Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis

Abstract

Background: Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oral potentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinical practice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF to outline the clinical behavior and challenges in the management of this high-risk group in clinical practice.

Material and methods: We retrospectively analyzed cases of six Indian patients (four with OSF) managed over a period of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, medical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits, the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or when surgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twice daily was initiated.

Results: All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesions were either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional or systemic metastasis. Despite thorough interventions, the patients died of, or with the disease.

Conclusions: The occurrence of two or more oral potentially malignant disorders poses challenges in patient management and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to assess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.

Figure 1

Clinical and histological changes from first visit (2005) to final follow-up (2016) illustrating spread of lesion and nodal involvement in case 1. a) Intraoral image of homogenous leukoplakia of tongue observed on the first visit (2005); b) Post-excision multiple white patches observed during follow-up (2006); c) Subsequent post-excision recurrent lesions (2013); d) Fourth follow-up (2013) showing extensive white patches covering the entire tongue; e) Enlarged lymph node observed on follow-up (2016); f) Hematoxylin and eosin (H & E) stained image (4x) of initial biopsy (2005) showing low-risk dysplastic lesion. g,h,i) Subsequent biopsies (2006 - 2013) showing high-risk dysplasia (H & E; 10x); j) Follow-up biopsy (2016) showing squamous cell carcinoma. (H & E; 10x).

Figure 2

Clinical and histological changes from first visit (2005) to final follow-up (2013) in case 2; a) Clinical image showing restricted mouth opening and intraoral extensive verrucous and red and white patches on the palate and buccal mucosa (2005); b,c) Clinical images showing recurrent lesions over the palate, buccal mucosa and commissure of mouth (2007,2008); d) Follow-up images (2013) showing white patches and a verrucous growth; e,f) Photomicrograph showing low- to high-risk dysplasia in biopsy of initial (H & E; 10x) and recurrent lesions (H & E; 40x); g,h) Photomicrograph of final biopsy showing early change to microinvasive squamous cell carcinoma (H & E; 10x).

Figure 3

Clinical, computed tomography and histological photographs from first visit (2014) to final follow-up (2020) for case 3. a) Intraoral photograph showing partially edentulous maxilla and diffuse erythroleukoplakia lesions over the alveolar mucosa and buccal mucosa. Posterior palate shows papillomatous exophytic lesions (2014); b,c,d) Post-excision extensive recurrence of erythroleukoplakia over the buccal mucosa, left tongue and palate (2017); e,f) In the sixth year (2020) extensive verrucous and ulcerated lesions were observed in the posterior maxilla and buccal mucosa; g,h) Extraoral photo showing restricted mouth opening (18mm) and involvement of commissure of lip; i) Computed tomography (2020) showing destructive lesions involving the left maxilla, orbit, infra temporal fossa and zygoma; j) Photomicrograph of final biopsy (2020) showing change to squamous cell carcinoma (H & E; 10x).

Figure 4

Clinical, radiograph and histological presentation from first visit to final follow-up (2017 to 2022) for case 4. a) Initial clinical presentation showing restricted mouth opening and homogenous white lesion covering the tongue (2017); b) New red-white lesions involving ventral surface of tongue (2017); c) Post-excision follow-up showing new nodular lesion over the anterior part of tongue (2018); d,e) Intraoral photographs showing new red-white lesions over the right lateral border of tongue (2019); f) Post reconstruction follow-up (2020) images showing reduced mouth opening and involvement of alveolar mucosa; g) Chest x-ray showing opacities in mediastinal region and lungs suggestive of distant metastasis (2022); h) Photomicrograph of initial biopsy showing low-risk dysplasia (H & E; 10x); i) Higher magnification of initial biopsy showing koilocytic change in the epithelium (H & E; 40x); j) Photomicrograph of third biopsy showing high-risk dysplasia with increased number of mitotic figures (H & E; 40x); k) Photomicrograph of subsequent follow up (2019) showing squamous cell carcinoma (H & E; 10x); l) Photomicrograph of final biopsy (2020) showing well-differentiated squamous cell carcinoma (H & E; 10x).