HPV related p16INK4A and HSV in benign and potentially malignant oral mucosa pathologies.

BACKGROUND: The association of Human Papilloma Virus (HPV) and Human Syncytial Virus (HSV) infection with inflammatory and potentially malignant disorders of the oral cavity (OPMD) is unknown. The aim of this cross-sectional study was to stablish the expression of the p16INK4A and HSV proteins, to test potential correlation between those parameters in biopsies from clinically diagnosed oral lesions. METHODS: Immunochemical analysis of 211 formalin-fixed, paraffin-embedded (FFPE) blocks from 211 individuals was provided. The clinical diagnosis included in the research were Oral lichen planus (N = 30), Oral Leukoplakia (N = 13) Mucocele (N = 25), Erosion/ulceration/ inflammation of mucosa (N = 8), Overgrowth of mucosa (N = 135). RESULTS: Two hundred eleven analyzed FFPE samples resulted with the median age of 58.5 years (the average age 54.0 years and SD ± 17 years). The female/male ratio was 2.3 (69.7% vs 30.3% respectively). All the samples positive for HSV also expressed p16INK4A (p = 0.000), that's showed various levels of association with the diverse clinical diagnosis reaching the higher level in OM 49.1% (29 positive samples) and OLP 30.5% (18). p16INK4A was associated with OLP at 30.5% (18), and fibroma 30.5%. HSV expression was mostly present in fibroma at 47.6% (10 positive samples). CONCLUSION: HSV and p16INK4A positivity in relation to diagnosis of the biopsies showed statistically most often p16INK4A in OLP and fibroma. The results of co-expression of p16INK4A and HSV in mucocele and fibroma in oral mucosa suggest a cooperation between the molecular alterations induced by these two viruses. Squamous papilloma samples positive for p16INK4A were also positive for HSV, suggesting that the putative pro-oncogenic action of HSV could be an early event.

Immunophenotypic and Gene Expression Analyses of the Inflammatory Microenvironment in High-Grade Oral Epithelial Dysplasia and Oral Lichen Planus.

BACKGROUND: Oral lichen planus (OLP) and oral epithelial dysplasia (OED) present diagnostic challenges due to clinical and histologic overlap. This study explores the immune microenvironment in OED, hypothesizing that immune signatures could aid in diagnostic differentiation and predict malignant transformation. METHODS: Tissue samples from OED and OLP cases were analyzed using immunofluorescence/immunohistochemistry (IF/IHC) for CD4, CD8, CD163/STAT1, and PD-1/PDL-1 expression. RNA-sequencing was performed on the samples, and data was subjected to CIBERSORTx analysis for immune cell composition. Gene Ontology analysis on the immune differentially expressed genes was also conducted. RESULTS: In OED, CD8 + T-cells infiltrated dysplastic epithelium, correlating with dysplasia severity. CD4 + lymphocytes increased in the basal layer. STAT1/CD163 + macrophages correlated with CD4 + intraepithelial distribution. PD-1/PDL-1 expression varied. IF/IHC analysis revealed differential immune cell composition between OED and OLP. RNA-sequencing identified upregulated genes associated with cytotoxic response and immunosurveillance in OED. Downregulated genes were linked to signaling, immune cell recruitment, and tumor suppression. CONCLUSIONS: The immune microenvironment distinguishes OED and OLP, suggesting diagnostic potential. Upregulated genes indicate cytotoxic immune response in OED. Downregulation of TRADD, CX3CL1, and ILI24 implies dysregulation in TNFR1 signaling, immune recruitment, and tumor suppression. This study contributes to the foundation for understanding immune interactions in OED and OLP, offering insights into future objective diagnostic avenues.

[Study of the kinetics of accumulation and distribution of the photosensitizer photoditazin in the oral mucosa in patients with lichen planus]. / Izuchenie kinetiki nakopleniya i raspredeleniya fotosensibilizatora fotoditazin v slizistoi obolochke rta u patsientov s krasnym ploskim lishaem.

THE AIM OF THE STUDY: Was to explore the accumulation and distribution of the photosensitizer Photoditazine in the oral mucosa when applied to pathological lesions in patients with severe forms of lichen planus. MATERIAL AND METHODS: A clinical and laboratory examination was carried out in 50 patients with severe forms of lichen planus (bullous and erosive-ulcerative) aged 18 to 70 years, including 6 men and 44 women. For autofluorescent imaging a LED device with a wavelength in the violet region of the spectrum (400±10 nm) was used. Quantitative registration of the kinetics of accumulation and distribution of the photosensitizer was carried out using the method of local fluorescence spectroscopy by measuring the fluorescence spectra. RESULTS: The measurements were made before applying the photosensitizer, 10, 20 and 30 minutes after application. The study showed that in most patients with erosive-ulcerative and bullous forms of lichen planus, the accumulation of the photosensitizer in the lesions on the oral mucosa increased as the exposure time increased from 20 to 30 minutes. The fastest accumulation of the photosensitizer occurred in the areas of mucosal lesions with the most pronounced vascularization, namely, in the area of the tongue and the bottom of the oral cavity. CONCLUSION: Using the method of local fluorescence spectroscopy, the kinetics of accumulation and destruction of photosensitizer in pathological areas of the oral mucosa was determined, and therefore the optimal time of laser exposure to the lesion was determined.

Evaluation of possible role of fluoride in pathogenesis of oral submucous fibrosis: A pilot study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Although areca nut chewing is an established risk factor, its low prevalence among nut chewers indicates additional factors likely facilitates pathogenesis. We recently demonstrated high fluoride levels in smokeless tobacco products and hypothesized a potential pathological role of fluoride in OSMF. Further exploring this novel role, this study compared fluoride levels in tissue, serum, and saliva samples from OSMF patients and healthy controls. METHODS: The ethically approved study included 25 clinically confirmed OSMF patients and 25 healthy matched controls. OSMF cases underwent buccal mucosal incisional biopsy, while controls had buccal mucosa tissue sampling during third molar removal. Fasting venous blood and unstimulated saliva were collected. Fluoride levels were analysed using ion chromatography and expressed as median (IQR). RESULTS: OSMF cases showed significantly higher fluoride concentrations compared with controls in tissue biopsies (30.1 vs. 0 mg/kg, p < 0.0001), serum (0.4 vs. 0 mg/L, p = 0.005) and saliva (1.3 vs. 0 mg/L, p < 0.0001). Majority (68%) of controls had undetectable fluoride levels across all samples. Tissue fluoride weakly correlated with OSMF severity (r = -0.158, p = 0.334). CONCLUSION: The preliminary findings demonstrated increased tissue fluoride levels in OSMF patients compared with healthy controls. Along with a previous study showing high fluoride content in smokeless tobacco products, these findings provided early evidence suggesting fluoride could play a contributory role in OSMF pathogenesis. Further large-scale investigation is warranted to definitively establish whether the association between fluoride exposure and OSMF is indicative of causation.

Proliferative verrucous leukoplakia: a general dental practitioner-focused clinical review.

Proliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis.

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-ß1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Cytomorphometric analysis of buccal mucosal cells in iron deficiency anemia: A cross-sectional study.

Background: Worldwide, at any given moment, more individuals have iron deficiency anemia (IDA) than any other health problems. Very few studies have been conducted to evaluate changes in oral mucosa in IDA. The present study is undertaken for cytomorphometric analysis of buccal mucosal cells in IDA. Nuclear diameter (ND), cell diameter (CD), nuclear area (NA), cell area (CA), and nuclear-cytoplasmic ratio (N/C) are measured and compared in buccal mucosal cells of IDA patients and controls. Aims: To evaluate cytomorphometric changes in epithelial cells of oral mucosa in IDA and to compare these changes with the controls. Settings and Design: A cross-sectional study. Methods and Materials: Forty cases of IDA and forty cases of control group were selected for the study. IDA cases were diagnosed with decreased Hb level, MCV, MCH, MCHC and confirmed by decreased serum iron and increased total iron-binding capacity levels. Cytomorphometric analysis of buccal mucosa was performed to study CA, CD, NA, ND, and N/C ratio. Statistical Analysis Used: Statistical analysis was done using t- test in SPSS software version 4. Result: Results of our study showed increased cell area, cell diameter, nuclear area, nuclear diameter, and nuclear-cytoplasmic ratio in anemic group as compared to controls. Conclusion: The study suggests that individuals with IDA regardless of clinically visible oral lesions show cytological changes in oral mucosal epithelium. Knowledge of quantitative alterations in oral epithelial cells of IDA patients is important as these alterations are similar to those seen in precancerous and radiation-induced changes. Cytomorphometry is an efficient tool to understand the extent of cellular changes that occur in oral epithelial cells in IDA.

Immune-mediated oral mucosal pathology: a comprehensive review and update for clinicians - part II.

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort, and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlap in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover recurrent aphthous stomatitis, pemphigus vulgaris and mucous membrane pemphigoid, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

Elastofibromatous changes in giant cell fibroma and amalgam tattoo: Unusual findings in common oral lesions.

Several cases of elastofibromatous lesion affecting the oral mucosa have been reported. Clinically, these lesions may appear as small exophytic lesions or less often as white lesions. Therefore, fibrous hyperplasia and leukoplakia are not uncommonly considered in clinical differential diagnosis. Microscopically, elastic and fibrous connective tissue deposition is seen. Rarely, elastofibromatous changes can be detected when assessing intraoral lesions, including cysts, salivary gland neoplasms, and epithelial dysplasia. Here we report two oral lesions showing elastofibromatous changes, expanding their clinicopathological spectrum. The first case was a 46-year-old man with a history of asymptomatic nodular lesion on the palate 1 year ago, diagnosed as giant cell fibroma with elastofibromatous changes. The second case was a 79-year-old woman who presented a pigmented and mildly symptomatic lesion on the mandibular alveolar mucosa several months ago, diagnosed as amalgam tattoo associated with elastofibromatous changes.

Identification of new head and neck squamous cell carcinoma molecular imaging targets.

OBJECTIVES: Intraoperative fluorescence imaging (FI) of head and neck squamous cell carcinoma (HNSCC) is performed to identify tumour-positive surgical margins, currently using epidermal growth factor receptor (EGFR) as imaging target. EGFR, not exclusively present in HNSCC, may result in non-specific tracer accumulation in normal tissues. We aimed to identify new potential HNSCC FI targets. MATERIALS AND METHODS: Publicly available transcriptomic data were collected, and a biostatistical method (Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling) was applied. TACNA-profiling captures downstream effects of CNAs on mRNA levels, which may translate to protein-level overexpression. Overexpressed genes were identified by comparing HNSCC versus healthy oral mucosa. Potential targets, selected based on overexpression and plasma membrane expression, were immunohistochemically stained. Expression was compared to EGFR on paired biopsies of HNSCC, adjacent macroscopically suspicious mucosa, and healthy mucosa. RESULTS: TACNA-profiling was applied on 111 healthy oral mucosa and 410 HNSCC samples, comparing expression levels of 19,635 genes. The newly identified targets were glucose transporter-1 (GLUT-1), placental cadherin (P-cadherin), monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2), and were evaluated by IHC on samples of 31 patients. GLUT-1 was expressed in 100 % (median; range: 60-100 %) of tumour cells, P-cadherin in 100 % (50-100 %), EGFR in 70 % (0-100 %), MCT-1 in 30 % (0-100 %), and NG2 in 10 % (0-70 %). GLUT-1 and P-cadherin showed higher expression than EGFR (p < 0.001 and p = 0.015). CONCLUSIONS: The immunohistochemical confirmation of TACNA-profiling results showed significantly higher GLUT-1 and P-cadherin expression than EGFR, warranting further investigation as HNSCC FI targets.

Prognosis of South Asian Buccal Mucosa Cancer Patients in the United States: Association of Race with Overall Survival.

BACKGROUND: Squamous Cell Carcinoma (SCC) of the buccal mucosa and gingiva accounts for approximately 10% of oral and pharyngeal cancers diagnosed in the United States each year, with a disproportionally higher incidence in individuals of South Asian descent. However, little has been documented regarding trends pertaining to overall survival. Thus, this research serves to identify predictors of survival and determine if overall survival (OS) differs for South Asians compared to other races once they develop non-metastatic buccal mucosa or gingiva squamous cell carcinoma. METHODS: A population-based, cohort study of patients registered in the National Cancer Database® (NCDB) between the years 2004-2016 was performed. Kaplan-Meyer Survival Curves were executed to examine overall survival, while univariable (UVA) and multivariable analysis (MVA) was performed to determine the effect of multiple variables on OS. RESULTS: South Asians had longer median OS at 88.7 months, compared to 58.6 months and 38.3 months for Caucasians and African Americans respectively (p<0.001). In UVA, race was highly significant, but when the cohort was selected to include only those who had undergone surgical resection, no statistically significant difference remained. On MVA, lack of surgery, older age, higher grade, higher T and N stage, use of chemotherapy, higher comorbidity scores were associated with worse OS, but race was not significant. CONCLUSION: South Asians in the US with non-metastatic buccal mucosa or gingiva SCC have better OS compared to Caucasians or African Americans, likely due to younger age at diagnosis (median 59 vs. 71 and 62 years old) and more frequent surgical resection (75% vs. 72% and 64%). In MVA, South Asians have similar OS as Caucasians.

Oral bacteriome and oral potentially malignant disorders: A systematic review of the associations.

INTRODUCTION: Periodontal bacteria can infiltrate the epithelium, activate signaling pathways, induce inflammation, and block natural killer and cytotoxic cells, all of which contribute to the vicious circle of carcinogenesis. It is unknown whether oral dysbiosis has an impact on the etiology or prognosis of OPMD. AIMS: Within this paradigm, this work systemically investigated and reported on the composition of oral microbiota in patients with oral potentially malignant disorders (OPMD) versus healthy controls. METHODS: Observational studies that reported next generation sequencing analysis of oral tissue or salivary samples and found at least three bacterial species were included. Identification, screening, citation analysis, and graphical synthesis were carried out. RESULTS: For oral lichen planus (OLP), the bacteria with the highest abundance were Fusobacterium, Capnocytophaga, Gemella, Granulicatella, Porphyromonas, and Rothia; for oral leukoplakia (OLK), Prevotella. Streptococci levels in OLK and OLP were lower. The usage of alcohol or smoke had no effect on the outcomes. CONCLUSIONS: An increase in periodontal pathogenic bacteria could promote the development and exacerbation of lichen. Effective bacteriome-based biomarkers are worthy of further investigation and application, as are bacteriome-based treatments.

The Effects of Black Raspberry as a Whole Food-Based Approach on Biomarkers of Oxidative Stress in Buccal Cells and Urine of Smokers.

Cigarette smoke is a rich source of free radicals that can promote oxidative stress and carcinogenesis, including head and neck squamous cell carcinoma (HNSCC) development; importantly, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-iso-prostaglandin F2α (8-isoprostane) are biomarkers of oxidative stress. Several mechanisms, including the antioxidant properties of black raspberry (BRB), account for their chemopreventive effects. In the present clinical trial, we tested the hypothesis that BRB administration reduces biomarkers levels of oxidative stress in buccal cells and urine of smokers. One week after enrolling 21 smokers, baseline buccal cells and urine samples were collected before the administration of BRB lozenges for 8 weeks (5/day, 1 gm BRB/lozenge). Buccal cells and urine samples were collected at the middle and the end of BRB administration. The last samples were collected after the BRB cessation (washout period). We analyzed levels of 8-oxodG and 8-isoprostane (LC/MS-MS), urinary cotinine (ELISA), and creatinine (spectrophotometry). BRB significantly reduced the levels of 8-oxodG by 17.08% (P = 0.00079) in buccal cells and 12.44% (P = 0.034) in urine at the middle of BRB administration as compared with baseline; the corresponding values at the end of BRB administration were 16.46% (P = 0.026) in buccal cells and 25.72% (P = 0.202) in urine. BRB had no significant effect on the levels of urinary 8-isoprostane. BRB's capacity to inhibit 8-oxodG formation of smokers' buccal cells and urine is clearly evident and the reduction in 8-oxodG suggests that antioxidant abilities are central to BRB's HNSCC chemopreventive properties. PREVENTION RELEVANCE: Cigarette smoke contains highly active components namely free radicals that can promote oxidative stress and oral cancer. We found that black raspberry (BRB) inhibited the formation of oxidative stress markers in the oral cavity and urine of smokers suggesting the antioxidant abilities of BRB in preventing oral cancer.

Different wavelengths of laser: are they significant for treatment of denture stomatitis?: an in-vitro study.

BACKGROUND: Denture stomatitis (DS) is an inflammatory disorder that affects the mucosal surface underneath the dentures and frequently causes oral mucosal irritation, discomfort, and altered taste perception, which prevents people from consuming enough nutrients. One of the main causes of DS is an overgrowth of the fungus Candida albicans (C. albicans). A possible alternative treatment for Candida infections is thought to be laser therapy. The aim of this study was to evaluate how different wavelengths of laser would affect growth and pathogenic properties of Candida albicans. METHODS: A concentration of 106 viable cells/ml of Candida albicans were used in the preparation process. Four groups were created from the specimens. Culturing of the control group was completed with no intervention. The other 3 groups received laser radiation for 60 seconds at a power of 1W. The 2nd and 3rd groups were irradiated with diode laser at a wavelength of 940 nm and 980 nm respectively. The 4th group was irradiated with Nd-YAG laser at a wavelength of 1064 nm. Turbidimetric growth was defined as variations in the optical density of fungal growth. These measures were made at three different times: baseline, 48 hours, and 72 hours. RESULTS: In both groups of diode laser, the growth of Candida albicans showed no remarkable differences at baseline, after 48 and 72 hours using a power of 1 W and duration of 60 seconds. The Nd-YAG group showed significant increase in optical density after 48 hrs then significant decrease after 72 hrs. The optical density values in the control group showed no notable difference between the control and diode study groups at different time periods. However, the Nd:YAG group showed a statistically significant difference compared to the control and the 2 diode laser groups. CONCLUSIONS: Different laser parameters have a different effect on growth and pathogenic properties of Candida albicans. Diode laser therapy with wavelengths 940 and 980 nm used in continuous mode with power of 1 W for duration of 60 seconds can result in proliferation of Candida albicans instead of destroying them. Nd:YAG laser, used in pulsed mode, with power of 1 W for a duration of 60 seconds can be used to destroy Candida albicans and therefore, can be used as an effective treatment for denture stomatitis.

Lichen planus pemphigoides induced by anti-PD-1 antibody: A case only involved in oral mucosa with excellent topical treatment efficiency.

Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal disease that can occur in patients receiving immune checkpoint inhibitors. Its clinical manifestations are combined with the characteristics of lichen planus with bullous pemphigoid that can occur on either skin or oral mucosa. It should be noted that oral LPP is very rare. Here, we report a novel case of oral LPP induced by an anti-PD-1 agent. The patient presented with typical clinical features in oral mucosa, and the diagnosis was based on histopathology and immunological studies. Given that the patient was receiving an anti-PD-1 agent, topical therapy was chosen, and a nice therapeutic effect was obtained. No significant recurrence was observed after a 2-year follow-up. A good and stable therapeutic effect achieved by rapid and local symptomatic medication suggests that accurate and sensitive diagnosis is necessary.

Oral mucosa involvement in pediatric patients with xeroderma pigmentosum: a comprehensive review.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage. This can lead to the development of neoplasms affecting multiple organ systems, with onset often in childhood. Unfortunately, no cure currently exists for XP, and management strategies focus on sun protection and early intervention for malignancies. Although most skin problems in XP patients are UV induced, various oral lesions are also described. However, the literature has not extensively characterized the oral manifestations and their prognostic significance. METHODS: We conducted a comprehensive review to evaluate the prevalence and nature of oral mucosal lesions in pediatric XP patients. RESULTS: Our literature search yielded 130 pediatric XP patients with oral involvement and 210 associated tumoral or non-tumoral lesions. Squamous cell carcinoma was the most common type of oral mucosal tumor reported, with other malignancies including basal cell carcinoma, melanoma, angiosarcoma, fibrosarcoma, and trichilemmal carcinoma. CONCLUSION: Given the potential morbidity and mortality associated with oral mucosal tumors in XP patients, our study aims to raise awareness of these manifestations. Early diagnosis and treatment are crucial for managing these lesions effectively, and routine oral exams should be considered a critical component of dermatological evaluations for XP patients, especially in the pediatric age group.

Demystifying oral epithelial dysplasia: a histological guide.

Oral epithelial dysplasia is a histologically diagnosed potentially premalignant disorder of the oral mucosa, which carries a risk of malignant transformation to squamous cell carcinoma. The diagnosis and grading of oral epithelial dysplasia is challenging, with cases often referred to specialist oral and maxillofacial pathology centres for second opinion. Even still there is poor inter-examiner and intra-examiner agreement in a diagnosis. There are a total of 28 features of oral epithelial dysplasia listed in the 5th edition of World Health Organization classification of tumours of the head and neck. Each of these features is poorly defined and subjective in its interpretation. Moreover, how these features contribute to dysplasia grading and risk stratification is even less well defined. This article discusses each of the features of oral epithelial dysplasia with examples and provides an overview of the common mimics, including the normal histological features of the oral mucosa which may mimic atypia. This article also highlights the paucity of evidence defining these features while offering suggested definitions. Ideally, these definitions will be refined, and the most important features identified to simplify the diagnosis of oral epithelial dysplasia. Digital whole slide images of the figures in this paper can be found at: https://www.pathogenesis.co.uk/r/demystifying-dysplasia-histology-dataset.

Oral carcinoma in situ in a middle-aged woman with systemic sclerosis: Report of a rare case and literature review.

Systemic sclerosis (SSc) is a rare multisystem rheumatic autoimmune disease involving the skin, connective tissue, and internal organs. Individuals with SSc are at increased risk of cancer. We herein contribute by reporting a case of carcinoma in situ affecting the lower lip and labial mucosa of a 56-year-old Brazilian female patient, which apparently represents the first case reported in Latin America. Surgical resection of the lesion was performed. After a 2-year follow-up, the patient has shown no evidence of recurrence. According to a literature review in PubMed, Web of Science, Scopus, and Embase databases on SSc-related oral and oropharyngeal cancer, 11 cases have been documented hitherto. Reports of oral carcinoma in individuals with SSc are rare. Clinicians should conduct regular examinations of the oral mucosa of these individuals to permit an early diagnosis, as done in the present case.

Variations of oral anatomy and common oral lesions.

Several topics related to the oral cavity are briefly addressed in this article, from anatomical variations that, when recognized, avoid unnecessary investigations, to diseases that affect exclusively the mouth, mucocutaneous diseases, as well as oral manifestations of systemic diseases. A complete clinical examination comprises the examination of the mouth, and this approach facilitates clinical practice, shortening the path to diagnosis in the outpatient clinic as well as with in-hospital patients. The objective of this article is to encourage the examination of the oral cavity as a useful tool in medical practice, helping to recognize diseases in this location.