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.

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.

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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Orofacial granulomatosis: review on aetiology and pathogenesis.

Orofacial granulomatosis (OFG) is considered as an uncommon disease and nomenclature of the disease was subjected to debate for a long time. Although various aetiological agents such as food substances, food additives, dental materials and various microbiological agents have been implicated in the disease process its precise pathogenesis is yet to be elucidated. Delayed type of hypersensitivity reaction appears to play a significant role, although the exact antigen inducing the immunological reaction varies in individual patients. However, evidence for the role of genetic predisposition to the disease is sparse. The underlying immunological mechanism appears to show some similarities between OFG and Crohn's disease, emphasizing the need for more comparative studies of the two entities. Therefore, we propose the term idiopathic OFG as a better term for those cases restricted to oral region without any identifiable known granulomatous disease and the diagnosis should not be changed until the patient develops systemic manifestations of a specific granulomatous condition. This review attempts to discuss the role of different aetiological agents and certain aspects of pathogenesis of OFG.

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.

Demographic, aetiological and survival differences of oral squamous cell carcinoma in the young and the old in Sri Lanka.

Oral squamous cell carcinoma (OSCC) is a major oncological problem in many regions of the world where tobacco habits are practiced in the form of chewing and/or smoking with or without alcohol intake. It accounts for 16.5% of all cancers in Sri Lankan patients with a male:female ratio of 4:1. In Sri Lanka nearly 5% of OSCC are diagnosed in young patients. This comparative study describes, demographic, aetiological and survival data from young and old patients with OSCC (n=56). Both younger and older groups showed a marked male predilection (male:female ratio was 4:1 and 3.7:1 in younger and older groups respectively). Tongue was the commonest site for younger group (41%, P<0.01) whilst buccal mucosa (37.5%, P<0.05) and alveolar mucosa (25%, P<0.01) were for older group. 39% of cancers in younger group were not associated with any identifiable risk factor (P<0.01) and 70% of SCC of the tongue has no associated habits (P<0.01). SCC of the tongue in the younger group shows poor prognosis than the older patients. Three-year survival rate for the total number showed no significant difference in two age groups. Survival appeared to be better in patients without associated habits in the older group.

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.

Clear cell odontogenic carcinoma-a case report and review of literature.

The clear cell odontogenic carcinoma (CCOC) is a rare, locally infiltrative neoplasm with a marked tendency for local recurrence and regional lymph node metastasis. The first description in 1985 included three cases of destructive jaw lesions. The entity was described as a clear cell odontogenic tumour in the previous WHO classification due to the fact that rarity of the lesion restricting pathologists to understand the spectrum of the degree of malignancy. These tumours have a peak incidence in the 5th-7th decades. CCOC tends to occur more frequently in the mandible, with a female predilection. The most striking histological feature is of large islands and strands of uniform cells with round or ovoid nuclei and clear cytoplasm. Presently we describe a case of clear cell odontogenic carcinoma in a 52-year-old female who presented with a bony-hard lump in the left body of the mandible. The patient is free of any recurrence after 2 years of follow-up.

Clinico-pathological conference 2002.

INTRODUCTION: Six cases are reported, each presented at the 11th Biennial Congress of the International Association of Oral Pathologists as an instructive case for differential diagnosis on the basis of clinical, imaging or histological features. CLINICAL PICTURE: Case diagnoses included a large, possibly intraosseous, myofibroma presenting with an oral mass; Langerhans cell histiocytosis with facial skin lesions; an intraosseous vascular hamartoma of the maxilla with worrying radiological features; an unusual mixed radiolucency of the jaw caused by cemento-ossifying fibroma; an osteosarcoma of the posterior mandible causing a well-defined radiolucency and an intraoral squamous cell carcinoma in a child.

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.

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.

Aberrant beta-catenin expression and adenomatous polyposis coli gene mutation in ameloblastoma and odontogenic carcinoma.

The Wnt pathway is involved in carcinogenesis and three regulatory genes of the Wnt pathway, APC (adenomatous polyposis coli), beta-catenin and Axin are frequently mutated in some primary human cancers. This study was conducted to clarify the relation of beta-catenin accumulation and the mutation of the CTNNB1 (beta-catenin) gene with the mutation of APC gene in the process of development of odontogenic tumors including ameloblastoma and odontogenic carcinoma (OC). beta-Catenin accumulation was examined by immunohistochemistry in formalin-fixed, paraffin-embedded samples of six ameloblastomas and eight OCs. We also performed a mutation analysis of CTNNB1 and APC to examine the cause of beta-catenin accumulation. All ameloblastoma cases and six out of eight (75%) OC cases exhibited beta-catenin accumulation in the nucleus. CTNNB1 mutation was only found in one OC case, whereas three of six (50%) ameloblastoma cases and two out of eight (25%) OC cases had APC mutations within the mutational cluster region. Our findings suggest that aberrant beta-catenin expression and APC missense mutation may play an important role for the pathogenesis of epithelial odontogenic tumors.

Odontogenic tumors in Sri Lanka: analysis of 226 cases.

PURPOSE: The purpose of this study was to analyze the relative prevalence of odontogenic tumors in Sri Lanka and compare it with prevalences reported for other countries. PATIENTS AND METHODS: A total of 226 cases of odontogenic tumors reported by the Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya between 1996 and 2002, were analyzed. RESULTS: The most prevalent tumor was ameloblastoma (69.8%); odontoma was the fourth most prevalent (4.5%). No gender predilection was seen, but the tumors occurred most frequently in the second to fifth decades of life (77.4%) and most commonly in the mandible (79.6%). CONCLUSIONS: The comparative data with statistically significant differences suggest a geographical difference in the relative prevalence of ameloblastoma among various continents. It is suggested that ameloblastoma most frequently occurs in the mandible (the posterior region) in all Asian, African, and South American countries.

Renal disease and the mouth.

Oral manifestations of renal disease are common. They may present as unique signs of multi-system disease affecting the kidneys (such as vasculitis), or as common oral pathologies found at an increased prevalence in patients with end-stage renal disease. Despite more oral and dental disease in patients on renal replacement therapy, attendance at dental clinics is infrequent, and physician awareness of the problem is low. In our short review, aimed at renal, transplant, and general physicians, we discuss the link between clinical changes in the mouth and multi-systemic disease involving the kidney. We suggest a standardized approach to oral examination to increase diagnostic yield and discuss common oral complications in patients on dialysis or successfully transplanted. Finally, we suggest potential treatments for oral disease that nephrologists might safely institute.

Clinicopathological analysis of osteosarcoma of jaw bones.

OBJECTIVES: To identify clinicopathological characteristics and prognosis of osteosarcoma of the jaw bones (JOS) and to compare the data with results of similar studies. To study the effectiveness of different treatment modalities currently available for this malignancy. SUBJECTS AND METHODS: Nineteen cases of JOS diagnosed from 1993 to 2003 were retrieved from the departmental archives. These were categorized into histopathological subtypes and graded according to the severity of the malignancies and the data analyzed. Fourteen cases were followed up and the success rate with different treatment modalities assessed. RESULTS: The mean age for JOS was 34.1 years. There were 11 mandibular lesions and eight maxillary lesions. Osteoblastic variant (53%) was the commonest histopathological subtype. High grade (grades III and IV) was more prevalent. All 14 followed up patients underwent surgical excision--five with adjuvant radiotherapy and six with adjuvant chemotherapy. Local recurrence was the commonest complication. Nine of the 14 were surviving with a survival rate of 64.2% for a median follow-up period of 5.25 years. CONCLUSIONS: JOS is a distinct group of lesions with a better prognosis if diagnosed and treated early. It does not show any ethnic variability. Existing histopathological typing and grading may not indicate the prognosis of JOS. Adjuvant chemotherapy is a better treatment modality than adjuvant radiotherapy.

Oral submucous fibrosis and oral yeast carriage - a case control study in Sri Lankan patients.

Oral submucous fibrosis (OSMF) is a well-known precancerous condition. Epithelial atrophy is one of the key features in OSMF. Presence of Candida in the mouth together with epithelial changes may predispose to candidal infection. Candidal infection together with other co-factors may also induce epithelial atypia and dysplasia leading to malignant change. The purpose of this study was to determine the prevalence of oral yeast carriage in patients with OSMF and to compare the carriage with the normal individuals. Thirty patients with histologically proven OSMF and healthy subjects were used as the test and control respectively. Oral rinse samples were collected from all the subjects and cultured on Sabouraud's agar. Species were identified using API 32C AUX identification kits. Nineteen (63.6%) of the test group and 15 (50%) of the control group had yeast isolated from their mouth. The carriage of yeast in the OSMF group was not statistically significant compared with the control group. We isolated C. dubliniensis in Sri Lanka for the first time and interestingly from the oral cavities of both OSMF patients and healthy individuals.

Prevalence of oral cancer and pre-cancer and associated risk factors among tea estate workers in the central Sri Lanka.

BACKGROUND: To screen for oral cancer or not is being debated, but for high-risk populations with minimal access to regular dental care systematic oral examinations could provide some benefit. METHODS: We undertook oral mucosal examinations of labourers employed in tea estate plantations in Sri Lanka. In a two-stage screening procedure, first by estate medical officers and then by visiting specialists, we examined 12 716 persons at their workplaces achieving a coverage of one-sixth of the total workforce. RESULTS: Fourteen oral cancers and 848 subjects with oral pre-cancer (6.7%) were detected giving population prevalences of 46.1 per 1000 for leukoplakia and 16.4 per 1000 for oral submucous fibrosis. Among subjects with any oral mucosal disorder (n = 1159) proportions of current users of betel quid, smokers and alcohol use was recorded at 92%, 31% and 61% respectively. The synergistic effect of these three risk habits on the development of oral leukoplakia was evident in mixed habit groups. CONCLUSIONS: The prevalence of oral pre-cancer in tea estate labourers was higher than estimates reported in previous studies. In the absence of state-sponsored preventive activities, it is necessary to improve the capacity of individual health practitioners and small medical centres to participate in oral health promotion and oral cancer/pre-cancer screening.

Synovial sarcoma of the mandible.

The term synovial sarcoma was first proposed for the histologically well defined entity by Knox in 1936. The name was proposed due to the fact that at least the cases reported in the early part showed some resemblance of the tumour to normal synovial tissue histologically. Thereafter, tumours have been diagnosed from areas without synovial tissue. The diagnosis of monophasic tumours can be difficult and immunostains appear to be a good diagnostic tool in those cases. The occurrence in the mandible is extremely rare. This is a case of synovial sarcoma arising in the condyle involving most of the ramus. The tumour was diagnosed as synovial sarcoma with predominant spindle cell component by correlation of histopathology with immunostains (cytokeratin, epithelial membrane antigen, actin and desmin). The patient has been treated with surgery and radiotherapy.