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Differences between primary MN and cancer associated secondary MN
It has been recently identified that the circulating auto-antibody to podocyte transmembrane glycoprotein M-type phospholipase A 2 receptor (PLA 2 R) is the cause of adult primary MN in majority of the cases.
These autoantibodies were not found in cases of secondary MN.
The nelow table helps summarize the potential ways one can differentiate primary MN from secondary MN associated with cancer.
Clinical Pathologic Features Differentiating Primary from Malignancies Associated Membranous Nephropathy
| CLINICOPATHOLOGIC PARAMETERS | PRIMARY MN | SOLID TUMOR ASSOCIATED MN |
|---|---|---|
| Historical clues | Younger age, no history of smoking | Age over 65 years, smoking for more than 20 pack years |
| Serological testing | Presence of circulating anti-PLA2R autoantibodies in serum | Absence of circulating anti-PLA2R autoantibodies in serum |
| Pathological findings | Predominance of glomerular IgG4 deposition, enhanced glomerular PLA2R staining, presence of less than 8 inflammatory cells per glomeruli | Predominance of IgG1,2 deposition, normal glomerular PLA2R staining, presence of more than 8 inflammatory cells per glomeruli |
IgG , Immunoglobulin G; MN , membranous nephropathy; PLA2R , phospholipase A2 receptor.
Thrombospondin type 1 domain containing 7A (THSD7A) is a target antigen in membranous glomerulonephritis associated with cancer. THSD7A was found in 2.6% of 1200 patients with MN.
These patients were mostly women. In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA2R-associated MN and malignant disease.
In all cohorts, they identified 40 patients with THSD7A-associated MN, 8 of whom developed a malignancy within a median time of 3 months from the diagnosis of MN.
In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, the immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis-infiltrated lymph node. Patients with THSD7A-associated MN should get more intensive screening for the presence of malignancies.
