Challenges in the Diagnosis of Leukoplakia: A Literature Review
DOI:
https://doi.org/10.5335/rfo.v31i1.18517Keywords:
Diagnosis, Leukoplakia, Mouth Neoplasms, Carcinoma, Squamous Cell, ReviewAbstract
Objectives: To synthesize available scientific evidence regarding the diagnosis of oral leukoplakia, emphasizing its clinical characteristics, differential diagnosis, adjunctive diagnostic methods, and aspects related to malignant transformation potential, in order to support the clinical practice of dental surgeons. Literature review: A narrative literature review was conducted by searching the PubMed, Embase, LILACS, and Cochrane databases, using the MeSH terms "Leukoplakia," "Oral Potentially Malignant," "Squamous Cell Carcinoma," "Mouth Neoplasms," and "Diagnosis." Observational studies, clinical studies, and narrative and systematic reviews published in English, Portuguese, and Spanish were included. A manual search of references and consultation of oral pathology textbooks were also performed. The literature shows that leukoplakia is the most prevalent potentially malignant oral lesion, exhibiting heterogeneous clinical behavior and a variable risk of malignant transformation. Diagnosis is essentially clinical, based on the exclusion of other white lesions, with biopsy being indispensable for diagnostic confirmation and the assessment of epithelial dysplasia. Final considerations: Early recognition of leukoplakia and an appropriate differential diagnosis are fundamental to reducing morbidity and mortality associated with squamous cell carcinoma and promoting better clinical outcomes.
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1. Montero PH, Patel SG. Cancer of the oral cavity. Surg Oncol Clin N Am. 2015;24(3):491-508. doi:10.1016/j.soc.2015.03.006.
2. Maia HC, Pinto NA, Pereira JS, Medeiros AM, Silveira EJ, Miguel MC. Lesões orais potencialmente malignas: correlações clínico-patológicas. Einstein (São Paulo). 2016;14(1):35-40. doi:10.1590/S1679-45082016AO3578.
3. Jain S, Dhall K, Brar GS, Gupta S, Jain K, Garg N, et al. Outcome of upfront surgically resected patients of oral tongue squamous cell carcinoma and factors affecting it: experience from tertiary care facility in North India. Indian J Otolaryngol Head Neck Surg. 2024;76(5):4479-4486. doi:10.1007/s12070-024-04889-0.
4. Scutti JAB, Pineda M, Emerick Jr E, Almeida ER. Carcinoma de células escamosas de cabeça e pescoço (HNSCC): desvendando os mistérios do microambiente tumoral. Rev Assoc Paul Cir Dent. 2016;70(2):156-163.
5. Cirillo A, Marinelli D, Romeo U, Messineo D, De Felice F, De Vincentiis M, et al. Correction: Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis. BMC Cancer. 2024;24:487. doi:10.1186/s12885-024-12249-y.
6. Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MÁ, Kerr AR, et al. Oral potentially malignant disorders: a consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021;27(8):1862-1880. doi:10.1111/odi.13704.
7. Silveira EJD, Lopes MFF, Silva LMM, Ribeiro BF, Lima KC, Queiroz LMG. Lesões orais com potencial de malignização: análise clínica e morfológica de 205 casos. J Bras Patol Med Lab. 2009;45(3):233-8. doi:10.1590/S1676-24442009000300008.
8. Ramos RT, Paiva CR, Filgueiras AMO, Silva-Junior GO, Cantisano MH, Ferreira DC, et al. Leucoplasia oral: conceitos e repercussões clínicas. Rev Bras Odontol. 2017;74(1):51-5. doi:10.18363/rbo.v74n1.p.51.
9. Speight PM, Khurram SA, Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):612-627. doi:10.1016/j.oooo.2017.12.011.
10. van der Waal I. Oral potentially malignant disorders: is malignant transformation predictable and preventable? Med Oral Patol Oral Cir Bucal. 2014;19(4):e386-90. doi:10.4317/medoral.20205.
11. Neville BW, Damm DD, Allen CM, Chi AC. Oral and maxillofacial pathology. 4th ed. St. Louis: Elsevier; 2016.
12. Regezi JA, Sciubba JJ, Jordan RCK. Oral pathology: clinical pathologic correlations. 7th ed. St. Louis: Elsevier Saunders; 2017.
13. González-Arriagada WA, Canedo-Marroquin G, Adorno-Farías D, Fernández-Ramires R. New insights into the role of the oral leukoplakia microenvironment in malignant transformation. Front Oral Health. 2024;5:1363052. doi:10.3389/froh.2024.1363052.
14. Aguirre-Urizar JM, Lafuente-Ibáñez de Mendoza I, Warnakulasuriya S. Malignant transformation of oral leukoplakia: systematic review and meta-analysis of the last 5 years. Oral Dis. 2021;27(8):1881-95. doi:10.1111/odi.13810.
15. Mohammed F, Fairozekhan AT. Oral leukoplakia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
16. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36(10):575-80. doi:10.1111/j.1600-0714.2007.00582.x.
17. Sivaramakrishnan G, Sridharan K. Prevalence of oral potentially malignant disorders in smokeless tobacco users with or without areca nut: a meta-analysis. J Oral Pathol Med. 2025 Nov;54(10):921-933. doi:10.1111/jop.70045.
18. Villa A, Sonis S. Oral leukoplakia remains a challenging condition. Oral Dis. 2018;24(1-2):179-83. doi:10.1111/odi.12781.
19. Warnakulasuriya S. Clinical features and presentation of oral potentially malignant disorders. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):582-90. doi:10.1016/j.oooo.2018.03.011.
20. Kharma MY, Tarakji B. Current evidence in diagnosis and treatment of proliferative verrucous leukoplakia. Ann Saudi Med. 2012;32(4):412-4. doi:10.5144/0256-4947.2012.412.
21. Zdrojewski J, Nowak M, Nijakowski K, Jankowski J, Scribante A, Gallo S, et al. Potential immunohistochemical biomarkers for grading oral dysplasia: a literature review. Biomedicines. 2024;12(3):577. doi:10.3390/biomedicines12030577.
22. Clarkson E, Hadioonzadeh R, Peters SM. Treatment of oral dysplasia. Dent Clin North Am. 2024;68(1):133-149. doi:10.1016/j.cden.2023.07.008.
23. Celentano A, Cirillo N. Diseases with oral malignant potential: Need for change to inform research, policy, and practice. J Oral Pathol Med. 2024;53(8):495-501. doi:10.1111/jop.13573.
24. Yang FR, Fang JK, Lan QY, Lu Y, Hua H, Zhou PR. Risk of malignant transformation in patients with oral leukoplakia and type 2 diabetes mellitus. Int Dent J. 2026 Aug;76(4):109600. doi:10.1016/j.identj.2026.109600.
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