Lignt chain-associated acute tubulointerstitial nephritis

Clinical presentation  of kidney involvement in plasma cell dyscrasia (PCD) are variable. Patients may present with nephrotic syndrome due to AL amyloidosis or acute kidney injury due to light chain cast nephropathy (LCN). Similarly, histopathology may show severe kidney injury as in LCN or subtle change as in light chain proximal tubulopathy. Cheung et al. reported a poorly recognized kidney involvement in PCD called light chain-associated acute tubulointerstitial nephritis (LC-ATIN). The entity is characterized by tubulointerstitial inflammatory cell infiltrate by LM, linear tubular basement membrane and granular cytoplasmic proximal tubular staining by kappa or lambda light chain by IF and atypical lysosomes in proximal tubular cells with focal granular punctate depostis in TBM by EM.

LM finding is indisguishable from acute tubulointerstitial nephritis due to drug hypersensivity. The detection of monoclonal light chain staining in linear pattern along TBM and granular cytoplasmic in proximal tubules is crucial for diagnosis. The deposition of punctate electron dense deposits along TBM seems to be at least focally, as immunogold EM labeling demonstrated the presence of monoclonal light chain in TBM without deposits. The TBM linear light chain staining and punctate deposits also characterize light chain deposition disease, but LCDD lacks significant tubulointerstitial infiltrate and usually presents with glomerular and/or vascular involvement. It is arguable that LC-ATIN may be an early stage of LCDD.

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A increased and atypical lysosomes in proximal tubular cells, B punctate deposits along TBM similar to LCDD, C-D immunogold labeling demonstrates monoclonal light chain in lysosomes and TBM (Image from Cheung et al.)

Cheng M, Gu X, Turbat-Herrera EA, Herrera GA. Tubular Injury and Dendritic Cell Activation Are Integral Components of Light Chain-Associated Acute Tubulointerstitial Nephritis. Arch Pathol Lab Med. 2019;143(10):1212-1224. doi:10.5858/arpa.2018-0032-OA

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits, light chain variant

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) is a type of monoclonal immunoglobulin deposition disease characterized by glomerular injury with membranoproliferative pattern and deposition of monoclonal IgG (usually IgG3). Nasr et al. described a case series of PGNMID with light chain deposition only. 

Unlike PGNMID-IgG, the light chain variant (PGNMID-LC) showed only monoclonal light chain deposits. All 17 patients had either underlying monoclonal gammopathy of renal significance (MGRS) or multiple myeloma. This was in contrast to PGNMID-IgG in which more than two-thirds of patients did not have MGRS or B/plasma cell neoplasm. All 6 patients who had anti-plasma cell therapy with complete hematologic response had renal response.

Although PGNMIC-LC is considered a variant of PGNMID-IgG, its hematological underlying is more like light chain deposition disease (LCDD). 

PGNMID-LC show large subendothelial deposits by LM resembling wire loop in lupus nephritis.
PGNMID-IgG usually has small subendothelial deposits best demonstrated by EM (Image from Nasr et al.)

Nasr SH, Larsen CP, Sirac C, et al. Light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits is associated with a high detection rate of the pathogenic plasma cell clone. Kidney Int. 2020;97(3):589‐601. doi:10.1016/j.kint.2019.10.025

Intralysosomal monoclonal immunoglobulin accumulation in a patient with multiple myeloma

Common renal involvements in patients with multiple myeloma are light chain cast nephropathy and AL amyloidosis. These entities usually show characteristic renal pathology by light microscopy. Rare patients show subtle renal histopathology which requires careful examination and high degree of suspicious from pathologists.

A myeloma patient showed mild proteinuria without renal impairment. By LM only subtle eosinophilic granules were detected in some endothelial cells of some glomeruli. Monoclonality was confirmed by IF to be IgG2/lambda. EM revealed accumulation of monoclonal immunoglobulin in lysosomes mainly in glomerular endothelial cells.

doi.org/10.1016/j.ekir.2019.09.012