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Proliferative Veruccous Leukoplakia: An Extensive Red and White Lesion
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Proliferative verrucous leukoplakia (PVL) is a rare form of leukoplakia, which was first described by Hansen et al. in the year 1985. PVL is a disease with aggressive behavior due to its high rate of recurrence and a high rate of malignant transformation, usually more than 70%. This is a long-term progressive condition, which is observed more frequently in females over the age of 60 years. In the course of time, PVL tends to become multifocal with progressive deterioration of the lesions, making it more and more difficult to control. Unlike other cases of leukoplakia, tobacco use does not seem to have a significant influence on the appearance and progression of PVL. As this condition is seen in non-smokers, the etiology of PVL remains unclear making the management and diagnosis difficult. The aim of this article is to present a case which is diagnosed based on the diagnostic criteria proposed by Cerero-Lapiadra et al. in the oral cavity with its malignant transformation rate varies from 0.13% to 17.5%. 6 A rare form of oral leukoplakia known as proliferative verrucous leukoplakia (PVL) was first reported barely a few decades ago by Hansen et al. It has a more aggressive biological behavior than other forms of leukoplakia as it has a tendency toward multifocality; a high probability of recurrence; and a high rate of malignant transformation, between 40 and 100% in a period of about 4.4-11.6 years. 7,8 In 1985 Hansen described PVL as a long-term progressive condition which develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic, and proliferative features. As per literature, PVL seems to have an increased predilection for non-smoking elderly female patients over the age of 60 years without any racial predilection unlike other cases of leukoplakia, which is prevalent in smoking males. 9,10 Tobacco does not seem to have a significant influence on the disease as PVL occurs both in smokers and non-smokers especially non-smokers. 11 These lesions usually present as slow-growing yet persistent, as well as irreversible and resistant to all forms of treatment with a high recurrence rate. During development, it is common to find erythematous and or verrucous areas that occasionally progress to verrucous carcinoma or squamous cell carcinoma (SCC).
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Objective: Proliferative verrucous leukoplakia (PVL) is a rare, recalcitrant, and lethal form of leukoplakia necessitating special attention. The purpose of this review is to further educate the otolaryngology community and to characterize the risk factors, clinical course, and optimal treatment for this highly aggressive, premalignant oral lesion.
Method: A retrospective review was performed on all PVL cases treated at WMHC from 1985 to 2010. This data was pooled with additional PVL cases identified following a systemic review of the English-language literature. Only articles addressing epidemiology, histopathology, treatment outcomes, and malignant progression were pooled and analyzed with our data.
Results: A total of 243 PVL cases met inclusion criteria. The mean patient age was 66 years. The majority of patients were female (72%) and nonsmokers (64.6%). HPV has not been found to be a risk factor. The average length of follow-up was 5.5 years, with an average of 10.7 biopsies per patient during this period. PVL exhibits histopathologic features along a progressive spectrum, evolving from leukoplakia and verrucous hyperplasia eventually to invasive carcinoma. Definitive treatment was rarely successful, with PVL recurrence rates reaching 88%. Rate of progression to verrucous carcinoma or oral squamous cell carcinoma was high (63.6%).
Conclusion: PVL is a rare but recalcitrant form of leukoplakia with a malignant transformation rate reaching 64%. PVL warrants high clinical suspicion, to include a lifetime of close follow-up by a physician well versed in oral carcinoma. Repeat biopsy should be considered an integral part of this routine follow-up.
Abstract Among 20 333 people aged 15 yr or above, the prevalences of oral white lesions were calculated based on a partly new classification. The total prevalences were: cheek and lip biting 5.1%, smoker's palate 1.1%, frictional white lesion 5.5%, snuff dipper's lesion 8.0%, preleukoplakia 6.4% and leukoplakia 3.6%. If all these lesions were pooled, the prevalence was 24.8% and if only the entities cheek and lip biting and smoker's palate were excluded it became 20.1%. If weak “preleukoplakic” lesions were excluded from the latter figure (he prevalence for marked whitish lesions was 13.8%. Etiologic and clinical subgroups of leukoplakia showed the following prevalences: using the etiologic subgroups, idiopathic leukoplakia 0.7% and tobacco-associated leukoplakia 2.9%; using the clinical subgroups, homogeneous leukoplakia 3.5% and non-homogeneous leukoplakia 0.3%. The intraoral location pattern of leukoplakias was preponderant in the commissural and buccal areas. However, the idiopathic leukoplakias showed a somewhat more even distribution and thus a more similar distribution to that of oral cancer.
University of California, Department of Stomatology, School of Dentistry, San Francisco, California.
Objectives/Hypothesis : To assess the efficacy of laser therapy for the management of premalignant oral lesions. Study Design : The study group consisted of seventy consecutive laser‐treated patients with oral leukoplakia. The microscopic diagnosis included idiopathic focal keratosis, dysplasias of all grades, and verrucous hyperplasia (proliferative verrucous leukoplakia). Thirty‐nine patients had some degree of microscopic dysplasia and six demonstrated high‐risk proliferative verrucous leukoplakia. The clinical appearances of the lesions were white (homogeneous leukoplakia) in 48, red and white (erythroleukoplakia) in 8, and verrucous in 14. There were 38 men and 32 women in this group. The average age was 63 years (range, 31–90 y). Methods : Lasers employed were the CO 2 and Nd:YAG lasers, and standard laser safety protocols were used. Results : There was no postoperative infection, hemorrhage, or paresthesia. Two patients developed pyogenic granulomas in their surgical sites. Fifty‐five of 70 patients were followed for more than 6 months; follow‐up averaged 32 months (range 6–178 mo). Twenty‐nine patients had complete control of their lesions; 19 patients had small recurrences removed with subsequent laser surgeries, leading to control; 2 patients had complete recurrences; and 5 patients developed squamous cell carcinoma at the lesion site. Verrucous lesions had an especially high rate of recurrence (83%), with 9 of 12 ultimately controlled with subsequent surgeries. Conclusions : Laser surgery of oral leukoplakia is an effective tool in a complete management strategy that includes careful clinical follow‐up, patient education to eliminate risk factors and report suspicious lesions, and biopsy of suspicious lesions when appropriate. However, recurrence and progression to cancer remain a risk. Key Words : oral cancer, laser, CO 2 , Nd:YAG, leukoplakia.
Proliferative verrucous leukoplakia (PVL) is a rare oral mucosa disorder, frequently involving periodontal sites, with a high rate of progression to oral squamous cell carcinoma (SCC) and verrucous carcinoma (VC). This article describes the clinical features and follow-up of a group of patients with PVL, with attention to the involvement of the mucosa covering the alveolar crest and its malignant transformation.
Patients were retrospectively evaluated for demographic data, risk habits (smoking and drinking), locations of PVL lesions, incidence, and locations of malignant transformation. Patients with malignant transformation were compared to a control group (patients affected by oral carcinoma without PVL).
Forty-seven patients were enrolled; PVL lesions were most frequently observed on the alveolar crest (41/47 [87.2%]), with gingival involvement in 22 of 47 (46.8%) cases. Nineteen patients (40.4%) developed 41 malignant lesions; the alveolar crest was the most affected site (12/41 [29.3%]). Compared to controls, patients with PVL were more likely to develop VC (odds ratio [OR] = 6.61; 95% confidence interval [CI]: 1.23 to 65.52) than SCC (OR = 0.15; 95% CI: 0.02 to 0.82), and they showed a higher incidence of cancer on masticatory mucosa (OR = 6.49; 95% CI: 1.78 to 29.12), particularly gingiva (P = 0.007) and the hard palate (P = 0.017).
The importance of PVL awareness for periodontists is underscored by the frequency of gingival involvement and the high prevalence of malignant transformation on masticatory mucosa, which usually can be suspected because of the onset of warning signs, such as rapid growth of verrucosity, area of erosion or ulceration, acquisition of red areas, induration, and positive response to toluidine blue staining.
In a recently held WHO workshop it has been recommended to abandon the distinction between potentially malignant lesions and potentially malignant conditions and to use the term potentially malignant disorders instead. Of these disorders, leukoplakia and erythroplakia are the most common ones. These diagnoses are still defined by exclusion of other known white or red lesions. In spite of tremendous progress in the field of molecular biology there is yet no single marker that reliably enables to predict malignant transformation in an individual patient. The general advice is to excise or laser any oral of oropharyngeal leukoplakia/erythroplakia, if feasible, irrespective of the presence or absence of dysplasia. Nevertheless, it is actually unknown whether such removal truly prevents the possible development of a squamous cell carcinoma. At present, oral lichen planus seems to be accepted in the literature as being a potentially malignant disorder, although the risk of malignant transformation is lower than in leukoplakia. There are no means to prevent such event. The efficacy of follow-up of oral lichen planus is questionable. Finally, brief attention has been paid to oral submucous fibrosis, actinic cheilitis, some inherited cancer syndromes and immunodeficiency in relation to cancer predisposition.
The need for an internationally accepted system of histologic classification of tumors was recognized by the World Health Organization as early as 1957, and for this purpose collaborating centers were established for the study of neoplasms in various parts of the body. It soon became apparent, however, that there was also a need for the study of precancerous lesions, since certain lesions had long been considered to have at least some precancerous potential. Because the mouth is a readily acceptable site for observation, biopsy, and follow-up, and because in some parts of the world oral cancer is a major public health problem, a WHO center for the study of these problems was established in 1967. The center was to characterize and define those lesions that should be considered in a study of oral precancer and to determine, if possible, their relative risk of becoming malignant. Although the observations involved in such studies are inevitably of a long-term nature, it is possible at this stage to characterize and define those lesions that are being considered by the center as relevant to the subject or oral precancer. In the present report, following an introductory presentation on the variations in the histology, structure and appearance of the noraml oral mucosa, the authors review the histopathology and differential diagnosis of epithelial dysplasia, carcinoma in situ, leukoplakia, nicotinic stomatitis, erythroplakia, oral lichen planus, candidiasis, the lesions caused by habitual cheek-biting, discoid lupus erythematosus, white sponge nevus and submucous fibrosis.
Up to 6% of oral leukoplakia, a relatively common mucosal disease, can be expected to become malignant. This report describes a long-term study of 30 patients in whom a particular form of leukoplakia was identified and labeled proliferative verrucous leukoplakia (PVL), a disease of unknown origin, which exhibits a strong tendency to develop areas of carcinoma. PVL begins as a simple hyperkeratosis but tends to spread and become multifocal. PVL is slow-growing, persistent, and irreversible, and in time areas become exophytic, wartlike, and apparently resistant to all forms of therapy as recurrence is the rule. The disease was most commonly seen in elderly women and had been present for many years. Patients were followed for 1 to 20 years. Thirteen died of or with their disease, 14 were alive with PVL, and 3 were alive without PVL at last contact. PVL rarely regressed despite therapy. All patients who died had persistent or recurrent disease. PVL appears to constitute a continuum of hyperkeratotic disease, ranging from a simple hyperkeratosis at one end to invasive squamous cell carcinoma at the other. Microscopic findings are dependent upon the stage of the disease's development and the location and adequacy of the biopsy.
A particularly aggressive form of oral leukoplakia that commences with a hyperkeratosis, spreads to become multifocal and verruciform in appearance, and later becomes malignant has been termed proliferative verrucous leukoplakia. Ten patients with persistent multifocal verruciform white patches were investigated. Lesions were often bilateral and affected predominantly mandibular alveolar and buccal mucosa. At first biopsy no lesion was graded higher than a verrucous hyperplasia, but subsequently all patients had squamous cell carcinoma, and two patients have died of their disease. Lesions were managed with surgery, carbon dioxide laser, and photodynamic therapy. The patients presented here confirm the existence of proliferative verrucous leukoplakia as a clinicopathologic entity. Careful examination of the whole mouth is essential when a hyperplastic white patch is seen to check for possible proliferative verrucous leukoplakia. Early aggressive treatment must then be started, and regular long-term review is crucial.
Proliferative verrucous leukoplakia is a unique form of oral leukoplakia that has a high risk for becoming dysplastic and transforming into squamous cell carcinoma. The purpose of this review is to update patient profiles, pathogenesis, and survival.
Fifty-four patients with proliferative verrucous leukoplakia (17 from a previous report) were followed prospectively in our clinic for a mean of 11.6 years after initial biopsy.
In the patient population studied, the mean age was 62 years, and women outnumbered men 4 to 1. Multiple intraoral sites were involved (mean, 2.6 per patient); the most common sites were buccal mucosa in women and tongue in men. In a mean time of 7.7 years, 70.3% of the patients developed a squamous cell carcinoma at a proliferative verrucous leukoplakia site, most frequently the gingiva and tongue. Twenty-one of the patients with proliferative verrucous leukoplakia died of proliferative verrucous leukoplakia-associated carcinoma. Only 31% of the 54 patients used tobacco in any form. Radiation did not appear to enhance surgical control.
Proliferative verrucous leukoplakia is a high risk precancerous lesion with a high mortality rate. Because of both the propensity for progression to dysplasia and malignancy, as well as a high recurrence rate, these patients must be treated aggressively and followed carefully.
To assess the efficacy of laser therapy for the management of premalignant oral lesions.
The study group consisted of seventy consecutive laser-treated patients with oral leukoplakia. The microscopic diagnosis included idiopathic focal keratosis, dysplasias of all grades, and verrucous hyperplasia (proliferative verrucous leukoplakia). Thirty-nine patients had some degree of microscopic dysplasia and six demonstrated high-risk proliferative verrucous leukoplakia. The clinical appearances of the lesions were white (homogeneous leukoplakia) in 48, red and white (erythroleukoplakia) in 8, and verrucous in 14. There were 38 men and 32 women in this group. The average age was 63 years (range, 31-90 y).
Lasers employed were the CO2 and Nd:YAG lasers, and standard laser safety protocols were used.
There was no postoperative infection, hemorrhage, or paresthesia Two patients developed pyogenic granulomas in their surgical sites. Fifty-five of 70 patients were followed for more than 6 months; follow-up averaged 32 months (range 6-178 mo). Twenty-nine patients had complete control of their lesions; 19 patients had small recurrences removed with subsequent laser surgeries, leading to control; 2 patients had complete recurrences; and 5 patients developed squamous cell carcinoma at the lesion site. Verrucous lesions had an especially high rate of recurrence (83%), with 9 of 12 ultimately controlled with subsequent surgeries.
Laser surgery of oral leukoplakia is an effective tool in a complete management strategy that includes careful clinical follow-up, patient education to eliminate risk factors and report suspicious lesions, and biopsy of suspicious lesions when appropriate. However, recurrence and progression to cancer remain a risk.