Clinical, histopathological characteristics and malignant transformation of proliferative verrucous leukoplakia with 36 patients: a retrospective longitudinal study

Abstract

Background: Proliferative verrucous leukoplakia (PVL), distinguished by its malignant transformation rate of 43.87% to 65.8%, stands as the oral potentially malignant disorder with the highest propensity for malignancy. PVL is marked by distinctive heterogeneity regarding the clinical or histopathological characteristics as well as prognostic factors pertinent to this condition. The purpose of this study is to compile and assess the clinicopathological features, malignant transformation, and associated risk factors in patients diagnosed with PVL.

Methods: This study is a hospital-based retrospective longitudinal study of 36 patients diagnosed with PVL from 2013 to 2023. We conducted complete clinical and histopathological evaluations of the patients.

Results: The cohort comprised 16 males and 20 females, yielding a male-to-female ratio of 1:1.25. The follow-up period ranged from 8 to 125 months, with an average of 47.50 months. The most common clinical type of lesion was the verrucous form (58.33%), and the gingiva was the most common site (44.44%). Each patient had between 2 to 7 lesions, averaging 3.36 per patient. During the follow-up period, twelve patients (33.3%) developed oral cancer, with an average time to malignant transformation of 35.75 months. Kaplan-Meier survival analysis indicated that patients with complaints of pain, roughness, or a rough sensation, with diabetes, and the presence of cytologic atypia histologically showed a higher risk of malignant transformation (p < 0.05). In this study, the rate of malignant transformation in the treatment group (5/23) was lower than that in the untreated group (7/13), however, no statistically significant difference (p = 0.05).

Conclusion: The main complaints of pain, roughness, or foreign body sensation, coupled with cytologic atypia histologically are indicative of an increased risk of malignant transformation in PVL. Further research is needed to elucidate the influence of these clinicopathological parameters on the malignant progression of PVL.

Keywords: Malignant transformation; Oral cavity; Oral epithelial dysplasia; Proliferative verrucous leukoplakia.

Fig. 1

The flow chart of the patients screening

Fig. 2

Oral clinical manifestations in patients with PVL: A a large area of white verrucous lesion with a raised and irregular surface texture is predominantly localized along the right lateral border of the tongue; B the widespread area of white, fissured plaque on the left buccal mucosa; C a thick white lesions spread along the gingival margin; D the white warty lesion with localized erythematous appearance involving the upper maxillary gingiva

Fig. 3

The histopathological characteristics in patients with patients with PVL: A marked orthohyperkeratosis and epithelial corrugation without dysplasia (H&E stain, original magnification × 200); B corrugated hyperorthokeratotic lesions with a verucco-papillary architecture with band-like lymphohistiocytic infiltrate (H&E stain, original magnification × 40); C epithelial proliferation with premature keratinization covered by sharp lateral margins (H&E stain, original magnification × 200); D the epithelium is bulky and thickened with cytologic atypia(H&E stain, original magnification × 80)

Fig. 4

A heat-map-like diagram illustrating the therapeutic interventions administered to the 23 patients, categorized by treatment sessions. Each cell represents a specific intervention and corresponds to a patient in the queue by columns and the respective treatment session by rows (Y: Yes, N: No, NA: Not available)

Fig. 5

Kaplan–Meier malignant transformation curves according to cytologic atypia

Fig. 6

Kaplan–Meier malignant transformation curves according to complaint

Fig. 7

Kaplan–Meier malignant transformation curves according to diabetes mellitus