A case of masked LCDD: Undetectable light chain by routine IF using frozen samples, but revealed by IF on pronase-digested paraffin sections

Background: Light chain deposition disease (LCDD) is a relatively frequent renal disease associated with dysproteinemia including multiple myeloma. Although the light chain deposits can be widespread, the kidney is the most frequently involved organ, and LCDD of the kidney is defined by renal biopsy. The morphological features of LCDD can be recognized by light microscopy (LM); however, the diagnosis can be made certain only by immunofluorescence (IF) microscopy, staining for kappa (κ) and lambda (λ) light chains (LC), and by electron microscopy (EM). IF is essentially diagnostic and characterized by usually strong, diffuse, linear staining with either κ- or λ-LC, along glomerular (GBM) and tubular (TBM) basement membranes and vessel walls. EM typically shows powdery and granular continuous electron-dense deposits along GBM and TBM.

Case presentation: We present the case of a 67-year-old female had urinary abnormalities (nephrotic range proteinuria and microhematuria) and renal dysfunction with monoclonal IgG-κ in serum and κ-LC in urine samples, associated with multiple myeloma. Renal biopsy demonstrated membranoproliferative glomerulonephritis (MPGN)-like glomerulopathy with spicules-like features by LM. IF failed to demonstrate the presence of κ -LC, and immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) sections indicated only weak glomerular staining of κ -LC in the kidney. Congo red stain appeared weak salmon pink in glomeruli, but no apple green birefringence in polarized light microscopy. Congo red stain under fluorescence microscopy with TRITC filter appeared red with more readily apparent in glomeruli and vessels. We firstly considered renal AL amyloidosis based on the LM, IF, and IHC findings. Thereafter, we observed EM findings that showed powdery and granular continuous electron-dense deposits along the GBM and TBM, indicating MIDD. Therefore, we performed IF on pronase-digested FFPE sections, and showed diffuse and linear staining of κ-LC along GBM and TBM. In this case, κ-LC deposition in kidney was detectable by IF on pronase-digested FFPE sections but not by IF on frozen sections, indicating masked κ-LC deposition in the kidney, indicating masked LCDD.

Discussion: In renal pathology, the deposited immunoglobulin in glomeruli, such as monoclonal immunoglobulin, could not be detected by IF on frozen tissue. However, these immunoglobulins could be detected by pronase-treated FFPE tissue. These deposited immunoglobulins are known as masked immunoglobulins, and are often monoclonal immunoglobulins associated with hematological disorders. Renal diseases associated with masked immunoglobulins include 1) Diseases of crystal deposits: light chain crystal tubulopathy, crystalglobulinemic GN, 2) Disease with deposition of monoclonal immunoglobulins: cryoglobulinemic GN, proliferative GN with monoclonal IgG deposits, and 3) Others. In LCDD, monoclonal LC are confirmed in over 90% of cases by IF on frozen sections; however, the existence of IF-negative LCDD cases was also known. In such cases, performing IF on pronase-treated FFPE tissue to confirm masked LC can clarify the pathology in these cases.

Conclusions: In this case, masked LCDD could be diagnosed using EM and IF on pronase-digested FFPE sections. This case is telling us the importance of IF on pronase-digested FFPE sections for detecting not only masked immunoglobulin, but also masked LC, in cases of paraproteinemic nephropathy. In addition, IF on pronase-digested FFPE sections is more sensitive method to detection of masked LC deposits in masked LCDD than paraffin-immunohistochemistry.