Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis.

OBJECTIVES: This study aims to elucidate the expression of circulating exosomal miRNAs miRNA 21, miRNA 184, and miRNA 145 in the studied groups, including patients with (i) leukoplakia; (ii) oral submucous fibrosis; (iii) oral submucous fibrosis with leukoplakia; (iv) oral squamous cell carcinoma; and (v) healthy individuals. STUDY DESIGN: An observational study was conducted among 54 patients who reported to the outpatient department of Saveetha Dental College and Hospitals. The patients were divided into three groups: Group I healthy individuals (n = 18), Group II: case group (leukoplakia, OSMF, and leukoplakia and OSMF) (n = 18), and Group III: OSCC (n = 18). Real-time polymerase chain reaction analysis was carried out to assess the expression profiles of miRNA 21, miRNA 184, and miRNA 145. The statistical analysis was calculated using SPSS software version 23. RESULTS: All three miRNAs showed a statistically significant difference in the one-way ANOVA test between the case group (leukoplakia, OSMF, and leukoplakia and OSMF), healthy group, and OSCC group (p < 0.005). The case group (leukoplakia, OSMF, leukoplakia and OSMF) showed upregulated expression of miRNA 21 and miRNA 184 with threefold change and fourfold change and downregulated expression of miRNA 145 with 1.5-fold change when compared to apparently healthy individuals. CONCLUSION: Plasma circulating exosomal miRNAs miRNA 21, miRNA 145, and miRNA 184 expression could be a novel panel of plasma biomarkers to categorise case group (leukoplakia, OSMF, leukoplakia and OSMF) patients with a high risk of malignant transformation.

Critical appraisal of different triggering pathways for the pathobiology of pemphigus vulgaris-A review.

Pemphigus vulgaris is an autoimmune blistering disease with an increased potential for mortality. The epithelium is key in understanding the pathobiology as it is specialized to perform functions like mechanical protection, immunological defense, and proprioception. In order to perform these array of functions, epithelial integrity is important. This integrity is maintained by a host of molecules which orchestrate the ability of the keratinocytes to function as a single unit. Desmoglein 3 antibodies formed in genetically susceptible individuals are known to cause the disruption of the intact oral mucosa leading to the formation of blisters in pemphigus vulgaris patients. However, there are underlying complex triggering pathways leading to the clinical disease. The aim of the review is to congregate and critically appraise the various triggering pathways which contribute toward the pathobiology of pemphigus vulgaris. Articles relevant to the pathobiology of pemphigus vulgaris were identified from various search databases till the year 2020. The pathogenesis of pemphigus vulgaris is complex, and it involves an in-depth understanding of the various predisposing factors, provoking factors, and progression mechanisms. Congregation of the various triggering pathways will open our minds to understand pemphigus vulgaris better and in turn develop a reliable treatment in the near future.

A Sociological Analysis and Exploration of Factors Associated with Commercial Preparations of Smokeless Tobacco Use in Sri Lanka.

BACKGROUND: Use and addiction to commercial preparation of Smokeless Tobacco (CPSLT) is creating new socio-cultural issues and health challenges in Sri Lanka.  The objective of this sociological study is to investigate and analyse the socio-cultural factors that influence CPSLT use Sri Lanka to enable development of effective interventions.  Methods: This is a qualitative study for which data was collected through in-depth interviews in selected groups that use CPSLT. Thirty-five interviews were carried out in seven of the 24 districts in the country representing urban, rural, plantation communities and different livelihood and ethnic, gender and age groups in the year 2016. Purposive and snowball sampling techniques were used for selecting interviewees. The data was analysed by using qualitative data analysis techniques and sociological perspectives. RESULTS: This study reveals that the CPSLT use has integrated with the culture of several sociological and livelihood groups. Products such Thool (tobacco powder) and Maawa (dried areca-nut with flaked tobacco and some flavoured chemicals) were identified as the most popular forms of CPSLT.  Use of CPSLT has developed as a silent sub-culture specific to several social and livelihood groups. The informal CPSLT industry operating in the urban and sub-urban areas is influencing the school children and youth engaged in sports. Different groups of users express different reasons and justifications for its use. CONCLUSION: Use of CPSLT is closely integrated with the day to-day lifestyle and values of people of specific groups. and is an unseen part of life. Therefore, interventions will be urgently required to control the use of CPSLT to prevent its significant health impacts, considering the different contexts, symbolisms and justifications of its among the different groups. 
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Areca Nut Chewing: Initiation, Addiction, and Harmful Effects Emphasizing the Barriers and Importance of Cessation.

Areca nut is a highly addictive substance with carcinogenic properties and causes many harmful effects to the human body. Alkaloids are the major chemicals found in areca nut, and their mechanism of action has been studied for several years. About 600 million people around the world use areca nut, and its usage is higher in Asian countries. Areca nut chewers get used to the habit mainly due to social influence, stress, or lack of awareness. Some studies have reported a dependence syndrome related to areca nut chewing. Even though there are many ongoing research studies regarding tobacco addiction, less concern has been given to the areca nut addiction. There are only few studies related to areca nut cessation, and even those few cessation programs are mainly designed using tobacco cessation methodology. Sociocultural influence, behavioral factors, and accessibility are the main barriers to cessation. Behavior changing interventions proved to be more effective in areca nut cessation, but recently studies on pharmacological therapies are also emerging.

Evaluation of Successfulness of Capacity Building Programmes on Smokeless Tobacco and Areca Nut Cessation.

BACKGROUND: Prevalence of smoking in Sri Lanka has shown a gradual reduction whilst the use of smokeless tobacco and areca nut exhibits an increasing trend. At present, only a few well-structured smokeless tobacco (SLT)/areca nut (AN) cessation programs have been conducted in Sri Lanka, which is a gross underachievement as betel chewing-related oral squamous cell carcinoma is the most common cancer in Sri Lankan males. As General Dental Practitioners (GDP) do not contribute significantly to SLT/AN cessation activities at present, capacity building programs on SLT/AN control were carried out. The study evaluated the knowledge, attitude and practices  imparted on SLT/AN control among dental surgeons. METHODS: Following a single day capacity building program on smokeless tobacco / areca nut control, two self-administered questionnaires were used to assess the improvement of knowledge and change of attitudes among 663 GDPs. RESULTS: Majority had a good knowledge on harmful effects of SLT but not on areca nut. Knowledge of the current legislation on SLT control in Sri Lanka and carcinogenicity of areca nut was not satisfactory. Almost all agreed that proper counseling leads to patient quitting the habit, a formal training is necessary to conduct tobacco control activities and it should be a part of the regular treatment modalities. More than 80% of the participants support strict legislation. Most important factors leading to poor involvement in tobacco cessation activities were lack of expertise and inadequate educational material and not breach of patient privacy and lack of financial incentives. 20.1% dental surgeons had consumed smokeless tobacco / areca nut products in the past and only a few were current users of tobacco and/or areca nut. CONCLUSIONS: Well planned workshops are efficient in improving knowledge, practices and attitudes of dental surgeons towards SLT/AN cessation.
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Impact of Histological and Molecular Parameters on Prognosis of Oral Squamous Cell Carcinoma: Analysis of 290 Cases.

BACKGROUND: Nodal metastasis is a critical factor in predicting the prognosis of oral squamous cell carcinoma (OSCC). When patients present with a clinically positive neck, the treatment of choice is radical neck dissection. However, management of a clinically negative neck is still a subject of significant controversy. AIM: This study was carried out in order to propose a model to predict regional lymph node metastasis of OSCC using histological parameters such as tumour stage, tumour size, pattern of invasion (POI), differentiation of tumour, and host immune response, together with the expression levels of six biomarkers (periostin, HIF-1α, MMP-9, ß-catenin, VEGF-C, and EGFR), and, furthermore, to compare the impact of all these parameters on recurrence and 3 yr and 5 yr survival rates. Materials and Method. Histological materials collected from the archives were used to evaluate histological parameters and immunohistochemical profiles. Standard methods were used for immunohistochemistry and for evaluation of results. Data related to recurrence and survival (3 and 5 years) was also recorded. Clinical data was collected from patients' records. RESULTS: Male to female ratio was 3 : 1. The commonest site of OSCC was the buccal mucosa, and majority of them were T3 or T4 tumours presented at stage 4. 62.5% of the tumours were well differentiated. Three-year and 5-year survival rates were significantly associated with lymph node metastasis and recurrence. POI was significantly correlated with tumour size, stage, 3-year survival, EGFR, HIF-1α, periostin, and MMP-9 (p < 0.05). Expression of EGFR showed a direct association with metastasis (p < 0.05). CONCLUSION: POI, level of differentiation, and expression of EGFR are independent prognostic markers for lymph node metastasis. Therefore, these parameters may help in treatment planning of a clinically negative neck.

An Evaluation of Clinical and Histopathological Aspects of Patients with Oral Submucous Fibrosis in the Background of Oral Squamous Cell Carcinoma.

BACKGROUND: The behavior and prognosis of oral squamous cell carcinoma (OSCC) is presumably different in patients with oral submucous fibrosis (OSF). The objective of this study was to assess the effects of demographic features, habits, and histopathological features in the transformation of OSF to OSCC. METHODS: Data were extracted from the archives and histopathological evaluation and presence of nodal metastasis were recorded. RESULTS: OSF was detected in 130 (48%) out of 273 OSCC patients. The mean age of presentation among OSF-positive patients was 57.7 years, while patients diagnosed only with OSCC had a comparatively higher age, 59.5 years. In the below 50 years of age group, presence of OSF with OSCC was less (40%). In the OSF-positive group, male to female ratio was 3.2:1. The common primary sites were buccal mucosa and tongue in both groups. Betel quid chewing was present in more than 95% of the sample. Betel chewing, smoking, and alcohol consumption were present in 26.15% of OSF-positive patients. Degree of fibrosis was neither associated with the level of histological differentiation of the tumor (p= 0.195) nor associated with the malignant transformation (p =0.373). Lymph node metastasis was not seen in 76.63% and 68.54% of the patients with and without OSF, respectively. CONCLUSIONS: High degree of prevalence of OSF was observed among the OSCC patients. There were also a male predilection and younger age at presentation in these patients. However, a significant association was not observed in the degree of fibrosis with malignant transformation or the level of histopathological differentiation of the tumor. Lymph node metastasis also failed to express a significant relationship with the presence of OSF.

A model to predict nodal metastasis in patients with oral squamous cell carcinoma.

Difficulty in precise decision making on necessity of surgery is a major problem when managing oral squamous cell carcinomas (OSCCs) with clinically negative neck. Therefore, use of clinical and histopathological parameters in combination would be important to improve patient management. The main objective is to develop a model that predicts the presence of nodal metastasis in patients with OSCC.623 patients faced neck dissections with buccal mucosal or tongue squamous cell carcinoma (SCC) were selected from patients' records. Demographic data, clinical information, nodal status, Depth of invasion (DOI) and pattern of invasion (POI) were recorded. The parameters which showed a significant association with nodal metastasis were used to develop a multivariable predictive model (PM). Univariate logistic regression was used to estimate the strengths of those associations in terms of odds ratios (OR). This showed statistically significant associations between status of the nodal metastasis and each of the following 4 histopathological parameters individually: size of the tumour (T), site, POI, and DOI. Specifically, OR of nodal metastasis for tongue cancers relative to buccal mucosal cancers was 1.89, P-value < 0.001. Similarly, ORs for POI type 3 and 4 relative to type 2 were 1.99 and 5.83 respectively. A similar relationship was found with tumour size; ORs for T2, T3, and T4 compared to T1 were 2.79, 8.27 and 8.75 respectively. These four histopathological parameters were then used to develop a predictive model for nodal metastasis. This model showed that probability of nodal metastasis is higher among tongue cancers with increasing POI, with increasing T, and with larger depths while other characteristics remained unchanged. The proposed model provides a way of using combinations of histopathological parameters to identify patients with higher risks of nodal metastasis for surgical management.

A Predictive Model to Determine the Pattern of Nodal Metastasis in Oral Squamous Cell Carcinoma.

BACKGROUND: Developing histological prediction models that estimate the probability of developing metastatic deposit will help clinicians to identify individuals who need either radical or prophylactic neck dissection, which leads to better prognosis. Identification of accurate predictive models in oral cancer is important to overcome extensive prophylactic surgical management for neck nodes. Therefore, accurate prediction of metastasis in oral cancer would have an immediate clinical impact, especially to avoid unnecessary radical treatment of patients who are at a low risk of metastasis. METHODS: Histologically confirmed OSCC cases with neck dissection were used. Interrelation of demographic, clinical, and histological data was done using univariate and multivariate analysis. RESULTS: 465 cases were used and presence of metastasis and extracapsular invasion were statistically well correlated with level of differentiation (p < 0.001) and pattern of invasion (p < 0.001). Multivariate analysis showed level of differentiation, pattern of invasion, and stage as predictors of metastasis. CONCLUSIONS: The proposed predictive model may provide some guidance for maxillofacial surgeons to decide the appropriate treatment plan for OSCC, especially in developing countries. This model appears to be reliable and simple and may guide surgeons in planning surgical management of neck nodes.

Exophytic Verrucous Hyperplasia of the Oral Cavity ­ Application of Standardized Criteria for Diagnosis from a Consensus Report

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the 'First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity' held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named 'Exophytic Verrucous Hyperplasia'. Previously described clinical features of OVH such as the 'blunt' or 'sharp' variants; and the 'mass' or 'plaque' variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of 'Exophytic Verrucous Hyperplasia' as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential.

Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study.

BACKGROUND: The use of oral cytology to diagnose malignant and premalignant lesions at an early stage is considered crucial. The aim of this study was to evaluate the diagnoses of the spatula and the cytobrush techniques compared with the gold standard histopathological findings, analysed according to different diagnostic criteria. METHODS: Cytological smears were obtained from 76 suspicious oral malignant lesions and 116 oral leukoplakia lesions using two techniques: cytobrush plus cell collector and metal spatula. Subsequently, a surgical biopsy was performed on each lesion to achieve a histopathological diagnosis. Evaluation was conducted with respect to three different diagnostic criteria. RESULTS: The sensitivity for diagnosing carcinoma in clinically malignant cases was 89.58% and 60.42% for cytobrush and spatula techniques, respectively. Inclusion of severe dysplastic cases for 'high-risk' lesions increased the sensitivity up to 96.36% and 78.18% for two techniques, respectively. In leukoplakia lesions, malignant and severely dysplastic cells were diagnosed at a sensitivity of 88.89% in the cytobrush and 55.56% in the spatula techniques. Extending the criteria by defining malignant or any dysplastic findings as positive, sensitivity was increased to 98.02% and 89.11% for the spatula and the cytobrush techniques, respectively. Specificity for both techniques increased to 100%. The difference between the diagnoses of histopathology and the spatula cytology was statistically significant (P < 0.01), while no such difference was found with the cytobrush technique (P > 0.1). CONCLUSION: The cytobrush, unlike the spatula, is a useful screening instrument for early diagnosis of suspicious oral lesions and could therefore contribute to improved oral cancer prognosis.

A retrospective analysis to determine factors contributing to the survival of patients with oral squamous cell carcinoma.

The clinical outcome of patients with OSCC is assessed based on TNM system and currently it is the most reliable indicator on which therapeutic decisions are made. The patients with advanced disease are managed with combined treatment modalities. The aim of this retrospective study was to identify the factors which influence survival of patients with OSCC in Sri Lanka. Four hundred and thirty patients who have been managed surgically using either (1) local excision, (2) local excision+supraomohyoid neck dissection, (3) local excision+modified radical neck dissection, (4) local excision+radical neck dissection, (5) local excision+contra-lateral neck dissection depending on TNM stage, with or without post-operative radiotherapy. Patients with incompletely excised tumours showed statistically significant poor survival which improved with radiotherapy (stage II P=0.002, stage III P=0.017). With reference to TNM stage IV tumours, the patients who had received surgical option 4, showed poor survival compared to surgical options 2, 3, and 5 (P=0.001). However, within the group of patients who had received surgical option 4, those who had nodal metastasis showed poorer survival compared to patients without nodal metastasis. In addition, survival improved in patients who had been treated with surgical option 4, with radiotherapy. Furthermore, margin status was also found to significantly influence the survival of patients with TNM stage IV tumours (P=0.003). The main factors that had significant impact on the survival were TNM stage, nodal metastasis and the state of excision margins.

Dysregulation of the suppressor of cytokine signalling 3-signal transducer and activator of transcription-3 pathway in the aetiopathogenesis of Sjögren's syndrome.

The suppressor of cytokine signalling 3 (SOCS3) negatively regulates the Janus kinase (JAK)/signal transducer and activator of transcription-3 (STAT-3)/interleukin (IL)-17 pathway. The proinflammatory cytokine IL-17 is over-expressed in Sjögren's syndrome (SS) and is a key factor in its pathogenesis. We hypothesized that IL-17 over-expression in SS results from ineffective regulation by SOCS3. The expression of SOCS3 was analysed in peripheral blood mononuclear cells (PBMC) from SS cases, sicca controls (SC) and healthy controls (HC) and tissue samples from SS, SC and healthy salivary glands (HSG). PBMC and salivary gland tissue from SS and controls were dual-immunostained for SOCS3 and IL-17. IL-6-stimulated PBMC from SS and controls were evaluated for time-dependent STAT-3 activation and SOCS3 induction, and for IL-17 expression. Immunoblotting revealed greater levels of SOCS3 in PBMC from SS than SC (P = 0·017) or HC (P < 0·001). Similarly, the proportion of salivary-gland tissue cells staining for SOCS3 was significantly higher in SS than SC (P = 0·029) or HSG (P = 0·021). The cells in PBMC/salivary gland samples from controls predominantly expressed either SOCS3 or IL-17. However, there was a high frequency of SOCS3/IL-17 co-expression within cells of SS samples. IL-6-stimulation of PBMC from SS cases revealed prolonged activation of STAT-3 with reduced negative regulation by SOCS3, and enhanced expression of IL-17. This study showed that SOCS3 expression is up-regulated in SS. However, the absence in SS of the normal inverse relationship between SOCS3 and pSTAT-3/IL-17 indicates a functional disturbance in this signalling cascade. Consequently, a reduction in function, rather than a reduction in expression of SOCS3 accounts for the unregulated expression of IL-17 in SS, and may play a crucial role in aetiopathogenesis.

Pigmented mucoepidermoid carcinoma with spindle cell differentiation.

Mucoepidermoid carcinoma is the most common malignant salivary gland tumor of children and adults, showing diverse histopathologic features. Mucoepidermoid carcinoma with both melanin pigmentation and spindle cell differentiation has not been previously reported. We report the first documented case of pigmented mucoepidermoid carcinoma with spindle cell differentiation in a 34-year-old woman who presented with a swelling of the floor of the mouth.

Relative frequency of odontogenic tumors in Sri Lanka: Analysis of 1677 cases.

Odontogenic tumors (OTs) constitute a heterogeneous group of lesions with diverse histopathological features and clinical manifestations. The present study is to determine the frequency of odontogenic tumors (OTs) in Sri Lankan population. A total of 1677 cases of OTs were retrieved and analyzed for age, gender and primary site of the tumors. Cases were re-classified according to the 2005 WHO classification of OTs. The relative frequency of different types of tumors was also analyzed and compared with the literature. OTs represent 3.75% of all cases received during a period of 30 years. Ninety-eight percent of these tumors were benign and the rest malignant. Mandible to maxilla ratio is 2.8:1. The posterior part, the molar region, is the most frequently affected site for the mandible whilst it is the anterior region for the maxilla. The age ranges from 1 to 80 years, with a mean age of 30.6 years. Ameloblastoma of solid/multicystic and unicystic types showed a high preponderance for the mandible (>90%) with a ratio of 12.9:1 and 10.8:1, respectively. Out of 1677 cases, 48.7% were ameloblastoma, and other tumors, such as keratocystic odontogenic tumor (KCOT) and odontoma, were 25.7% and 10.1%, respectively. There is a significant change in the frequency of OTs after the inclusion of odontogenic keratocyst as a tumor. Although odontoma is said to be the commonest in western countries, our results showed ameloblastoma as the commonest followed by KCOT, and the relative frequencies of different tumors have changed significantly as a result of inclusion of KCOT in the new classification.

Grading oral epithelial dysplasia: analysis of individual features.

BACKGROUND: Assessing epithelial dysplasia to predict malignant transformation remains problematic in many tissues because grading systems are poorly structured and individual features poorly defined. Dysplasia grading is criticised for lack of reproducibility and poor predictive value. Grading systems for upper aerodigestive tract dysplasia have evolved over several decades and are not supported by good outcome experimental data. METHODS: This study analysed the individual features of dysplasia in 86 oral dysplastic lesions and determined the reproducibility of scoring for each, and correlated them with other features and clinical factors using complex clustering analyses. RESULTS: A uniform pattern of dysplasia was found in 37 lesions, focal dysplasia in 36 and in 13 lesions dysplasia formed complex discontinuous patterns. There was wide variation in reproducibility of scoring of individual features and many, including thickness, some types of rete morphology, basaloid cell anisonucleosis, basal dyscohesion, and dyskeratosis as deep single cells correlated with sub-sites. Rete morphology, type of keratinisation, hyperchromatism of the basaloid compartment, prickle cell anisonucleosis and extension down salivary ducts correlated with smoking. Conventional grading and oral intraepithelial neoplasia (OIN) grading by 'thirds affected' showed strong correlation overall but scores obtained with the OIN system tended to a higher grade at all sites except soft palate/fauces. There was poor correlation between the systems for moderate dysplasia and also severe dysplasia at some sites. Individual features could not be shown to cluster to form distinct patterns of dysplasia. CONCLUSIONS: These variations may account in part for the lack of reproducibility and poor predictive value of the grading systems in current use and could inform the design of future grading systems.

Genetics/epigenetics of oral premalignancy: current status and future research.

Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long-term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.

A Rare Clinical Presentation of Intraoral Darier's Disease.

Darier's disease, also known as keratosis follicularis or dyskeratosis follicularis, is a rare disorder of keratinization. It is an autosomal dominant genodermatosis with high penetrance and variable expressivity. Its manifestation appears as hyperkeratotic papules primarily affecting seborrheic areas on the head, neck, thorax, and less frequently the oral mucosa. When oral manifestations are present, the palatal and alveolar mucosae are primarily affected. They usually asymptomatic and are discovered in routine dental examination. Histologically, the lesions present as suprabasal clefts in the epithelium with acantholytic and dyskeratotic cells represented by "corps ronds and grains." This paper reports a case of an adult male patient who presented with painful whitish lesions on buccal mucosa with crusty lips as the only clinical sign of Darier's disease. As this patient did not have skin lesions or family history, an intraoral biopsy confirmed the diagnosis of Darier's disease by a multidisciplinary team.

Distribution pattern of cholinesterase enzymes in human tooth germs.

The two distinct molecular forms of cholinesterase (ChE) are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Our previous studies have reported that ChE is involved in tooth development. However, further experiments are needed to understand the precise action of ChE in tooth development. This study aimed to localise types of ChE in human tooth germs, and identify their distribution pattern. ChE were localised in frozen sections of jaws which were prepared from dead fetuses, neonates and stillborns who were free from visible abnormalities by Karnovsky and Root method. AChE was identified in the inner and outer enamel epithelia including the cervical loop region, stratum intermedium and preameloblasts of tooth germs at bell stage. Secretory ameloblasts were free from staining. The bud and cap stages of permanent tooth germs showed AChE activity on the lingual aspect and top surface of the epithelial ingrowths, respectively. BuChE activity was localised in the degenerating dental lamina. Our study reported the first evidence of localisation of ChE in human tooth development and identified the possible molecular form of ChE in tooth germs as AChE. Also, our results have provided strong evidence to speculate the action of AChE is on the cells of enamel organ during tooth development.