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Pathologic classification of lupus glomerulonephritis The primary clinical purposes for pathologic classification system are to: Facilitate communication:

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Presentation on theme: "Pathologic classification of lupus glomerulonephritis The primary clinical purposes for pathologic classification system are to: Facilitate communication:"— Presentation transcript:

1 Pathologic classification of lupus glomerulonephritis The primary clinical purposes for pathologic classification system are to: Facilitate communication: Between pathologists Between pathologists and clilinicalans Between clinicians In understanding the literature Facilitate clinical management: Guiding treatment Suggesting prognosis Indicating an etiology or pathogenic mechanism

2 Baldwin’s morphologic classification of lupus nephritis  Mesangial lupus nephritis  Focal proliferative lupus nephritis  Diffuse proliferative lupus nephritis  Membranous lupus nephritis *Mesangial lupus nephritis was add in a 1977 publication (Am J Med 62:12-30, 1977) to the other three categories that were published in 1970 (Ann Intern Med 73:929, 1970)

3 Who classified lupus nephritis? “Original WHO Classification” Buffalo, NY, 1974; or Geneva, 1975 “Modified WHO Classification ” ISKDC, Paris, 1980 (Churg and Sobin, 1982) “Modified WHO Classification ” Jacob churg 1995

4 Sinniah and Feng, Clin, Nephrol. 6:340-51, 1976 (“preliminary histologic categories put forward by the WHO committee on Morphologic classification and Nomenclature or Renal diseases, Geneva, June, 1975 ”)  Minimal (“nil”) lesion (normal by light microscopy)  Minimal lesion with mesangial hypercellularity  Focal and segmental glomerulonephritis  Membranous glomerulonephritis  Diffuse proliferative glomerulonephritis  Diffuse membranoproliferative glomerulonephritis

5 Appel, Silva, Pirani, et al, Medicine 57: ,1978 (“according to a classification proposed by the WHO ”)  Class I. normal normal by LM, IM and IF  Class II. Messangial changes A.minimal alterations (normal by LM, mesangial deposits by IF and EM) B. mesangial glomerulitis (mesangial hypercellularity)  Class III. Focal and segmental proliferative glomerulonephritis (<50% glomeruli involved)  Class IV. Diffuse proliferative glomerulonephritis (<50% glomeruli involved)  Class V. membranous glomerulonephritis Pure Mixed patterns (such as Class III associated with Class V)

6 Jacob churg, 1982 (based on modifications at the ISKDC): “WHO morphologic classification of Lupus Nephritis”  I. normal a. Nil (by all techniques) b. normal by LM but deposits by EM or IF  II. Pure mesangial alterations (mesangiopathy) a. mesangial widening mild hypercellularty b. moderate hypercellularity  III. Focal segmental glomerulonephritis a. active necrotizing lesions b. active and sclerosing lesions c. sclerosing lesions  IV. Diffuse glomerulonephritis a. without segmental lesions b.c. and d. like a.b and c. above  V. diffuse membranous glomerulonephritis a. pure b. associated with category II c. associated with actegory III d. associated with category IV  VI. Advanced sclerosing glomerulonephritis

7 Jacob Churg 1995: WHO morphologic classification of Lupus nephritis (modified)  I. Normal a. nil( by all techniques) b. normal by LM but deposits by EM or IF  II Pure Mesangial Alteration (Mesangiopathy) a. mesanglal widening mild hypercellularity b. moderate hypercellularity  III Focal Segmental Glomerulonephritis a. active necrotizing lesion b. active and sclerosing lesions c. sclerosing lesions  IV. Diffuse Glomerulonephritis a. without segment lesions b. c. and d, like A, B, and C above  V. Diffuse Membranous Glomerulonephritis a. pure b. associted with category II  VI. Advanced Sclerosing Glomerulonephritis

8 Controversies in WHO classification (WHO I and II ) Majority approach  Class I: no lesion by LM, EM, IM  Class IIA. no lesion by LM, but mesangial deposits by IM and/or EM  IIB. mesangial hypercellularty Minority approach  IA. No lesion by LM, EM or IM  IB. no lesion by LM but mesangial deposits by EM and/or IM  IIA. mild mesangial hypercellularty  IIB. moderate mesangial hypercellularity

9 Controversies in WHO classication (WHO III and IV) Majority apporach Class III :focal GN affecting <50% of glomeruli Class IV: diffuse GN affeceting > 50% of glomeruli Class V: membranous GN A. no hypercellularity B. plus class II Mixed class III or IV plus V Minority approach Segmental GN affecting 50% of glomeruli Diffuse non-seegmental GN Affecting <50 % of glomeruli Membranous GN  A. no hypercellularity  B. plus class II  C. plus class III  D. plus class IV

10 Anyone WHO isn’t confused really doesn’t understand the situsion. Edward R. Murrow

11 Proposal of the international society of nephrology and renal pathological society working group on the classification of lupus glomerulonephritis “The major objective is to standardize definitions, emphasize clinically relevant lesions, and encourage uniform and reproducible reporting between centers.”

12 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary)  Class I. Minimal mesangial lupus glomerulonephritis (LGN)  Class II. Mesangial proliferative LGN  Class III. Focal LGN ( involving < 50 % of glomeruli)  Class IV.Diffuse LGN ( involving 50% or > glomeruli)  Class V. Membranous LGN  Class VI.Advanced sclerotic LGN ( >90 % sclerotic glomeruli ) *for classes III and IV, the diagnosis should include one of the following: with active lesions/with active and chronic lesions/Inactive with scars *for classes III and IV, the diagnosis should include the percentage of glomeruli with fibrinoid necrosis and/or cellular crescents when present *for class IV, the diagnosis should include one of the following: predominantly segmental (IV-S)/predominantly global (IV-G) *class V may occur in combination with III or IV in which case both will be diagnosed

13 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class I. Minimal mesangial lupus glomerulonephritis Normal glomeruli by LM but mnesangeial immune deposits by IF and/ or EM.

14 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class II. Mesangial proliferative LGN Purely mesangial hyhpercellularity of any degree or mesangial matrex expansion by LM with immune deposits, predominatly mesangial with none or few, isolated subepithelial and/or subendothelial deposits by IF and/or EM not visible by LM.

15 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class II. Mesangial proliferative lupus glomerulonephritis Purely mesangial hyhpercellularity of any degree or mesangial matrex expansion by LM with immune deposits, predominatly mesangial with none or few, isolated subepithelial and/or subendothelial deposits by IF and/or EM not visible by LM.

16 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class III. Focal lupus glomerulonephritis Active or inactive focal, segmental and /or global endo- and /or extracapiliary GN, typically with focal, subendothelial immune extracapillary GN, with or without focal or diffuse mesangial alterations. III (A)Active focal proliferative LGN III (A/C)Active and sclerotic focal proliferative LGN III (C)Inactive sclerotic focal LGN *Indicate the proportion of glomeruli with active and with sclerotic lesions *Indicate the proportion of glomeruli with fibrinoid necrosis and/or cellular crescents

17 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class IV. Diffuse segmental (IV-S) or global (IV-G) LGN Active or inactive diffuse (50% or more involved glomeruli), segmental or global endo- or extracapiliary GN with diffuse subendothelial immune deposits, with or without mesangial alterations. This class is divided into diffuse segmental (IV-S) when >50% of the involved glomeruli have segmental lesions, and diffuse global (IV-G) when >50% of the involved glomeruli have ealobal lesions. IV (A) Active diffuse segmental or global proliferative LGN IV (A/C) Diffuse segmental or global proliferative & sclerotic LGN IV (C) Diffuse segmental or global sclerotic LGN *Indicate the proportion of glomeruli with active and with sclerotic lesions *Indicate the proportion of glomeruli with fibrinoid necrosis and/or cresents

18 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class V. membranous LGN Numerous global or segmental subepithelial immune deposits or their morphologic sequelae by LM and/or IF and/or EM with or without mesangial alterations. May occur in combination with III or IV in which case both will be diagnosed

19 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary) Class VI. Advanced sclerotic lupus glomerulonephritis 90 % or > glomeruli globally sclerosed without residual activity

20 2002 ISN/RPS Consensus Conference on the Classification of Lupus Nephritis (preliminary)  Class IMinimal mesangial lupus glomerulonephritis (LGN)  Class IIMesangial proliferative LGN  Class IIIFocal LGN (Involving < 50% of glomeruli)  Class IV Diffuse LGN (Involving >= 50% gloeruli, IV-S and IV-G)  Class VMembranous LGN  Class VIAdvanced sclerotic LGN (> 90% sclerotic glomeruli)

21 References 1. Slnnlah R, Feng PH: Lupus nephritis: correlation between light, electron microscopic and immunofluorescent findings and renal function. Clinical Nephrol 6: , Appel GB, Silva FG, Pirani CL: Renal Involvement In systemic lupus erythematosus (SLE): a study of 56 patients emphasizing histologic classification. Medicine 75: , Churg J, Sobin LH: Renal disease: Classification and atlas of glomerular disease. Tokyo, Igaku-Shoin, Churg J, Bernstein J, Glassock RJ: Renal disease: classification and atlas of glomerular diseases, second edition. New York, Tokyo, Igaky-Shoin, Weening JJ, D’Agati VD, Schwartz M, Seshan SV, et al.: Classification of gloerulonephritis in systemic lupus erythematosus, in preparation, 2003


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