[Precancers of the oral mucosa: clinic, diagnostics]. / Predraki slizistoi obolochki rta: klinika i diagnostika.

OBJECTIVE: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant¼ diseases of the oral mucosa. MATERIALS AND METHODS: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein. RESULTS: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases. CONCLUSION: To diagnose early manifestations of neoplastic processes in «potentially malignant¼ diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.

Oral erythroplakia and oral erythroplakia-like oral squamous cell carcinoma - what's the difference?

BACKGROUND: Oral erythroplakia (OE) is a rare oral potentially malignant disorder, that has a high rate of malignant transformation. The definition of OE still lacks uniformity. In particular, lesions that look clinically like erythroplakias, but are histopathologically diagnosed as squamous cell carcinomas are still sometimes called erythroplakias. The purpose of this study is to present demographic and clinicopathologic features of a series of OEs and clinically oral erythroplakia -like squamous cell carcinomas (OELSCC), to study their differences and to discuss the definition of OE. METHODS: A multicenter retrospective case series of OEs and OELSCCs. Descriptive statistics were used to analyze the data. RESULTS: 11 cases of OEs and 9 cases of OELSCCs were identified. The mean age of the OE patients was 71 years and 72.7% were female, while the mean age of the OELSCC patients was 69 years, and all were female. 9% of the OE and 22% of the OELSCC patients had smoked or were current smokers. 72.7% of the OEs and 55.5% of OELSCCs were uniformly red lesions. 63.6% of the OE and 22% of the OELSCC patients had a previous diagnosis of oral lichenoid disease (OLD). The malignant transformation rate of OE was 9% in a mean of 73 months. CONCLUSIONS: OE and OELSCC may arise de novo or in association with OLD. Tobacco and alcohol use were not prevalent in the present cases. The clinical features of OEs and OELSCC are similar, but symptoms, uneven surface and ulceration may be more common in OELSCCs than in OEs. Clinical recognition of OE is important since it may mimic other, more innocuous red lesions of the oral mucosa. The diagnosis of OE requires biopsy and preferably an excision. Clarification of the definition of OE would aid in clinical diagnostics.

A successful treatment with ALA-PDT: A case-report on erythroplasia of Queyrat misdiagnosed as urethritis.

Queyrat erythroplasia is an intraepidermal squamous cell carcinoma localized on the glans penis or the inner side of the foreskin. It accounts for about 10% of all penile malignancies and up to 33% cases may lead to invasive squamous cell carcinoma and the intraurethral erythroplasia of Queyrat is relatively rare. Treatment of Queyrat erythroplasia present a challenge especially if the proximal urethra is involved. Here, we report a case of intractable Queyrat erythroplasia involving the urethral meatus. This case suggested that 5-aminolaevulinic acid photodynamic therapy is effective and safe in the treatment of Queyrat erythroplasia, which provides a new choice for the patients with Queyrat erythroplasia with poor therapeutic effect.

Label-Free Proteomics of Oral Mucosa Tissue to Identify Potential Biomarkers That Can Flag Predilection of Precancerous Lesions to Oral Cell Carcinoma: A Preliminary Study.

Oral squamous cell carcinomas are mostly preceded by precancerous lesions such as leukoplakia and erythroplakia. Our study is aimed at identifying potential biomarker proteins in precancerous lesions of leukoplakia and erythroplakia that can flag their transformation to oral cancer. Four biological replicate samples from clinical phenotypes of healthy control, leukoplakia, erythroplakia, and oral carcinoma were annotated based on clinical screening and histopathological evaluation of buccal mucosa tissue. Differentially expressed proteins were delineated using a label-free quantitative proteomic experiment done on an Orbitrap Fusion Tribrid mass spectrometer in three technical replicate sets of samples. Raw files were processed using MaxQuant version 2.0.1.0, and downstream analysis was done via Perseus version 1.6.15.0. Validation included functional annotation based on biological processes and pathways using the ClueGO plug-in of Cytoscape. Hierarchical clustering and principal component analysis were performed using the ClustVis tool. Across control, leukoplakia, and cancer, L-lactate dehydrogenase A chain, plectin, and WD repeat-containing protein 1 were upregulated, whereas thioredoxin 1 and spectrin alpha chain, nonerythrocytic 1 were downregulated. Across control, erythroplakia, and cancer, L-lactate dehydrogenase A chain was upregulated whereas aldehyde dehydrogenase 2, peroxiredoxin 1, heat shock 70 kDa protein 1B, and spectrin alpha chain, nonerythrocytic 1 were downregulated. We found that proteins involved in leukoplakia were associated with alteration in cytoskeletal disruption and glycolysis, while in erythroplakia, they were associated with alteration in response to oxidative stress and glycolysis across phenotypes. Hierarchical clustering subgrouped half of precancerous samples under the main branch of the control and the remaining half under carcinoma. Similarly, principal component analysis identified segregated clusters of control, precancerous lesions, and cancer, but erythroplakia phenotypes, in particular, overlapped more with the cancer cluster. Qualitative and quantitative protein signatures across control, precancer, and cancer phenotypes explain possible functional outcomes that dictate malignant transformation to oral carcinoma.

Evaluation of P53 gene expression by immunohistochemistry to diagnosis oral precancerous lesions.

Oral Precancerous lesions include leukoplakia, erythroplakia, and mucosa palate changes due to reverse smoking. Assessing the prevalence of these lesions in a cross-sectional study can be effective in the timely prevention and treatment of lesions, in any community. Hence, in the present study, evaluation of P53 gene expression was done by immunohistochemistry method to diagnosis oral precancerous lesions. For this purpose, 111 Chinese patients (54 women and 57 men) were selected for examination. The age range of these patients was 22 to 69 years, and their average age was 32.6 years. All patients were examined by one physician. Oral mucosa was used for immunohistochemical evaluations. All samples taken from patients' mucosa were evaluated by one pathologist under a light microscope. 80 cases of the 111 patients were smokers and 27 were non-smokers. Among the 80 smokers, 56.25% had leukoplakia, 3.75% had erythroplakia, and 40% had mucosa palate changes. Regarding non-smokers, 74.07% had leukoplakia and 25.93% had erythroplakia. None of the non-smokers had mucosa palate changes. In terms of the lesion location, in patients with leukoplakia 89.23%, and patients with erythroplakia 90% of the lesion was located in the cheek mucosa and buccal vestibule. Also, in patients with leukoplakia 9.23%, and patients with erythroplakia 10% of the lesion was located in the lips vestibular mucosa. Only 1.54% of leukoplakia had a lesion in the vermilion border, and none of the erythroplakia patients had a lesion on the vermilion border. 76 patients (68.46%) showed positive expression of the P53 gene. The expression level of the P53 gene did not show a significant relationship with age, and the genders did not have a statistically significant difference in terms of gene expression. The expression level of the P53 gene was 59.8% in leukoplakia, 70% in erythroplakia, and 40% in Mucosa palate changes. The present study showed that the evaluation of P53 gene expression was well able to detect oral precancerous lesions and their severity by increasing their expression rate.

DNA aneuploidy with image cytometry for detecting dysplasia and carcinoma in oral potentially malignant disorders: A prospective diagnostic study.

BACKGROUND: Current evidence on diagnostic value of aneuploidy with DNA image cytometry (ICM) using brushings for oral potentially malignant disorders (OPMD) is limited by sample size and inconsistent classification criteria of aneuploidy. This study aimed to explore the optimal cut-off values of DNA content and evaluate the diagnostic accuracy of DNA-ICM for detecting dysplasia and/or carcinoma in OPMD. MATERIALS AND METHODS: A total of 401 consecutive patients with OPMD were enrolled in this prospective diagnostic study. Brushing and biopsy sample form each patient was processed by DNA-ICM and histological examination respectively. RESULTS: When the optimal cut-off of at least one aneuploid cell with DNA index (DI) ≥2.3, the area under the curves (AUC) was 0.735 and positive predictive value was 92.7% for detecting dysplasia within OPMD. When the optimal cut-off of at least one aneuploid cell with DI ≥ 3.5, the AUC was 0.851 and negative predictive values was 96.8% for detecting carcinoma within OPMD. Importantly, multivariate analysis revealed that aneuploidy with DI ≥ 2.3 in OPMD was significantly associated with dysplasia risk (adjusted OR, 5.52; 95%CI, 2.90-10.51; P < .001), and aneuploidy with DI ≥ 3.5 in OPMD was strongly associated with malignant risk (adjusted OR, 21.05; 95%CI, 9.34-47.41; P < .001). CONCLUSIONS: This largest-scale diagnostic study optimized the criteria of aneuploidy cytology for noninvasive detection of oral dysplasia and carcinoma within OPMD. DNA aneuploidy in OPMD was an independent marker that strongly associated with oral dysplasia/carcinoma. Our findings suggest that DNA-ICM may serve as a useful noninvasive adjunctive tool for oral cancer and OPMD screening.

Podoplanin and ABCG2 expression in oral erythroplakia revisited: Potential evidence for cancer stem cells driving the process of field cancerization.

A model of field cancerization orchestrated by the cancer stem cells (CSC) was proposed. Podoplanin and ABCG2 are promising marker of CSCs for head and neck cancer. We revisited the correlation of the two markers with the follow-up data of the patients with oral erythroplakia (OE). Strikingly, we observed that the expression of podoplanin and ABCG2 within a single pre-neoplastic OE lesion significantly correlate with subsequently developing multiple and multifocal carcinomas, thus to some extent demonstrating the concept of field cancerization. Collectively, a point to highlight was that a preliminary evidence that provided by this revisited study supported the perspective on cancer stem cells driving the process of field cancerization.

The White Lesion, Hyperkeratosis, and Dysplasia.

Laryngeal mucosal precursor lesions represent a challenging clinical entity. Updated classification systems allow for grade-based categorization. Multiple management options exist, with treatment decisions made jointly by physician and patient and focused on both appropriate lesion treatment and preservation of laryngeal structure and function. Traditional methods include cold steel and CO2 laser excision, with newer modalities using angiolytic lasers for lesion ablation. Both operating room-based and office-based treatment options exist, and there are advantages and disadvantages to each approach. Research is ongoing to advance the understanding of lesion biology, and to optimize prevention and treatment.

[Potentially malignant disorders of the oral mucosa]. / Pathologies médicales potentiellement malignes de la muqueuse buccale.

Potentially malignant disorders of the oral mucosa. The term "precancerous" is now abandoned in favor to « potentially malignant disorder ¼ which provide a better view of the evolution a far from systematic. Of these disorders, leukoplakia is the most common while erythroplakia is rare. Their diagnoses are still defined by exclusion of other known white or red lesions. Despite progress in molecular biology, there is no marker enabling to predict malignant transformation. When feasible, excision of these lesions is recommended, irrespective of the presence or the absence of dysplasia, a pure histologic notion. It is unknown if such removal can really prevent the development of a squamous cell carcinoma. The risk of malignant transformation of oral lichen planus, lower than in leukoplakia, is better known. There is no therapeutic enabling to prevent such event. Other potentially malignant disorders such as oral submucous fibrosis, actinic cheilitis, lupus and immunodeficiency conditions are rare.

Pathologies médicales potentiellement malignes de la muqueuse buccale. Le terme « précancéreux ¼ ne doit plus être utilisé au bénéfice de « potentiellement malin ¼ qui rend mieux compte d'une évolution loin d'être systématique. Parmi les affections potentiellement malignes, la leucoplasie est la plus fréquente et l'érythroplasie est plutôt rare. Elles sont toujours définies par exclusion des lésions blanches ou érythémateuses d'origine connue. En dépit des nombreux progrès de la biologie moléculaire, aucun marqueur ne permet actuellement, en pratique, de prévoir la transformation maligne. Quand il est possible, le principal traitement de ces lésions est chirurgical, qu'il y ait ou non une dysplasie, notion purement histologique. On ignore s'il permet réellement d'éviter la survenue d'un carcinome épidermoïde, principal cancer de la muqueuse orale. La transformation maligne du lichen plan buccal, nettement inférieure à celle des leucoplasies, est mieux connue. Aucun traitement ne permet actuellement de l'éviter. Les autres affections potentiellement malignes, fibrose sous-muqueuse, chéilite actinique, lupus et déficits immunitaires sont plus rares.

[Precancerous lesions of the buccal epithelium]. / Les lésions précancéreuses épithéliales buccales.

Squamous cell carcinomas of the oral cavity and lips consistently have a high incidence (they constitute the fifth most common form of cancer in France) and carry a heavy prognosis, particularly if diagnosed late. According to different studies, between 10 and 80% of such carcinomas occur in a pre-existing or precancerous lesion. The World Health Organisation (WHO) recommends the use of two terms for such lesions: precursor lesions, i.e. histological lesions associated with intraepithelial neoplasia (IEN) and verrucous hyperplasia (VH), frequently resulting clinically in leukoplakia or erythroplakia; "at risk" lesions, which include lichen planus, submucosal oral fibrosis and certain forms of genodermatosis.

Clinical characteristics of narrow-band imaging of oral erythroplakia and its correlation with pathology.

BACKGROUND: To analyze the clinical application of endoscope with narrow-band imaging (NBI) system in detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral erythroplakia. METHODS: The demographic, histopathological data, and NBI vasculature architectures of patients receiving surgical intervention for oral erythroplakia were retrospectively reviewed and analyzed statistically. RESULTS: A total of 72 patients, including 66 males and 6 females, with mean age of 54.6 ± 11.2 years, were enrolled. The odds ratio of detecting high-grade dysplasia, carcinoma in situ, and carcinoma by twisted elongated morphology and destructive pattern of intraepithelial microvasculature was 15.46 (confidence interval 95%: 3.81-72.84), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.95%, 78.43%, 60.71%, 90.91%, and 79.17%, respectively, which were significantly better than other two established NBI criteria (p < 0.001). CONCLUSIONS: Twisted, elongated, and destructive patterns of intraepithelial papillary capillary loop of NBI images are indicators for high-grade dysplasia, carcinoma in situ, and invasive carcinoma in oral erythroplakia.

[Oral precancer and cancer]. / Precáncer y cáncer bucal.

We reviewed the concept of oral precancerous lesions, oral cancer, and the possibility of early diagnosis. With the keywords: premalignant oral lesions prevention, a search was performed over the past 10 years. Also clinical trials are searched from January 2011 until today with the keywords: oral cancer prevention AND dentistry. It is emphasized that there can be no significant changes related to the concept of precancerous lesions and cancer, and those relating to the early diagnosis. Despite the numerous described methods of screening, biopsy remains the most useful test, and therefore it is essential, mainly if we consider the new possibilities of molecular studies.

Mouth Cancer for Clinicians Part 6: Potentially Malignant Disorders.

UNLABELLED: A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team, in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. CLINICAL RELEVANCE: This article offers the dental team an overview of oral potentially malignant disorders.

The clinical effectiveness of reflectance optical spectroscopy for the in vivo diagnosis of oral lesions.

Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green-amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the Identafi(®) system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using Identafi(®) device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker (CD34) were performed on these tissue samples. The clinical vascular grading using the green-amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to 3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.

Oral potentially malignant disorders: Is malignant transformation predictable and preventable?

Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event cannot truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event cannot truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed

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Tongue squamous cell carcinoma in young nonsmoking and nondrinking patients: 3 clinical cases of orthodontic interest.

Oral squamous cell carcinoma traditionally affects older men who smoke and drink. A change in this profile has been reported because of an increased incidence in young nonsmoking and nondrinking patients. The purpose of this article was to describe a series of young nonsmoking and nondrinking patients diagnosed with tongue squamous cell carcinoma who had recently received orthodontic treatment or evaluation. Details regarding diagnosis, treatment, follow-up, and disease evolution are presented, with a review of the pertinent literature. Orthodontists often treat young adults, who have frequent dental appointments and long-term follow-ups. Thus, practitioners should pay special attention to young patients during dental consultations, since the incidence of malignant oral lesions in this segment of the population seems to be increasing.