Abstract Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. Malignancy has been reported more frequently in MN associated with thrombospondin type-1 domain-containing 7A (THSD7A) or neural epidermal growth factor-like 1 (NELL1), whereas phospholipase A2 receptor (PLA2R) positivity is commonly interpreted as supporting primary MN. We describe a 63-year-old man with nephrotic syndrome whose kidney biopsy showed MN with granular PLA2R staining along the glomerular capillary walls. During follow-up, the patient experienced four separate episodes of malignancy, including colorectal adenocarcinoma, right upper lobe lung adenocarcinoma, pharyngeal squamous cell carcinoma, and left lower lobe lung squamous cell carcinoma. In the first two malignancy episodes (colorectal adenocarcinoma and right lung adenocarcinoma), nephrotic syndrome remitted after curative tumor resection without immunosuppressive therapy, a course compatible with malignancy-associated MN. During the latter two episodes (pharyngeal squamous cell carcinoma and left lung squamous cell carcinoma), increases in proteinuria, even below the nephrotic range, were observed before malignancy detection. This case suggests that PLA2R-associated MN may occur in the setting of multiple malignancy episodes. Serial monitoring of proteinuria may be clinically informative during follow-up, as changes in proteinuria may coincide with malignancy detection in patients with MN and a prior history of malignancy.
Komori et al. (Fri,) studied this question.