The evolving molecular characterisation, histological criteria and nomenclature of adenoid ameloblastoma as a World Health Organisation tumour type.

Adenoid ameloblastoma (AA) was recently recognised as a separate tumour type in the most recent World Health Organisation (WHO) classification of head and neck tumours. This decision has been considered controversial by several groups, who have described AA as a subtype of ameloblastoma, a hybrid odontogenic tumour or to fall within the spectrum of other recognised odontogenic tumours, including dentinogenic ghost cell tumour and adenomatoid odontogenic tumour. Here we review the reasons for the WHO decision to classify AA as a separate tumour type.

Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study.

Purpose: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC.

Experimental Design: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012.

Adenoid ameloblastoma harbors beta-catenin mutations.

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown.

Aneuploidy and loss of heterozygosity as risk markers for malignant transformation in oral mucosa.

The ability to predict malignant transformation in oral potentially malignant disorders would inform targeted treatment, provide prognostic information and allow secondary prevention. DNA ploidy and loss of heterozygosity assays are already in clinical use, and loss of heterozygosity has been used in prospective clinical trials. This review appraises published evidence of predictive ability and explores interpretation of heterogeneous studies, with different diagnostic methods, criteria and intention.

Dysplasia and DNA ploidy to prognosticate clinical outcome in oral potentially malignant disorders.

Background: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes.

Methods: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA ploidy analysis was performed using established methods.

Targeted Next-Generation Sequencing and Allele-Specific Quantitative PCR of Laser Capture Microdissected Samples Uncover Molecular Differences in Mixed Odontogenic Tumors.

The molecular pathogenesis of mixed odontogenic tumors has not been established, and understanding their genetic basis could refine their classification and help define molecular markers for diagnostic purposes. Potentially pathogenic mutations in the component tissues of 28 cases of mixed odontogenic tumors were assessed. Laser capture microdissected tissue from 10 ameloblastic fibromas (AF), 4 ameloblastic fibrodentinomas (AFD), 6 ameloblastic fibro-odontomas (AFO), 3 ameloblastic fibrosarcomas (AFS), and 5 odontomas (OD) were screened by next-generation sequencing and results confirmed by TaqMan allele-specific quantitative PCR.

DNA aneuploidy and tissue architecture in oral potentially malignant disorders with epithelial dysplasia assessed by a 10 locus FISH panel.

Subjectivity in oral dysplasia grading has prompted evaluation of molecular‑based tests to predict malignant transformation. Aneuploidy detected by DNA image‑based cytometry (ICM) is currently the best predictor but fails to detect certain high risk lesions. A novel multiplex fluorescence in situ hybridization (FISH) panel was used to explore possible explanations by detecting aneuploidy at the single cell level.

Data Set for the Reporting of Malignant Odontogenic Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

A data set has been developed for the reporting of excisional biopsies and resection specimens for malignant odontogenic tumors by members of an expert panel working on behalf of the International Collaboration on Cancer Reporting, an international organization established to unify and standardize reporting of cancers. Odontogenic tumors are rare, which limits evidence-based support for designing a scientifically sound data set for reporting them. Thus, the selection of reportable elements within the data set and considering them as either core or noncore is principally based on evidence from malignancies affecting other organ systems, limited case series, expert opinions, and/or anecdotal reports.

Predicting malignant progression in clinically high-risk lesions by DNA ploidy analysis and dysplasia grading.

The value of image cytometry DNA ploidy analysis and dysplasia grading to predict malignant transformation has been determined in oral lesions considered to be at 'high' risk on the basis of clinical information and biopsy result. 10-year follow up data for 259 sequential patients with oral lesions clinically at 'high' risk of malignant transformation were matched to cancer registry and local pathology database records of malignant outcomes, ploidy result and histological dysplasia grade. In multivariate analysis (n = 228 patients), 24 developed carcinoma and of these, 14 prior biopsy samples were aneuploid.

Image cytometry DNA ploidy analysis: Correlation between two semi-automated methods.

Background And Objectives: Quantitation of cell DNA content, DNA ploidy, has been established as a research and prognostic technique for decades. A variety of instruments have been used although only a few commercially available systems have established quality assurance and published outcome data. The aim of this study was to compare two automated systems.

Meta-analysis of the predictive value of DNA aneuploidy in malignant transformation of oral potentially malignant disorders.

DNA aneuploidy is an imbalance of chromosomal DNA content that has been highlighted as a predictor of biological behavior and risk of malignant transformation. To date, DNA aneuploidy in oral potentially malignant diseases (OPMD) has been shown to correlate strongly with severe dysplasia and high-risk lesions that appeared non-dysplastic can be identified by ploidy analysis. Nevertheless, the prognostic value of DNA aneuploidy in predicting malignant transformation of OPMD remains to be validated.

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression.

Chromosomal instability, leading to aneuploidy, is one of the hallmarks of human cancers. USP44 (ubiquitin specific peptidase 44) is an important molecule that plays a regulatory role in the mitotic checkpoint and USP44 loss causes chromosome mis-segregation, aneuploidy and tumorigenesis in vivo. In this study, it was investigated the immunoexpression of USP44 in 28 malignant salivary gland neoplasms and associated the results with DNA ploidy status assessed by image cytometry.

Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma.

Background: Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with Cu-ATSM PET/CT.

Methods: Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients.

Image-based DNA ploidy analysis aids prediction of malignant transformation in oral lichen planus.

Objectives: To investigate the potential of image-based DNA ploidy analysis to predict malignant transformation in patients with oral lichen planus (OLP).

Study Design: DNA ploidy analysis was performed on biopsy samples from 14 patients with OLP who underwent malignant transformation. As controls, 42 OLP lesions showing unusual clinical features suggesting a transformation risk and 68 samples of clinically and histologically typical OLP were included.

Dental Stigmata of Congenital Syphilis: A Historic Review With Present Day Relevance.

Syphilis was the first sexually transmitted disease to be diagnosed in childhood. Most developed countries controlled syphilis effectively after the 1950s and congenital syphilis became rare. Since the late 1990s there has been a resurgence of syphilis in developed and developing countries and the WHO estimates that at least half a million infants die of congenital syphilis every year.

A method for accurate spatial registration of PET images and histopathology slices.

Background: Accurate alignment between histopathology slices and positron emission tomography (PET) images is important for radiopharmaceutical validation studies. Limited data is available on the registration accuracy that can be achieved between PET and histopathology slices acquired under routine pathology conditions where slices may be non-parallel, non-contiguously cut and of standard block size. The purpose of this study was to demonstrate a method for aligning PET images and histopathology slices acquired from patients with laryngeal cancer and to assess the registration accuracy obtained under these conditions.

Stensen's Duct Carcinoma with a Papillary Architecture.

Primary carcinoma of the parotid duct (Stensen's duct carcinoma) is a rare entity, first described in 1927 and with approximately thirty-one cases reported in the English literature. Criteria for diagnosis are primarily demonstration of an origin from the Stensen's duct lining and exclusion of parotid gland, accessory parotid, oral mucosal and adjacent minor salivary gland origin. The carcinoma is usually of a specific type, and most have been described as squamous, mucoepidermoid, or undifferentiated adenocarcinomas.

Odontogenic tumors, WHO 2005: where do we go from here?

As our knowledge of disease improves, its classification continually evolves. The last WHO classification of odontogenic tumors was 9 years ago and it is time for revision. We offer the following critique as a constructive, thought provoking challenge to those chosen to provide contemporary insight into the next WHO classification of odontogenic cysts, tumors, and allied conditions.

STAG2 loss of expression is rare in aneuploid malignant salivary gland neoplasms.

Background: STAG2 depletion leads to loss of centromere cohesion in vitro, and some human neoplasms have been shown to lose expression of this protein. As a result, STAG2 loss has been shown to cause chromosomal instability and aneuploidy in human cancer cell lines.

Methods: We tested the hypothesis that aneuploid salivary gland tumours lose immunoexpression of STAG2 compared with diploid tumours using image cytometry to determine DNA ploidy and immunohistochemistry to assess STAG2 protein expression in 30 malignant salivary gland neoplasms.

Student acceptability of high-stakes e-assessment in dental education: using privacy screen filters to control cheating.

Acceptability is a required quality for a sound assessment. For students, acceptability of a test is strongly influenced by perception of fairness. Computer-based assessment has been reported to be preferred by students provided that strict controls to prevent cheating are in place.

Predictive value of dysplasia grading and DNA ploidy in malignant transformation of oral potentially malignant disorders.

Dysplasia grading is widely used to assess risk of transformation in oral potentially malignant disorders despite limited data on predictive value. DNA ploidy analysis has been proposed as an alternative. This study examines the prognostic value for both tests used in a routine diagnostic setting to inform clinical management.

Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis.

Histopathological discordance with molecular phenotype of many human cancers poses clinically challenging tasks for accurate cancer diagnosis, which impacts on treatment strategy and patient outcome. Hence, an objective, accurate and quantitative method is needed. A quantitative Malignancy Index Diagnostic System (qMIDS) was developed based on 14 FOXM1 (isoform B)-associated genes implicated in the regulation of the cell cycle, differentiation, ageing, genomic stability, epigenetic and stem cell renewal, and two reference genes.

Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma.

Mucoepidermoid carcinoma is the most common salivary gland malignancy, and includes a spectrum of lesions ranging from non-aggressive low-grade tumors to aggressive high-grade tumors. To further characterize this heterogeneous group of tumors we have performed a comprehensive analysis of copy number alterations and CRTC1-MAML2 fusion status in a series of 28 mucoepidermoid carcinomas. The CRTC1-MAML2 fusion was detected by RT-PCR or fluorescence in situ hybridization in 18 of 28 mucoepidermoid carcinomas (64%).

Implications of a positive sentinel node in oral squamous cell carcinoma.

Background: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome.

Methods: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified.