in the literature.² Identification of immunoglobulin G4 (IgG4) autoimmune activity among these cases has begun to improve our understanding of the inflammatory nature of this rare disease process.³This case demonstrates the involvement of immune-mediated IgG4 within a case of pelvic retroperitoneal fibrosis.

Case Report

A 68-year-old man presented to a local hospital with severe bilateral flank pain, dysuria, and worsening obstructive voiding complaints. On presentation, his creatinine level was elevated to 5.3 mg/dL, and his bladder was distended. A Foley catheter was placed and returned over 1 L of urine. Urine culture was positive for Escherichia coli, and antibiotic coverage was adapted for empiric management. Computed tomography (CT) revealed bilateral hydronephrosis and significant bladder wall thickening. Although his creatinine level improved following bladder drainage, it began to rise within 48 hours despite bladder decompression noted on CT.

Urologists were consulted and the patient proceeded to the operating room for retrograde stent placement. This proved unsuccessful secondary to marked edema of the bladder and inability to identify the ureteral orifices. Bilateral nephrostomy tubes were placed, and his creatinine level improved to 0.8 mg/dL. He had antegrade placement of ureteral stents and his nephrostomy tubes were eventually removed.

The patient transferred his care to our clinic with indwelling stents for over 6 weeks, and clinically he returned to baseline. However, despite the indwelling stents, his creatinine levels began to rise from extrinsic compression, and nephrostomy tubes were replaced. His creatinine levels improved to 1.5 mg/dL at that time. Magnetic resonance imaging (MRI) was then obtained to follow up his previous CT, which showed significant bladder wall thickening and extensive infiltrative soft tissue in the pelvis encasing the rectosigmoid, ­bilateral ureters, and iliac ­vasculature (Figure 1).

Based on these MRI findings, we proceeded to the operating room for bladder, prostate, and perirectal biopsies. Pathologic examination showed acute and chronic cystitis with marked stromal fibrosis. No neoplasm was identified. Serum inflammatory laboratory values were elevated for C-reactive protein: 0.8 mg/dL (normal, < 0.6 mg/dL); erythrocyte sedimentation rate: 125 mm/h (normal, 0-20 mm/h); and IgG: 2142 mg/dL (normal, 540-1822 mg/dL). To confirm the clinical suspicion of IgG4-related sclerosing disease, immunohistochemistry for IgG4 was performed, which highlighted an increased ratio of IgG4-positive plasma cells (Figure 2) over IgG-positive plasma cells (not shown). The patient was diagnosed with IgG4-related retroperitoneal fibrosis and was started on high-dose corticosteroids. He was treated with a 60-mg dose every other day for 2 months and then tapered over 6 months. Repeat MRI at 2 months demonstrated significant reduction of the inflammation (Figure 1). His previously elevated inflammatory markers all normalized. His nephrostomy tubes were eventually removed, and resonance metallic ureteral stents placed. His creatinine level has remained at 1.5 mg/dL, and he is without any significant bothersome lower urinary tract symptoms. Currently, he is followed with serial stent exchanges and serum creatinine. Unfortunately, there is currently very little in the literature on the long-term management and the inherent risk of recurrence or progression of disease in these patients.

Discussion

RPF occurs in approximately 1 out of 200,000 people. It typically occurs in men in the fifth and sixth decades of life.² RPF is characterized by the presence of fibrous dense plaque in the retroperitoneum, which starts at the aortic bifurcation and gradually envelops the aorta, inferior vena cava, and ureters.⁴ Etiology includes medications, surgery, hemorrhage, infections, abdominal aortic aneurysms, and, in 8% to 10% of cases, malignancy.² Therefore, the importance of biopsy before therapy in all suspected cases is quite clear.  Approximately two-thirds of RPF cases are idiopathic. Elevated serum IgG4 can indicate an autoimmune origin. Previous cases of IgG4-related sclerosing disease demonstrate extensive infiltration of IgG4-positive plasma cells and elevation of serum IgG levels.⁵ It has been postulated that IgG4-related sclerosing disease is a systemic disease that can manifest itself in multiple organ systems.⁶ However, it remains unknown whether all cases of RPF are related to IgG4, and, if not, whether the clinicopathologic characteristics of IgG4-related cases are different from those of non–IgG4-related cases.³ Treatment has been successful with systemic corticosteroids.

This case represents an atypical location for retroperitoneal fibrosis. Once malignancy was excluded, further studies demonstrated the inflammatory nature of this patient’s disease process. Tissue confirmation of IgG4-dense inflammation assisted in confirming the diagnosis, leading to remarkable response to corticosteroid therapy.  

References

1. Vivas I, Nicolás AI, Velázquez P, et al. Retroperitoneal fibrosis: typical and atypical manifestations. Br J ­Radiol. 2000;73:214-222.
2. Salemis NS, Tsiambas E, Tsohataridis E. Pelvic confined idiopathic retroperitoneal fibrosis mimicking a large tumor. Adv Med Sci. 2009;54:296-298.
3. Zen, Y, Onodera M, Inoue D, et al. Retroperitoneal fibrosis: a clinicopathologic study with respect to immunoglobulin G4. Am J Surg Pathol. 2009;33: 1833-1839.
4. Kottra JJ, Dunnick NR. Retroperitoneal fibrosis. ­Radiol Clin N Am. 1996;34:1259-1275.
5. Yoshino T, Moriyama H, Fukushima M, Sanda N. A case of IgG4-related retroperitoneal fibrosis ­mimicking renal pelvic cancer. Urol Int. 2013;90:365-368.
6. Kamisawa T, Okamoto A. IgG4-related sclerosing disease. World J Gastroenterol. 2008;12;3948-3955.