Concurrent isolated IgG2-positive membranous nephropathy and malignant B-cell lymphoma

Abstract

A recent systematic review showed that hematological malignancy is often complicated by membranous nephropathy (MN). Histologically, the deposition of IgG subclasses other than IgG4 may imply secondary MN, such as malignancy-associated MN (M-MN). We describe a very rare case of concurrent isolated IgG2-positive MN and B-cell lymphoma. An 83-year-old woman was hospitalized at our institute for facial and lower extremity edema persisting for 2 months. Laboratory tests showed urinary protein level of 10.8 g/day, serum albumin level of 1.6 g/dl, and serum creatinine level of 2.34 mg/dl. Soon after diagnosis of nephrotic syndrome, treatment with corticosteroid was initiated, but it proved to be ineffective. Renal biopsy showed isolated IgG2-positive MN with highly infiltrated CD20-positive lymphoid cells in the kidney. Computed tomography revealed systemic lymphadenopathy, and aberrant B-cells with immunoglobulin light chain restriction were detected in peripheral blood and bone marrow, which led to the diagnosis of mature B-cell lymphoma. Although rituximab (375 mg/m/week) was administered, the patient suddenly died from gastrointestinal bleeding on day 40 of hospitalization. It is, thus, necessary to consider hematological malignancy when a diagnosis of MN is made. Further studies are expected to elucidate the pathogenesis and to help establish the adequate treatment for this rare situation.

Network analysis of membranous glomerulonephritis based on metabolomics data

“…A deterioration in renal function and the development of end-stage renal disease occur in ~40% of patients with primary MGN ( 5 ). Proteinuria ( 6 , 7 ), edema ( 8 , 9 ), hyperlipidemia ( 10 , 11 ) and hypoalbuminemia ( 12 , 13 ) are non-specific clinical symptoms of MGN. However, renal biopsy is the only definitive diagnostic approach, although it is an invasive procedure.…”

Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report

“…What is more worthy of our attention is that the suggestive role of IF and IHC in renal biopsy should not be underestimated. Among them, anti-PLA2R antibody and type 1 platelet reactive protein containing the 7 A structural domain (THSD7A) have important diagnostic significance for MN; moreover, deposition of IgG4 mainly in the glomeruli indicates primary MN (PMN), whereas significant deposition of other IgG subclasses may suggest SMN [ 8 – 10 ]. The absence of glomerular IgG4 deposits in patients with MN may be indicative of malignancy, and thus, IgG4 may also serve as a contrasting predictor of malignant tumorigenesis.…”

Secondary Membranous in the Cancer Patient

“…26,27 Two cases involved a diagnosis of membranous nephropathy on renal biopsy with lymphomatous invasion. 22,24 In both cases the diagnosis of lymphoma was not known prior to renal biopsy. And the final case involves a patient with lymphoma who underwent allogenic bone marrow transplant with no history or evidence of acute or chronic GVHD.…”

“…Since then, the current authors performed a similar PubMed search with criteria “lymphoma,” “leukemia,” “Waldenstrom,” and “membranous nephropathy” published since 2006 and identified 7 additional cases associated with chronic lymphocytic leukemia, 16–19 one case associated with Waldenstrom’s macroglobulinemia, 9 and 10 additional cases associated with lymphoma, predominantly non-Hodgkin’s lymphoma. 20–28…”

“…Since then, the current authors performed a similar PubMed search with criteria "lymphoma," "leukemia," "Waldenstrom," and "membranous nephropathy" published since 2006 and identified 7 additional cases associated with chronic lymphocytic leukemia, [16][17][18][19] one case associated with Waldenstrom's macroglobulinemia, 9 and 10 additional cases associated with lymphoma, predominantly non-Hodgkin's lymphoma. [20][21][22][23][24][25][26][27][28] In paraneoplastic membranous nephropathy, only 10% of patients were diagnosed with cancer before their diagnosis of membranous nephropathy. 29,30 The remaining 40% were diagnosed simultaneously and 45% were diagnosed with cancer after their diagnosis of membranous with a mean time to diagnosis of 1 year.…”