Pathological diagnosis and differential considerations of renal diseases with organized deposits under an electron microscope: key points in diagnosis.

Abstract

Electron microscopy is crucial for detecting ultrastructural changes that are undetectable by conventional histology. A key application is the identification of organized electron-dense deposits with distinct morphologies, such as fibrillar, microtubular, lamellar, or crystalline forms. These structures, occasionally observed in renal biopsy specimens, provide important diagnostic clues and are often associated with monoclonal immunoglobulin-related or matrix-derived materials. Renal diseases with organized deposits encompass a broad and heterogeneous spectrum of conditions, including amyloidosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, cryoglobulinemic glomerulonephritis, crystalline nephropathies, and hereditary matrix-associated conditions. The clinical importance of detecting these deposits is highlighted by the emergence of monoclonal gammopathy of renal significance, even in patients with a low clonal burden. Careful differentiation from mimickers, such as non-specific matrix changes, fibrin tactoids, spheroids, and artifacts, is essential to avoid misdiagnosis. Diagnostic precision requires a multidisciplinary approach incorporating light microscopy, immunofluorescence, special stains such as Congo red, and advanced molecular tools, including mass spectrometry. The discovery of disease-specific markers, such as the DnaJ Heat Shock Protein Family Member B9, has greatly improved the diagnostic accuracy of fibrillary glomerulonephritis. Identifying organized deposits can prompt additional clinical evaluations, including hematologic workups, and help guide management. In conclusion, organized deposits provide key diagnostic insights and reflect a diverse spectrum of underlying pathologies. Owing to their structural complexity, careful ultrastructural assessments are essential for accurate diagnosis. Advances in proteomic and genomic methods will refine disease classification and support the development of targeted therapies. Continued interdisciplinary collaboration is crucial for optimizing care for complex renal disorders.