Histological clonal change - A feature for dysplasia diagnosis
Main Article Content
Abstract
Aims: Histological diagnostic criteria are used for the assessment of the degree of dysplasia and hence the risk of cancer progression for premalignant lesions. Clonal changes in the form of hyperorthokeratosis and hyperchromasia that are sharply demarcated from adjacent areas are not currently part of the criterion for dysplasia diagnosis. The objective of this study was to determine whether such clonal change should be regarded as a diagnostic feature for dysplasia. The following histological conditions were used to define such change: (1) hyperorthokeratosis; (2) hyperchromatism but no other features of dysplasia; (3) sharp margin demarcation from adjacent area by both the hyperorthokeratosis and hyperchromasia (clonal change), and (4) no prominent rete ridges, marked acanthosis or heavy inflammation. Lesions fitting these criteria were termed orthokeratotic lesions with no dysplasia.
Methods: Patients from a population-based longitudinal study with more than 10 years of follow up were analyzed. Of the 214 patients with primary oral premalignant lesions, 194 had mild or moderate dysplasia (dysplasia group) and 20 fit the criteria for orthokeratotic lesions without dysplasia (orthokeratotic with no dysplasia group). The two groups were compared for their cancer risks using clinical (site and toluidine blue), histological (nuclear phenotype score), and molecular criteria (loss of heterozygosity) and by outcome (progression).
Results and conclusions: The lesions from orthokeratotic with no dysplasia group showed a similar cancer risk (clinical, histological and molecular risk) and time to progression as the dysplastic lesions. We recommend that the clonal change should be included as a criterion for dysplasia diagnosis.
Article Details
Copyright (c) 2018 Zhang L, et al.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Barnes L, Eveson JW, Reichart P, Sidransky D. World Health Organization Classification of Tumours, Pathology & Genetics of Head and Neck Tumours. Lyon, IARC Press, 2005.
Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: Predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008; 37: 127-133. Ref.: https://tinyurl.com/y7wlgsle
Woo SB, Grammer RL, Lerman MA. Keratosis of unknown significance and leukoplakia: a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014; 118: 713-724. Ref.: https://tinyurl.com/y7clxpgq
Kramer IR, El-Labban N, Lee KW. The clinical features and risk of malignant transformation in sublingual keratosis. Br Dent J. 1978; 144: 171-180. Ref.: https://tinyurl.com/y74lhmbp
Zhang L, Williams M, Poh CF, Laronde D, Epstein JB, et al. Toluidine blue staining identifies high-risk primary oral premalignant lesions with poor outcome. Cancer Res. 2005; 65: 8017-8021. Ref.: https://tinyurl.com/y9hh4kpf
Poh CF, Ng SP, Williams PM, Zhang L, Laronde DM, et al. Direct fluorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device. Head Neck. 2007; 29: 71-76. Ref.: https://tinyurl.com/y93npsns
Guillaud M, Zhang L, Poh C, Rosin MP, MacAulay C. Potential use of quantitative tissue phenotype to predict malignant risk for oral premalignant lesions. Cancer Res. 2008; 68: 3099-3107. Ref.: https://tinyurl.com/y9qyhj7s
Poh CF, Zhu Y, Chen E, Berean KW, Wu L, et al. Unique FISH Patterns Associated with Cancer Progression of Oral Dysplasia. J Dent Res. 2012; 91: 52-57. Ref.: https://tinyurl.com/yd4hysrh
Zhang L, Poh CF, Williams M, Laronde DM, Berean K, et al. Loss of heterozygosity (LOH) profiles-validated risk predictors for progression to oral cancer. Cancer Prev Res. 2012; 5: 1081-1089. Ref.: https://tinyurl.com/y9u7g2ya
Garnis C, Rosin MP, Zhang L, Lam WL. Alteration of AKAP220, an upstream component of the Rb pathway, in oral carcinogenesis. Int J Cancer. 2005; 116: 813-819. Ref.: https://tinyurl.com/yay2c495
Tsui IFL, Poh CF, Garnis C, Rosin MP, Zhang L, et al. Multiple pathways in the FGF signaling network are frequently deregulated by gene amplification in oral dysplasias. Int J Cancer. 2009; 125: 2219-2228. Ref.: https://tinyurl.com/y8xptat6
Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res. 2000; 6: 357-362. Ref.: https://tinyurl.com/y7c8t8fs
13. Zhang L, Lubpairee T, Laronde DM, Rosin MP. Should severe epithelial dysplasia be treated? Oral Oncol, 2016 (60), 125-129. https://goo.gl/72tPq6
Kobayashi T, Maruyama S, Abé T, Cheng J, Takagi R, et al. Keratin 10-positive orthokeratotic dysplasia: A new leucoplakia-type precancerous entity of the oral mucosa. Histopathology. 2012; 61: 910-920. Ref.: https://tinyurl.com/yb4bb2me
Aida J, Kobayashi T, Saku T, Yamaguchi M, Shimomura N, et al. Short telomeres in an oral precancerous lesion: Q-FISH analysis of leukoplakia. J Oral Pathol Med. 2012; 41: 372-378. Ref.: https://tinyurl.com/y8on84og