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10 December 2020 - Case of the Month #498

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Thanks to Dr. Nicole Andeen, Oregon Health and Science University, Portland, Oregon (USA), for contributing this case and writing the discussion and to Dr. Debra Zynger, The Ohio State University Wexner Medical Center, Columbus, Ohio (USA), for reviewing the discussion.




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Case of the Month #498

Clinical history:
A 54 year old woman with a history of diabetes presented with nephrotic syndrome and was found to have a 1 cm enhancing lower pole renal mass. She underwent partial nephrectomy.

Histopathology images:


What is your diagnosis?

Click here for diagnosis, test question and discussion:



Diagnosis: Clear cell renal cell carcinoma and membranous nephropathy

Test question (answer at the end):
What is the clinical utility of identifying anti-PLA2R antibodies in a patient with membranous nephropathy?

A. It is characteristic of primary membranous nephropathy and evaluation for an underlying neoplasm or autoimmune disorder is not needed
B. It suggests an underlying autoimmune disorder
C. It suggests an underlying malignancy
D. It supports a diagnosis of secondary membranous nephropathy


Stains:

Jones stain

IgG




Discussion:
Membranous nephropathy (MN) is an immune complex mediated glomerulopathy which clinically presents with nephrotic syndrome and is characterized by subepithelial glomerular capillary wall immune deposits on kidney biopsy. Light microscopy generally shows “holes” or “spikes” in the glomerular basement membrane on Jones silver stain. Immunofluorescence demonstrates granular capillary wall staining for polyclonal IgG and electron microscopy demonstrates corresponding subepithelial (on the urinary side of the glomerular basement membrane, under the podocyte) immune deposits and widespread podocyte foot process effacement.

Approximately 80% of MN are “primary” or renal limited and 20% are “secondary” and associated with systemic diseases, neoplasms (as in this case) or exposures. Most cases of primary MN (about 70%) are due to an autoantibodies to phospholipase A2 receptor (PLA2R), a podocyte antigen (N Engl J Med 2009;361:11). In these patients, PLA2R can be detected in the renal biopsy tissue and anti-PLA2R can be detected in the serum. Although anti-PLA2R associated MN comprises the majority of cases, other antigens have recently been identified in a minority of patients and have different clinical associations. Specifically, antibodies to thrombospondin type I domain containing 7A (THD7A) may be seen in 3% of cases and have been described both in primary and secondary (ie, associated with systemic autoimmune disease or neoplasia) settings (N Engl J Med 2014;371:2277). Using mass spectrometry, exostosin 1 and 2 (EXT1 / EXT2) antigens have recently been identified in patients with secondary membranous nephropathy, commonly in the setting of lupus (J Am Soc Nephrol 2019;30:1123). Finally, neural epidermal growth factor-like 1 protein (NELL-1) was recently discovered as an antigen, mostly in older adult patients without systemic conditions (Kidney Int 2020;97:163). Together these advance our understanding of the antigens and autoantibodies involved in this immune complex glomerulopathy.

Treatment strategies vary and include conservative therapy and various immunosuppressives including rituximab. Outcomes also vary but, in general, MN spontaneously resolves in approximately one third of patients and 10 - 20% develop end stage renal disease.

Test question answer:
A.
It is characteristic of primary membranous nephropathy, and evaluation for an underlying neoplasm or autoimmune disorder is not needed.

Image 01 Image 02