Abstract: TH-PO0807
Delayed Presentation of IgG4-Related Disease and Subsequent Lymphoma in Phospholipase A2 Receptor (PLA2R)(-) Membranous Nephropathy
Session Information
- Glomerular Case Reports: Membranous, PGN, GBM, and More
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Fong, Jie Ming Nigel, Sengkang General Hospital, Singapore, Singapore
- Guo, Weiwen, Sengkang General Hospital, Singapore, Singapore
- Tong, Tong, Singapore General Hospital, Singapore, Singapore
- Wong, Kye Ling, Singapore General Hospital, Singapore, Singapore
- Yeoh, Lee Ying, Sengkang General Hospital, Singapore, Singapore
Introduction
Membranous nephropathy (MN) is associated with autoimmune disease and malignancy. Renal manifestations of IgG4-related disease (IgG4-RD) include tubulointerstitial nephritis (TIN), MN, and obstructive uropathy from retroperitoneal fibrosis. We present a case of PLA2R(-) MN which developed features of IgG4-RD 4 years later and lymphoma after 6 years.
Case Description
A 49-year-old man presented with microscopic haematuria, 2g/day proteinuria, and creatinine (Cr) 0.9mg/dL. Renal biopsy was classical for MN, without TIN. Serum and tissue PLA2R was negative. Workup for secondary MN, including CT urogram, was negative. He was treated as low-risk PLA2R(-) primary MN with lisinopril.
4 years later, repeat CT displayed bilateral ureteric thickening. 4 ureteroscopies were normal; biopsy showed benign urothelium without plasma cells or fibrosis. Serum IgG4 (23.7g/L [0.04-0.86]) and IgG4/IgG ratio (0.62 [<0.4]) were high. IgG4 stain on the earlier renal biopsy and serum protein electrophoresis were unremarkable. Patient declined PET-CT or more invasive biopsies. Multidisciplinary consensus favoured IgG4-RD. As he was well with normal Cr and urine protein/creatinine ratio (UPCR) 0.4-0.9g/g, steroids were not given.
6 years from MN diagnosis, he developed acute kidney injury and an enlarged submandibular gland, biopsy of which found diffuse large B cell lymphoma on a chronic inflammatory background with >100/hpf IgG4+ plasma cells and IgG4/IgG ratio >0.5. PET-CT revealed advanced disease. He was given rasburicase for spontaneous tumor lysis, then polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisolone chemoimmunotherapy. He responded with ~50% decrease in size of lymph nodes, submandibular gland, and retroperitoneal soft tissue in 3 months, normalisation of Cr (0.7mg/dL) and UPCR (0.1g/g).
Discussion
This case highlights the need for continued vigilance for secondary causes of PLA2R(-) MN, even with negative initial screen. IgG4-RD is a diagnostic challenge, as IgG4 levels are nonspecific, and retroperitoneum is inaccessible for biopsy. We postulate that immune dysregulation in IgG4-RD may increase lymphoma risk. In this case, the submandibular gland, commonly involved in IgG4-RD, retained IgG4-rich features at DLBCL diagnosis. Alternatively, he may have had indolent lymphoma mimicking IgG4-RD, which transformed into DLBCL.