Lichenoid areas may arise in early stages of proliferative verrucous leukoplakia: A long-term study of 34 patients

Abstract

Background: Proliferative verrucous leukoplakia is considered an uncommon oral potentially malignant disorder with a high malignant transformation rate. The objective of this paper was to define its cancer incidence and related risk factors.

Methods: A retrospective audit of 34 patients diagnosed with proliferative verrucous leukoplakia from a university-based unit, during the period from 1995 to 2019 was performed. The mean number of visits was 23 ± 18.6. The follow-up was divided into four-time intervals to evaluate the clinical presentation, number of lesions, dysplasia grade, and malignant transformation rate.

Results: The majority of patients were females 29 (85.3%), with verrucous component (77.8%), with a gingival presentation (31.8%), and with a preceding lichenoid area (44.1%). Eleven patients (32.4%) were affected by oral cancer during the follow-up, developing a total of 15 carcinomas. The mean age of malignant transformation was 67.2 ± 12.9 years, particularly 8 ± 8.5 from the onset of the lesions. Warty forms presented a higher mean estimate for malignant transformation (15.2 years, 95% confidence interval 4.4-26 years) than nodular forms (1.9 years, 95% confidence interval 1.9-1.9) (p = 0.019). Patients with an initial proliferative verrucous leukoplakia diagnosis suffered a higher risk of malignancy, particularly 15.55 times (95% confidence interval 1.69-143.17; p = 0.015) than those who did present a preceding area with lichenoid morphology.

Conclusion: Proliferative verrucous leukoplakia presented a high malignant transformation rate and sometimes displayed preceding oral lichenoid areas in early stages. Further studies are needed to understand the impact of these lichenoid areas in proliferative verrucous leukoplakia progression.

Keywords: dysplasia; malignant transformation; oral lichen planus; oral lichenoid lesions; proliferative verrucous leukoplakia.

FIGURE 1

Representative cases of patients affected by proliferative verrucous leukoplakia. (A, B) Patient with a widespread non‐homogenous leukoplakia of the buccal mucosa that ended up in a verrucous carcinoma. (C, D) Patient with a widespread homogenous gingival and palatal leukoplakia that progressed to a conventional squamous cell carcinoma. (E, F) Patient affected by a gingival proliferative verrucous leukoplakia treated with laser vaporization. Images in (G, H) present a patient with an initial gingival leukoplakia that underwent lately a conventional squamous cell carcinoma of the hard palate.

FIGURE 2

Heat‐map‐like diagram representing the increase/decrease of number of lesions in each affected site for patient, according to the location and the time intervals. Each number across tables reflects the number of lesions during the transition of time intervals and studied regions (columns) in the cohort of patients (rows). In terms of colors: red implies an increase in the number of lesions of the studied area, yellow implies a static clinical behavior, and green a reversal in the number of affected regions. Time intervals were segmented as follows: T0 the initial visit with histopathological assessment, T1 ¼ of the follow‐up, T2 ¾ of the follow‐up, and TF the last recorded appointment.

FIGURE 3

Kaplan–Meier malignant transformation curves according to the polypharmacy use (A) and clinical form (B)