Quantitative Components of Banff Classification of Renal Allograft Pathology (Banff Lesion Grading System)

2019.09.01 開始 2023.02.06更新

Specimen Adequacy (a necessary prerequisite for numeric coding) [Banff '97]
Unsatisfactory
    Less than 7 glomeruli & no arteries
Marginal
    7 glomeruli with one artery
Adequate
    10 or more glomeruli with at least two arteries

Minimum Sampling
    7 slides
    3 H&E, 3 PAS or silver stains, and 1 trichrome, section thickness 3-4 microns.

Examples of kidney allograft biopsy report
Example1
Kidney, status post transplantation, needle biopsy:
- No remarkable findings (Category 1).
  Banff 2019 scores:
   Acute scores: i0, t0, v0, g0, ptc0, C4d0
   Chronic scores: ci0, ct0, cv0, cg0
   Acute & chronic scores: ti0, i-IFTA0, t-IFTA0
   Other scores: ah0, aah0, mm0
Example 2
Kidney, status post transplantation (3 months), needle biopsy:
- Active antibody-mediated rejection (Category 2).
  Banff 2019 scores:
   Acute scores: i1, t0, v0, g0, ptc3, C4d1
   Chronic scores: ci1, ct1, cv0, cg0, ptcmlNA
   Acute & chronic scores: ti2, i-IFTA1, t-IFTA1, pvl0
   Other scores: ah0, aah0, mm0




Quantitative Criteria for Inflammation ("i") in non-scarred areas of cortex* [Transplantation 2018; 102: 1795-1814] 瘢痕のない部分の炎症
 TCMR に関連する所見。
i0: No inlammation or  in  <10% of non-scarred cortex
i1: Inflammation in 10 to 25% of non-scarred cortex
i2: Inflammation in 26 to 50% of non-scarred cortex
i3: Inflammation in >50% of non-scarred cortex
*An asterisk indicates presence of remarkable numbers (>10% of total cells) of
eosinophils, polys, or plasma cells (specify which) with an asterisk on i (eg, i1*)

Quantitative Criteria for Tubulitis ("t" score) 瘢痕でない皮質での尿細管炎
 TCMR に関連する所見
t0: No mononuclear cells in tubules
t1: Mild- Foci with 1 to 4 cells/tubular cross section or 10 tubular cells
t2: Moerate- Foci with 5 to 10 cells/tubular cross section
t3: Severe- Foci with >10 cells/tubular cross section, or the presence of at least two areas of tubular basement membrane destruction accompanied by i2/i3 inflammation and t2 tubulitis elsewhere in the biopsy.

Quantitative Criteria for Endarteritis (intimal arteritis) ("v") 内膜動脈炎
 ATMR と TCMR に共通して関連する所見。
v0: No arteritis
v1: Mild-to-moderate intimal arteritis in at least one arterial cross section
v2: Severe intimal arteritis with at least 25% luminal area lost in at least one arterial cross section
v3: Arterial fibrinoid change and/or transmural arteritis with medial smooth muscle necrosis with lymphocytic inflammation

Quantitative Criteria for Glomerulitis ("g") 糸球体炎
 ABMR に関連する所見。1個の糸球体に5個以上の炎症細胞浸潤があれば糸球体炎とする報告がある (Batal I. Am J Transplant 2010)。また,どこかで内皮腫大を伴う係蹄内腔の閉塞を示す。
g0: No glomerulitis
g1: Glomerulitis in <25% of glomeruli
g2: Segmental or global glomerulitis in about 25 to 75% of glomeruli
g3: Glomerulitis (mostly global) in >75% glomeruli

Quantitative Criteria for Peritubular Capillaritis ("ptc")* [AJT 2008; 8: 753-60]傍尿細管毛細血管炎
 ABMR に関連する所見。
ptc0    No significant cortical ptc, or <10% of PTCs with inflammation
ptc1    ≥10% of cortical peritubular capillaries with capillaritis, with max 3 to 4 luminal inflammatory cells
ptc2    ≥10% of cortical peritubular capillaries with capillaritis, with max 5 to 10 luminal inflammatory cells
ptc3    ≥10% of cortical peritubular capillaries with capillaritis, with max >10 luminal inflammatory cells

*It is recommended that one comment on the composition (mononuclear cells vs. neutrophils) and extent (focal, < or 50% vs. diffuse, >50%) of peritubular capillaritis.

Quantitative Criteria for total inflammation ("ti") (total = scarred and unscarred)[Banff 2015] 瘢痕と非瘢痕部の全体での炎症
 主に慢性 TCMR に関連する所見。下記の i-IFTA と合わせて判断する。
ti0: No or trivial interstitial inflammation (<10% of total cortical parenchyma)
ti1: 10 to 25% of total cortical parenchyma inflamed
ti2: 26 to 50% of total cortical parenchyma inflamed
ti3: >50% of total cortial parenchyma inflamed

Quantitative criteria for inflammation in area of interstitial fibrosis and tubular atrophy: i‐IFTA score [Banff 2015] 線維 化と尿細管萎縮のある領域における炎症
 主に慢性 TCMR に関連する所見。
i‐IFTA0: No inflammation or <10% of scarred cortical parenchyma
i‐IFTA1: Inflammation in 10–25% of scarred cortical parenchyma
i‐IFTA2: Inflammation in 26–50% of scarred cortical parenchyma
i‐IFTA3: Inflammation in >50% of scarred cortical parenchyma

Tubulitis in tubules within scarred cortex: t-IFTA score [Banff 2019] 瘢痕部での尿細管炎
 主に慢性 TCMR に関連する所見。
t-IFTA0:  none
t-IFTA1: mild, 1-4 mononuclear leukocytes per tubular cross-section or 10 tubular epithelial cells in most severely involved tubule
t-IFTA2: moderate, 5-10 mononuclear leukocytes
t-IFTA3: severe, >10 mononuclear leukocytes

Scoring of C4d staining ("C4d") [Banff 2015]
 ABMR に関連する所見。蛍光抗体法と酵素抗体法で閾値が異なる。
C4d0: No staining of PTCs (0%)
C4d1: Minimal C4d staining (>0 but <10% of PTCs)
C4d2: Focal C4d staining (10-50% of PTCs)
C4d3: Diffuse C4d staining (>50% of PTCs)

Quantitative Criteria for Allograft Glomerulopathy ("cg")[Banff 2015] 基底膜の二重化
 
慢性 ABMR に関連する所見。新生基底膜が1個で出現すれば cg1以上。電子顕微鏡でも確認する必要がある。
cg0: No GBM* double contours by light microscopy or EM
cg1a: No GBM double contours by light microscopy but GBM double contours (incomplete or circumferential) in at least three glomerular capillaries by EM, with associated endothelial swelling and/or subendothelial electron-lucent widening
cg1b: Double contours of the GBM in 1-25% of capillary loops in the most affected nonsclerotic glomerulus by light microscopy; EM confirmation is recommended if EM is available
cg2: Double contours affecting 26 to 50% of peripheral capillary loops in the most affected glomerulus
cg3: Double contours affecting more than 50% of peripheral capillary loops in the most affected glomerulus
*GBM, glomerular basement membrane

Peritubular capillary basement membrane multilayering (requires EM): ptcml 電子顕微鏡必要
 慢性ABMRに関連する所見。
ptcml1: ≥7 basement membrane layers in the most affected PTC AND ≥5 layers in two additional PTCs
ptcml0: 基準を満たさない
ptcmlNA: 電子顕微鏡実施していない

Quantitative criteria for mesangial matrix expansion: ("mm") メサンギウム基質沈着
 
拒絶反応の診断基準に含まれていない。再発糸球体腎炎(MPGN や FSGS など)でもみられる特異性に乏しい慢性変化である。硬化していない糸球体で判定する。2細胞のメサンギウム幅を超える基質増加で中等度と判定する。
mm0: No more than mild mesangial matrix increase in any glomerulus
mm1: At least moderate* mesangial matrix increase in up to 25% of nonsclerotic glomeruli
mm2: At least moderate mesangial matrix increase in 26–50% of nonsclerotic glomeruli
mm3: At least moderate mesangial matrix increase in >50% of nonsclerotic glomeruli
* The threshold criterion for the moderately increased "mm" is the expanded mesangial interspace between adjacent capillaries. If the width of the interspace exceeds two mesangial cells on the average in at least two glomerular lobules the "mm" is moderately increased

Quantitative Criteria for Arteriolar Hyaline Thickening ("ah") 細動脈硝子様肥厚
 拒絶反応の診断基準に含まれていない。CNI 障害を示唆する所見である。
ah0: No PAS-positive hyaline arteriolar thickening
ah1: Mild to moderate PAS-positive hyaline thickening in at least one arteriole
ah2: Moderate to severe PAS-positive hyaline thickening in more than one arteriole
ah3: Severe PAS-positive hyaline thickening in many arterioles
Indicate arteriolitis (significance unknown) by an asterisk on ah

Alternate quantitative scoring for Hyaline Arteriolar Thickening ("aah") [AJT 2008; 8: 753-60]
 拒絶反応の診断基準に含まれていない。 ah スコアの再現性が乏しいために,硝子様沈着物の範囲(血管の数,全周性か否か)で判定する aah スコアが導入された。
aah0: No typical lesions of calcineurin-inhibotor-related arteriolopathy
aah1: Replacement of degenerated smooth muscle cells by hyaline deposits
present in only one arteriole, no circumferential involvement.
aah2: Replacement of degenerated smooth muscle cells by hyaline deposits
present in more than one arteriole, no circumferential involvement.
aah3: Replacement of degenerated smooth muscle cells by hyaline deposits
present with circumferential involvement, independent of the number
of arterioles involved.

Quantitative Criteria for Fibrous Intimal Thickening ("cv") [Banff 2015] 線維性内膜肥厚
 
   慢性 ABMR に関連する所見(新規に出現すれば)。
cv0: No chronic vascular changes
cv1: Vascular narrowing of up to 25% luminal area by fibrointimal thickening
cv2: Vascular narrowing of 26–50% luminal area by fibrointimal thickening
cv3: Vascular narrowing of >50% luminal area by fibrointimal thickening

Quantitative Criteria for Interstitial Fibrosis ("ci") 間質線維化
 拒絶反応の診断基準に含まれていない。特異性に乏しい慢性変化である。
ci0: Interstitial fibrosis in up to 5% of cortical area
ci1: Mild- Interstitial fibrosis in 6 to 25% of cortical area
ci2: Moderate- Interstitial fibrosis of 26 to 50% of cortical area
ci3: Severe- Interstitial fibrosis of >50% of cortical area

Quantitative Criteria for Tubular Atrophy ("ct") [Banff 2015] 尿細管萎縮
 拒絶反応の診断基準に含まれていない。特異性に乏しい慢性変化であ る。
ct0: No tubular atrophy
ct1: Mild- Tubular atrophy involving up to 25% of the area of cortical tubules
ct2: Moderate- Tubular atrophy involving 26 to 50% of the area of cortical tubules
ct3: Severe- Tubular atrophy involving in >50% of the area of cortical tubules

Intrarenal polyomavirus load level ポリオーマウイルス腎症(SV40免疫染色)
pvl0: None
pvl1: Mild, positive cells in ≤1% of tubules
pvl2: Moderate, >1% and <10%
pvl3: Severe, ≥10%).

References
    1.    Solez K, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: The Banff working classification of kidney transplant pathology. Kidney Int 1993;44(2):411-22.
    2.    Solez K, et al. Report of the third Banff conference on allograft pathology (July 20-24, 1995) on classification and lesion scoring in renal allograft pathology. Trans Proc 1996;28(1):441-4.
    3.    Racusen LC, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999;55:713-723
    4.    Racusen LC, et al. Antibody-Mediated Rejection Criteria - an Addition to the Banff '97 Classification of Renal Allograft Rejection. Am J Transplant 2003;3:708-714.
    5.     Solez K, et al. Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant 2007;7:518-526.
    6.     Solez K, et al. Banff '07 classification of renal allograft pathology: Updates and Future Directions. Am J Transplant 2008;8:753-760.
    7.     Sis B, et al. Banff '09 meeting report: antibody mediated graft deterioration and im- plementation of Banff working groups. Am J Transplant 2010;10:464-471.
    8.    Mengel M, et al. Banff 2011 Meeting report: new concepts in antibody-mediated rejection. Am J Transplant. 2012;12:563-70.
    9.    Haas M, et al. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014; 14: 272-283.
  10.     Loupy A, et al. The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology. Am J Transplant 2017;17:28-41.
  11.     Haas M, et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant 2018;18:293-307.
  12. Roufosse C, et al. A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology. Transplantation. 2018 Nov;102(11):1795-1814.
  13.  Loupy A, et al. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020 Sep;20(9):2318-2331.


拒絶反応 rejection  のカテゴリー (Category 1〜6)の概略(より詳細な診断基準は文献13など参照のこと)

Category 1 正常ないし非特異的変化 normal biopsy or nonspecific changes

Category 2 抗体関連変化
    活動性抗体関連拒絶反応 active ABMR
    下記1〜3すべて満たす
  1. 急性組織障害,どれか1個以上
        (a) (g>0 and/or ptc>0), ただし TCMRや感染があるときは g≥1 が必須
        (b) 内膜/貫壁動脈炎 (v>0)
        (c) 急性血栓性微小血管症 (TMA),他の原因を除外
        (d) 急性尿細管障害
,他の原因を除外
       2. C4d沈着 (IFなら>1, IHCなら>0)
       3. DSAの存在
    慢性活動性抗体関連拒絶反応 chronic active ABMR

    下記1〜3すべて満たす
     1. 慢性組織障害,どれか1個以上
         (a) 移植糸球体症 (cg>0)
         (b) ptc の多層化 (≥7, EMで確認)
         (c) 新規の動脈内膜線維化±白血球
       2. C4d沈着 (IFなら>1, IHCなら>0)
       3. DSAの存在

  拒絶反応の証拠のないC4d染色 C4d staining without evidence of rejection
    下記1〜4すべて満たす
       1. C4dの沈着 (IF>1, IHC>0)
       2. 上記の急性・慢性組織障害を満たさない
       3. 分子的なABMRの証拠がない
       4. TCMRや境界変化(下記)がない

Category 3 境界変化 borderline changes
    急性T細胞関連拒絶反応疑い(境界病変)Suspicious (borderline) for acute TCMR
       尿細管炎 (t1, t2, または t3) と
軽度 (i1) の間質炎症細胞浸潤,
  あるいは軽度 (t1) の尿細管炎 と中等度から高度の間質炎症細胞浸潤 (i2-3)。
      
t1: Mild- Foci with 1 to 4 cells/tubular cross section or 10 tubular cells

Category 4 T細胞関連拒絶反応
 急性T細胞関連拒絶反応 acute TCMR
       Grade IA      中等度の尿細管炎 t2 (高度萎縮でない)+ 中等度以上の間質炎症細胞浸潤 i2-3
       Grade IB      高度の尿細管炎 t3
(高度萎縮でない)+ 中等度以上の間質炎症細胞浸潤 i2-3
       Grade IIA     軽度-中等度の内膜動脈炎 v1
       Grade IIB     高度の内膜動脈炎 v2
       Grade III      高度の内膜動脈炎 v3
   慢性活動性T細胞関連拒絶反応 chronic active TCMR
       Grade IA  
中等度の尿細管炎 t2 (高度萎縮でない)+ 皮質全体の中等度以上の炎症 ti2-3 + 中等度以上の瘢痕部の炎症 i-IFTA2-3
       Grade IB   高度の尿細管炎 t3(高度萎縮でない)+ 皮質全体の中等度以上の炎症 ti2-3 + 中等度以上の瘢痕部の炎症 i-IFTA2-3
       Grade II    慢性グラフト動脈症(動脈内膜線維化 + 線維化部への単核炎症細胞浸潤)

Category 5: ポリオーマウイルス腎症
  PVN Class 1: pvl1 and ci0-1
  PVN Class 2: pvl1 and ci2-3 OR pvl2 OR pvl3 and ci0-1
  PVN Class 3: pvl3 and ci2-3

Category 6: その他?
(PTLD, CNI毒性, 急性尿細管障害, 原疾患再発, de novo 糸球体症, 腎盂腎炎、薬剤性間質腎炎)