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. 2020 Sep 19;10(4):788–799. doi: 10.1016/j.jobcr.2020.09.005

Table 2.

Various grading systems proposed for oral epithelial dysplasia.

GRADING SYSTEM CRITERIA USED GRADES ADVANTAGES DISADVANTAGES REFERENCE NUMBER
SMITH and PINDBORG (1969) 1. Drop shaped rete ridges.
2. Loss of stratification regularity.
3. Keratin formation by individual cells.
4. Hyperplasia of basal layer
5. Loss of intercellular adherence.
6. Loss of basal cell polarity.
7. Nuclear hyperchromatism.
8. Increased N:C ratio.
9. Anisocytosis, Anisonucleosis.
10. Cellular and nuclear pleomorphism.
11. Increased mitotic activity.
12. Presence of mitotic figures in superficial half of epithelium.
13. Abnormal mitosis.		 Criteria were categorized as absent, slight and marked.
Scoring:
Absent = zero,
Slight or marked = 1 and 10.
The scores were cumulated = EAI
*varied from 0-75.
Total score:
0-10 (No dysplasia)
11-25 (Mild dysplasia)
26-45 (Moderate dysplasia)
45-75 (Severe dysplasia)
  • •

    Objective and semiquantitative.

  • •

    Numerical values help in providing statistical analysis.
  • •

    Monotonous.

  • •

    Time consuming.

  • •

    Can’t explain the reason for evidence of dysplasia in non-neoplastic lesions.

 18
BANOCZY and CSIBA (1976) 1. Loss of epithelial stratification.
2. Hyperplasia of basal / spinous cell layer or both.
3. More number of mitotic figures.
4. Increased N:C ratio.
5. Loss of polarity of basal cells.
6. Pleomorphic nuclei.
7. Hyperchromasia.
8. Keratinization of single cells.
9. Loss of intercellular adherence.		 Mild : When 2 of the listed histological changes are observed.
Moderate: When 2 -4 of the listed histological changes are observed.
Severe : When 5 or more of the listed histological changes are observed.
  • •

    Simple.

  • •

    Less time consuming.
  • •

    Only subjective interpretation.

  • •

    Can’t explain the associated risk factors.

 23
WHO (1978) 1. Loss of basal cell polarity.
2. Multiple layers of cells having basaloid appearance.
3. Increased N:C ratio.
4. Drop shaped epithelial ridges.
5. Loss of stratification.
6. More number of mitotic figures.
7. Mitotic figures in the superficial layers.
8. Cellular polymorphism.
9. Nuclear hyperchromatism.
10. Enlarged nucleoli.
11. Reduction of cellular cohesion.
12. Keratin pearls in spinous cell layer.		 Mild: Dysplastic features in the lower 1/3rd of epithelium.
Moderate: Dysplastic features in the lower 2/3rd of epithelium.
Severe : Dysplastic features involving >2/3rds of epithelium.
  • •

    Simple.

  • •

    Less time consuming.

  • •

    Includes both cellular and architectural features.
  • •

    Lack of providing associated risk factors.

  • •

    Observer agreement variability.

 24
KRAMER (1980) 1. Drop shaped epithelial ridges.
2. Disturbed polarity of the basal cells.
3. Basal cell hyperplasia.
4. Loss of stratification.
5. Anisocytosis.
6. Nuclear hyperchromasia.
7. Prominent nucleoli.
8. Increase N:C ratio.
9. Cell crowding.
10. More mitosis.
11. Mitosis in upper layers.
12. Abnormal mitosis.
13. Loss of cellular adhesion.
14. Intraepithelial keratinization.		 No grading system.
The epithelium is dysplastic when ≥2 criteria are present.
  • •

    Provides no specific grade.

  • •

    Just a subjective interpretation.

 25
BURKHARDT and MAERKAR (1981) 1. Basal cell hyperplasia.
2. Loss of basal cell polarity.
3. Cellular pleomorphism.
4. More mitotic figures.
5. Dyskeratosis.
6. Abnormal and lack of epithelial stratification.
Additional indicators for dysplasia:
1. Increase in subepithelial lymphocytes, plasma cells and interepithelial cells.
2. Candida species.		 Low: Presence of only first 2 criteria.
Medium: Presence of first 5 criteria.
High: All 6 criteria are present
CIS: More marked features of high degree dysplasia seen.
  • •

    Also signifies some other associated risk factors.
  • •

    Suffers inter and intra-observer variability.

  • •

    Not a reliable and accurate method.

 26
SHAFER (1983) 1.More and abnormal mitosis.
2. Keratin formation by single cell.
3. Epithelial pearls within spinous layer.
4.Altered N:C ratio.
5. Loss of polarity.
6. Large prominent nucleoli.
7. Dyskeratosis.
8. Poikilocytosis.
9. Basilar cell hyperplasia.		 Mild (Grade I dysplasia): Proliferation of atypical or immature basal cells above the parabasal region.
Moderate (Grade II dysplasia): Proliferation into the middle one-third of the epithelium.
Severe (Grade III dysplasia): Abnormal proliferation from the basal layer into the upper third of the epithelium.
  • •

    Simple.

  • •

    Involves both cellular and tissue alterations.
  • •

    No evidence of associated risk factors.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

  • •

    Observer disagreement.

 28
LUMERMANN et al. (1995) 1. Basal cell hyperplasia.
2. Nuclear enlargement and hyperchromatism.
3. Drop-shaped epithelial ridges.		 Mild: ‘Minimal’ dysplastic alterations confined to the lower third of the epithelium.
Moderate: Dysplastic changes confined up to 2/3rds of the thickness of the epithelium.
Severe: Dysplastic changes found in more than 2/3rds but less than the entire thickness of the epithelium.
CIS: Dysplastic changes are seen throughout the entire thickness of the epithelium with no invasion into the sub-mucosa.
Verrucous hyperplasia with dysplasia: The epithelium exhibits considerable thickening with surface papillations, hyper-parakeratosis and para-keratin plugging and occasional dysplastic cells confined to the lower 1/3rd of the epithelium.
  • •

    Introduced new category as “verrucous hyperplasia with dysplasia”.
  • •

    Can’t determine dysplasia accurately.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

  • •

    Observer disagreement.

 8
NEVILLE (1995) 1. Enlarged nuclei.
2. Large and prominent nucleoli.
3. Increased N:C ratio.
4. Hyperchromatic nuclei.
5. Cellular and nuclear pleomorphism. Dyskeratosis.
6. Increased mitotic activity.
7. Abnormal mitotic figures.
Additional criteria –
1. Teardrop-shaped or bulbous ridges.,
2. Loss of polarity,
3. Keratin or epithelial pearls.
4. Loss of epithelial cell cohesiveness		 Mild: Pleomorphic and hyperchromatic nuclei are seen in basal and parabasal cell layers.
Moderate: Dysplasia extends to middle of the spinous cell layer.
Severe : Disordered arrangement with cellular crowding is seen throughout the cell layers. Slight maturation and flattening of cells are seen at epithelial surface.
CIS: Entire thickness of the epithelium contains dysplastic features.
  • •

    Simple.

  • •

    Involves both cellular and tissue alterations.
  • •

    No evidence of associated risk factors.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

  • •

    Observer disagreement.

 29
SPEIGHT et al. (1996) WHO 1978 criteria Mild: Dysplasia present in parabasal cells.
Moderate: Dysplastic features extending up to middle 1/3rd layer.
Severe: Dysplastic features extending to upper layer.(similar to the WHO grading except for the absence of Carcinoma-in-situ)
  • •

    Simple.

  • •

    Involves both cellular and tissue alterations.
  • •

    Observer disagreement.

  • •

    Variability in thickness of oral epithelial lining leads to inaccurate grading.

 30
SOAMES (1998) WHO 1978 criteria Mild: Dysplasia involving the lower third of epithelium showing pleomorphism, suprabasal mitosis and loss of stratification.
Moderate: Dysplasia involving the 2/3rd of epithelium.
Severe: Marked cellular atypia with disturbed stratification.
  • •

    Simple.

  • •

    Involves both cellular and tissue changes.
  • •

    Variation in observer agreement.

  • •

    Variability in thickness of oral epithelial lining leads to inaccurate grading.

 31
KUFFER and LOMBARDI (2002) WHO 1978 criteria Risk lesions: Lesions without dysplasia.
Precursors of oral squamous cell carcinoma: Lesions with dysplasia.
  • •

    Introduced new terminologies.
  • •

    Lack of evidence of malignant transformation in both categories.

  • •

    Observer disagreement.

 32
LJUBLJANA (2003) 1.Increased prickle cell layer without changes in of basal and parabasal layers.
2.Proliferation of basal and parabasal cell layers extending up to one half of total epithelial thickness, containing cells with moderately enlarged nuclei, show occasional normal mitosis, and contains <5% of dyskeratotic cells.
3.Stratification is preserved, Nuclear atypia (enlarged nuclei containing irregular nuclear contours, with marked variations in staining intensity), increased prominent nucleoli increased N:C, increased mitoses, more dyskeratotic cells.
4. Loss of stratification of epithelium, marked cellular alteration, increased mitosis with abnormal pattern, extending up to high levels of epithelium		 Simple hyperplasia: Criteria 1
Abnormal hyperplasia: Criteria 2
Atypical hyperplasia: Criteria 3
Carcinoma in situ: Criteria 4
  • •

    Focuses on important associated risk factors.

  • •

    Provides an indication to identify the lesions accurately for implementing proper treatment plan.
  • •

    Can’t categorize dysplasia in atrophied epithelium.

  • •

    Lack of numerical values.

  • •

    Complex.

  • •

    Time consuming.

 36
BROTHWELL et al. (2003) 1. Basal and parabasal cell hyperplasia.
2. Nuclear hyperchromatism.
3. Nuclear pleomorphism.
4. Bulbous retes.		 0. No dysplasia.
1.Mild dysplasia: Increase in number of cells in basal and parabasal cells showing nuclear hyperchromatism and pleomorphism.
2.Moderate dysplasia: Features of Grade 1 also involving prickle layer and Presence of bulbous rete pegs.
3.Severe dysplasia: Features of grade 2 throughout the epithelium.
4 CIS: Atypical changes in the full thickness of the epithelium indicating early invasion without any clinical evidence.
  • •

    Good inter and intra-observer variability.

  • •

    Numerical values help to provide statistical analysis.
  • •

    Time consuming.

  • •

    Tedious.

  • •

    Does not indicate associated risk factors.

  • •

    Does not include all the cellular and tissue changes.

 37
TAKASHI SAKU et al., (2004) Depending on the potential for malignant transformation. Mild: Lesions with atypical features whose potential for malignant transformation is unknown.
Moderate: Lesions characterized by carcinomatous potential. It is also regarded as true dysplasia.
CIS: Characterized by true but not invasive neoplasm.
  • •

    Provides detailed features of CIS.
  • •

    Omitted the term ‘severe dysplasia’.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

 38
WHO (2005) Architectural features:
1. Irregular epithelial stratification.
2. Loss of polarity of basal cells.
3. Basal cell hyperplasia.
4. Drop-shaped rete ridges.
5. Increased number of mitotic figures.
6. Abnormal superficial mitosis.
7. Dyskeratosis.
8. Keratin pearls within rete ridges.
Cytological features:
1. Anisonucleosis.
2. Nuclear pleomorphism.
3. Anisocytosis.
4. Cellular pleomorphism.
5. Increased N:C ratio.
6. Increase in nuclear size.
7. Atypical mitotic figures.
8. Increased number and size of nucleoli.
9. Hyperchromasia.		 Hyperplasia: Hyperplasia of basal/parabasal cell layers without cellular atypia.
Mild dysplasia: Architectural changes limited to lower third of the epithelium accompanied by cytological atypia.
Moderate dysplasia: Architectural changes limited to middle third of the epithelium.
Severe dysplasia: Architectural disturbances extending above 2/3rds of the epithelium.
CIS : Architectural abnormalities in full thickness accompanied by cytological atypia.
  • •

    Includes both cytological and architectural changes.

  • •

    Also includes the term ‘hyperplasia’ providing more details.

  • •

    Exhibits good observer agreement.
  • •

    Variability in thickness of oral epithelial lining leads to inaccurate grading.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

  • •

    Does not provide associated risk factors.

 39
SIN DYSPLASIA CLASSIFICATION (2005) WHO 2005 criteria. SIN 1: Similar to mild dysplasia.
SIN 2: Similar to moderate dysplasia.
SIN 3: Combination of severe dysplasia and CIS.
  • •

    Simple.

  • •

    Also involves other regions of upper aerodigestive tract.
  • •

    Only subjective interpretation.

  • •

    Lack of evidence of malignant transformation.

  • •

    Overlapping of features leads to inaccurate grading.

 41
BINARY SYSTEM (2006) WHO 2005 criteria. High-risk lesions: Lesions presenting with at least 4 architectural changes and 5 cytological changes.
Low-risk lesions: Lesions presenting with <4 architectural changes or <5 cytological changes.
  • •

    Objective.

  • •

    Good observer agreement.

  • •

    Help clinicians to identify the risk potential.
  • •

    Large scale studies still needed to investigate its accuracy and reliability.

 44
BOUQUOT et al., (2006)
  • •

    Cellular atypia or dysplasia similar to squamous cell carcinoma.

  • •

    No evidence of invasion into underlying stroma.

  • •

    Epithelium with more number of atypical cells have more risk of becoming malignant.

  • •

    Epithelium with most extreme atypia of cells has the greatest risk of malignant transformation.

  • •

    Final grading is based on the most severely involved area of change, even if that area includes no more than a few rete ridges.

 Mild : Proliferation of atypical or immature basal cells above parabasal region up to lower 3rd of epithelium.
Moderate: Proliferation into middle 3rd of epithelium.
Severe: Abnormal proliferation of atypical cells from basal layer into upper 3rd of epithelium.
  • •

    Simple.
  • •

    Subjective.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

 46
OIN/CIS (JSOP) SYSTEM (2010) WHO criteria 2005 OIN1: <1/3rd of epithelium shows dysplastic features.
OIN2: 1/3rd-2/3rds of epithelium show dysplastic features.
OIN3: Full thickness of epithelium show dysplasia.
*Based on “Bethesda classification” for cervical cancer, the system with 3 grades for OIN was replaced by a 2 grade system later.
Low grade oral intraepithelial neoplasia (loin): OIN 1
High grade oral intraepithelial neoplasia (hoin): OIN2 and OIN3
  • •

    Simple.

  • •

    Less tedious.

  • •

    Less time consuming.

  • •

    Can distinguish features of OSCC from cervical cancer.
  • •

    Subjective.

  • •

    Observer variability.

  • •

    Thickness of epithelium may vary leading to improper grading.

 47
WHO (2017) Architectural features:
1. Irregular epithelial stratification.
2. Loss of polarity of basal cells.
3. Drop-shaped rete ridges.
4. Increased number of mitotic figures.
5. Abnormal superficial mitosis.
6. Dyskeratosis.
7. Keratin pearls within rete ridges.
8. Loss of epithelial cell cohesion**
Cytological features:
1. Anisonucleosis.
2. Nuclear pleomorphism.
3. Anisocytosis.
4. Cellular pleomorphism.
5. Increased N:C ratio.
6. Atypical mitotic figures.
7. Increased number and size of nucleoli.
8. Hyperchromasia.		 Mild dysplasia:
Confined to the lower 1/3rd of the epithelium exhibiting cytologic and/or architectural alterations.
Moderate dysplasia:
Changes from 1/3rd – middle 3rd of the epithelium.
Severe dysplasia/ CIS:
Changes up to upper 2/3rd third to the entire thickness of the epithelium.
  • •

    Simple.

  • •

    Improved WHO 2005 system.
  • •

    Subjective.

  • •

    Does not imply the continuous progression of dysplasia.

  • •

    Can’t predict malignant potential.

  • •

    Variability in thickness of oral epithelial lining leads to inaccurate grading.

  • •

    Lack of numerical values leading to failure in providing statistical analysis.

 48

CIS- Carcinoma in situ; EAI- Epithelial atypical index; JSOP- Japanese Society for Oral Pathology; N:C- Nuclear cytoplasmic ratio; OIN- Oral intraepithelial neoplasia; OSCC-Oral squamous cell carcinoma; SIN- Squamous intraepithelial neoplasia; WHO-World health organization.