IAP Athens 2008

date from - to Sunday 12 October 2008 − Friday 17 October 2008
type & language Global meeting − Spoken language: English
location Megaron Athens International Conference Centre, Athens, Greece
organizer International Academy of Pathology
website http://www.iap2008.com
announced by Prof. Dr. Michael J. Mihatsch
last updated at 2009-03-06 20:30:31

Lectures for category «Native Kidney Pathology - Glomerular diseases»

title
Cryoglobulins and the kidney
author

Cryoglobulins and the Kidney
M.J. Mihatsch, H. Hopfer and F.Gudat

Institute for Pathology, University Hospital Basel
Basel, Switzerland Schönbeinstrasse 40

Cryoglobulins are immunoglobulins which reversibly precipitate between 4 and 20°C. They can form thrombi in all organs and may cause inflammation. Clinically the most prominent lesions are found in the skin and the kidneys.
Cryoglobulins are classified according to their composition into three types:
Type I: consisting only of monoclonal IgM (kappa) or IgG (kappa). They are found in hematolymphoid neoplasms e.g. myeloma, M. Waldenström, B-cell lymphomas.
TypeII (mixed cryoglobulins): consist of a monoclonal immunoglobulin (IgM kappa) with antibody activity against the polyclonal IgG (rheumatoid factor activity). This type is mostly associated with hepatitis C, rarely with other viral diseases.
Type III: consist of two polyclonal immunoglobulins (IgM-IgG; IgG-IgG). They are mainly found in SLE, other autoimmune diseases or infections.
In the following, we will mainly focus on the most important and most common form of glomerulonephritis in mixed IgG-IgM cryoglobulinemia (type II).
The most common clinical manifestation is that of systemic vasculitis with palpable purpura (leukocytoclastic vasculitis), arthalgia, Renaud phenomenon, fever, hepato- and more rarely splenomegaly, hypocomplementemia and, years later, glomerulonephritis. The symptoms of renal disease are uncharacteristic and highly variable: nephrosis, nephritis, isolated proteinuria or hematuria or proteinuria and hematuria. Hypertension is common. The clinical course is characterized by exacerbations and remissions.
Glomerulonephritis in mixed (type II) cryoglobulinemia is one of the most fascinating forms of glomerulonephritis, since the dynamics of the glomerular lesion and the capacity of the glomeruli to remodel may be studied in repeat biopsies. The disease is most common in adult women.
The basic pattern of GN is membranoproliferative GN (type I). The evolution may be arbitrarily divided into three different stages of development.
Stage A: Hyaline thrombi obstructing the glomerular capillary loops, or large subendothelial deposits cover the peripheral basement membranes in a wallpaper-like pattern. In addition, large monocytes with hyaline inclusions are present. The hyaline thrombi differ from fibrin thrombi in that the underlying endothelium is preserved.
Stage B: Large subendothelial deposits, monocytes and many polymorphnuclear leukocytes are accompanied by prominent mesangial proliferation and basement membrane doubling with mesangial interposition in some peripheral loops.
Stage C: The classical picture of membranoproliferative GN (type I) with global basement membrane doubling with mesangial interposition, variable mesangial proliferation and mesangial matrix increase is present.
In later stages, depending on the evolution, either glomerular obsolescence or remodelling of the glomerulus with regression of glomerular lesions may be present. In case of regression, light microscopy may suggest the diagnosis of mesangioproliferative GN or, in extreme cases, minor glomerular abnormalities. In these cases, electron microscopy still reveals remnants of former basement membrane lesions i.e. membranoproliferative glomerulonephritis. Crescents are rare and if present involve only a minority of the glomeruli. Tubulo-interstitial inflammation is usually slight and vasculitis rare. The disease may recur in transplants.
Electron microscopy exhibits in unselected material large subendothelial deposits in 95%, hyaline thrombi in 70%, subepithelial deposits in 40%, intramembraneous deposits in 30% and deposits along the mesangial basement membrane in less than 10% of the cases.
The common diagnostic feature of all deposits is its crystalloid/paracrystalline substructure: Curvilinear (in cross sections annular) tubules with a diameter of about 30 (10 – 100) nm. This substructure may be found in deposits at all sites, including the vessels of the skin and in cryoprecipitates in vitro. The substructure is usually difficult to identify in the center of deposits but is better visualised in the periphery, especially in deposits surrounded by a translucent rim.
Immunohistochemistry is, in contrast to electron microscopy, not of diagnostic value. The immunoglobulin and complement deposits are variable,most frequent are IgM, kappa, and IgG followed by C3. Other immunoglobulins and complement factors are usually limited and rare. Thrombi may consist of IgG and IgM, or of IgM only.
A still unexplained problem is the development and the functional significance of hyaline thrombi in glomerular capillary loops. It is unlikely that the thrombi occlude the glomerular loops in a way similar to fibrin thrombi, more likely they are the result of sluggish blood flow or highly concentrated cryglobulin-complexes containing plasma. It may be assumed that these thrombi do not cause permanent obstruction of glomerular loops nor trigger the development of glomerulonephritis. Even the possibility that the hyaline cryoglobulin thrombi arise during tissue processing due to cooling and fixation should be considered.

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LCAT Disaese
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Lectures for category «Native Kidney Pathology - Tubulo-interstitial diseases»

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Pathology of Fabry disease and iatrogenic chloroquine-induced lipidosis mimicking Fabry disease
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Lectures for category «Transplant Pathology - Others»

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Vascular changes in donor kidneys may have an impact on late graft dysfunction
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Viral renal allograft infections: diagnostic clues and pitfalls
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Plasma cell infiltrates in polyoma virus associated nephropathy (Poster)
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Lectures for category «Transplant Pathology - Rejection related topics»

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Humoral rejection: What the pathologist should know
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Multilayering of peritubular capillary basement membranes: Is it diagnostic for chronic allograft rejection?
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immunophenotype of inflammatory cells in renal allograft biopsies with acute cellular rejection
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