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Nephropathies can be associated with both solid organ and hematologic neoplasms. It's essential to consider systemic conditions that may mimic a lymphoproliferative syndrome (LPS) when making a differential diagnosis.
This case illustrates a significant shift in diagnosis in a patient with Hodgkin's lymphoma (HL) and renal failure while undergoing the ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine).
A 61 y/o man presented with left submandibular enlargement, abdominal pain, and unexplained weight loss. A CT scan in October 2019 revealed multiple adenopathies above and below the diaphragm, along with mild splenomegaly and enlarged kidneys. A biopsy of an adenopathy demonstrated morphological and immunohistochemical (IHC) features consistent with classic HL, with no bone marrow involvement. The patient started ABVD chemotherapy, but subsequently developed KDIGO stage I acute kidney injury with significant proteinuria (5.9 g/24h). Additionally, his albumin level was 2.5 g/dL, total protein at 8.8 g/dL, and an elevation in immunoglobulin G (IgG).
A renal biopsy revealed findings indicative of glomerulonephritis attributed to organized deposits within the fibrillary/immunotactoid group, which was associated with IgG4-related disease (IgG4RD), with severe chronic tubulointerstitial involvement. IHC for IgG4 exhibited strong positivity in the cytoplasm of plasmacytoid cells, with a count of 15-40 cells per high power objective (HPO). Plasma IgG subclasses were assessed, indicating elevated IgG1 (1745 mg/dL) and IgG4 (1534.7 mg/dL) levels. In the adenopathy initially diagnosed as HL, IHC showed a polyclonal plasmacytosis pattern with an increased presence of IgG4(+) plasma cells. An intense immunoreactivity for IgG4 in plasmacytes was observed, with over 100 cells per HPO and an IgG4/IgG ratio of 100%.
After a thorough multidisciplinary evaluation, it was concluded that the patient's condition aligned more with IgG4RD rather than HL. Treatment was initiated in October 2020 with prednisone 1 mg/kg, resulting in a positive systemic response. However, the patient experienced progressive renal failure, leading to the initiation of dialysis. A PET-CT scan conducted after four months of steroid therapy reported the absence of systemic involvement related to IgG4. The patient gradually regained renal function, discontinuing dialysis in March 2021 with persistent proteinuria (3 g/24h). Subsequently, rituximab was administered, without renal response. The patient remained in good overall health. However, due to the progression to stage 4 chronic kidney disease, it was decided not to pursue aggressive immunosuppressive treatment further.
In January 2022, IgG4 levels were measured, showing a slight elevation and C3-C4 levels were low. A new PET-CT scan was conducted, revealing no systemic involvement attributable to IgG4RD. Hemodialysis was resumed in October 2023.
This case highlights the importance of considering IgG4RD, recently described, which could be a new "great mimicker", in the differential diagnosis of LPS. Additionally, it is remarkable how the patient's systemic response to steroids was swift. At the renal level, we believe that the presence of fibrillary and immunotactoid patterns secondary to IgG4RD contributed to the persistent proteinuria and subsequent renal failure.