A subset of ectomesenchymal chondromyxoid tumours of the tongue show EWSR1 rearrangements and are genetically linked to soft tissue myoepithelial neoplasms: a study of 11 cases.

AIMS: Ectomesenchymal chondromyxoid tumour (ECT) is a rare, benign intraoral neoplasm showing a predilection for the anterior dorsum of the tongue. The World Health Organization includes ECT in the pathological spectrum of soft tissue myoepithelioma. EWS RNA-binding protein 1 gene (EWSR1) rearrangement is found in 45% of cutaneous, soft tissue and bone myoepithelial neoplasms, and pleomorphic adenoma gene 1 (PLAG1) aberrations are found in 37% of EWSR1-negative soft tissue myoepitheliomas. The aim of this study was to evaluate the presence of EWSR1 and PLAG1 rearrangements in ECTs. METHODS AND RESULTS: Eleven formalin-fixed, paraffin-embedded ECTs were evaluated with fluorescence in-situ hybridization probes for EWSR1 (22q12) and PLAG1 (8q12). Among the 11 ECTs tested, three (27.3%) showed EWSR1 rearrangement in >15% of tumour cells, whereas eight (72.7%) cases did not show EWSR1 rearrangement. Eight of nine (89%) ECTs showed gain of EWSR1, probably representing gain of all or part of chromosome 22, in a varying proportion of neoplastic cells ranging between 1.4% and 27.9%. PLAG1 rearrangement was not detected in the successfully hybridized tissue sections (7/11). No correlation was observed between the molecular and histopathological findings, such as morphology of the neoplastic cells, the presence of atypia, and matrical type. CONCLUSIONS: We identified EWSR1 rearrangement in >25% of ECTs. These results suggest that some ECTs are at least genetically related to myoepithelioma of the soft parts. Finally, PLAG1 aberrations do not appear to be critical in the pathogenesis of ECT of the tongue.

Oral leiomyomatous hamartoma: presentation of 3 cases and review of the literature.

Oral leiomyomatous hamartoma (OLH) is a rare lesion, with only 40 cases reported in the literature. It typically presents early in life as a nodule on the anterior maxillary alveolar tissues or the tongue. Its growth potential is limited, with few cases reaching dimensions >2.0 cm, and its microscopic composition includes an intact surface mucosa with an underlying fibrovascular stroma possessing an unencapsulated proliferation of smooth muscle fascicles. Excision is considered the definitive treatment. Here we describe the clinical, microscopic, histochemical, and immunohistochemical features and management of 3 cases of OLH and review the literature. The findings we present here can assist in performing differential diagnosis, particularly in discriminating between OLH and similar yet non-hamartomatous processes and in selecting appropriate management.

Conditional ablation of E-cadherin in the oral epithelium progeny results in tooth anomalies.

OBJECTIVES: The objective of this study is to confirm the developmental origin of the enamel organ and evaluate the role of E-cadherin in tooth development by conditional deletion in the oral epithelium and its enamel organ progeny. K5-Cre;ROSA26 compound mice were included in this study in order to confirm the oral epithelial origin of the enamel organ, as well as of the action of the K5-Cre transgene in ablating E-cadherin in the enamel organ. K5-Cre;Ecadfl/fl knockout mice were included to evaluate the effects of the conditional E-cadherin ablation onto tooth development. MATERIAL AND METHODS: K5-Cre transgenic mice were crossed into the ROSA26 reporter mouse to trace the cell fate of the oral epithelium and its progeny in vivo. Moreover, K5-Cre mice were crossed into the Ecadfl/fl mice to produce K5-Cre;Ecadfl/fl compound mouse, as well as K5-Cre;Ecadfl/+ and Ecadfl/fl littermate controls. These litters were euthanized at postnatal day P2 to study the effects of conditional E-cadherin ablation in vivo. RESULTS: The K5-Cre;ROSA26 compound mouse demonstrated that the origin of the enamel organ and the structures thereof are of oral epithelial origin. Furthermore, using the K5-Cre;Ecadfl/fl compound mouse, we determined that conditional ablation of E-cadherin in the oral epithelium, and its progeny, results in dental anomalies involving elongation of the molar root, shrinkage of the pulp space, and alterations of the periapical area, including cementum hyperplasia. The K5-Cre;Ecadfl/fl mice also displayed a smaller overall stature compared with heterozygotes and wild-type littermates. CONCLUSIONS: E-cadherin is important in tooth development, including the formation of enamel, the crown, pulp space, and the roots.

Point-of-care oral cytology tool for the screening and assessment of potentially malignant oral lesions.

BACKGROUND: The effective detection and monitoring of potentially malignant oral lesions (PMOL) are critical to identifying early-stage cancer and improving outcomes. In the current study, the authors described cytopathology tools, including machine learning algorithms, clinical algorithms, and test reports developed to assist pathologists and clinicians with PMOL evaluation. METHODS: Data were acquired from a multisite clinical validation study of 999 subjects with PMOLs and oral squamous cell carcinoma (OSCC) using a cytology-on-a-chip approach. A machine learning model was trained to recognize and quantify the distributions of 4 cell phenotypes. A least absolute shrinkage and selection operator (lasso) logistic regression model was trained to distinguish PMOLs and cancer across a spectrum of histopathologic diagnoses ranging from benign, to increasing grades of oral epithelial dysplasia (OED), to OSCC using demographics, lesion characteristics, and cell phenotypes. Cytopathology software was developed to assist pathologists in reviewing brush cytology test results, including high-content cell analyses, data visualization tools, and results reporting. RESULTS: Cell phenotypes were determined accurately through an automated cytological assay and machine learning approach (99.3% accuracy). Significant differences in cell phenotype distributions across diagnostic categories were found in 3 phenotypes (type 1 ["mature squamous"], type 2 ["small round"], and type 3 ["leukocytes"]). The clinical algorithms resulted in acceptable performance characteristics (area under the curve of 0.81 for benign vs mild dysplasia and 0.95 for benign vs malignancy). CONCLUSIONS: These new cytopathology tools represent a practical solution for rapid PMOL assessment, with the potential to facilitate screening and longitudinal monitoring in primary, secondary, and tertiary clinical care settings.

Intraoral benign mesenchymoma: a report of 10 cases and review of the literature.

A benign mesenchymoma is an unencapsulated soft tissue neoplasm composed of 2 or more mature mesenchymal tissues not normally associated with each other, excluding fibrous connective tissue. No single mesenchymal tissue should predominate with respect to the other mesenchymal elements. Ten well-documented examples of intraoral benign mesenchymoma have been reported in the English language literature. The purpose of this report is to document 10 additional cases and to review the clinicopathologic characteristics of this uncommon tumor.

Generation of intra-oral-like images from cone beam computed tomography volumes for dental forensic image comparison.

UNLABELLED: Identification of unknown individuals using dental comparison is well established in the forensic setting. The identification technique can be time and resource consuming if many individuals need to be identified at once. Medical CT (MDCT) for dental profiling has had limited success, mostly due to artifact from metal-containing dental restorations and implants. DESCRIPTION: The authors describe a CBCT reformatting technique that creates images, which closely approximate conventional dental images. METHOD: Using a i-CAT Platinum CBCT unit and standard issue i-CAT Vision software, a protocol is developed to reproducibly and reliably reformat CBCT volumes. The reformatted images are presented with conventional digital images from the same anatomic area for comparison. CONCLUSION: The authors conclude that images derived from CBCT volumes following this protocol are similar enough to conventional dental radiographs to allow for dental forensic comparison/identification and that CBCT offers a superior option over MDCT for this purpose.

Ectodomain-specific E-cadherin antibody suppresses skin SCC growth and reduces tumor grade: a multitargeted therapy modulating RTKs and the PTEN-p53-MDM2 axis.

Tumor cell survival consists of an intricate balance between cell growth and cell death pathways involving receptor tyrosine kinases [RTK; i.e., HER1-4, insulin-like growth factor-1 receptor (IGF-1R), etc.], MDM2, and the tumor suppressor proteins phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p53. We recently demonstrated that shedded E-cadherin extracellular domain fragment (sEcad) is a valid oncogenic target that is significantly increased in human clinical skin squamous cell cancers (SCC) samples, UV-induced mouse tumors, and cells and promotes tumor cell proliferation, migration, and invasion by interacting and activating with the HER-phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) axis. In resected human SCC tumors, we reported enhanced sEcad-HER1, sEcad-HER2, and sEcad-IGF-1R, but not FL-Ecad-RTK interactions. Here, we demonstrate that a sEcad antibody against the ectodomain of E-cadherin suppressed SCC growth and increased tumor differentiation in orthotopic cutaneous SCC xenografts by inhibiting proliferation and inducing apoptosis. A similar anti-sEcad antibody-induced inhibition of proliferation and induction of cell death was evident in PAM212 cells in vitro. Mechanistically, anti-sEcad administration upregulated an array of cell death pathways (i.e., Bad, active caspase-3, and cleaved PARP) and inhibited inhibitors of apoptosis (IAP; survivin, livin, etc.), RTKs (HER1, HER2, p95HER2, and IGF-1R), MAPK and PI3K/mTOR prosurvival signaling. Interestingly, in anti-sEcad mAb-treated tumors and PAM212 cells, this effect was associated with a profound increase in membrane, cytosolic, and nuclear levels of PTEN; enhanced cytosolic p53; and a decrease in MDM2 levels. Overall, our studies suggest that an antibody-based therapy against sEcad may be a novel therapeutic platform for cutaneous SCCs by hampering key proto-oncogenes (RTKs, IAPs, and MDM2) and activating potent tumor suppressor proteins (PTEN and p53) intricately linked to tumor growth and survival.

Isolation of Staphylococcus aureus from environmental surfaces in an academic dental clinic.

BACKGROUND: Staphylococcus aureus is an important health care-associated pathogen that often is resistant to antibiotics. The authors conducted a pilot study to determine if abiotic surfaces in a dental clinic were contaminated frequently. METHODS: The authors sampled surfaces with swabs that they then used to inoculate selective and differential media. CHRO-Magar Staph aureus (DRG International, Mountainside, N.J.) was the most effective. They used phenotypic and genotypic tests to identify presumptive S. aureus colonies. They determined the sensitivity of S. aureus isolates to five antibiotics, including oxacillin, according to the Kirby-Bauer method. RESULTS: The authors recovered S. aureus from 20 of 429 surfaces (4.7 percent). Most isolates were resistant to penicillin but none were resistant to the other antibiotics. No isolate carried the mecA gene encoding resistance to methicillin. The authors considered one site to be highly contaminated (> 200 colony-forming units [CFUs]), but all other sites that tested positive yielded fewer than 5 CFUs. CONCLUSIONS: Abiotic surfaces in the authors' dental clinic were not a reservoir for methicillin-resistant S. aureus. The authors identified and eliminated one nonclinical site of potential methicillin-sensitive S. aureus cross-contamination. CLINICAL IMPLICATIONS: Periodic sampling of surfaces for S. aureus may be a useful adjunct to standard infection control practices in dental health care settings.