Targeted therapies in ameloblastomas and amelobastic carcinoma-A systematic review.

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.

Immunohistochemical Expression of E-Cadherin and ß-Catenin in Oral Squamous Cell Carcinoma.

Background: The E-cadherin/ß-catenin protein complexes are actively involved in the epithelial-to-mesenchymal transition. Alterations in cadherin or catenin expression or function, play important roles in the development of invasive or metastatic phenotypes of cancers. Objectives: The aim of this study was to assess the expression of E-cadherin and ß-catenin in oral squamous cell carcinoma (OSCC) patients and to compare this with their clinico-pathological parameters. Materials and Methods: This was a cross-sectional study to assess the immunohistochemical expression of E-cadherin and ß-catenin in 41 cases of OSCC. Data were analyzed using version 26 of SPSS software. Qualitative data were compared using chi-square statistics. Quantitative data were summarized using mean, standard deviation, and confidence interval and compared using a one-way analysis of variance test. The level of significance was set at P < 0.05. Results: Overall, 95.1% of the cases had positive membrane expression for E-cadherin, while cytoplasmic staining was seen in 90.2% cases. Positive nuclear staining was seen in 46.3% cases. There was a decrease in the percentage of cytoplasmic and nuclear expression of E-cadherin as the OSCC became more poorly differentiated (χ2 = 13.96, P = 0.016). Also, a decrease in the percentage of nuclear expression of ß-catenin in poorly differentiated cases was seen. However, no statistically significant difference was seen in the expression of ß-catenin between the different histologic grades (χ2 = 4.8, P = 0.4). Conclusion: This study shows a reduction in the expression of E-cadherin and ß-catenin as OSCC becomes less differentiated.

Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study.

BACKGROUND: Salivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only. METHODS: This study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019. RESULTS: A total of 5739 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (68%) of the SGT presented in major and 32% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (47%) for malignant tumours. Pleomorphic adenoma (70%), and Warthin's tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (26%) and adenoid cystic carcinoma (17%) were the most frequent malignant tumours. CONCLUSIONS: This multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.

Relationship between CD4+ count, serum inflammatory cytokines, and oral melanotic hyperpigmentation in newly diagnosed HIV-seropositive patients: a nested case-control study.

OBJECTIVE: Oral melanotic hyperpigmentation (OMH) in patients with human immunodeficiency virus (HIV) infection has been attributed to the use of antifungal or antiretroviral drugs, as well as HIV-induced cytokine dysregulation. This research aimed to determine the relationship between immunosuppression and cytokine dysregulation in newly diagnosed HIV-seropositive subjects with OMH. STUDY DESIGN: The study was conducted among newly diagnosed HIV-seropositive patients at the Infectious Disease Clinic, Ibadan, Nigeria. The cases were patients with OMH matched for age and sex with control subjects without OMH. CD4+ count and cytokine levels (interleukin-6 and tumor necrosis factor-α) were compared between the cases and control subjects. SPSS version 21 software was used for data analysis. RESULTS: Seventy newly diagnosed HIV-seropositive patients were studied, which comprised of 35 cases and 35 control subjects. The median CD4+ counts for cases and control subjects were 174 cells/mm3 (interquartile range [IQR], 57-250) and 324 cells/mm3 (IQR, 107-424), respectively. Severe immunosuppression (CD4+ count, ≤200 cells/mm3) was found in over half of the study participants, being more prevalent among the cases than among the control group (P = .019). Serum cytokine levels did not significantly vary between the cases and control subjects. CONCLUSIONS: There was a significant association between HIV-OMH and severe immunosuppression in the newly diagnosed HIV-seropositive patients.

Orofacial lesions associated with long-term highly active antiretroviral therapy among HIV-seropositive adults in Ibadan, Nigeria.

INTRODUCTION: highly active antiretroviral therapy (HAART) has contributed to a reduction in HIV- related oral lesions and improved quality of life among HIV seropositive patients. However, the therapy is not without its side effects. This study was aimed at assessing the self- reported orofacial manifestations due to long term use of HAART, as well as the pattern of oral lesions on examination. METHODS: this was a cross-sectional study conducted among HIV seropositive adult patients in Ibadan, who had been on HAART for at least two years. Data were collected using an interviewer-administered questionnaire. Clinical diagnosis of HIV-related oral lesions was made according to the EC-Clearinghouse criteria. Data analysis was done using SPSS version 25. RESULTS: the study participants comprised of 227 HIV seropositive patients who were HAART experienced, with 54 (24%) males and 173 (76%) females. Their mean age (±SD) was 44.7 (±9.4) years. The participants CD4 count ranged from 13-1338cells/mm3, with a median count of 341 cells/mm3. About half (45%) of the participants noted one or more orofacial changes since they commenced HAART. These oral changes included dryness of mouth, burning sensation, abnormal taste, melanotic hyperpigmentation, oral thrush, ulcers, and parotid swelling. Most of those who reported oral changes had been on HAART over 10 years (p=0.03), and the changes were more reported among those on the first-line regimen. CONCLUSION: melanotic hyperpigmentation was the most common oral lesion found and burning mouth syndrome was the most commonly reported complain among HIV-seropositive adults who are on long-term HAART.

A geographical analysis of ethnic distribution of jaw ameloblastoma in Nigerians.

INTRODUCTION: Ameloblastoma is the most common odontogenic tumour in Nigeria. A definite geographic variation has been observed in the frequency of odontogenic tumors from different parts of the world. However, there is no study on the regional variations in Nigeria. Hence, this study was designed to document the ethnic and geographical distribution of jaw ameloblastoma in Nigeria. METHODS: Archival data on ameloblastoma from 10 health facilities were obtained. Global Moran's I detected geographic clustering in its distribution while Local Getis Ord indicated the location of ameloblastoma clusters. Chi-square tested associations between variables at 0.05 level of significance. RESULTS: A total of 1,246 ameloblastoma cases were recorded in Nigeria. Besides substantial state variations, a South-North gradient was noticed in its distribution. Significant positive spatial autocorrelation was observed in the three major groups while ameloblastoma hotspots were found in the SouthWestern and Northwestern Nigeria. The Igbos had a higher prevalence of ameloblastoma outside their home region than within. CONCLUSION: The study hypothesized that the geographical distribution of ameloblastoma in Nigeria is the result of all or one of the following: the country's tropical climate, migration patterns and health seeking behavior. Hopefully, these claims should lead to further enquiry on the underlying causes.

Descriptive epidemiology of salivary gland neoplasms in Nigeria: An AOPRC multicenter tertiary hospital study.

OBJECTIVES: Accurate diagnosis of salivary gland neoplasms (SGN) in many centers in Africa is limited by poor diagnostic resources and ancillary services. Hence, we have carried out a multicenter epidemiological study to understand the true burden of SGN in Nigeria. METHOD: In this descriptive cross-sectional study, we have deployed resources available to members of the African Oral Pathology Consortium (AOPRC) to examine the burden of salivary gland lesions in Nigeria, using a multicenter approach. Data from seven major tertiary health institutions in northern, western, and southern Nigeria were generated using a standardized data extraction format and analyzed using the Epi-info software (Version 7.0, Atlanta, USA). RESULT: Of the 497 cases examined across the seven centers, we observed that SGN occurred more in females than males. Overall, pleomorphic salivary adenoma (PA) was found to be the most common. PA was found to be the commonest benign SGN while adenocystic carcinoma (ADCC) was the commonest malignant SGN. Regional variations were observed for age group, diagnosis, and gender distribution. Significant statistical differences were found between males and females for malignant SGNs (p-value=0.037). CONCLUSION: We found regional variation in the pattern of distribution of SGN in Nigeria. This is the largest multicenter study of SGN in Nigeria, and our findings are robust and representative of the epidemiology of this neoplasm in Nigeria.

A review of 640 Oral squamous cell carcinoma cases in Nigeria.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm in the oral cavity and accounts for 70% to 90% of all oral malignant neoplasms. The aim of this study was to examine the demographic distribution of OSCC in five Tertiary Health centres in Nigeria. MATERIAL AND METHODS: All cases diagnosed as OSCC during the period from 1970 -2014 were retrieved from the records of five teaching hospitals in Nigeria. Hematoxylin and eosin stained histological slides of all cases that had a diagnosis of OSCC were reviewed for confirmation and inclusion. Data from all the centers was collated at the University College Hospital, Ibadan by 2 researchers. The data was entered into and analyzed with the SPSS for Windows (version 20.0; SPSS Inc. Chicago, IL). Simple descriptive and comparative analyses were done, with the test of statistical significance set at p ≤ 0.05. RESULTS: A total of 640 cases of OSCC were seen out of 1560 oral malignant neoplasms representing 41% of all the oral malignancies seen. The mean age of occurence of OSCC was 55.5 (±17.0) years and a peak age incidence in the sixth and seventh decades of life. OSCC occurred more in males (60.9%) than females (39.1%) with a male: female ratio of 1.6:1. The well differentiated OSCC with 309 (48.3%) cases, was the most common grade, while the moderately differentiated and poorly differentiated OSCC accounted for 232 (36.2%) and 92 (14.4%) cases respectively. CONCLUSIONS: This study showed that OSCC is more common in males, most commonly seen in the 60-69 age group and the commonest site of occurrence was the mandibular mucosa. The well differentiated OSCC was the most common histology sub-type. Key words:Oral squamous cell carcinoma, tongue, palate, mandible.

A retrospective review of 61 cases of adenomatoid odontogenic tumour seen in five tertiary health facilities in Nigeria.

INTRODUCTION: Adenomatoid odontogenic tumor (AOT) is a benign lesion originating from the dental lamina or its remnants. It is a relatively uncommon neoplasm representing about 3% of all odontogenic tumors. The aim of this study was to examine the clinical and radiological characteristics of AOTs in five major tertiary centres in Nigeria. METHODS: Archival hospital-based data stores of five tertiary health facilities in Nigeria were accessed. Case files and biopsy records were retrieved to obtain relevant information. Data was collected according to a proforma for standardization and entered into and analysed using SPSS for Windows (version 20.0; SPSS Inc. Chicago, IL). RESULTS: 61 (4.5%) cases of AOT were documented. The age range was 8-46 years with a mean age of 20.4±9.9 years. Male: Female ratio was 1:1.3. The anterior maxilla had 34 (55.8%) cases and the anterior mandible had 20 (32.8%) cases. 40 (65.6%) follicular cases, 20 (32.8%) extra-follicular cases and 1(1.6%) extra-osseous case were found. 31 cases (61.1%) were associated with impacted teeth and the upper canine was involved in 19 (57.6%) cases. CONCLUSION: This study showed AOT to be more common in the maxilla, more in females, most often associated with impacted canines, however, the suggestion of AOT being a "Two third tumour" was not observed in this study.

Malignant salivary gland tumours of the head and neck region: a single institutions review.

INTRODUCTION: Malignant salivary gland tumours (MSGTs) comprise about 3% of all head and neck cancers; they demonstrate an unpredictable clinical course. The purpose of this study is to review MSGTs seen at a tertiary Health centre, and compare findings with those of previous studies. METHODS: The records of the Department of Oral Pathology and the Department of Pathology, University College Hospital Ibadan were reviewed over a 19 year period and lesions diagnosed as MSGTs according to 2005 WHO histological classification were analysed for age, gender and site using SPSS for Windows (version 20.0; SPSS Inc. Chicago, IL). RESULTS: MSGTs were more common in males (55.2%) than females (44.8%). The mean age of was 47.9 (±17.0) years and peak age was the fifth decade. The parotid gland was the commonest site with 62 (28.1%) cases. The palate was the commonest intraoral site with 61(27.6%). The nose with 19 (8.6%) was the commonest minor extra-oral site. CONCLUSION: The findings were essentially similar to reports from Europe and America. Adenoid Cystic Carcinoma was the most common MSGT in this series. A high proportion of salivary gland tumours in sublingual gland were malignant. The reason(s) for high proportion of MSGTs in sublingual glands requires further investigation.

Immunohistochemical expression of MMP-2 and MMP-8 in oral squamous cell carcinoma.

BACKGROUND: Matrix metalloproteinases (MMPs) are endopeptidases that can degrade extracellular matrix components and affect invasiveness and aggressiveness of oral squamous cell carcinoma (OSCC). The aim of this study was to examine the immunohistochemical expression of MMP-2 and MMP-8 in OSCCs in patients presenting at the Tertiary Health facility in Nigeria. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded (FFPE) OSCC samples diagnosed between the years 2010 and 2012 were used for his study. The FFPE were processed for MMP-2 and MMP-8 using the specifications of the manufacturer. Two investigators reviewed the slides scoring the pattern and intensity of staining as negative (0), weakly positive (+1), moderately positive (+2) and strongly positive (+3). The data were analysed using version 20 of the SPSS. The level of significance was set at P < 0.05. RESULTS: Twenty-five OSCC consisting of 14 (56%) males and 11 females (44%) were used. The mean age was 54.6 ± 17.9 years. A higher proportion (100%) of poorly differentiated OSCC strongly expressed MMP-2 compared with the well differentiated and moderately differentiated OSSC. There was no significant difference in the expression of MMP-2 amongst the three grades of OSCC (X2 = 2.87; p= 0.17). Only 5 (20%) OSCC cases positively expressed MMP-8. Moderate expression of MMP-8 was only seen in well-differentiated OSCCs. CONCLUSIONS: This study showed that a higher proportion of poorly differentiated OSSC strongly expressed MMP-2. Eighty percent of cases that express MMP-8 were females and moderate expression of MMP-8 was seen only in well differentiated OSCC. Key words:Oral squamous cell carcinoma, MMP-2, MMP-8, immunohistochemistry.

Stoichiometric expression of MMP-2/TIMP-2 in benign and malignant tumours of the salivary gland.

The aim of this study was to determine the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitors of matrix metalloproteinase 2 (TIMP-2) and the MMP-2/TIMP-2 expression ratio in salivary gland tumours (SGTs). Forty-three FFPE SGTs were prepared for antibody processing to MMP-2 and TIMP-2. Two investigators utilizing Sinicrope's method scored the uptake of immuno-stains. Cytoplasmic staining was considered as positive. Data was analysed using SPSS version 20. The significance level was set at p < 0.05. In benign SGTs, the mean score for MMP-2 was not significantly lower than that of TIMP-2 (p = 0.37). However, the mean scores for MMP-2 stain intensity and proportion were significantly higher in malignant than benign SGTs (p = 0.01 and p = 0.02 respectively). There was no significant difference in the mean MMP-2/TIMP-2 expression ratio of the malignant SGTs according to histological grade and histogenesis (p = 0.4 and p = 0.19 respectively). The MMP-2/TIMP-2 expression ratio has a higher prognostic value than the separate expressions of MMP-2 and TIMP-2.

PTCH-1 and MDM2 expression in ameloblastoma from a West African sub-population: implication for chemotherapeutics.

INTRODUCTION: Ameloblastoma is a slow growing, painless odontogenic swelling which can attain sizes that result in severe deformities of the craniofacial complex. It is the most commonly encountered odontogenic tumor in Nigeria. Surgical intervention is currently the method of treatment; however identification of altered molecular pathways may inform chemotherapeutic potential. The Protein Patched homolog 1 (PTCH-1) is overexpressed in ameloblastoma. Also, mutation in the MDM2 gene can reduce the tumor suppressor function of p53 and promote ameloblastoma growth. No study however has characterized the molecular profile of African cases of ameloblastoma with a view to developing chemotherapeutic alternatives. The objective was to characterize the PTCH-1 genetic profile of Ameloblastoma in Nigerian patients as a first step in investigating its potential for chemotherapeutic intervention. METHODS: Twenty-eight FFPE blocks of ameloblastoma cases from Nigerian patients were prepared for antibody processing to PTCH-1 (Polyclonal Anti-PTCH antibody ab39266) and MDM2 (Monoclonal Anti-MDM2 antibody (2A10) ab16895). Cytoplasmic brown staining was considered as positive for PTCH while nuclear staining was positive for MDM2. RESULTS: Moderate and strong expressions for PTCH in ameloblast and stellate reticulum were 78.6% and 60.7% respectively. Only 3 (10.7%) cases expressed MDM2. CONCLUSION: The importance of our study is that it supports, in theory, anti-PTCH/SHH chemotherapeutics for Nigerian ameloblastoma cases and also infers the possible additional use of anti-p53 agents.

Spindle cell hemangioma: Unusual presentation of an uncommon tumor.

Spindle cell hemangioma (SCH) is an uncommon tumor that usually presents as subcutaneous or deep dermal nodule affecting the extremities and is typically <2 cm in size. A few cases have been reported in the head and neck region. To the best of the authors' knowledge, there are no previous reports of SCH occurring in the orbit in the English literature. We, therefore, report the case of a large SCH involving the right orbit of a healthy 9-year-old Nigerian girl.

Palatal rugae as a tool for human identification.

OBJECTIVE: This study was conducted to assess the accuracy of palatal rugae as a tool for human identification and to determine factors that may limit accuracy. This will serve as a potential basis for advising national health policy formulation on human identification as forensic rugoscopy is unexplored in sub-Saharan Africa. MATERIALS AND METHODS: One hundred consenting participants were recruited; impressions of the upper jaws were taken and cast with dental stone. All the teeth on the models were trimmed off to prevent identification by tooth morphology and the models were coded. Five uncalibrated dentists independently pair-matched the models based on the pattern of the palatal rugae. RESULTS: The overall accuracy for all 50 paired models ranged from 72 to 96%, while the percentage correct match for each of the 50 paired models range from 40-100%. All the examiners properly matched 60% of the models. CONCLUSION: Rugoscopy is a useful technique for human identification due to the unique rugae pattern in every individual. However, without the aid of ancillary aids, visual inspection alone can be challenging. CLINICAL RELEVANCE: This study provides useful information on an additional clinical technique relevant for human identification.

Bimaxillary keratocystic odontogenic tumour: a case of diagnostic and therapeutic difficulty.

Keratocystic odontogenic tumour (KCOT) is a benign cystic intraosseous tumour of odontogenic origin that is usually solitary except when syndromic. It rarely occurs in the maxilla; therefore a rapidly progressive, nonsyndromic bimaxillary KCOT with locoregional extension poses significant diagnostic and management challenges. To the best of the authors' knowledge, documentation of a nonsyndromic bimaxillary KCOT is nonexistent in the English literature. We therefore present the case of an extensive bimaxillary KCOT in a 38-year-old Nigerian male.

Fibro-osseous lesions of the jaws in Ibadan, Nigeria.

BACKGROUND: Fibro-osseous lesion is a broad term for a diverse group of jaw disorders characterized by the replacement of normal bone by a benign fibrous connective tissue matrix. The present study reviewed the clinico-pathologic characteristics of all biopsied cases of fibro-osseous lesions at our hospital from 1990 to 2011, which we hope will serve as a reference database regionally. METHODS: A retrospective clinicopathological review of all histologically diagnosed cases of jaw fibro-osseous lesions seen at our Hospital between January 1990 and December 2011. RESULTS: A total of one hundred and twenty one fibro-osseous lesions of jaws were histological diagnosed in the 22-year period. The lesions documented included ossifying fibroma (62%), fibrous dysplasia (37.2%) and florid cemento-osseous dysplasia (0.8%). Fibro-osseous lesions of jaws were more in females (61.2%) than males (38.8%), giving a male to female ratio of 1:1.6. CONCLUSION: Fibro-osseous lesions of jaw are a diverse group and since it may not be possible to adequately separate them histologically, the development of a more rigorous clinical algorithm as indicated in this study is essential in reaching a final diagnosis especially in resource-limited settings.

Clear cell variant of squamous cell carcinoma of skin: A report of a case.

Clear cell squamous cell carcinoma (SCC) is a rare variant of SCC of skin in which ultraviolet radiation has been suggested as possible etiology. This case is that of a 62-year-old male concrete block maker/bricklayer who presented with a 6 months history of a non-healing ulcer on the left side of his face. Histology showed features of malignant epithelial neoplasm composed of islands of large oval to polyhedral malignant squamous cells with eosinophilic to amphophilic cytoplasm and vesicular nuclei and there were areas showing clear cell differentiation and isolated areas of keratin pearl formation. The lesion was also negative for periodic acid schiff, mucicarmine, and alcian blue stains but was strongly positive for AE1/AE3 (immuno-stain). This case showed an aggressive and bizarre clinical presentation but more report of cases are needed to have a better characterization of the clinical presentation and prognosis of this variant of SCC.

Non-doctor consultations and self-medication practices in patients seen at a tertiary dental center in Ibadan.

AIM: The aim of this study was to determine the prevalence of self-medication practices among dental out patients presenting at a tertiary health care center in Ibadan, and to determine factors that are associated with these practices. MATERIALS AND METHODS: All patients presenting over a 4-month period, who consented to participate in the study, had a semi-structured questionnaire, highlighting age, sex, income and educational qualification, history of past practice of self-medication, substances used and reasons for resorting to self-medication administered to them. Data obtained were analyzed with the SPSS 12.0.1 software. Frequency tables were generated and statistical relationship between the variables was analyzed using the Chi-square test. Statistical significance was set at P>0.05. RESULTS: There were 108 (38.03%) males and 176 (61.97%) females. A total of 139 (48.9%) of the respondents claimed that they have been involved in self-medication. 54.7% of the people involved in self-medication were female, while 41.7% were male. There was a statistically significant difference in self-medication between males and females (P=0.001). 71.2% of the respondents had post-secondary education and only 28.8% had secondary education or less. CONCLUSION: Self-medication practices were quite high in this study, and these practices were also prevalent among the educated people. Drug control enforcement needs to be intensified and dental public health education needs to be given greater priority in the overall public health campaigns.