Time to Recurrence of Ameloblastoma and Associated Factors in a Multi-institutional Black Patient Cohort.

Ameloblastoma is a highly recurrent odontogenic neoplasm with variable global distribution. However, impact of race and ethnicity on ameloblastoma recurrence are still unclear. The primary aim of this study was to assess duration of time between primary and recurrent ameloblastomas in a predominantly Black multi-institutional patient cohort and secondarily to determine whether recurrent ameloblastomas are more readily discovered when clinically-symptomatic rather than by radiographic surveillance. A retrospective cross-sectional design was used to evaluate demographic, clinical, and pathological information on recurrent ameloblastomas patients. Outcome variable was time to recurrence, determined as period between the diagnosis of primary and recurrent ameloblastomas. We assessed associations between outcome variable and race, time lapse between primary and recurrent ameloblastomas and clinical symptoms of recurrent ameloblastomas at time of diagnosis. Among 115 recurrent ameloblastomas identified, 90.5% occurred in adults, 91.3% in Blacks, and similarly, 91.3% were conventional ameloblastomas. About 41% affected the posterior mandible. 93.9% were clinically symptomatic at time of presentation while 6.1% non-symptomatic lesions were discovered by routine diagnostic radiology. Median time to presentation of recurrent tumor was significantly longer in females (90 months, p = 0.016) and clinically symptomatic group of ameloblastoma patients (75 months, p = 0.023). Ameloblastoma recurrence was distinctively high in Black patients, occurred faster in males than females and was located mostly in the posterior mandible. Concomitant with delayed access to healthcare of Black individuals, routine post-surgical follow-up is essential because time lag between primary and recurrence tumors was longer in clinically symptomatic ameloblastomas at the time of diagnosis.

Comparison of diagnostic methods for detection of BRAFV600E mutation in ameloblastoma.

BACKGROUND: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E-inhibitor therapy The study objective was to identify a sensitive low-cost test for BRAFV600E-positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin-fixed paraffin-embedded tissues for BRAFV600E mutation is a low-cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. METHODS: Tissues from 40 ameloblastoma samples were retrieved from either formalin-fixed paraffin-embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre-fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System-PCR and immunohistochemistry (IHC). RESULTS: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System-PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (𝜒2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64-0.90) and 0.9 (95% CI: 0.75-0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System-PCR detection method were 0.7 (95% CI: 0.53-0.80) and 0.9 (95% CI = 0.67-0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). CONCLUSION: Low-cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E-inhibitor therapies.

SATB2 and MDM2 Immunoexpression and Diagnostic Role in Primary Osteosarcomas of the Jaw.

Primary osteosarcomas of the jaw (OSJ) are rare, accounting for 6% of all osteosarcomas. This study aims to determine the value of SATB2 and MDM2 immunohistochemistry (IHC) in differentiating OSJ from other jawbone mimickers, such as benign fibro-osseous lesions (BFOLs) of the jaw or Ewing sarcoma of the jaw. Certain subsets of osteosarcoma harbor a supernumerary ring and/or giant marker chromosomes with amplification of the 12q13-15 region, including the murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes. Special AT-rich sequence-binding protein 2 (SATB2) is an immunophenotypic marker for osteoblastic differentiation. Cases of OSJ, BFOLs (ossifying fibroma and fibrous dysplasia) of the jaw, and Ewing sarcoma of the jaw were retrieved from the Departments of Oral Pathology and Oral Medicine, Faculty of Dentistry, Obafemi Awolowo University and Lagos State University College of Medicine, Nigeria. All OSJ retrieved showed histologic features of high-grade osteosarcoma. IHC for SATB2 (clone EP281) and MDM2 (clone IF2), as well as fluorescence in situ hybridization (FISH) for MDM2 amplification, were performed on all cases. SATB2 was expressed in a strong intensity and diffuse staining pattern in all cases (11 OSJ, including a small-cell variant, 7 ossifying fibromas, and 5 fibrous dysplasias) except in Ewing sarcoma, where it was negative in neoplastic cells. MDM2 was expressed in a weak to moderate intensity and scattered focal to limited diffuse staining pattern in 27% (3/11) of cases of OSJ and negative in all BFOLs and the Ewing sarcoma. MDM2 amplification was negative by FISH in interpretable cases. In conclusion, the three cases of high-grade OSJs that expressed MDM2 may have undergone transformation from a low-grade osteosarcoma (LGOS). SATB2 is not a dependable diagnostic marker to differentiate OSJ from BFOLs of the jaw; however, it could serve as a valuable diagnostic marker in differentiating the small-cell variant of OSJ from Ewing sarcoma of the jaw, while MDM2 may be a useful diagnostic marker in differentiating OSJ from BFOLs of the jaw, especially in the case of an LGOS or high-grade transformed osteosarcoma.

BRAF V600E mutation-specific immunohistochemical analysis in ameloblastomas: a 44-patient cohort study from a single institution.

PURPOSE: The aim of this study is to investigate the presence and prevalence of BRAF V600E mutation in ameloblastomas using anti-BRAF V600E monoclonal antibody (VE1 clone) and to identify any clinicopathologic correlation with BRAF V600E mutation in ameloblastoma. MATERIALS AND METHODS: The pathology files of the Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, Lagos State University College of Medicine, Lagos, Nigeria, were searched for the diagnosis of ameloblastoma from 2016 to 2020. Archived non-decalcified formalin-fixed paraffin-embedded tissue underwent immunohistochemistry using anti-BRAF V600E antibody at the University of Pittsburgh, Pennsylvania. Clinicopathologic data such as age at diagnosis, gender, jaw bone involved (mandible or maxilla), tumor location (anterior or posterior) and histologic subtype were collected. The clinicopathologic parameters were analyzed using Chi-square test and Fisher's exact test according to the BRAF status. RESULTS: Forty-four cases of ameloblastoma were retrieved. The male to female ratio was 1.32:1. The average age of patients at diagnosis was 33.3 years. Thirty-nine cases were located in the mandible and 5 cases in the maxilla. Only cases in the mandible were positive for anti-BRAF V600E antibody (n = 15/39; 38.5%). There was a significant correlation between BRAF V600E expression in mandibular tumors and histologic subtype (p = 0.02); however, no significance was observed for gender, age and tumor location. CONCLUSION: BRAF V600E mutation preferentially occurs in mandibular ameloblastomas, especially in non-plexiform ameloblastomas. These patients may benefit therapeutically from the use of BRAF inhibitors.

Pattern of distribution of reactive localised hyperplasia of the oral cavity in patients at a tertiary health institution in Nigeria.

BACKGROUND: Reactive localized hyperplastic lesions of the oral cavity (RHLs) are relatively common peripheral lesions which present as a range of clinically similar lesions at dental centers. Diagnosis can be challenging if dentists are unfamiliar with their clinicopathological across various populations. OBJECTIVE: This study reviews the pattern of distribution of RHLs of the oral mucosa in a hospital- the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife. MATERIALS AND METHODS: We reviewed 10 years data from the archives of the Department of Oral Maxillofacial Surgery and Oral Pathology, Obafemi Awolowo University, Nigeria. Information on RHLs were extracted and recorded on standardized data forms and analyzed using STATA. RESULTS: The most common lesions were pyogenic granuloma (43.7%) and focal fibrous hyperplasia (39.7%), respectively. RHLs were found to be more frequent in women (66.7%) than men (33.3%). The most common locations of involvement was the gingivae (84.6%), and lesions were more common in the 9-29 year age group and the mean age was 37.7 (±21.1) years. The relationship between age group and reactive lesions was however not statistically significant. CONCLUSION: The major benefit of this study is an improved knowledge of the frequency and distribution of oral reactive lesions in sub-Saharan Africa which may be highly beneficial when establishing a diagnosis and treatment plan in clinical practice.

Evaluation of SOX2 as a potential marker for ameloblastic carcinoma.

OBJECTIVE: Ameloblastic carcinoma often poses diagnostic challenges in its separation from benign ameloblastoma with atypical cytologic features or an unusual clinical course. This study aimed to determine whether SOX2 (sex determining region-Y-related high mobility group box 2), a protein expressed in the epithelial basal proliferative zone in dentigerous cysts, is a marker for ameloblastic carcinoma as well as for high-grade transformation in ameloblastic neoplasms. STUDY DESIGN: Immunoperoxidase stains were performed according to a standard protocol. Immunostains were interpreted independently by 3 pathologists, and scores were recorded based on the percentage of staining and intensity of staining in the cells of interest. RESULTS: The diffuse strong nuclear staining pattern has 86.4% specificity (19 of 22) to indicate the presence of high-grade features and has 76.9% sensitivity (10 of 13) in comparison with benign counterparts (P = .0021). Although previously shown as a marker for ameloblastic neoplasms, calretinin is weakly positive in a few cells in 50% (5 of 10) of ameloblastic carcinoma and 43% (3 of 7) of benign ameloblastic neoplasms, with little value in highlighting the high-grade change (P = .36). CONCLUSIONS: The diffuse nuclear staining pattern of SOX2 is suggestive of a high-grade process in ameloblastic neoplasms. Numerous aggregates of cells harboring dense nuclear stain should raise concern for a malignancy.

Clinicopathological analysis of histological variants of ameloblastoma in a suburban Nigerian population.

BACKGROUND: This study was carried out to establish the relative incidence and provide clinico-pathologic information on the various histological types of ameloblastoma seen at the Obafemi Awolowo University Teaching Hospital complex, Ile-Ife in order to provide a baseline data which will be of significance to the pathologist and clinician. METHODS: Clinico-pathologic data on a total of 77 histologically diagnosed cases of ameloblastoma archieved at the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife over a 15 year period were obtained and analysed descriptively. RESULTS: Follicular ameloblastoma was the most common histological type (50 cases, 64.9%), followed by plexiform ameloblastoma (10 cases, 13.0%). 4 (5.2%) cases of desmoplastic and 3 (3.9%) cases of acanthomatous ameloblastoma were seen while the basal cell variant accounted for 2 (2.6%) cases. Only 1 case of the unicystic type was seen. Some of the 77 cases presented as a mixture of two or more histological types. Ameloblastoma occurred over an age range of 11 to 70 years with a peak age incidence in the 3rd decade. CONCLUSION: This study provides a baseline data on variants of ameloblastoma as obtained in a suburban Nigerian population. Since variants of ameloblastoma differ in biologic behaviour, the data collected in this study provides clinicopathologic information which is of significance to the pathologist and clinician.

Is malaria a predisposing factor for third molar pericoronitis in the tropics?

BACKGROUND: Malaria is an important disease in the tropics, and its role as a predisposing factor or co morbidity has been investigated in many diseases including HIV infection and tuberculosis. There are very few studies, which have investigated its role in oral and dental diseases. Our study aimed to demonstrate the possible role of malaria in predisposing to pericoronitis, an infection affecting impacted third molars predominantly. PATIENTS AND METHODS: Thirty-eight patients presenting with pericoronitis were tested for malaria parasites and results compared with that obtained from controls that were equally susceptible to pericoronitis but did not have the infection. RESULTS: 19.7% of the study group compared to 6.6% of control group had malaria parasite in their blood. This difference was statistically significant, P=0.018 (Fisher's exact). The odds ratio was 4.3 (95% CI=1.2-17.0). CONCLUSIONS: Malaria appears to be a predisposing factor to pericoronitis in this study. There is a need for further studies on the possible role of malaria in oral and dental diseases.

Clinical experience with parotid gland enlargement in HIV infection: a report of five cases in Nigeria.

A changing picture of oral lesions associated with HIV/AIDS has been documented. With the use of antiretroviral therapy, salivary gland swellings and other less common conditions associated with HIV/AIDS are now becoming more common. Our review of the literature showed the presence of parotid swelling in HIV-1 infection has increased from a range of 5-10% to 20% in AIDS. However, to the best of our knowledge, none from sub-Saharan Africa, which is the epicenter of the HIV infection and where access to antiretroviral therapy is poorest, has been primarily reported in literature. This report documents five cases of bilateral parotid gland enlargement as the presenting clinical manifestation of HIV/AIDS. The combination of a fine needle aspiration (FNA) biopsy, ultrasound imaging, and histological diagnosis increased the accuracy of diagnosis. While two patients had access to antiretroviral therapy, other modes of management were cystic aspiration and parotidectomy. One of the patients treated with parotidectomy had facial nerve injury, and the short-term aesthetic outcome between surgical treatment and antiretroviral therapy did not appear different. However, all our patients were lost to follow-up within a 2-year period. For a resource-constrained environment like Nigeria where stigma and discrimination is high and access to antiretroviral therapy is limited, there is a need to understand how best to manage a lymphoepithelial lesion in HIV/AIDS patients.