Management of ureteral IgG4-Related Disease: The great masquerader

Abstract

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition that can mimic malignancies, including ureteric urothelial carcinoma (UCC). This case report describes a 65-year-old female presenting with obstructive uropathy due to IgG4-related ureteritis. Initial imaging suggested UCC, however ureteric biopsy was negative. Elevated serum IgG4 levels (3.77 g/L) supported the diagnosis of IgG4-related ureteritis. Treatment with methotrexate, prednisolone, and rituximab led to significant improvement, with subsequent imaging showing resolution of obstructive uropathy. This case highlights the importance of considering IgG4-RD in the differential diagnosis of ureteric malignancies to prevent unnecessary invasive procedures and optimize patient outcomes through appropriate immunosuppressive therapy.

Highlights

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IgG4-related ureteritis mimics ureteric malignancies, making diagnosis challenging.
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Elevated serum IgG4 levels are key for diagnosing IgG4-related ureteritis.
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Methotrexate, prednisolone, and rituximab induce remission in IgG4-related ureteritis.
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Accurate diagnosis and a multidisciplinary approach prevent unnecessary invasive procedures.

1 Introduction

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition characterized by the presence of tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 levels. It can affect various organs, including the pancreas, salivary glands, kidneys, and ureters. ^, Ureteritis secondary to IgG4-RD is a rare manifestation that can present with features mimicking ureteric urothelial carcinoma (UCC), posing significant diagnostic challenges. Accurate diagnosis is critical to avoid unnecessary invasive procedures and to preserve renal function. Herein, we present a case of IgG4-related ureteritis and secondary obstructive uropathy successfully managed with medical therapy.

1.1 Case presentation

A 65-year-old female presented with a septic obstructed left kidney due to a thickened pelvi-ureteric junction (PUJ). The patient’s medical history was notable for breast cancer, rheumatoid arthritis, depression, and hypothyroidism. Her hormone sensitive invasive lobular breast carcinoma was diagnosed in 2014 and treated with neoadjuvant chemotherapy, wide local excision, radiotherapy, and ongoing letrozole for hormonal blockade. Her rheumatoid arthritis was diagnosed in 2004 and was initially treated with 15 mg methotrexate, which achieved remission and was ceased at the time of her breast cancer diagnosis. However, flares of rheumatoid arthritis recurred over the preceding 18 months, particularly affecting the right metacarpophalangeal joints, pelvis and both feet.

At the time of her presentation, CT IVP showed an enhancing soft tissue mass within the renal pelvis extending into the PUJ and proximal ureter, resulting in moderate left-sided hydronephrosis and altered perfusion of the kidney ( Fig. 1 ). Aside from mildly prominent sub-centimetre retroperitoneal and axillary lymph nodes, there was no other abnormality seen in the chest, abdomen and pelvis. Initial laboratory findings included an ESR of 20 mm/hr, CRP of 20 mg/L, GFR of >90 ml/min/1.73 m ² and creatinine at 54 μmol/L. The patient underwent rigid cystoscopy, left flexible ureteropyeloscopy, bladder and left renal pelvis biopsy, and JJ stent insertion. The cystoscopy revealed two bladder tumors at the right bladder neck, which were biopsied. On direct visualisation of the proximal ureter, narrowing at the PUJ was noted with thickened and abnormal urothelium, but there was no obvious papillary tumour typical for UCC. Histopathology revealed a low-grade transitional cell carcinoma (LG pTa) in the bladder and reactive urothelium in the left PUJ biopsy with no malignancy. Atypical urothelial cells were noted in the left ureteric washings, but no malignant cells were seen.

A follow-up FDG PET scan indicated low-grade activity in small left para-aortic lymph nodes and multiple FDG-avid right axillary and subpectoral lymph nodes. Serum IgG levels measured showed elevated IgG1 (12.6 g/L) and IgG4 (3.77 g/L), with a total IgG of 22.0 g/L ( Fig. 2 ). Serum ACE and ANCA were negative. The patient was subsequently reviewed by rheumatology and treatment included methotrexate 20 mg, 5 mg folate, and prednisolone 50 mg daily, tapering gradually. Two months later, CT IVP demonstrated treatment response with a decrease in mural wall thickening of the left renal pelvis and ureter with resolution of hydroureteronephrosis, and no interval enlargement of retroperitoneal or pelvic sidewall lymph nodes ( Fig. 1 ). Subsequent repeat retrograde pyelography and stent removal revealed persistent but improved narrowing at the PUJ ( Fig. 3 ). Ureteric stent was removed at this time. At her subsequent rheumatological review, ESR decreased from 94 to 35 mm/hr, and CRP was 1 mg/L. The patient commenced rituximab 1g at weeks 0 and 2 as a steroid-sparing agent and treatment for presumed IgG4-RD.