ORAL EPITHELIAL DYSPLASIA: recognition, grading, and clinical significance.pptx

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

6. FEATURES OF EPITHELIAL DYSPLASIA

7. 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

8. 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)

9. 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 .

10. 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. H as 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.

11. Mild dysplasia limited to basal or para basal layer

12. Moderate dysplasia limited to basal to granular layer

13. Severe dysplasia involving basal, middle and upper layer

14. 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

15. 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)

16. 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

17. 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

18. 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.

19. 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 .

20. 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

21. 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.

22. 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.