The two most common variants of MPGN are type I MPGN (also called mesangiocapillary glomerulonephritis) and type II MPGN (also called dense deposit disease). Type I is much more common than type II, which is a rare disease.
The H&E stained section in slide 41 shows the characteristic histologic features of type I MPGN (and most cases of type II MPGN). There is thickening of capillary walls. This is usually global and diffuse but is occasionally at least focally and segmentally variable. There is also hypercellularity. Much of this hypercellularity is mesangial proliferation, and some of the capillary wall thickening is caused by mesangial interposition into the subendothelial zone of the capillary loops. This is the basis for the term mesangiocapillary glomerulonephritis.
Slide 42 shows the appearance of type I MPGN with PAS and trichrome stains. Typically, there is doubling or complex replication of the basement membrane. This is shown in this PAS- stained panel. This differs from the uniform narrow linear staining of normal glomerular basement membranes. A trichrome stain reveals thickening of capillary walls and mesangial matrix expansion, but it usually does not demonstrate the basement membranes well enough to see the replication. The higher magnification silver stain in slide 43 demonstrates the so-called railroad track or tram track appearance of the replicated basement membrane. The hypercellularity and capillary wall thickening may cause hypersegmentation. The old name for this category of glomerulonephritis was lobular glomerulonephritis because of this hypersegmentation. It is really not an increase in segmentation at all. The segmentation is always there. Normally, however, there is so much lucency from the capillary lumens that the segmentation is not apparent.
The sine qua non of type I MPGN is at the ultrastructural level and is the basis for the thickening in the capillary walls. Electron microscopy demonstrates the difference between type I and type II MPGN. The basis for the thickening in type I MPGN (mesangiocapillary glomerulonephritis) is circumferential interposition of mesangial cytoplasm into the peripheral capillary loop (slide 44), in response to subendothelial immune complex type electron dense deposits. New matrix material is laid down resulting in replication of basement membrane material. There is mesangial hypercellularity associated with mesangial dense deposits, and varying numbers of subepithelial dense deposits. When the deposits in the subepithelial zone are as numerous as in membranous glomerulopathy, the glomerulonephritis may be designated type III membranoproliferative glomerulonephritis or mixed membranous and proliferative glomerulonephritis (although the term type III MPGN also has been used for another patterns of glomerular injury characterized by irregular electron-lucent thickening of glomerular basement membranes). The electron micrograph in slide 45 illustrates features of type I MPGN. Moving from urinary space to capillary limen there is the urinary space, effaced foot processes, the lamina lucida externa, lamina densa, the subendothelial electron dense deposits which are lying adjacent to the little fingers of mesangial cytoplasm that have extended into the subendothelial zone, new basement membrane material, and endothelial cell with pores. Most of the time, however, the ultrastructure looks like slide 46 with a very confused appearance. This electron micrograph shows the urinary space, the effaced foot processes, the original basement membrane, and conspicuous subendothelial deposits.
Immunofluorescence microscopy (slide 47) typically demonstrates peripheral granular or band-like staining that may outline the hypersegmentation. In many patients with type I MPGN, C3 will be the most conspicuous component in the deposits, especially in the idiopathic childhood variant. Patients with MPGN often have hypocomplementemia and a circulating autoantibody called C3 nephritic factor, which binds to the C3 convertase of the alternative pathway. Type I MPGN may be secondary to an identifiable process, for example, a neoplasm or infection. Hepatitis C infection is a common cause for type I membranoproliferative glomerulonephritis, especially if it is accompanied by mixed cryoglobulinemia. When mixed cryoglobulinemia is present, sometimes as shown in slide 48, there will be globular accumulations of cryoglobulin in the capillary lumens. These can be seen by light microscopy as hyaline thrombi.
Sometimes, when the immune complexes are derived from cryoglobulins, there will be tubular arrays in the deposits that have about a 30-40 nanometer diameter. When these immunotactoids are present in the absence of cryoglobulinemia, the appropriate diagnostic term is immunotactoid glomerulopathy (slide 49). This is an uncommon disease that is sometimes accompanied by a B-cell neoplasms. Immunotactoid glomerulopathy should not be confused with the more common disease called fibrillary glomerulonephritis, which is characterized ultrastructurally by approximately 20 nm diameter fibrils (slide 50).