Oral Carcinoma Arising Under Implant-Supported Prosthesis: Progression of Proliferative Verrucous Leukoplakia Initially Mimicking Lichen Planus.

Proliferative verrucous leukoplakia (PVL) is a non-homogenous type of oral leukoplakia, characterized by multifocal white plaques, propensity to recur after treatment, with strong tendency towards malignant transformation. Interestingly, some studies show that, at initial stages, PVL may resemble oral lichen planus (OLP), potentially leading to misdiagnosis. A 52-year-old woman, with a previous OLP diagnosis, was referred to our service for implant installation and follow-up of OLP lesions. After clinicopathological re-evaluation, a diagnosis of PVL (early stage) was made, and a maxillary full-arch implant-supported prosthesis supported by implants was installed. After 6 years of follow-up, the patient developed squamous cell carcinoma around the implants. The current case emphasizes that PVL patients with oral lesions suggesting peri-implantitis or peri-implant mucositis deserve a more meticulous investigation.

Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.

Macrophages CD163+ and Factor XIIIa+ Provide a First-Line Defence against Proliferative Verrucous Leukoplakia Antigens.

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.

Prognostic outcomes of oral squamous cell carcinoma derived from proliferative verrucous leukoplakia: A systematic review.

OBJECTIVE: This study aimed to evaluate prognostic outcomes of PVL-derived oral squamous cell carcinomas (P-OSCC) based on recurrence, new primary tumour, metastasis and survival information. STUDY DESIGN: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P-OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies. RESULTS: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P-OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years. CONCLUSION: Apparently, P-OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P-OSCC; therefore, specific studies must be performed to achieve a better comparison between P-OSCC and conventional OSCC progression.

High density of CD8 T cell and immune imbalance of T lymphocytes subsets are associated with proliferative verrucous leukoplakia.

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.

Leucoplasia verrucosa proliferativa: a proposito de un caso / Proliferative verrucose leucoplasia: a purpose of a case

RESUMEN Las lesiones blancas de la mucosa oral son patologías relativamente frecuentes, siendo la leucoplasia oral (LO) motivo de consulta habitual en Estomatología. Existen muchas variantes de LO y la leucoplasia verrucosa proliferativa (LVP) es una de las menos frecuentes. La LVP es una enfermedad de pronóstico desfavorable, con características clínico-patológicas distintivas, de lento y progresivo crecimiento, de difícil diagnóstico temprano. La etiología permanece incierta aunque se han implicado hábitos tóxicos como el tabaquismo y agentes infecciosos como Papiloma Virus Humano, Candidaalbicans, Virus de Epstein Barr, entre otros. Suele afectar la encía y mucosa alveolar pero el compromiso puede ser de cualquier sitio de la boca. Inicialmente se observa como una placa blanquecina que se tornahiperqueratósicay genera placas irregulares con áreas rojas y zonas verrucosas, que podrían sufrir transformación maligna. Este artículo realiza una revisión bibliográfica de LVP a partir de un caso clínico.

ABSTRACT The white lesions of the oral mucosa are relatively frequent pathologies, being the oral leukoplakia (OL) reason for frequent consultation in Stomatology. There are many variants of OL and proliferative verrucous leukoplakia (PVL) is one of the least frequent. PVL is a disease with unfavorable prognosis, with distinctive clinical-pathological characteristics, of slow and progressive growth and difficult to diagnose early. The etiology remains uncertain although toxic habits have been implicated, like smoking and infectious agents such as Human Papilloma Virus, Candida albicans, Epstein Barr Virus, among others. It usually affects the gum and alveolar mucosa but any partof the mouth can be affected. Initially it is observed as a whitish plaque that becomes hyperkeratotic, generating irregular plaques with red and warty areas, which could undergo malignant transformation. This article performs a bibliographic review of PVL from a clinical case.

Proliferative verrucous leukoplakia: diagnosis, management and current advances / Leucoplasia verrucosa proliferativa: diagnóstico, conduta e avanços atuais

Abstract Introduction: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. Objective: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. Methods: A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized. Results: There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. Conclusion: More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.

Resumo Introdução: Leucoplasia verrucosa proliferativa (LVP) é uma lesão multifocal e progressiva da mucosa oral, com etiologia desconhecida e comumente resistente a todas as tentativas terapêuticas, com recorrências frequentes. É caracterizada por uma alta taxa de transformação em carcinoma de células escamosas e carcinoma verrucoso da cavidade oral. Objetivo: Analisar os estudos sobre LVP e elaborar uma atualização resumida. Método: Foi realizada uma pesquisa na base de dados Pubmed que identificou estudos (pesquisas laboratoriais, séries de casos e revisões de literatura) que avaliaram pacientes com LVP. Resultados e discussão: Não há estudos suficientes sobre LVP na literatura. Os poucos estudos encontrados não apresentam consenso quanto aos critérios de etiologia e diagnóstico. Embora várias estratégias de tratamento tenham sido propostas, a maioria ainda apresenta alta taxa de recorrência. Conclusão: Mais pesquisas sobre LVP são necessárias para entender e tratar essa doença.

Proliferative verrucous leukoplakia: diagnosis, management and current advances.

INTRODUCTION: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. OBJECTIVE: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. METHODS: A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized. RESULTS: There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. CONCLUSION: More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.

Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leukoplakia.

AIM: To elucidate the profile of the salivary proteome. METHODS: Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia (PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach, followed by analyses of variance and logistic regression tests. RESULTS: A total of two hundred and eighty-three proteins were confidently identified in saliva. By combining two low abundance proteins from the PVL group, angiotensinogen (AGT) and dipeptidyl peptidase 1 (DPP1), a model for group differentiation was built with a concordance index of 94.2%, identifying both proteins as potential etiologic biomarkers for PVL. CONCLUSION: This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.

Proliferative verrucous leukoplakia may initially mimic lichenoid reactions.

Proliferative verrucous leukoplakia is an intriguing disease, which occurs particularly in women aged greater than 60 years, is not associated with tobacco and alcohol, and has a high risk of recurrence and malignant transformation. Although it is well known that the typical presentation is characterized by multifocal and verrucous white lesions, there is no description that its initial clinical presentation may simulate a lichenoid reaction.

Leucoplasia verrucosa proliferativa: a propósito de un caso clínico / Proliferative verrucous leukoplakia: a clinical case

La Leucoplasia Verrucosa Proliferativa (LVP) es una placa blanca, verrucosa, exofítica, de crecimiento lento, que no se desprende al raspado y que tiende a comprometer diversos sitios de la mucosa oral. Es resistente al tratamiento independiente de la terapia adoptada y presenta una alta tasa de recidiva posterior al tratamiento quirúrgico. Desde 1985, cuando fue descrita por primera vez por Hansen, hasta le fecha, se ha mantenido como una entidad patológica compleja. Reportamos un caso de una paciente de sexo femenino de 72 años de edad que consulta por una lesión blanca, verrucosa, asintomática, que no se desprende al raspado, en el borde y vientre lingual y piso de boca. Se realizaron 2 biopsias incisionales del borde lateral de la lengua. Al examen microscópico se observó en ambas biopsias un grueso revestimiento epitelial acantósico, con marcada hiperparaqueratosis, una membrana basal nítida y cambios displásicos mínimos. Al mes de realizadas las biopsias la lesión presentó recidiva, manteniendo las mismas características clínicas encontradas inicialmente. Considerando la evolución, comportamiento biológico y las características histopatológicas, la lesión se diagnosticó como una LVP. Hasta la fecha, no hay protocolo de tratamiento establecido para estas lesiones. En este caso en particular, tomando en cuenta la extensión de la lesión, los sitios comprometidos, las escasas atipias presentes al examen histopatológico, la edad y escaso nivel socioeconómico de la paciente, se decidió no realizar la remoción quirúrgica de la lesión y mantenerla en control clínico cada 3 meses. Después de varios controles realizados durante un periodo de 3 años, se observó que la lesión mantuvo sus características clínicas iniciales. Esto confirma que haber optado por un tratamiento conservador, en este caso en particular de LVP, fue la decisión correcta...

The proliferative verrucous leukoplakia (PVL) is a white plate, wart-like, exophytic , slow growth , which does not follow the scaling that tends to compromise various oral mucosal sites . It is resistent to independent therapy and has a high rate of recurrence after surgical treatment. Since 1985, when it was first described by Hansen, and to date it has remained a complex pathological disorder. We report a case of a 72-year-old female patient who complains of a white, verrucous and asymptomatic lesion. The lesion does not detach by scraping the edge, lingual belly or mouth floor. Two Incisional biopsies were performed on lateral border of the tongue. Upon microscopic examination of both biopsies, thick epithelial lining, with marked hyperparakeratosis, a basement membrane, and minimal dysplasia alterations were observed. One month following biopsies of the lesion were performed, lesion relapsed and maintained the same clinical features found initially. Considering the evolution, biological behavior and histopathological features, the lesion is diagnosed as an PVL. To date, there is no established treatment protocol for these injuries. In this particular case, taking into account the extent of the injury, compromised sites, the few atypia present histopathological examination, age and low socioeconomic level of the patient, it was decided not to perform surgical removal of the lesion and maintain clinical monitoring every 3 months. Following several examinations carried out over a three-year period, it was observed that the injury kept initial clinical features. This confirms that having opted for conservative treatment, in this particular case of PVL, was the right decision...