Published online Jun 16, 2024. doi: 10.12998/wjcc.v12.i17.3200
Revised: March 15, 2024
Accepted: April 23, 2024
Published online: June 16, 2024
Processing time: 118 Days and 16.2 Hours
Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities. Renal amyloid heavy and light chain (AHL) is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin (Ig) heavy chain and a single light chain, further supported by mass spectrometry (MS) and serum studies for monoclonal protein. But polyclonal light chain staining can pose a challenge.
Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma (IgG) staining pattern by immunofluorescence. The patient is a 62-year-old Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria. Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence, ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm. Congo red was positive while DNAJB9 was negative. MS suggested a diagnosis of amyloid AHL type with IgG and lambda, but kappa light chains were also present supporting the immunofluorescence staining results. Serum immunofixation studies demonstrated IgG lambda monoclonal spike. The patient was started on chemotherapy. The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.
Tissue diagnosis of AHL amyloid can be tricky. Thorough confirmation using other available diagnostic techniques is recommended in such cases.
Core Tip: Amyloidosis and fibrillary glomerulonephritis are the two most commonly encountered glomerulopathies with fibrillary deposits. Accurate diagnosis and differentiation between these two entities are important for patient management. Furthermore, accurate subtyping is also required for amyloidosis cases to further guide treatment. This case report highlights an uncommon diagnostic pitfall that a nephropathologist may encounter while distinguishing light and heavy chain amyloid from fibrillary glomerulopathy. The possible underlying mechanisms are discussed, and we reiterate the importance of a clinical-pathological correlation and the use of multiple available diagnostic modalities if needed, particularly for these overlapping diagnostic entities.