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Case 158
Diagnosis
 
     
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Diagnosis: Dense Deposist Disease

In this case the diagnosis is confirmed for the presence of deposits along tubular basement membranes, the strong PAS positivity of ribbon like capillary walls in glomeruli, negativity of this ribbon like deposits for metenamine-silver stain, the immunostaining for C3 alone, without Igs, the presence of "mesangial rings" on immunofluorescence, and the very dark dense deposits in the lamina densa of the glomerular basement membranes evidenced on EM.

DDD is a rare lesion, so named because of the appearance on electron microscopy of extremely dark, ribbon-like, electron-dense material in the central layer (lamina densa) of the glomerular basement membrane. Deposits also may occur in the mesangium, Bowman’s capsule, and tubular basement membrane. DDD has variable morphology on light microscopy, with a membranoproliferative appearance being most common. Other patterns, including endocapillary proliferative and crescentic, are described in both native disease and post-transplant recurrence. DDD is therefore a more accurate name for this lesion than type 2 membranoproliferative glomerulonephritis. Immunofluorescence typically shows intense glomerular C3 staining with little or no immunoglobulin. In a 2007 French series of 19 patients, Servais et al (Servais A, et al. J Med Genet. 2007;44:193-199 [PubMed link]) introduced the term C3 glomerulonephritis (C3GN) to describe isolated glomerular C3 without intramembranous deposits. Accordingly, the term C3 glomerulopathy was proposed for all glomerular lesions, including DDD, that are characterized by predominant C3 accumulation within the glomerulus using IF (Barbour TD, et al. Dense deposit disease and C3 glomerulopathy. Semin Nephrol. 2013;33(6):493-507 [PubMed link]).

DDD is defined by the intramembranous location of these deposits, their intensely osmiophilic appearance forming ribbons, and the associated transformation of the GBM. Confirmation of DDD requires EM, although the diagnosis can be suspected with a high degree of confidence if the typical LM and IF features are present. The distinction between DDD and C3GN is sometimes difficult even using EM, with debates about the extent of intramembranous deposits required for EM diagnosis of DDD. Furthermore, because the ribbons of DDD typically are discontinuous and may be more prominent in some capillary loops than others, they may be missed as a result of biopsy sampling error, leading to a diagnosis of C3GN (Barbour TD, et al. Dense deposit disease and C3 glomerulopathy. Semin Nephrol. 2013;33(6):493-507 [PubMed link]).

See the chapter: Membranoproliferative Glomerulonephritis and Dense Deposit Disease of our Tutorial.

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References

  • Bomback AS, Santoriello D, Avasare RS, Regunathan-Shenk R, Canetta PA, Ahn W, Radhakrishnan J, Marasa M, Rosenstiel PE, Herlitz LC, Markowitz GS, D'Agati VD, Appel GB. C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy. Kidney Int. 2018;93(4):977-985. [PubMed link]
  • Figuères ML, Frémeaux-Bacchi V, Rabant M, Galmiche L, Marinozzi MC, Grünfeld JP, Noël LH, Servais A. Heterogeneous histologic and clinical evolution in 3 cases of dense deposit disease with long-term follow-up. Hum Pathol. 2014;45(11):2326-33. [PubMed link]
  • Barbour TD, Pickering MC, Terence Cook H. Dense deposit disease and C3 glomerulopathy. Semin Nephrol. 2013;33(6):493-507 [PubMed link].
  • Seif EI, Ibrahim EA, Elhefnawy NG, Salman MI. Dense deposit disease: a 29-years electron microscopy experience. Arab J Nephrol Transplant. 2013;6(3):153-60. [PubMed link]
  • Servais A, Frémeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B, Grünfeld JP, Lesavre P, Noël LH, Fakhouri F. Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. J Med Genet. 2007;44(3):193-9. [PubMed link]

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