A case of immunofluorescence-negative light chain deposition disease diagnosed by mass spectrometry.

Abstract

A 53-year-old man was referred to our department for the evaluation of kidney dysfunction and edema. Kidney biopsy revealed nodular glomerular lesions; however, immunofluorescence showed no specific deposition of immunoglobulins or light chains, and a definitive diagnosis could not be confirmed. Serum and urine immunofixation electrophoresis detected κ-type Bence Jones protein, raising suspicion of monoclonal immunoglobulin-related kidney disease. Bone marrow examination led to a diagnosis of multiple myeloma. Electron microscopy revealed band-like, powdery, electron-dense deposits extending from the glomerular basement membrane to the subendothelial area as well as deposits along the tubular basement membranes, suggestive of monoclonal immunoglobulin deposition disease. However, additional evaluation using immunofluorescence on paraffin-embedded tissues and immunohistochemical staining failed to demonstrate light-chain deposition, and a pathological relationship between the plasma cell disorder and kidney lesion could not be established. Laser microdissection followed by liquid chromatography-tandem mass spectrometry identified κ light chain deposition, leading to a definitive diagnosis of light chain deposition disease and providing pathological evidence linking the plasma cell disorder to the kidney lesion. Plasma cell-directed therapy was subsequently initiated, resulting in improved kidney function and the avoidance of dialysis. This case highlights the potential utility of mass spectrometry for establishing a definitive diagnosis and guiding therapeutic decision-making when light-chain deposition cannot be demonstrated by conventional or additional immunostaining.