Characteristic electron-microscopic features of cryofibrinogen-associated glomerulonephritis: a case report.

BACKGROUND: Cryofibrinogenemia is a rare disorder that mainly affects the skin and occasionally the kidney. However, there are few published reports of cryofibrinogenemia-associated renal pathology. We therefore report a patient with cryofibrinogen-associated glomerulonephritis. Samples from this patient were examined by electron microscopy, laser microdissection, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE PRESENTATION: A 78-year-old Japanese man presented with declining renal function, proteinuria, and gross hematuria. Kidney biopsy showed a membranoproliferative pattern with crescent formation and dominant C3c deposition in which subendothelial deposits with uniquely organized electron-microscopic features were observed. Additional ultrastructural analysis of cryoprecipitates extracted from plasma revealed similar structures of the glomerular subendothelial deposits. LC-MS/MS identified an increase in fibrinogen α, ß, and γ chains, fibronectin, filamin-A, and C3. The glomerular lesions were diagnosed as cryofibrinogen-associated glomerulonephritis on the basis of these findings. CONCLUSIONS: Although there are few reports of cryofibrinogen-associated glomerulonephritis, we believe that accurate diagnosis can be achieved by performing LC-MS/MS and ultrastructural analysis.

Organized deposits in the kidney and look-alikes.

Organized or structured deposits are encountered during electron microscopic examination of kidney tissue in a wide variety of primary renal and multisystemic disorders. They are most commonly seen in the renal glomerulus, though extraglomerular sites are occasionally involved. In some cases, organized deposits herald the presence of a specific disease process. Included in this category are organized substances containing immunoglobulin molecules or parts thereof as well as non-immunoglobulin-containing materials that accumulate in several rare heritable disorders. A second broad category of structured deposits includes substances that accumulate in response to nonspecific tissue injuries. In many instances, such "look-alikes" can be difficult to distinguish from disease-specific structured deposits. Ultrastructural pathology is central to the detection and characterization of organized deposits in the kidney and is the primary focus of this paper. Correlative light microscopic studies are often useful, however, and will be described as well.

Ultrastructural 'fingerprint' in cryoprecipitates and glomerular deposits: a clinicopathologic analysis of fingerprint deposits.

Organized glomerular electron-dense deposits with a fingerprint pattern are well known in some patients of lupus nephritis or cryoglobulinemia. In general, these two diseases are always discussed separately as the causes of such deposits. However, 3 of our 5 lupus patients with glomerular fingerprint deposits also had cryoglobulinemia. One of the remaining 2 patients died and the other was lost to follow-up. The purpose of our study was to seek an appropriate clinicopathologic assessment of fingerprint deposits. All these patients showed overt proteinuria, active urinary sediment, a high degree of activity of lupus nephritis, and diffuse proliferative glomerulonephritis (WHO class IV). Their cryoprecipitates and renal biopsy specimens were investigated by means of immunochemistry, immunofluorescence and electron microscopy. The ultrastructural 'fingerprint' structures were exactly the same in the cryoprecipitates and in the glomerular deposits in 2 of 3 lupus patients with cryoglobulinemia, as were IgG, IgM and IgA. Therefore, these observations furnish emerging morphologic evidence for the glomerular deposition of immune complexes of circulating cryoglobulins in lupus nephritis. In addition, electron microscopic fingerprint deposits on renal biopsy or cryoprecipitate can be regarded as a very sensible marker of concomitant or subsequent development of diffuse lupus nephritis. If the patient is accompanied by nephritic syndrome, an early trial of immunosuppressive therapy may be warranted.

Cytoplasmic inclusions in leukocytes. An unusual manifestation of cryoglobulinemia.

Cryoglobulins are circulating immunoglobulins characterized by reversible, cold-induced precipitation. A variety of laboratory abnormalities, including hypocomplementemia, elevated erythrocyte sedimentation rate, rheumatoid factor activity, pseudoleukocytosis, and pseudothrombocytosis, are associated with cryoglobulinemia. Extracellular, faintly basophilic, amorphous deposits of cryoglobulins occasionally have been described in blood smears. In the present study, smears prepared from blood collected at room temperature from 6 patients with cryoglobulinemia exhibited neutrophil and, occasionally, monocyte inclusions containing clear, light pink, or faintly basophilic amorphous material. The inclusions were absent in smears from blood collected and maintained at 37 degrees C. Ultrastructural examination revealed that the material within the leukocyte inclusions was consistent with phagocytosed immunoglobulins. The identification of characteristic cytoplasmic inclusions in leukocytes may be an important clue in the early recognition of cryoglobulinemia.

Cryocrystalglobulinemia mimicking rheumatoid arthritis and vasculitis.

We describe a patient with longstanding arthropathy resembling rheumatoid arthritis (RA) and cold induced purpura for many years, concomitant with IgG kappa paraproteinemia. At autopsy, the patient was found to have evidence of widespread vascular occlusions due to precipitated crystals as well as tissue deposition of crystals. Neither vasculitis nor synovitis was observed despite the clinical picture of both. Blood and synovial fluid obtained antemortem were found to spontaneously form crystals when stored at 4 degrees C, and the washed crystals were composed of the same monoclonal IgG kappa previously found in serum. Cryocrystal formation occurred at 33 degrees C and neutral pH. This patient thus had cryocrystalglobulinemia mimicking clinical manifestations of RA and vasculitis.

Immunoelectron identification of endoneurial IgM deposits in four patients with Waldenström's macroglobulinemia: a specific ultrastructural pattern related to the presence of cryoglobulin in one case.

In four patients with Waldenström's macroglobulinemia and peripheral neuropathy, direct immunofluorescence on a peripheral nerve biopsy revealed the presence of IgM deposits in the endoneurium. At ultrastructural examination, these endoneurial deposits were granulo-fibrillar in three cases, and tubular in the fourth, in whom a cryoglobulin was evidenced in the serum. In each case the endoneurial deposits were also identified as IgM by post-embedding immunoelectron microscopy with good preservation of the characteristic ultrastructural details.