Type II Membranoproliferative



Franco Ferrario and Maria Pia Rastaldi

Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital
Milan, Italy



Dense deposit disease (DDD) was first reported in 1962 and is characterized by the presence of an extremely electron dense transformation of the glomerular basement membrane. In the early 1970s,  DDD was classified as subtype II of membranoproliferative glomerulonephritis (MPGN). Over the last thirty years, marked differences in etiology and pathogenesis between Type I MPGN and DDD have become apparent. Recent observations have shown that DDD can be seen with markedly different light microscopy appearances with apparently different prognostic significance.

Type II MPGN is characterized by a dense homogenous deposition along the glomerular basement membrane and in the mesangium. Deposits can be different, in dimension and diffusion, even among the glomeruli of a given biopsy. When deposition is mild, ultrastructural examination is fundamental for diagnosis.




The glomerular basement membrane is diffusely thickened by dense homogenous deposits, very evident at higher magnification.




The same dense deposits frequently involve the Bowman’s capsule.




The tubular basement membranes may contain the deposits as well.




Type II MPGN shows variable histological features. The most common form is similar to the classic form of Type I MPGN, with intense mesangial proliferation and mesangial matrix increase.




Also in Type II MPGN there are cases of focal and segmental membranoproliferative lesions.




In some cases only minimal lesions can be observed and differential diagnosis has to be made from minimal change disease, stage I MGN and some cases of IgA GN.




Although at higher magnification it is possible to recognize the segmental thickening of the capillary wall, an accurate diagnosis is only possible by electron microscopy examination.




Segmental extracapillary proliferation can be present.

Rare cases can show diffuse circumferential extracapillary proliferation. Type II MPGN diagnosis is difficult when the glomerular tuft is compressed by the extracapillary proliferation.




C3 immune deposits are intense along the glomerular basement membrane and in the mesangium. This peculiar immunohistological pattern has been variably described as linear, pseudolinear, ribbon-like, granular or nodular. The deposits are also found on the Bowman’s capsule and on some tubular basement membranes.




Electron microscopy is essential for diagnosis and shows the linear ribbon-like deposits in the glomerular basement membrane (x 1700).

Ribbon-like deposits alternate with short normal tracts of basement membrane. (x 3600 - x 3600).




Ribbon-like deposits can be of various thickness (x 6000 - x 6000).




The Bowman’s capsule and the tubular basement membrane show the same electrondense deposition. (x 3600)






1. Dense  Deposit Disease in Children: Prognostic Value of Clinical and Pathologic Indicators. A Report of the Southwest Pediatric Nephrology Study Group. Am J Kid Dis 6: 161-169, 1985.
2. Muda AO, Barsotti P, Marinozzi V: Ultrastructural histochemical investigations of „dense deposit disease“. Pathogenetic approach to a special type of mesangiocapillary glomerulonephritis. Virch Arch 413: 529-537, 1988.
3. Kashtan CE, Burke B, Burch G, et al: Dense intramembranous deposit disease: a clinical comparison of histological subtypes. Clin Nephrol 33: 1-6, 1990.
4. Joh K, Aizawa S, Matsuyama N, et al: Morphologic variations of dense deposit disease: Light and electron microscopic, immunohistochemical and clinical findings in 10 patients. Acta Pathol Japonica 43:552-565, 1993.
5. Mullins RF, Russell SR, Anderson DH et al : Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14:835-846, 2000.
6. Nakopoulou L: Membranoproliferative glomerulonephritis. Nephrol Dial Transplant 16S:71-73, 2001.
7. Hoschek JC, Dreyer P, Dahal S, et al: Rapidly progressive renal failure in childhood. Am J Kid Dis 40:1342-1347, 2002.
8. Sethi S, Sahani M, Som Oei L, et al: Crescentic glomerulonephritis and dense deposit disease in a woman with breast carcinoma on immunosuppressive chemotherapy. Am J Kid Dis 44:E33-E37, 2004.
9. Appel GB, Cook HT, Hageman G, et al: Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol 16:1392-1404, 2005.