CME on Renal Pathology, 17th December 08, Pune Indian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008 CASE- 1 Col N S Mani Prof & Head Dept of Pathology Armed Forces Medical College, Pune
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CME on Renal Pathology, 17th December 08, Pune Indian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology.
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CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
CASE- 1
Col N S ManiProf & Head
Dept of PathologyArmed Forces Medical College, Pune
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Case History17 yr old femaleClinical onset: 5 yr backPersistent nephrotic syndrome x 5 yrsPresently hematuria Clinical impression– Mesangioproliferative nephropathy– IgA Nephropathy
Urine: Active sediment with RBCs Raised creatinine/ BUNSerum Complement: C3 Mildly decreasedASO titre normal
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Light Microscopy: H&E
Varying patterns of glomerular morphologyLobular accentuation with endocapillary proliferationMesangial prominenceOccasional fibrous crescentObsolescent glomeruli (40%)
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Light Microscopy: H&E
Segmental proliferationGlobal membrane thickeningEndocapillary proliferation withSolidification of glomerular lobules
Focal interstitial fibrosis with tubular atrophyFoam cells in interstitium
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
PAS: Intense PAS positivity in glomeruli Positivity along GBM Refractile appearance Absence of inflammatory cells in glomeruli
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
PASM Thin outlining of GBM Splitting of GBM with central lucencies Focal mesangial sclerosis
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Masson Trichrome
Intense fuchsinophilia of glomeruliGBM shows refractile thickening
Focal interstitial sclerosis highlighted
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Direct Immunofluorescence
Strong granular positivity in glomeruli for C3 Positivity along GBM and in mesangial areas Negative for IgG, IgA, IgM
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Transmission Electron MicroscopyIntensely osmiophilic deposits along GBMVarying thickness and discontinuousContinuous in some glomeruliDeposits intramembranousNo substructure to depositsMesangium shows only few such depositsNo subepithelial humpy depositsAssociated foot process effacement of podocytesSegmental mesangial proliferation
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
Final Diagnosis
Type II Membranoproliferative glomerulonephritis
(Dense deposit disease)
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
DiscussionDefined in 1963- Berger and Galle5-33% of all MPGNM:F:: 1:1Children and young adultsC/F: – Acute nephritis (16-38%)/ renal insufficiency precede CRF– Microscopic & gross hematuria at presentation (11-57%)– Nephrotic syndrome common (12-65%)– Preceding URTI in 50% , ASO raised in 21-45%– Associations: Partial lipodystrophy, narcotics, acquired cutis
laxa, SLE, MGUS, after meningococcemia– Persistent activation of alternate complement pathway
C3 decreased in 80%, 20% fluctuatingC1q & C4 normal
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
DiscussionLM– Variety of picture seen– Normal glomeruli with capillary thickening (>MPGN I, <MGN)– DPGN Pattern (cellularity, endothelial swelling with
narrowing of capillary lumina)– Mesangial matrix increase>> sclerotic nodules like DN– Irregular intramembranous deposits- ribbon like, strongly
eosinophilic, refractile– Subepithelial GBM deposits like DPGN, Mesangial deposits– Crescents +/- – PAS: Intense PAS positive– MT: Strong fuchsinophilia– Toluidine blue: dark blue– PASM: splitting with deposits negative
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
DiscussionImmunofluorescence– Intense C3 along glomerular capillary walls and often mesangium– Patterns: Linear, pseudolinear, smooth, ribbon like, granular, nodular– C3:
Double linear appearance- railroad tracksMesangial rings in mesangial areas
– Immunoglobulins absent. Only in FSGS form and usually IgM
Electron Microscopy– Deposits in GBM, lamina of Bowman’s capsule, TBM (Prox>Distal),
mesangial– Deposits replace width of lamina densa or part of it– Fusiform thickening or irregular masses, often discontinuous– No substructure to deposits
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
DiscussionLong term prognosis poor >> ESRD in (1 ½ -10yrs)
Prognosis– Clinical
Nephrotic syndromeAbsence of clinical remissionsInitial decrease in renal functionGross hematuria
– Bx featuresMesangial depositsDegree of mesangial proliferationGlomerular sclerosisCrescentsIncreased glomerular lobulation/ Increased PMN in glomeruli
Pathogenesis– More likely to be transformation of Lamina densa of GBM than immune deposits– Highly osmiophilic- ?? High lipid content– Factor B & Properdin are low- alternate pathway of complement activation– ? Primary alteration of GBM > generates substances >> complement activation
CME on Renal Pathology, 17th December 08, PuneIndian Society of Renal and Transplantation Pathology in collaboration with Indian Society of Nephrology (ISN) -ISNCON 2008
ReferencesAppel G, Cook TH, Hageman G, et al. Membranoproliferative glomerulonephritis Type II (dense deposit disease). An Update. J Am Soc Nephrol 2005, 16; 1392.
Zhou XJ, Silva FG. Membranoproliferative glomerulonephritis In: Jennette JC, Olson JL, Schwartz MM, Silva FG, editors Heptinstall’s Pathology of the Kidney 6th ed. Vol 1 Philadelphia Lippincott Williams & Wilkins, 2007; 254-319.