Oral Proliferative Verrucous Leukoplakia Research Articles

Malignant transformation of oral proliferative verrucous leukoplakia: A systematic review and meta‐analysis

To investigate the available evidence on the malignant transformation (MT) of oral proliferative verrucous leukoplakia (PVL). We searched six main electronic and three grey literature databases in a two-phase process. Cohort studies investigating MT of PVL were eligible for inclusion. The risk of bias (RoB) was assessed using a specific tool developed by the Joanna Briggs Institute. Proportion meta-analyses were performed using a random-effects model. Study selection resulted in the inclusion of 17 studies. The pooled proportion of MT was 43.87% (95% CI=31.93-56.13). Females (64.02%, 95% CI=54.87-72.75) were more affected by PVL than males (35.98%, 95% CI=27.25-45.13). Gingiva (39.6%) and buccal mucosa (21.6%) were the most frequent PVL sites. No conclusive results were found between MT and sex or age distribution, tobacco, or alcohol consumption. Gingiva was the most common site for MT (39.9%), and the most frequent histopathological subtype was conventional squamous cell carcinoma (62.1%). Four studies were classified as low, nine as moderate, and four as high RoB. The MT pooled proportion was 43.87%. Among OPMDs, PVL has the highest risk to transform to malignancy. Development and agreement on diagnostic criteria for PVL would reduce the heterogeneity among future studies.

Lichenoid morphology could be an early feature of oral proliferative verrucous leukoplakia

Recognition and differentiation of early forms of proliferative verrucous leukoplakia (PVL) could be a challenge to both clinicians and pathologists. To report on a retrospective study that was carried out on 51 cases of PVL that were initially diagnosed as frictional keratosis, oral leukoplakia or oral lichen planus. A secondary objective is to report on the outcome of malignant transformation during follow-up. Records of patients seen at an oral medicine clinic with the final clinical diagnosis of PVL were audited for early clinical and histopathologic features in their biopsy at first presentation, and for subsequent malignant transformation. Fifty-one patients (25 men and 26 women) with a mean age 51years (men) and 53years (women) at initial presentation were studied. 28% men and 11.5% women were current smokers. Initial clinical diagnoses were frictional keratoses (n=4), Leukoplakia (n=17) and lichen planus (n=30). Epithelial dysplasia was reported in the initial biopsy in 12 cases and lichen planus/lichenoid features in 22 cases (22/51; 43%). Malignant transformation occurred in 11/51 patients (21.5%). Lichen planus or lichenoid lesions could be the initial presentation of many PVL cases that later develop multiple leukoplakic lesions with a final diagnosis of PVL.

Malignant transformation of oral proliferative verrucous leukoplakia: a series of 48 patients with suggestions for management

Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral mucosal leukoplakia of unknown origin, characterized by high rates of malignant transformation. Different diagnostic criteria, terminologies, and therapeutic approaches have been proposed since the first report in 1985. There remains no general agreement regarding the clinical and histological diagnosis, prevention, and correct management of this disease. This retrospective study investigated 48 patients affected by PVL showing at least one malignant transformation and followed up at 2-month intervals. Twenty-five were female (52.1%) and 23 (47.9%) were male; their median age was 67 years (range 40–93 years). Follow-up ranged from 18 to 240 months. Clinical examination included the use of Lugol’s solution to prevent clinical underestimation of the margins and toluidine blue for suspicious areas. Surgical excision by scalpel was the preferred treatment for suspicious lesions, with only five carcinomas surgically removed by diode laser and two by CO2 laser. All specimens were accurately mapped after formalin fixation. Fifteen patients (31.3%; 10 female, five male) developed one oral carcinoma, while 33 (68.7%) developed two or more primary tumours (range 3–12). Only four patients (8.3%), who developed between 2 and 8 oral squamous cell carcinomas (OSCCs), died of tumour-related causes. The pre-surgical clinical workup, subsequent surgical treatment, and follow-up are key to success for patients affected by PVL with malignant transformation into stage 1 OSCC and/or verrucous carcinoma, leading to a high overall survival rate.

Oral proliferative verrucous leukoplakia: An enigmatic lesion with emphasis on its differential diagnosis

Oral proliferative verrucous leukoplakia (OPVL) is a distinct clinical form of oral leukoplakia (OL). It is one of the rare clinicopathological entities that is considered as a potentially malignant oral mucosal disorder with an increased rate of progression to oral squamous cell carcinoma (OSCC) and a very high recurrence rate. Initially, the condition develops as focal clinical hyperkeratosis that progresses gradually and becomes a wide multifocal disease with gross exophytic features. It is a slow-growing, long-term progressive, and enigmatic lesion that is difficult to define and disclose. We report here, a case of OPVL in the right mandibular alveolar ridge, clinical and diagnostic aspects, differential diagnosis, and histologic features of this relatively rare entity.

Proliferative verrucous leukoplakia and its tumor markers: Systematic review and meta-analysis.

The aim was to update information on oral proliferative verrucous leukoplakia (PVL), a disease of verrucous-like lesions with high risk of malignancy, and its biomarkers. A systematic search of literature on PVL and its biomarkers showed 22 biomarkers that were investigated in 19 papers. A meta-analysis was possible for human papillomavirus (HPV), aneuploidy, Ki-67, and p53. Aneuploidy was found consistently (I2 = 0%, P = 0.61) in 92% (95% CI 80%-99%) of the PVL cases. P53 positivity prevalence was 27% (95% CI 15%-40%) in two available studies (I2 = 0%, P = 0.64). With HPV and Ki-67, the most outlying studies needed to be removed and after that the pooled HPV positivity prevalence (I2 = 24%, P = 0.27) was 5% (95% CI 0%-14%) and for Ki-67 (I2 = 9%, P = 0.33) 14% (95% CI 6%-26%). With the evidence of the current literature, aneuploidy could value as a biomarker of PVL but should be further validated.

Diode laser surgery in the treatment of oral proliferative verrucous leukoplakia associated with HPV-16 infection

BackgroundProliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder, characterized by multifocal expression, progressive clinical evolution, and a high rate of malignant transformation. Evidence-based information regarding optimal PVL management is lacking, due to the paucity of data. The present report describes a case of PVL associated with HPV-16 infection and epithelial dysplasia treated by diode laser surgery, and the outcome of disease clinical remission over a 2-year follow-up period.Case reportA 61-year-old Caucasian male with oral verrucous hyperkeratosis presented for diagnosis. The lesions were localized on the maxillary gingiva and palatal alveolar ridge. Multiple biopsy specimens have been taken by mapping the keratotic lesion area. Microscopic examination was compatible with a diagnosis of PVL with focal mild dysplasia, localized in the right maxillary gingiva. Polymerase chain reaction (PCR) was done for human papillomavirus (HPV) detection which revealed presence of HPV DNA, and the genotype revealed HPV 16 in the sample. The PVL in the right gingival area was treated on an outpatient basis by excision with a diode laser. This approach resulted in good clinical response and decreased morbidity over a 2-year follow-up period.ConclusionsThis case illustrates the benefit of a conservative approach by diode laser treatment than wide surgical excision for management of the PVL lesions associated with mild dysplasia and HPV-16 infection.

PROLIFERATIVE ERYTHRO-LEUKOPLAKIA: A VARIANT OF PROLIFERATIVE VERRUCOUS LEUKOPLAKIA?

Oral proliferative verrucous leukoplakia (PVL) is a rare form of progressive multifocal leukoplakia with a high rate of malignant transformation (MT). However, not all PVLs are entirely white/keratotic or fissured. This study aims to characterize PVL from a clinical and histopathologic standpoint.

Proliferative verrucous leukoplakia: A diagnostic dilemma

Oral leukoplakia is one of the most common potentially malignant disorders of the oral cavity. Many variants of oral leukoplakia exist, with oral proliferative verrucous leukoplakia (OPVL) being one. OPVL, a slow growing, long-term progressive lesion was first described in 1985 by Hansen et al. It is an aggressive form of oral leukoplakia with multifocal presentation, high rates of malignant transformation and recurrence. It is a rare clinico-pathological entity, which remains an enigma even today. The term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Its etiology too remains unclear until date. Tobacco use does not seem to have a significant influence on the appearance or progression of PVL. These lesions are known to occur in both smokers and nonsmokers. In the light of current information available, this article describes the etiology, clinical aspects, histological features, and various diagnostic criteria of OPVL.

Oral proliferative verrucous leukoplakia with oral submucous fibrosis treated with CO2laser

Oral leukoplakia is one of the most common physiologic as well as pathologic white lesion in the oral cavity. Of the many variants, oral proliferative verrucous leukoplakia (OPVL) is a rare clinicopathological entity of unknown etiology. OPLV initially develops as a white hyperkeratotic plaque that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. Published case series with long-term follow-up describes OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. This article describes a rare case report of OPVL associated with oral submucous fibrosis in the light of current information with clinical and histological aspect in a young patient, which was successfully treated with CO2Laser.

Oral proliferative verrucous leukoplakia treated with the photodynamic therapy: a case report

About 60% of the oral cancer arise on a pre-existent potentially malignant disorder of oral mucosa like the oral proliferative verrucous leukoplakia. The treatment with the photodynamic therapy of these lesions represents, in the last years, an innovative, non-invasive and effective therapeutic possibility to achieve the secondary prevention of oral cancer. In the last decade, case reports have described patients with similar treated through a photochemical reaction induced by laser light. The aim of this study is to evaluate the effectiveness of the topical 5-ALA photodynamic therapy in the treatment of a case of Oral proliferative verrucous leukoplakia. A female patient of 80 years old affected by white verrucous plaques on the right buccal mucosa was recruited for our case report. The right side lesion was treated with the photodynamic therapy with topical administered 5-aminolevulinic acid using the 635 nm laser light to activate the photosensitizer. The lesion showed complete response after 4 sessions of photodynamic therapy and no recurrence was noticed after 12 months. The photodynamic therapy can be considered an effective treatment in the management of oral verrucous proliferative leukoplakia, but more clinical trials, with prolonged follow-up controls, are necessary to evaluate its effectiveness in the mid and long time period.

A Case Report of Conservative Management of Extensive Proliferative Verrucous Leukoplakia Using a Carbon Dioxide Laser

The purpose of this report was to describe a clinical case of conservative management of extensive proliferative verrucous leukoplakia (PVL) using a carbon dioxide laser, as an alternative to complete glossectomy, which led to a sustained successful outcome over a 12-year follow-up period. Patients with oral PVL, a high risk premalignant condition, are often treated by wide surgical excision. This approach can lead to significant morbidity and compromised quality of life. A 50-year-old male with PVL and superficially invasive carcinoma, who had previously refused a complete glossectomy, presented for treatment. A baseline MRI and careful clinical evaluation by symptom review, inspection, palpation, toluidine blue staining, and biopsy were performed at baseline and at each follow-up to rule out invasive carcinoma. The PVL was treated on an outpatient basis by serial carbon dioxide laser excisions and/or vaporizations. This approach resulted in good clinical response and decreased morbidity over a 12-year follow-up period, as compared with the option of wide surgical excision. This case illustrates the benefit of a more conservative treatment approach than wide surgical excision for PVL with superficially invasive carcinoma. This approach requires greater skills, training, and experience in the evaluation of oral premalignant or malignant changes. However, decreased long-term morbidity and improved quality of life make it a valuable treatment option for PVL.

High incidence of DNA ploidy abnormalities and increased Mcm2 expression may predict malignant change in oral proliferative verrucous leukoplakia

To assess the DNA content of cases of oral proliferative verrucous leukoplakia (PVL) and correlate the DNA ploidy findings with the expression of Mcm2, geminin, and Ki67, and with clinicopathological data. DNA quantification was performed by image cytometry using the ACIS III Automated Cellular Imaging System. Expression of Ki67, Mcm2 and geminin was determined by immunohistochemistry. There were 21 cases of PVL, the female/male ratio was 6:1, and the average age was 65.5years. Seventeen patients (81.0%) did not report tobacco and alcohol consumption. Nine patients (42.9%) developed verrucous or squamous cell carcinoma. Levels of Mcm2 expression showed a positive correlation with increasingly severe epithelial changes (P=0.03). Twenty patients had their DNA examined by ACIS III, and 19 (95%) showed aneuploidy. The frequency and severity of aneuploidy (P<0.0001), the mean values of the DNA heterogeneity index (P<0.0001) and the 5n-exceeding fractions (P= 0.0007) increased according to epithelial alterations. Abnormal DNA content was observed even in the more indolent lesions. Mcm2 expression and DNA ploidy analysis could be used to predict areas of malignant transformation. The clinicopathological findings associated with the immunohistochemical and DNA ploidy results support the distinct and aggressive profile of this entity.

Oral proliferative verrucous leukoplakia: A case report with an update

White lesions both physiologic as well as pathologic are relatively frequent in the oral cavity, the most common pathology being oral leukoplakia (OL). There are many variants of OL, one of which is oral proliferative verrucous leukoplakia (OPVL). OPVL is a rare clinico-pathological entity, which is slow growing, long-term progressive lesion, but remains an enigmatic and difficult to define. The etiology of OPVL remains still unclear. Tobacco use does not seem to have a significant influence on the appearance of OPVL. These lesions may occur both in smokers and non-smokers. It is observed more frequently in women and elderly patients over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. Various published case series have presented OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. This article describes the clinical aspects and histologic features of an OPVL case that demonstrated the typical behavior pattern in a long-standing, persistent lesion and discusses this relatively rare entity in light of current information.

High incidences of DNA ploidy abnormalities associated with MCM2 immunoexpression may contribute to predict areas prone to malignization in oral proliferative verrucous leukoplakia

High incidences of DNA ploidy abnormalities associated with MCM2 immunoexpression may contribute to predict areas prone to malignization in oral proliferative verrucous leukoplakia

Oral proliferative verrucous leukoplakia: Underdiagnosed oral precursor lesion that requires retrospective clinicopathological correlation

We present herein a case of oral proliferative verrucous leukoplakia (OPVL) and discuss this relatively rare entity in light of current information. A 59-year-old woman, non-smoker, presented with a verrucous plaque at the left ventral and dorsal surfaces of the tongue that she had first noticed in 2001. At that time, the plaque was excised and revealed benign hyperkeratosis. The growth recurred and was again excised. Histologically it was characterized by a verrucous epithelial hyperplasia, hyperkeratosis and mild epithelial dysplasia. Human papillomavirus (HPV) DNA typing for low, intermediate, and high-risk groups was also performed and no etiological link between HPV and this lesion was found. The overall progressive clinical and histopathological findings were considered diagnostic for OPVL. Because of the lack of specific histological features and the progressive proliferative characteristic of OPVL, the recognition of this underdiagnosed entity is critical because apparently innocent looking oral verrucous lesions, irrespective of the presence of dysplasia, may progress into carcinoma. On the other hand, it is of interest that the early phase of these lesions usually exhibits an interface lymphocytic infiltrate that may mimic an oral lichenoid stomatitis such as lichen planus. It is therefore important to follow-up closely any patient with oral leukoplakia and those diagnosed with non-specific lichenoid stomatitis.

Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL

Abstract.Proliferative verrucous leukoplakia (PVL) is a unique oral white lesion in which human papillomavirus (HPV) may play a role. PVL behaves far more aggressively than other forms of leukoplakia with a high rate of recurrence after surgical excision, and relentless progression to verrucous hyperplasia and to verrucous or squamous cell carcinomas. The treatment of PVL is usually by surgery, but there is often early recurrence.This study was an open trial of surgery in 25 patients with oral HPV-positive PVL, compared with combined therapy using surgery and methisoprinol in another group of 25 patients with oral PVL. Six months postoperatively there was a significant difference, with 18 recurrences in the patients treated by surgery alone compared to only two recurrences in the patients treated also with methisoprinol (isoprinosine or inosine pranobex), a synthetic agent with immunomodulatory properties and some antiviral activity against HPV. Eighteen months postoperatively there were no further recurrences in the patients treated by surgery alone but another two recurrences in the patients treated with methisoprinol. Overall, by 18 months follow-up, there were 18 recurrences in the group treated by surgery alone, compared with four in those also receiving methisoprinol.The use of this antiviral agent appeared to offer a significant enhancement to the surgical management of PVL.

Proliferative verrucous leukoplakia of the gingiva.

The purpose of this study was to describe the clinical-pathologic features of what appears to be a gingival form of proliferative verrucous leukoplakia. Ten adult patients with recurrent and histologically progressive gingival leukoplakias who were diagnosed and treated at the University of California, San Francisco between 1994 and 1999, comprised the subject group for this investigation. Clinical and microscopic features were reviewed. Proliferation indices and p53 expression were evaluated immunohistochemically, and the presence of human papillomavirus (HPV) DNA was determined by using polymerase chain reaction (PCR) amplification. Lesions presented as solitary or regional flat/papillary/verrucal leukoplakias of the free and attached gingiva (tooth-bearing areas only). With time, flat lesions developed a papillary or verruciform profile. Although lesions were recurrent, they were confined to the gingiva, and multiple lesions did not develop. Half the patients used tobacco, and HPV could not be detected by using PCR. Microscopically, 6 cases began as hyperkeratotic lesions, and 4 initially exhibited a psoriasiform pattern with a marked inflammatory component. With recurrences, the lesions became progressively atypical histologically. The proliferation indices for these lesions showed modest increases over normal epithelium, and positive p53 staining was evident in 4 of 10 cases, indicating a disruption of the keratinocyte cell cycle in these lesions. The mechanism associated with the positive p53 staining (protein binding to wild type p53 versus mutation of the p53 gene) was not determined. Lesions recurred after conservative scalpel or laser excision, and many developed into verrucous or squamous cell carcinoma. Proliferative verrucous leukoplakia of the gingiva (PVLG) appears to be a subset of oral proliferative verrucous leukoplakia. It can be characterized as a solitary, recurring, progressive white patch that develops a verruciform architecture and may not be associated with HPV. PVLG has an unpredictable course and is at risk for development into verrucous or squamous cell carcinoma. Currently, there is no way to determine or predict which gingival white lesions will follow the clinical course described for this group of patients with PVLG.