pre malignant lesion

1. ORAL EPITHELIAL DYSPLASIA: RECOGNITION, GRADING
AND CLINICAL SIGNIFICANCE
Dr. KUNAL RANJAN JHA
SENIOR CONSULTANT
DEPARTMENT OF HEAD & NECK ONCOLOGY
MAHAVIR CANCER SANSTHAN AND RESEARCH CENTRE
PATNA

2. • INTRODUCTION
• MOLECULAR PATHOLOGY
• FEATURES OF EPITHELIAL DYSPLASIA
• CLASSIFICATION AND GRADING SYSTEM
• CLINICAL CONTEXT AND SIGNIFICANCE
• OPTIMISATION AND INTERPRETATION OF DYSPLASIA
REPORTING

3. INTRODUCTION
• It refers to microscopic changes characterised by cellular
atypia, loss of maturity and stratification.
• Altered epithelium with an increased likelihood for
progression to squamous cell carcinoma ( WHO 2005)
• Criteria : architectural changes, cytological changes
• Histological changes only no clinical morphological equivalent
like OPMD( ORAL PREMALIGNANT DISORDERS)

4. MOLECULAR PATHOLOGY
• High mutational load and gross chromosomal changes
• Fertile enviornment of chromosomal instability in which
carcinoma development is more likely
• Not a stage in cancer development always, as carcinoma may
develop suddenly
• Genetically altered field not Cancerised field

5. • A study by Razavi et al. demonstrated that
vascularization with VEGF has paramount role
in dysplasia progression.
• Lectine is a membrane protein marker which
attaches to the membrane carbohydrate and
have function in cell membrane.
• Mutation in the gene of lectine, alters cell
membranes and leads to metastatic tumoral
cells

8. FEATURES OF EPITHELIAL DYSPLASIA

9. • Architectural changes more important then
cytological
• Proliferative verrucous leukoplakia has high
risk of transformation despite minimal
cytological changes
• Hyperplasia removed as a feature as it is
reactive and reversible

10. CLASSIFICATION & GRADING
 Smith and Pindborg photographic methods (1969)
 Ljubljana classification (2003)
 Squamous Intraepithelial Neoplasia/dysplasia (SIN/dysplasia)
classification (2005)
 Oral Intraepithelial Neoplasia/ Carcinoma in situ (Japanese
Society for Oral Pathology), OIN/CIS (JSOP) system (2010)
 World Health Organization (WHO) classification systems
• World Health Organization (WHO) 1978 classification
• World Health Organization (WHO) 2005 classification
• World Health Organization (WHO) 2017 classification
 Binary system (2006)

13. • Based on the architectural and cytological alterations, the epithelium is divided into “thirds,”
and the lesions are classified into five categories
• 1. Hyperplasia (Squamous hyperplasia): Lesions with an increase in cell number in the
spinous layer and/or in the basal/parabasal cell layers. There is presence of regular
stratification and no cellular atypia
• 2. Mild dysplasia: Architectural disturbance present only in the lower third of the epithelium
with cytological atypia
• 3. Moderate dysplasia: The criteria postulate that architectural disturbance extending into
the middle third of the epithelium, but the degree of cytological atypia may require
upgrading it to “severe dysplasia”
• 4. Severe dysplasia: Architectural disturbance observed in greater than two thirds of the
epithelium, with cytological atypia
• 5. Carcinoma in situ (CIS): Is a noninvasive carcinoma, classified as a precursor lesion of
OSCC. CIS is characterized by full thickness or almost full thickness of epithelial architectural
disturbance in the viable cell layers accompanied by pronounced cytological atypia.

14. • Binary system (2006) Warnakulasuriya et al.
two-tier classification – low risk (no ⁄ questionable ⁄
mild); high risk (moderate ⁄ severe) for better
reproducibility and clinical utility.
• Kujan et al. in their study show that the binary system
that uses four architectural and five cytological
features.
• Has an increased inter-observer agreement (κ = 0.5) as
compared to the WHO (κ = 0.22).
• Nankivell et al. also contend that the binary system
has a superior reproducibility.

16. Mild dysplasia limited to basal or para basal layer

17. Moderate dysplasia limited to basal to granular layer

18. Severe dysplasia involving basal, middle and upper layer

19. NOMENCLATURE
Clinical nomenclature
• World Health Organisation proposed in 1978 :
precancerous lesion & condition
• WHO monograph on Head and Neck Tumours
(2005) uses the term ‘epithelial precursor lesions’.
• Most recently ,oral potentially malignant
disorders (OPMDs): oral leukoplakia,
erythroplakia, oral submucous fibrosis, lichen
planus (OSMF),verrucous leukoplakia, actinic
keratosis

20. Histological diagnosis:
• Hyperplasia: Reactive phenomenon
acanthosis( increase thickness of spinous
layer) and increase in basal cells
• Hyperkeratosis :
• Oral epithelial dysplasia (OED)
• Oral squamous cell carcinoma (OSCC)

21. CLINICAL SIGNIFICANCE
 Gender predilection
• In India, malignant transformation of leukoplakia are greater
in men than in women, possibly because of the association
with chewing tobacco and smoking habits whereas in Europe
and other western countries, it is greater in women than men.
 Duration
Cancers from dysplastic lesions usually develop over a period of
2–5 years, but can occur much later.
 Smokers versus non-smokers
• Lesions in non-smokers are 7.1 times more likely to undergo
malignant transformation compared to heavy smokers.
Vander wall And Le JJ

22. Anatomical location
The floor of the mouth and/or on the lateral tongue has a
high risk for malignant transformation.
 Other clinical determinants
Large lesions (≥200 mm2), multifocal or multiple leukoplakia,
and proliferative verrucous leukoplakia are also associated
with increased risk of malignant transformation. Advancing
age is also shown be an important determinant of malignant
transformation. The presence of aneuploidy has been found
to signify a high risk of malignant transformation in
leukoplakia

24. • The chances of malignancy in mild to moderate dysplastic
lesions are 4 to 11% and 2 to 35% for severe dysplastic
changes.
• Homogenous, thick leukoplakia undergoes malignant
transformation in 1%–7% of cases.
• Verruciform, the malignant transformation potential
becomes 4%–15%.
• Erythroleukoplakia carries an average transformation
potential of 28%, but the rates vary from 18% to 47% in
different studies.

25. OPTIMISATION AND INTERPRETATION OF DYSPLASIA REPORTING
• A good biopsy is paramount for correct diagnosis of OED
including adequate depth, size, and orientation and fixation,
and it must be accompanied by a detailed and precise clinical
description.
• A standard operating protocol should be available covering all
aspects of laboratory handling of mucosal biopsies and
excisions.
• Biomedical technologists should be trained and competency
assured for mucosal specimen handling.

26.  Brush biopsy
 Toluidine blue: rinsed mucosa is exposed to acetic acid
followed by Toluidine blue dyes cell’s DNA which makes
observing dysplastic changes possible.
 Vizilite technique: suspicious mucosa is evaluated by blue
light which the unusual mucosa would appear as dark
zones
 Oral auto fluorescence:Fluorescent light with wavelength of
400- 460nm in a dark room can localize danger zones as
“blue”, “green and black” or “black and black” appearances
 Molecular markers: EGFR, Ki67, p53, MMP9, CYCLIN D e.t.c

27.  CLINIC AL INTERPRE TATION OF DYSPL A SIA REPORTING
• Mild epithelial dysplasia follow conservative protocols of
surveillance with habit and dietary analysis.
• Eliminating habituated condition.
• Intervention, surgical, laser or topical chemotherapy, is
reserved for moderate or severe dysplasia.
• Re-examination of other parts of the mouth, and possibly
upper aerodigestive tract, for other lesions.

28. CONCLUSION
• Oral squamous cell carcinoma is often
diagnosed in the late stages of the disease.
• Delayed diagnosis precludes successful
treatment and favorable outcomes.
• With the finding of oral epithelial dysplasia on
tissue biopsy remaining the gold standard in
guiding management.