Cases Of Proliferative Verrucous Leukoplakia Research Articles

MALIGNANT TRANSFORMATION OF PROLIFERATIVE VERRUCOUS LEUKOPLAKIA INTO ORAL SQUAMOUS CELL CARCINOMA AFTER A LONG FOLLOW-UP: SERIES OF 3 CASES

Proliferative verrucous leukoplakia (PVL) is a rare and enigmatic pathology characterized by multiple nonhomogeneous white plaques of slow growth and high rate of malignant transformation. We presented 3 cases of PVL that underwent transformation to squamous cell carcinoma after a long period of treatment and clinical follow-up. All patients were female, from 45 to 73 years old at the diagnosis of PVL, not smokers or alcoholics, and had no symptoms. In the clinical examination, multiple white plaques with rough surfaces and undefined limits were observed. They affected palate (2 cases), tongue (3 cases), buccal floor (2 cases), alveolar ridge (2 cases), and buccal mucosa (3 cases). Malignant transformation occurred, on average, after 8 years of the first examination. Treatment of squamous cell carcinoma consisted of resection surgery (2 cases) and radiotherapy (1 case). The patients have been monitored on regular follow-up.

CLINICAL AND PATHOLOGIC CRITERIA TO DIAGNOSE PROLIFERATIVE VERRUCOUS LEUKOPLAKIA: AN UPDATE REVIEW AND A CASE REPORT

Objectives The objectives of this study were to describe clinical and pathologic features of the proliferative verrucous leukoplakia (PVL), including differential diagnosis and current criteria to diagnose PVL, and to report a case of PVL. Study Design Electronic research was carried out for the previous 5 years in the PubMed, BVS, and Scielo databases using “proliferative verrucous leukoplakia” as search the term. Results A total of 76 papers were found through databases, and 34 of them were eligible. We identified 3 studies that proposed new diagnosis clinical and histologic criteria. The lesion size and architectural histologic features are important factors to diagnose PVL. Not all PVLs exhibit a verrucous appearance. The most common differential diagnoses reported were lichenoid and reactive lesions. The risky sites to develop PVL and cancer are gingiva, especially that forming a “ring around the collar” in marginal gingiva, followed by buccal mucosa, tongue, and palate in female patients. Our case initially involved the tongue of a 79-year-old female patient with malignant transformation after 13 years of follow-up. Conclusions Even though the findings are helpful, there is no standardized criteria to diagnose PVL. Therefore, close clinical follow-up with periodic biopsies is the best approach to diagnose PVL and its progression to carcinoma. The objectives of this study were to describe clinical and pathologic features of the proliferative verrucous leukoplakia (PVL), including differential diagnosis and current criteria to diagnose PVL, and to report a case of PVL. Electronic research was carried out for the previous 5 years in the PubMed, BVS, and Scielo databases using “proliferative verrucous leukoplakia” as search the term. A total of 76 papers were found through databases, and 34 of them were eligible. We identified 3 studies that proposed new diagnosis clinical and histologic criteria. The lesion size and architectural histologic features are important factors to diagnose PVL. Not all PVLs exhibit a verrucous appearance. The most common differential diagnoses reported were lichenoid and reactive lesions. The risky sites to develop PVL and cancer are gingiva, especially that forming a “ring around the collar” in marginal gingiva, followed by buccal mucosa, tongue, and palate in female patients. Our case initially involved the tongue of a 79-year-old female patient with malignant transformation after 13 years of follow-up. Even though the findings are helpful, there is no standardized criteria to diagnose PVL. Therefore, close clinical follow-up with periodic biopsies is the best approach to diagnose PVL and its progression to carcinoma.

SUCCESSFUL LONG-TERM MANAGEMENT OF PROLIFERATIVE VERRUCOUS LEUKOPLAKIA: A CASE REPORT

<h3>Introduction</h3> Proliferative verrucous leukoplakia (PVL) is a rare condition that is difficult to diagnose, difficult to treat, and often progresses to malignancy. We present a case of PVL followed over twelve years that was managed both surgically and medically, impacting this patient's dental treatment options and overall quality of life. <h3>Objectives</h3> Retinoic acid can help manage PVL when part of a comprehensive treatment plan, including selec- tive surgical excisions in the form of biopsies, because it may inhibit epithelial proliferation and keratinization. New research has shown that conservative management and routine close follow-up by a "multidisciplinary team" may have similar outcomes with less morbidity compared to routine surgical excisions, but uncertainty about recur- rence restricts treatment options. <h3>Findings</h3> This case illustrates successful management of a very difficult condition to treat. Despite a tendency to recur and evolve, this patient's PVL remained relatively stable by diligent topical retinoid application, selective biopsy, and strict follow-up. Although the patient lost teeth due to a yet unknown mechanism, the PVL did not transform to VC or OSCC. Living with PVL has had a profound effect on this patient's oral functional capacity and quality of life. The patient was not advised to replace missing teeth with implants, and dental treatment was prolonged due to uncertainty about the condition. <h3>Significance for Practice</h3> The purpose of this case report is to present a case of PVL, managed conservatively, and suggest that clinicians should not rush to surgery. Still, this case illustrates that quality of life is affected as treatment options for missing teeth are limited.

A Scoping Review on Gaps in the Diagnostic Criteria for Proliferative Verrucous Leukoplakia: A Conceptual Proposal and Diagnostic Evidence-Based Criteria.

Simple SummaryProliferative verrucous leukoplakia is considered as an oral potentially malignant disorder that presents the highest tendency to recurrence and malignant transformation, alt-hough published diagnostic criteria are inconsistent. A precise evidence-based diagnosis is im-portant to differentiate this lesion from others on the oral mucosa with less tendency for cancer progression, and thus establish specific management protocols aimed at the early diagnosis of oral cancer. In this scoping review the published conceptual and diagnostic criteria for prolifera-tive verrucous leukoplakia were comprehensively analyzed, and a conceptual proposal for fu-ture diagnosis is proposed based on current evidence.Proliferative verrucous leukoplakia (PVL) is considered as an oral potentially malignant disorder (OPMD) that presents with a high tendency to recurrence after treatment and has the highest malignant transformation ratio among all OPMD (50%). Evidence-based publications have indicated that the malignant evolution reported is significantly related to the inconsistent diagnostic criteria used in primary-level studies; so, it has been hypothesized that the risk of oral cancer for this disease could even be underestimated. This is important because PVL requires specific management protocols, evidence-based, aimed at the early diagnosis of cancer developing in these lesions. We present a scoping review—a novel approach to mapping the available literature on a given topic to provide an overview of the available research evidence and to highlight possible gaps in the evidence—especially related in our study to the diagnostic aspects of PVL, and to issue a conceptual proposal and diagnostic criteria for PVL. We conclude that PVL is a white, multifocal and progressive lesion with a high malignant transformation rate which is diagnosed mainly around the age of 60 years without any specific histological characterization. We also advise a personal reflection on the level of certainty with which the clinician makes the diagnosis of a particular case of PVL.

Proliferative Verrucous Leukoplakia Revisited: A Retrospective Clinicopathological Study.

(1) Objective: To review the criteria proposed by Cerero-Lapiedra et al. and to retrospectively identify the under-diagnosed disease in patients diagnosed with proliferative verrucous leukoplakia. (2) Materials and methods: In this study, we included patients who were diagnosed with leukoplakia (histological label consistent with the clinical diagnosis, n = 95), and cases with a final diagnosis within the spectrum of proliferative verrucous leukoplakia (n = 110) as defined by Batsakis et al. We applied the criteria proposed by Cerero-Lepiedra et al. to screen for the possible cases of proliferative verrucous leukoplakia. (3) Results: Although many of our patients satisfied specific isolated criteria, only 11 cases satisfied specific combinations of the guidelines to satisfy a diagnosis of proliferative verrucous leukoplakia. However, due to the lack of follow-up data, the disease is not confirmed in these 11 cases. (4) Conclusion: A limited number of cases of proliferative verrucous leukoplakia were diagnosed using the criteria given by Cerero-Lapiedra et al. The true natural history of the disease could not be studied due to the lack of follow-up data. (5) Clinical relevance: Proliferative verrucous leukoplakia presenting as hyperkeratosis or mild epithelial dysplasia are often not followed up, and they subsequently transform into carcinoma. Thus, clinicians must be vigilant whenever they encounter leukoplakia, especially with multifocal presentations. In such cases, the follow-up data are the key to understanding the true nature of the disease entity.

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.

THREE CASE REPORTS OF PROLIFERATIVE VERRUCOUS LEUKOPLAKIA MISDIAGNOSED AS LICHEN PLANUS

Proliferative verrucous leukoplakia (PVL) is a potentially malignant disorder of unknown etiology and has a progressive and multifocal behavior. Characteristically, PVL presents with high rates of recurrence and malignant transformation to squamous cell carcinoma or verrucous carcinoma. We reported 3 cases that initially presented as oral lichenoid lesions spread by the oral mucosa and the microscopic analysis in all cases revealed epithelial hyperplasia and lymphohistiocytic infiltrate in a subepithelial pattern, compatible with a lichen planus diagnosis. However, some years after, some lichenoid areas evolved into dysplastic white lesions and 2 of the patients developed squamous cell carcinoma. We have concluded these to be cases of PVL. Thus, we emphasize that diffuse white lesions of the oral mucosa with a verrucous aspect can present, in the initial phases, clinical pathologic features similar to lichen planus, leading to initial failure to correctly diagnose and treat PVL.

Proliferative Verrucous Leukoplakia Showing Lichenoid Areas

Proliferative verrucous leukoplakia (PVL) mainly affects the gingiva and buccal mucosa and shows slow and irreversible growth; the etiology remains unclear. Malignant transformation rates range from 70% to 100%. Four cases of PVL with areas similar to oral lichen planus (OLP) were evaluated. There were only Caucasian women, ranging from 44 to 79 years of age, who were smokers with sporadic alcohol consumption. Clinical examination revealed white plaques and reticulated lesions in the buccal mucosa. The initial clinical hypothesis was OLP in all cases; however, it was observed that the lichenoid areas increased in size and turned verrucous during follow-up. On performing biopsy and histopathological analysis, and evaluating clinical and follow-up data, they were all diagnosed as PVL. The follow-up lasted for a mean of 3 years, without malignant transformation. Dentists must be aware of lesions that mimic lichen planus, and perform close follow-up, as these may yield a PVL diagnosis.

Proliferative Verrucous Leukoplakia: A Case Report with Emphasis on Diagnosis and Treatment

Proliferative verrucous leukoplakia (PVL) is characterized by development of multiple keratotic plaques with roughened surface projections. Since its introduction in 1985 by Hansen et al., PVL of the oral mucosa still remains an enigma and is difficult to define as a sub-entity of leukoplakia. Although the lesion typically begins as simple, flat hyperkeratosis indistinguishable from ordinary leukoplakic lesion, PVL exhibits persistent growth and eventually becomes exophytic and verrucous in nature. As the lesion progresses, they may go through a stage indistinguishable from verrucous carcinoma but may later develop dysplastic changes or transform into full-fledged squamous cell carcinoma usually within 8 years of initial PVL diagnosis. PVL is unusual among the leukoplakia variants in having a strong female predilection and minimal association with tobacco usage. Presenting here, a case of PVL transforming into verrucous carcinoma with areas of suspected malignancy in a 53-year-old male with habit of chewing tobacco quid and beedi smoking 4-6 times a day since 20 years, with a chief complaint of pain and burning sensation of the oral cavity and multiple oral lesions for 1 month. This paper will elaborate typical behavior pattern of the lesion and will discuss this rare entity in light of current information.

Clinicopathologic diagnostic criteria of an enigmatic entity: Proliferative verrucous leukoplakia

Proliferative verrucous leukoplakia (PVL) is a rare, unique type of oral leukoplakia, which is enigmatic in etiology and behaves in a far more aggressive fashion than other forms of leukoplakia. Diagnosis is often late with the disease in an advanced stage when it is especially refractory to treatment. There are no definite criteria that dictate how extensive the leukoplakic changes should be, how many or which oral subsites should be involved, or how many recurrences should have occurred, in order to qualify for the diagnosis of PVL. The lack of definitive diagnostic criteria is the prime reason for PVL not being treated appropriately and in a timely fashion, thereby leading to the very concept of PVL being questioned. This article discusses the various clinicopathologic diagnostic criteria for this enigmatic entity and also reports a case of PVL in a 73-year-old female.

Proliferative verrucous leukoplakia: Case report and a comprehensive review of literature

Proliferative verrucous leukoplakia (PVL) is a rare form of oral leukoplakia, which was first described in 1985 by Hansen et al. Since then, various published case series have presented PVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation, usually higher than 70%. PVL is a long-term progressive condition, and tends to become multifocal with a progressive deterioration of the lesions, making it more and more difficult to control. According to reported literature tobacco use does not seem to have a significant influence on the appearance or progression of PVL as these lesions may occur both in smokers and nonsmokers. At present, the etiology of PVL remains unclear as well as its management and diagnosis, which is still retrospective, late and poorly defined, lacking consensus criteria.Here we present a case of PVL and intend to discuss the key features related to etiology, diagnosis, management and prognosis of proliferative verrucous leukoplakia.

The role of Ki-67, p16, CD34, Bcl-2, cyclooxygenase-2 in the pathogenesis of proliferative verrucous leukoplakia.

Proliferative verrucous leukoplakia (PVL) is a highly persistent and aggressive oral pre-malignant lesion with an obscure etiopathogenesis and a malignant transformation rate of 85-100%. The aim of the present study is to assess the role of Ki-67, p16, CD34, Bcl-2, cyclooxygenase-2 (COX-2) in the spectrum of PVL to ascertain their role in its etiopathogenesis. A retrospective chart analysis was carried out on a series of seven confirmed cases of PVL, which were followed-up for 2 years. Immunohistochemical appraisal of these cases was carried out by a panel of markers, related to cell proliferation, cell cycle regulation, angiogenesis, apoptosis and inflammation. The expression of these markers was correlated with patients' clinicopathological profile. The frequency distribution of the group data was analyzed. The latest labeling index of Ki-67 in our cases ranged from 8.18 to 12.6. p16 was positive in 3/7 cases. Bcl-2 expression was moderately positive in 2/7 cases. All cases were intensely positive for COX-2 staining. Microvascular density assessed by CD34 staining ranged from 11 to 20/high power fields. One case which transformed into squamous cell carcinoma demonstrated increased Ki-67, Bcl-2, COX-2, CD34 expression, but negative p16 and Bcl-2 expression. Application of these markers in understanding the behavior of PVL suggests that an imbalance between the proliferation apoptosis dynamics of the lesion accompanied by an increase in inflammation and angiogenesis underlie the molecular pathogenesis of the PVL spectrum.

OP227: Conventional squamous cell carcinoma (C-SCCA) vs. proliferative verrucous leukoplakia associated squamous cell carcinoma (P-SCCA): An immunohistochemical and clinicopathological study

Introduction Proliferative verrucous leukoplakia (PVL), a clinical variant of oral leukoplakia, is characterized by its clinical progression from hyperkeratosis to verrucous hyperplasia and/or verrucous carcinoma and its resistance to treatment resulting in a high potential to develop squamous cell carcinoma in multiple locations within the oral cavity, principally in low risk areas such as the buccal mucosa and alveolar ridge. The aim of our study was to determine whether the pathogenesis and biological behavior of PVL-associated carcinomas (P-scca) is distinctive from conventional scca (C-scca) by comparing their clinical and biological differences including cellular proliferation (KI67), p53 expression and the causative relationship of HPV. Methods A retrospective search of the pathology archives in our institution uncovered 50 cases of SCCA from the alveolar ridge/gingiva and buccal mucosa were selected and divided into 2 groups: 30cases of C-scca and 20 cases of P-scca (10 cases of PVL). Immunohistochemical analysis for p53, ki67 and P16 were performed and the clinical and histological features were compared.

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.

Proliferative Verrucous Leukoplakia of the Gingiva: A Rare Palatal Presentation

Proliferative verrucous leukoplakia (PVL), distinct clinical form of oral leukoplakia, is a rare potentially malignant oral mucosal disorder with a high rate of progression to oral squamous cell carcinoma (SCC) and verrucous carcinoma (VC). It frequently involves periodontal sites. PVL is characterized by a high recurrence rate. The condition develops initially as focal clinical hyperkeratosis that progressively becomes a wide multifocal disease with gross exophytic features. Multiple oral sites such as buccal mucosa, gingiva, alveolar ridges and tongue are affected, but gingiva is one of the most frequently involved site. A clinically distinctive form of PVL, called PVL of the gingiva, was proposed by some investigators to identify a subset of patients with only gingival involvement. This paper attempts to describe a case of PVL with a rare palatal presentation with periodontal involvement.

Proliferative verrucous leukoplakia and its progression to oral carcinoma: report of three cases

Proliferative verrucous leukoplakia (PVL) is a distinct clinical form of oral leukoplakia defined by its progressive clinical course, changing clinical and histopathologic features, and potential to develop into cancer. PVL behaves in a more aggressive and relentless manner than the more innocuous white oral lesions that it can resemble clinically. We present three cases of PVL that progressed to carcinoma and discuss the histopathologic findings that may either hinder or assist in the diagnosis.

DNA ploidy in proliferative verrucous leukoplakia

Proliferative verrucous leukoplakia (PVL) is a clinicopathologically distinctive form of oral leukoplakia presenting with multifocal flat, nodular and verrucous lesions that progress inexorably to squamous carcinoma. The aims of this investigation were to describe the clinical and histopathological features of six cases of PVL and to determine whether lesional epithelium demonstrates DNA ploidy anomalies prior to malignant transformation. The clinical and pathological features of six patients were reviewed and all biopsy specimens were subjected to image-based DNA ploidy analysis. The female:male ratio was 5:1 and the average age on first biopsy was 66 years. Only one patient reported both tobacco smoking and alcohol intake. The most frequently affected sites were alveolar ridge and/or gingiva (6/6), buccal mucosa (3/6), palate (3/6), tongue (2/6), buccal sulcus (2/6), and lip (1/6). Three patients developed multiple primary carcinomas, either invasive or verrucous. A ploidy anomaly at any oral site would have predicted malignant transformation in four cases and probably in a fifth for whom DNA ploidy failed to meet diagnostic criteria but was suspicious of aneuploidy. The site of transformation was predicted by ploidy and histopathology for three carcinomas and a further carcinoma showed severe dysplasia and a suspicious ploidy result in adjacent tissue. Both conventional histopathology and DNA ploidy proved effective in predicting the site of transformation in this limited series.

Proliferative verrucous vs conventional leukoplakia: no significantly increased risk of HPV infection

Proliferative verrucous leukoplakia (PVL) is a very aggressive form of oral leukoplakia (OL) with high morbidity and mortality rates, hypothesised to be linked to HPV infection. This study aimed to determine the presence of HPV DNA in PVL in comparison with OL, and in relation to social-demographical variables (age, gender, smoking and drinking habits) in an Italian multi-centric hospital-based study. The study group consisted of 58 cases of PVL and 90 cases of OL as controls (47 homogeneous (H) and 43 non-homogeneous (non-H) form), both recruited from four Italian cohorts. HPV DNA was identified in exfoliated mucosal cells by nested PCR ( nPCR) with MY09/MY11 and GP5+/GP6+ primer pairs and the HPV genotype determined by direct DNA sequencing. HPV DNA was found in 24.1% (14/58)of PVL and in 25.5% (23/90) of OL; there was thus no significant difference found between PVL and OL (both forms) for risk of HPV infection (OR = 0.93; 95% IC:0.432–1.985). Similarly, in both groups of PVL and OL lesions, no statistic association was found between any demographical variable considered and HPV infection. HPV-18 was the most frequently detected genotype in all tissues, being found in 78.5% and 60.8% of HPV+ve PVL and OL, respectively. Other more rarely detected genotypes were HPV-16 (28.6% in PVL and 13% in OL), HPV-6 (17.4% in OL) and HPV-53 (8.8% in OL). PVL does not appear more likely to be associated to HPV infection than conventional OL lesions.

１６型ヒトパピローマウイルス感染を認めた口腔粘膜のＰｒｏｌｉｆｅｒａｔｉｖｅ ｖｅｒｒｕｃｏｕｓ ｌｅｕｋｏｐｌａｋｉａの１例

A case of proliferative verrucous leukoplakia (PVL) in the oralmucosa of a 67-year-old woman is reported. PVL was first described in 1985 as an unique type of oral leukoplakia that has a high risk of malignant transformation. In our patient, the initial lesion was hyperkeratosis associated with mild dysplasia of the buccal mucosa. This condition recurred repeatedly and spread to the upper and lower gingivas, lower lip, and palate. The lesions changed to verrucous hyperplasia and finally developed into verrucous carcinomas. The patient was not cured of the disease, though she received surgical excision 6 times over a period of 7 years 10 months. She died of rupture of a thoracic aortic aneurysm. Immunohistochemical staining for human papillomavirus type 16 (HPV16)-related protein was positive in the epithelial cells of the lesions, suggesting that HPV16 was involved in the pathogenesis of PVL.

Proliferative verrucous leukoplakia with cutaneous involvement

Proliferative verrucous leukoplakia (PVL) is a distinct variant of oral leukoplakia characterized by a high rate of malignant transformation. Histologic features are variable and range from epithelial dysplasia to verrucous squamous cell carcinoma. To our knowledge, there have been no previous reports of cutaneous PVL. We present an interesting case of PVL involving the skin. (J Am Acad Dermatol 1999;41:481-3.)