Table 3

Histological items for disease activity assessment in immune checkpoint inhibitor-associated colitis

StatementMedian rating (mean absolute-deviation from the median)Clinical care (CC) vs research context (RC)
The Geboes score should be used as an instrument for assessing histological disease activity in ICIC6 (0.91)CC+RC
The Robarts Histopathology Index (RHI) as calculated from the Geboes score should be used as an instrument for assessing histological disease activity in ICIC6 (1.00)CC+RC
The Nancy index should be used as an instrument for assessing histological disease activity in ICIC5 (0.82)CC+RC
A new instrument is needed to assess histological disease activity in ICIC8 (1.09)RC
The degree of structural (architectural) change should be used as a measure for assessing histological disease activity in ICIC7 (1.00)CC
In ICIC, the degree of structural (architectural) change should be scored according to the Geboes score as:7 (1.00)CC+RC
 0 No abnormality
 1 Mild abnormality
 2 Mild or moderate diffuse or multifocal abnormalities
 3 Severe diffuse or multifocal abnormalities
In ICIC, the degree of crypt architectural distortion (loss of parallel crypt architecture, including the finding of crypt branching, variation in spacing, shape, and size of crypts) should be scored as:6 (1.00)CC+RC
 0 None (normal)
 1 Mild (focal)
 2 Severe (diffuse)
The degree of chronic inflammatory infiltrate (lymphocytes and/or plasma cells in lamina propria) should be used as a measure for assessing histological disease activity in ICIC7 (1.36)CC
In ICIC, the degree of chronic inflammatory infiltrate (lymphocytes and/or plasma cells in lamina propria) should be scored according to the Geboes score as:7 (0.82)CC+RC
 0 No increase
 1 Mild but unequivocal increase
 2 Moderate increase
 3 Marked increase
Basal plasmacytosis should be used as a measure for assessing histological disease activity in ICIC6 (1.18)CC
In ICIC, basal plasmacytosis should be scored as:
 Absent or present6 (1.00)CC+RC
 Absent, focal, or diffuse6 (1.09)CC+RC
The degree of lamina propria eosinophils should be used as a measure for assessing histological disease activity in ICIC5 (0.45)CC+RC
In ICIC, the degree of lamina propria eosinophils should be scored according to the Geboes score as:6 (0.73)CC+RC
 0 No increase
 1 Mild but unequivocal increase
 2 Moderate increase
 3 Marked increase
The degree of lamina propria neutrophils should be used as a measure for assessing histological disease activity in ICIC8 (1.09)CC
In ICIC, the degree of lamina propria neutrophils should be scored according to the Geboes score as:8 (0.73)CC+RC
 0 None
 1 Mild but unequivocal increase
 2 Moderate increase
 3 Marked increase
The degree of neutrophils in epithelium should be used as a measure for assessing histological disease activity in ICIC8 (0.91)CC
In ICIC, the degree of neutrophils in epithelium should be scored according to the Geboes score as:8 (0.64)CC+RC
 0 None
 1 <5% crypts involved
 2 5%–50% crypts involved
 3 >50% crypts involved
In ICIC, cryptitis (neutrophils within crypt epithelium) should be scored as absent or present6 (1.27)CC+RC
Crypt abscesses (neutrophils within crypt lumens) should be used as a measure for assessing histological disease activity in ICIC7 (0.82)CC
In ICIC, crypt abscesses (neutrophils within crypt lumens) should be scored as absent or present7 (0.55)CC+RC
The degree of crypt destruction should be used as a measure for assessing histological disease activity in ICIC8 (1.36)CC
In ICIC, the degree of crypt destruction should be scored according to the Geboes score as:7 (1.00)CC+RC
 0 None
 1 Probable—local excess of neutrophils in part of crypt
 2 Probable—marked attenuation
 3 Unequivocal crypt destruction
The degree of erosion or ulceration should be used as a measure for assessing histological disease activity in ICIC9 (0.64)CC
In ICIC, the degree of erosion or ulceration should be scored according to the Geboes score as:7 (0.91)CC+RC
 0 No erosion, ulceration, or granulation tissue
 1 Recovering epithelium and adjacent inflammation
 2 Probable erosion—focally stripped
 3 Unequivocal erosion
 4 Ulcer or granulation tissue
In ICIC, ulcers should be distinguished from erosions7 (1.27)CC
The degree of apoptosis should be used as a measure for assessing histological disease activity in ICIC9 (1.00)CC
In ICIC, the degree of apoptosis should be scored as:
 The number of apoptotic bodies in 10 consecutive crypts7 (1.00)CC+RC
 The percentage of crypts with ≥1 apoptotic body6 (1.20)CC+RC
 Absent or present6 (1.64)CC+RC
In ICIC, apoptosis should be defined as having more than three apoptotic bodies within the epithelium of 10 crypts6 (1.18)CC+RC
The degree of withered crypts with apoptosis and/or necrotic debris (different from a Geboes score of 4.2, which is characterized by attenuated epithelium due to a neutrophilic crypt abscess) should be used as a measure for assessing histological disease activity in ICIC8 (0.91)CC+RC
In ICIC, the degree of withered crypts with apoptosis and/or necrotic debris (different from a Geboes score of 4.2, which is characterized by attenuated epithelium due to a neutrophilic crypt abscess) should be scored as:7 (0.64)CC+RC
 0 None
 1 Rare withered crypt due to apoptosis
 2 Frequent withered crypts due to apoptosis, but not confluent
 3 Confluent withered crypts due to apoptosis
The degree of surface intraepithelial lymphocytosis should be used as a measure for assessing histological disease activity in ICIC8 (1.27)CC
In ICIC, the degree of surface intraepithelial lymphocytosis should be scored as:7 (0.91)CC+RC
 0–4 per 100 colonocytes
 1 Borderline (5–20 per 100 colonocytes)
 2 Increased (>20 per 100 colonocytes)
 3 Increased (>20 per 100 colonocytes, with associated surface epithelial injury) (different from Geboes scores 5.1 and 5.2 by the absence of neutrophilic inflammation)
In ICIC, increased intraepithelial lymphocytes (IELs) should be scored as absent or present7 (1.09)CC+RC
In ICIC, increased IELs should be defined as having:
 >10 IELs within 100 surface epithelial cells4 (0.91)CC+RC
 >20 IELs within 100 surface epithelial cells8 (0.55)CC+RC
 >25 IELs within 100 surface epithelial cells5 (0.82)CC+RC
Surface intraepithelial lymphocytosis should be distinguished from deep crypt lymphocytosis for assessing histological disease activity in ICIC6 (1.36)CC+RC
In ICIC, the degree of deep crypt lymphocytosis should be scored as:7 (0.91)CC+RC
 0 Absent
 1 Present, focal
 2 Present, diffuse
The degree of subepithelial collagen should be used as a measure for assessing histological disease activity in ICIC7 (1.64)CC
In ICIC, the degree of subepithelial collagen should be scored as:7 (1.00)CC+RC
 0 Normal
 1 Patchy thickening
 2 Diffuse thickening
Granulomas (not cryptolytic) should be used as a measure for assessing histological disease activity in ICIC5 (0.73)CC+RC
In ICIC, granulomas (not cryptolytic) should be scored as absent or present7 (0.91)CC+RC
Mucin depletion (≤1 goblet cell in 8–10 colonocytes) should be used as a measure for assessing histological disease activity in ICIC6 (0.91)CC+RC
In ICIC, mucin depletion (≤1 goblet cell in 8–10 colonocytes) should be scored as absent or present6 (1.09)CC+RC
An ischemic injury pattern should be used as a measure for assessing histological disease activity in ICIC6 (1.00)CC+RC
In ICIC, an ischemic injury pattern should be scored as absent or present7 (0.91)CC+RC
  • Green indicates statements voted as appropriate, yellow indicates uncertain appropriateness without disagreement, and red indicates uncertain appropriateness with disagreement.

  • ICIC, immune checkpoint inhibitor-associated colitis.