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Challenges in the recognition and diagnosis of renal diseases with organized deposits

Electron microscopy is essential for the recognition and categorisation of organized deposits in the renal parenchyma. By electron microscopy, various types of fibrillar, microtubular or vaguely structured deposits may be found. Although some of these appearances are pathognomonic for a particular disease, most of them require additional correlation with immunoflouorescence (IF) and light microscopic (LM) findings. Non-branching fibrillary deposits are most commonly seen in amyloidosis (Fig. 1 and 2), a group of different diseases, all characterised by abnormal deposition of certain proteins in various organs. Other diseases associated with fibrillary deposits are fibrillary glomerulonephritis (FGN)(Fig.3 and 4) and diabetic fibrillosis. Fibril size sometimes may overlap in these conditions, so additional methods are necessary for separating various types of amyloid from fibrillary structures in FGN and diabetes. All types of amyloid fibrils stain positive with Congo red/Thioflavin. Further distinction between types of amyloid is based on results of IF (kappa or lambda light chain in AL amyloidosis) and immunohistochemical (AA amyloid, transthyretin) stains. Distinguishing FGN from amyloidosis is based on negative Congo red/Thioflavin stains and the demonstration of slightly thicker fibril diameter in FGN (generally 9-11 nm for amyloid and 12-30 for FGN). By IF, FGN shows smudgy to ribbon- like positivity for IgG, C3 and both light chains. Fibrillary deposits in diabetic fibrillosis may be difficult to separate from fibrils in amyloidosis or FGN, however, clinicopathologic data along with LM (PAS positive/Congo red negative) and IF (negative or weak linear IgG and albumin) results are helpful to rule out other conditions. Immunotactoid glomerulopathy (ITG) is most commonly associated with underlying hematological malignancies. The typical microtubular structures may be variable in diameter (10-90 nm) and may assume different arrangements (Fig. 5 and 6). Cryoglobulinemic glomerulonephritis, commonly associated with autoimmune diseases, hepatitis C infection and some paraprotein-related diseases, may have similar, highly organized microtubular (usually 20-30 nm) or christaline structures. Both ITG and cryoglobulinemic glomerulonephritis have PAS positive/Congo red negative deposits on LM and show IF positivity. IgM dominance is more common in cryoglobulinemic glomerulonephritis, while ITG more common shows clonal IgG. A fingerprint type of organization, different whorl-like and tubulary structures (Fig. 9, 10) may be seen in deposits in patients with lupus nephritis. Characteristic clinical presentation and IF (positive IgG, IgA, IgM, C3, C1q, kappa and lambda light chains) and proliferative glomerular lesions on LM are helpful to assure the right diagnosis. Focal substructure may also be found in diseases without immune deposits, such as fibronectin glomerulopathy, collagen III glomerulopathy and Fabry disease. Distinction from other diseases with organized deposits is based on clinicopathological correlation and results of additional IF, IHC and molecular studies. In conclusion, electron microscopy is necessary for diagnosis of specific types of deposits with unusual organisation. Integration of all findings will allow correct specific diagnosis and assure appropriate treatment for the patients.

Renal diseases; organized deposits; electron microscopy

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