Exostosin-Associated Membranous Nephropathy Secondary to Lupus with Castleman-Like Features

Introduction: Membranous Nephropathy (MN), an immune-mediated kidney disease characterized by subepithelial immune complex deposition, is caused by circulating autoantibodies targeting podocyte surface antigens. The landmark identification of the M-type phospholipase A2 receptor (PLA2R) as the major podocyte autoantigen has led to a paradigm shift in the diagnosis and management of MN in the past two decades. By utilizing laser microdissection of glomeruli followed by mass spectrometry, more putative podocyte autoantigens have been identified recently. Herein we present a case of MN secondary to systemic lupus erythematosus (SLE) with Castleman Disease (CD)-like features diagnosed on the basis of positive exostosin (EXT) staining on kidney biopsy. Case Description: 42 year old female with history of PLA2R-negative MN noticed increased foamy urine without other systemic manifestations, including skin rash. Prior secondary MN evaluation was unremarkable except for positive ANA (1:1280). Over 6 months her urine protein to creatinine ratio rose from 1.42 g/g to 4.6 g/g with new hypocomplementemia prompting repeat renal biopsy. Pathology unchanged from previous with exception of scattered mesangial deposits and positive EXT2 staining. Amidst her proteinuria evaluation she developed new right subpectoral lymphadenopathy. PET/CT revealed multiple hypermetabolic lymph nodes (LNs) above and below the diaphragm. Excisional LN biopsy showed reactive follicular hyperplasia with partial vascular proliferation of nodes and onion skinning of follicles concerning for CD, a rare lymphoproliferative disorder. Although high levels of interleukin 2 receptor and vascular endothelial grow factor support the diagnosis of CD, she does not have any clinical manifestations of CD. Discussion: Our patient received a preliminary diagnosis of CD; however, autoimmune conditions like SLE can resemble CD and must be excluded for precise diagnosis. Adding complexity to the case, the patient’s renal pathology was atypical for lupus MN given the lack of full-house immunofluorescence staining, numerous subepithelial electron dense deposits with scattered mesangial deposits. The advent of novel autoantigens like EXT1/2 will aid in accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.