The Journal of Contemporary Dental Practice

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 21 , ISSUE 6 ( June, 2020 ) > List of Articles


Histopathological Classifications of Oral Leukoplakia and its Relation to Cell Proliferative Activity: A Case Series

Jéssica F de Camargo, Sara de F Ribeiro, Gisele Rovani, Carla Piardi, Valquíria de J Freitas, Diego J Gambin, Micheline S Trentin, Maria S Sandini Linden, João P de Carli

Keywords : Argyrophilic nucleolar organizer regions, Diagnosis, Histological classification, Leukoplakia, Prognosis

Citation Information : de Camargo JF, Ribeiro SD, Rovani G, Piardi C, Freitas VD, Gambin DJ, Trentin MS, Linden MS, Carli JP. Histopathological Classifications of Oral Leukoplakia and its Relation to Cell Proliferative Activity: A Case Series. J Contemp Dent Pract 2020; 21 (6):651-656.

DOI: 10.5005/jp-journals-10024-2840

License: CC BY-NC 4.0

Published Online: 23-07-2020

Copyright Statement:  Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.


Aim: This study relates the average number of nucleolar organizing regions (NORs) obtained in a series of cases of oral leukoplakia, with three methods of histopathological classification of such lesion. Materials and methods: This is a histopathological–histochemical laboratory cross-sectional study. The 18 cases of leukoplakia analyzed were filed at Pathology Service of the Biological Sciences Institute of the University of Passo Fundo, Rio Grande do Sul, Brazil (SDH/ICB/UPF) (2017 and 2018), from which epidemiological data were extracted. New histological sections were performed for impregnation by the argyrophilic nucleolar organizer regions (AgNOR) technique. The histopathological slides were analyzed by photon microscopy (1,000×), and the nuclei of 100 epithelial cells were photographed to count the number of NORs. Three methods were used for the lesions’ histopathological classification [World Health Organization (WHO), Brothwell, and binary system]. The means of NORs were compared with the three histopathological classifications by means of the t or analysis of variance (ANOVA) statistical tests, at a significance level of 5%. Results: According to the WHO classification method, most cases (11–61.1%) had a moderate classification. Evaluations by the Brothwell method showed moderate and mild classification in 50 and 38.9% of cases, respectively. According to the binary system, most cases (10–55.6%) had low risk. The average NORs found in 100 nuclei of each of the 18 lesions ranged from 2 to 4. When crossing the average NORs with the histopathological classification methods of the lesions by means of the t test or ANOVA, no significant relationship was noted. Conclusion: The average of NORs is not associated with the histological classifications of leukoplakias. Thus, the AgNOR method should be used with caution when differentiating different histological grades of leukoplakias. Clinical significance: The AgNOR method should be used with caution to determine the clinical treatment of oral leukoplakias, since no agreement was observed between this method and the histopathological classifications available for such lesion.

PDF Share
  1. Van Der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 2009;45(5):317–323. DOI: 10.1016/j.oraloncology.2008.05.016.
  2. Rhodus NL, Kerr AR, Patel K. Oral câncer: lukoplakia, premalignancy and squamous cell carcinoma. Dent Clin North Am 2014;58(2): 315–340. DOI: 10.1016/j.cden.2013.12.004.
  3. Queiroz SIML, Medeiros AMC, Silva JSP, et al. Clinical and histopathological evaluation and habits associated with the onset of oral leukoplakia and erythroplakia. J Bras Patol Med Lab 2014;50(2):144–149. DOI: 10.5935/1676-2444.20140008.
  4. Carreras-Torras C, Gay-Escoda C. Techniques for early diagnosis of oral squamous cell carcinoma: systematic review. Med Oral Patol Oral Cir Bucal 2015;20(3):305–315. DOI: 10.4317/medoral.20347.
  5. El-Naggar AK, Chan J, Takata T, et al. WHO classification of tumours. Pathology and Genetics of Head and Neck Tumors. 4th ed., Lyon, France: IARC Press; 2017.
  6. Warnakulasuriya S. Clinical features and presentation of oral potentially malignant disorders. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;125(6):582–590. DOI: 10.1016/j.oooo.2018.03.011.
  7. Starzyńska A, Pawłowska A, Renkielska D, et al. Estimation of oral leukoplakia treatment records in the research of the Department of Maxillofacial and Oral Surgery, Medical University of Gdansk. Postepy Dermatol Alergol 2015;32(2):114–122. DOI: 10.5114/pdia.2014. 40791.
  8. Ranganathan K, Kavitha L. Oral epitelial dysplasia: classifications and clinical relevance in risk assessment of oral potentially malignant disorders. J Oral Maxillofac Pathol 2019;23(1):19–27. DOI: 10.4103/jomfp.JOMFP_13_19.
  9. Yang YH, Ho PS, Lu HM, et al. Comparing doseresponse measurements of oral habits on oral leukoplakia and oral submucous fibrosis from a community screening program. J Oral Pathol Med 2010;39(4): 306–312. DOI: 10.1111/j.1600-0714.2009.00820.x.
  10. Mendez M, Carrard VC, Haas AN, et al. A 10-year study of specimens submitted to oral pathology laboratory analysis: lesion occurrence and demographic features. Braz Oral Res 2012;26(3):235–241. DOI: 10.1590/S1806-83242012000300009.
  11. Hallikeri K, Naikmasur V, Guttal K, et al. Prevalence of oral mucosal lesions among smokeless tobacco usage: a cross-sectional study. Indian J Cancer 2018;55(4):404–409. DOI: 10.4103/ijc.IJC_178_18.
  12. Mello FW, Miguel AFP, Dutra KL, et al. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med 2018;47(7):633–640. DOI: 10.1111/jop.12726.
  13. Narayan TV, Shilpashree S. Meta-analysis on clinicopathologic risk factors of leukoplakias undergoing malignant transformation. J Oral Maxillofac Pathol 2016;20(3):354–361. DOI: 10.4103/0973-029X.190900.
  14. Cho KJ, Song JS. Recent changes of classification for squamous intraepithelial lesions of the head and neck. Arch Pathol Lab Med 2018;142(7):829–832. DOI: 10.5858/arpa.2017-0438-RA.
  15. Baykul T, Yilmaz H, Aydin Ü, et al. Early diagnosis of oral cancer. J Int Med Res 2010;38(3):737–749. DOI: 10.1177/147323001003800302.
  16. Gale N, Blagus R, El-Mofty SK, et al. Evaluation of a new grading system fot laryngeal squamous intraepithelial lesions- a proposed unified classification. Histopathology 2014;65(4):456–464. DOI: 10.1111/his.12427.
  17. Abdalla Z, Walsh T, Thakker N, et al. Loss of epithelial markers is an early event in oral dysplasia and is observed within the safety margin of dysplastic and T1 OSCC biopsies. PLoS ONE 2017;12(12):e0187449. DOI: 10.1371/journal.pone.0187449.
  18. Geetha KM, LeeKy M, Narayan TV, et al. Grading of oral epitelial dysplasia: Points to ponder. J Oral Maxillofac Pathol 2015;19(2):198–204. DOI: 10.4103/0973-029X.164533.
  19. Tomazelli KB, Modolo F, Rivero ER. Evaluation of AgNORs in oral potentially malignant lesions. J Oncol 2015. 218280. DOI: 10.1155/2015/218280.
  20. Nikitakis NG, Pentenero M, Georgaki M, et al. Molecular markers associated with development and progression of potentially premalignant oral epitelial lesions: current knowledge future implications. Oral Surg Oal Med Oral Pathol Oral Radiol 2018;125(6):650–669. DOI: 10.1016/j.oooo.2018.03.012.
  21. Brothwell DJ, Lewis DW, Bradley G, et al. Observer agreement in the grading of oral epithelial dysplasia. Community Dent Oral Epidemiol 2003;31(4):300–305. DOI: 10.1034/j.1600-0528.2003.00013.x.
  22. Kujan O, Oliver RJ, Khattab A, et al. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol 2006;42(10):987–993. DOI: 10.1016/j.oraloncology.2005.12.014.
  23. Ploton D, Menager M, Jeannesson P, et al. Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level. J Histochemical 1986;18(1):5–14. DOI: 10.1007/bf01676192.
  24. Lee JJ, Hung HC, Cheng SJ, et al. Carcinoma and dysplasia in oral leukoplakias in Taiwan: prevalence and risk factors. Oral Surg, Oral Med, Oral Pathol, Oral Radiol, Endod 2006;101(4):472–480. DOI: 10.1016/j.tripleo.2005.07.024.
  25. Ferreira A, Souza EEL, Oliveira TC, et al. Prevalence and factors associated with oral potentially malignant disorders in Brazil's rural workres. Oral Dis 2016;22(6):536–542. DOI: 10.1111/odi.12488.
  26. Madan M, Chandra S, Raj V, et al. Evaluation of cell proliferation in malignant and potentially malignant oral lesions. J Oral Maxillofac Pathol 2015;19(3):297–305. DOI: 10.4103/0973-029X.174613.
  27. Chowdhry A, Deshmukh RS, Shukla D, et al. Quantitative estimation of AgNORs in normal, dysplastic and malignant oral mucosa. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014;158(2): 282–287. DOI: 10.5507/bp.2013.002.
  28. Sowmya G, Nahar P, Astekar M, et al. Analysis of silver binding nucleolar organizer regions in exfoliative cytology smears of potentially malignant and malignant oral lesions. Biotech Histochem 2017;92(2):115–121. DOI: 10.1080/10520295.2017.
  29. Manchanda A, Shetty DC. Reproducibility of grading systems in oral epithelial dysplasia. Med Oral Patol Oral Cir Bucal 2012;17(6): e935–e942. DOI: 10.4317/medoral.17749.
  30. Spolidorio LC, Neves KA, Soares CP, et al. Evaluation of argyrophilic nucleolar organizer regions in oral tumor progression. Micron 2002;33(7-8):605–608. DOI: 10.1016/s0968-4328(02)00031-8.
  31. Carmo MA, Silva EC. Argyrophilic nucleolar organizer regions (AgNORs) in ameloblastomas and adenomatoid odontogenic tumours (AOTs). J Oral Pathol Med 1998;27(4):153–156. DOI: 10.1111/j.1600-0714.1998.tb01932.x.
  32. Khushbu B, Chalishazar M, Kale H, et al. Quantitative and qualitative assessment of argyrophilic nucleolar organizer regions in normal, premalignant and malignant oral lesions. J Oral Maxillofac Pathol 2017;21(3):360–366. DOI: 10.4103/jomfp.JOMFP_52_15.
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.