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Histological Grading Systems of Epithelial Dysplasia & Squamous REVIEW ARTICLE HISTOLOGICAL GRADING SYSTEMS OF EPITHELIAL DYSPLASIA & SQUAMOUS CELL CARCINOMA Parikshit Sharma1, Diksha Singh2,*, Janhavi Dixit3, Manish Kumar Singh4, Naveen Kumar5 1Senior resident, 2Assistant Prof., 3Senior Resident, Oral Pathology FODS, KGMU Lucknow 4Asst. Prof., HOD, Social and Preventive Medicine, BRD Medical College, Gorakhpur 5PGT, Dr. R Ahmed Dental College, kolkata *Corresponding Author: Email: [email protected] Abstract: Oral precancer lesions or conditions are primary indication to be alert about oral health. As there are high chances of oral precancer to turn into malignant lesion. It is difficult to asses that which precancer lesion is highly malignant and which is not. There are lots of classification and grading systems about the grading of oral precancerous lesion, which shows great variabilty and inter observer bias. This review gets importance as we reviewd all grading systems for oral precancer and cancer lesions with their post and cones. Key words: Oral Precancer, Cancer, Tobacco, Dysplasia, Classification INTRODUCTION of the subsequent development of carcinoma. But dysplasia can be found in association with a variety The term ‘dysplasia’ was introduced by of non-neoplastic conditions, such as in the Reagon in 1958 in relation to the cells exfoliated neighbourhood of chronic inflammatory ulceration or from lesions of the uterine cervix. Dysplasia means burns. Furthermore, dysplasia may regress, as has abnormal, atypical proliferation, encountered been shown in the case of the cervix.1,2 principally in the epithelium. In past epithelial Oral precancer lesions can be defined as dysplasia, epithelial atypia and dyskeratosis were altered epithelial lesions which have an increased used synonymously. Pindborg (1977) defined likelihood of progressing to squamous cell epithelial dysplasia as the term used for “A lesion in carcinoma. The nomenclature, natural history and which part of the thickness of the epithelium is predictive value of this group of lesions was replaced by the cells showing varying degrees of reviewed at an expert workshop held in London in cellular atypia.”Burkhart and Maerker (1981) stated 2005, and has been reported in a series of recent that the degree of dysplasia is determined “As a papers3,4. The group recommended that the measure of tissue and cellular deviation from the distinction between potentially malignant lesions and normal.” Kumar et al (1992) defined dysplasia “as conditions should be abandoned in favour of a disturbance in the maturational sequence of the common terminology of Oral potentially malignant stratified squamous epithelium and disturbance in disorders3,5. This recognises the fact that even in cell kinetics of the proliferative compartment with patients with lesions such as leukoplakia, malignancy cytological changes.” Exposur of a cell to carcinogen may arise elsewhere as a result of field change. The leads to cyt5ological changes, depending on the most common disorders recognised as potentially extent and duration of stimuli. An increase in cell malignant are leukoplakia and erythroplakia. The proliferation, diminishing the cytosolic volume and WHO definition of these lesions is generally regarded the associated organelle load, could be an attempt in as unsatisfactory, since it largely a definition by this direction. In the context of oral epithelium, an exclusion. The Working group recommended a new accelerated growth phase depicted by broadening of definition for Leukoplakia which recognises the lack the progenitor compartment (hyperplasia) is the of evidence about risk and the nature of the lesions earlier sequel of exposure to an irritant. When the ‘The term leukoplakia should be used to recognise irritant persists, the epithelium shows features of white plaques of questionable risk having excluded cellular atrophy, again a well characterized feature of (other) known diseases or disorders that carry no adaptation. At a later stage when the stages of increased risk for cancer’ However even this remains adaptation and reversible cell damage surpasses, the unsatisfactory and a clear definition of precursor cells progressively slips into a stage of irreversible lesions may have to wait for further diagnostic cell damage, manifest either as cell death or criteria based on molecular or genetic markers. For neoplastic transformation. The changes of dysplasia, the present time, the prognostic significance of an are in many cases the earliest microscopic evidence individual lesion is difficult to determine, and none of Journal of Oral Medicine, Oral Surgery, Oral Pathology and Oral Radiology;2015;1(1):7-20 7 Sharma et al. Histological Grading Systems of Epithelial Dysplasia & Squamous Cell Carcinoma the currently available molecular markers have benign hyperplastic lesions which may be proved to be prognostically significant and none have encountered. In oral and maxillofacial pathology yet been evaluated in large prospective studies. The therefore, oral epithelial dysplasia is regarded as the gold standard for the assessment of oral potentially standard terminology 4,7. malignant disorders remains the microscopic evaluation of haematoxylin and eosin stained sections Criteria for the diagnosis of oral epithelial dysplasia for the presence of epithelial dysplasia. Some texts The diagnosis and grading of oral epithelial use the terms squamous intraepithelial neoplasia dysplasia is based on a combination of architectural (SIN) or squamous intraepithelial lesions (SIL)6. The and cytological changes6, but evaluation of these is categories under each scheme are similar, but the subjective and has been subject to considerable inter- terminology is different. In the oral cavity, use of the and intra-observer variations in the grading of SIL terminology of ‘atypical hyperplasia’ may lead to lesions, with Kappa values showing only fair to confusion because of the large number of common moderate agreement between observers8,9,10. Table 1: Cytological and architectural features of oral epithelial dysplasia 13. Cellular changes: Architectural (Tissue) changes: Abnormal variation in nuclear size and shape Loss of polarity (anisonucleosis and pleomorphism) Disordered maturation from basal to squamous Abnormal variation in cell size and shape cells (anisocytosis and pleomorphism) Includes top-to-bottom change of carcinoma in Increased nuclear/cytoplasmic ratio situ Enlarged nuclei and cells Increased cellular density Hyperchromatic nuclei Basal cell hyperplasia Increased mitotic figures Dyskeratosis (premature keratinization and Abnormal mitotic figures (abnormal in shape or keratin pearls deep in epithelium) location) Bulbous drop shaped rete pegs Increased number and size of nucleoli. Secondary extensions (nodules) on rete tips. Table 2: Observer variability in head and neck lesions. Studies/ localisation Number of Histopathological Number of agreement Kappa value references slides classification examinators Abbey et al. oral cavity/ 120 WHO° 6 35.8-57.5% 0.15–0.41 1995 oropharynx Fischer et al. oral cavity/ 87 WHO° 24 - 0.59 20041 oropharynx (95% CI: 0.45– 0.72) 0.70 (95% CI: 0.56–0.84)2 Karabulut et oral cavity/ 100 WHO° 4 49–69% 27–45%3 al. 1995 oropharynx Tabor et al. oral cavity/ 43 WHO° 3 53% 0.58 2003 oropharynx Abbey et al. oral cavity/ 120 WHO° 6 38.5% 0.174 1998 oropharynx Brothwell et oral cavity/ 64 WHO° 3 51% 0.37 al. 2003 oropharynx Kujan et al. oral cavity/ 68 WHO and binary 4 WHO: WHO: 2006. oropharynx system 37.7% 0.22 (95% CI: ("low-risk" or (unweighte 0.11–0.35 "high-risk") d) unweighted) 92.8% 0.63 (95% CI: (weighted) 0.42–0.78 Binary weighted) system: Binary system: 74.3% 0.50 Mclaren et larynx 100 WHO and two 13 - WHO: 0.32 al. 2000 grade Two-grade: 0.52 (low and high Grade ° = WHO is not explicitely stated, but terms are in agreement with this system. Journal of Oral Medicine, Oral Surgery, Oral Pathology and Oral Radiology;2015;1(1):7-20 8 Sharma et al. Histological Grading Systems of Epithelial Dysplasia & Squamous Cell Carcinoma 1 = The unweighted kappa considers all disagreements to be equally important, while the weighted kappa (Kw) yields a higher reliability when disagreements between raters are small compared with when they are large. 2 = the pathologic diagnoses are restricted to three categories ('no abnormality/hyperkeratosis', 'mild, moderate, or severe dysplasia', 'carcinoma in situ/carcinoma'). 3 = when comparing the kappa values between the two pairs of pathologists with the same education, these values did not diverge from the general level of kappa values, indicating that the interobserver variability was due to individual differences rather than to educational background. 4 = Clinical information submitted with biopsy. More recently there has been an attempt to significant in the diagnosis of severe dysplasia. more carefully define the criteria for grading of Abnormal shaped rete pegs may also be seen, with epithelial dysplasia7,8. Largely this has involved an lateral extensions or small branches. These are quite adaptation of the scheme used in cervical pathology abnormal and may be the earliest signs of invasion. where it has been traditional to grade cervical Occasional lesions may show prominent acantholysis intraepithelial neoplasia (CIN) according to the with severe disruption of the architecture. Although thickness or levels of involved epithelium. It should the epithelium may be thickened, severe dysplasia is be noted however that full thickness change sometimes accompanied by marked epithelial analogous
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