Intracranial calcification in Fam20c-deficient mice recapitulates human Raine syndrome.

FAM20C (family with sequence similarity 20-member C) is a protein kinase that phosphorylates secretory proteins, including the proteins that are essential to the formation and mineralization of calcified tissues. FAM20C loss-of-function mutations cause Raine syndrome in humans, characterized by generalized osteosclerosis, distinctive craniofacial dysmorphism, along with extensive intracranial calcification. Our previous studies revealed that inactivation of Fam20c in mice led to hypophosphatemic rickets.

LED-based Hyperspectral Endoscopic Imaging.

Hyperspectral endoscopy can offer multiple advantages as compared to conventional endoscopy. Our goal is to design and develop a real-time hyperspectral endoscopic imaging system for the diagnosis of gastrointestinal (GI) tract cancers using a micro-LED array as an in-situ illumination source. The wavelengths of the system range from ultraviolet to visible and near infrared.

SP140 inhibits STAT1 signaling, induces IFN-γ in tumor-associated macrophages, and is a predictive biomarker of immunotherapy response.

Background: Understanding the role and potential therapeutic targeting of tumor-associated macrophages (TAMs) is crucial to developing new biomarkers and therapeutic strategies for cancer immunotherapies. The epigenetic reader SP140 has emerged as a master regulator of macrophage transcriptional programs; however, its role in the signaling of TAMs and response to immunotherapy has not been investigated.

Methods: We evaluated the correlation between SP140 expression in head and neck squamous cell carcinoma (HNSCC) TAMs and clinical outcomes.

Cone-beam computed tomographic imaging of central giant cell granuloma: A comprehensive review.

Purpose: The aim of this study was to characterize the cone-beam computed tomographic (CBCT) imaging features of central giant cell granuloma (CGCG) of the jawbone.

Materials And Methods: This study retrospectively reviewed 26 CBCT studies of histologically proven cases of CGCG during a period of 20 years, from 1999 to 2019. Patients' demographic data were recorded, and radiographic features were assessed (location, border, cortication, appearance of the internal structure, locularity, septation, expansion, cortical perforation, effects on surrounding tissue, whether the lesion crossed the midline, and lesion volume).

Designing a Mucoadhesive ChemoPatch to Ablate Oral Dysplasia for Cancer Prevention.

Oral cancer has a high mortality rate, and its treatment often causes debilitating complications. More than 90% of oral cancers are oral squamous cell carcinomas (OSCCs) that may develop from clinically recognizable oral premalignant lesions (OPLs). To eradicate OPLs before they turn into cancers, a non-invasive topical formulation is developed based on a novel combination of synergistically acting oxaliplatin (OXP) and mycophenolate (MPS) embedded in a controlled-release mucoadhesive patch fabricated by computer-aided 3D printing.

Adenomatoid odontogenic tumor: evidence for a mixed odontogenic tumor.

Objective: Adenomatoid odontogenic tumor (AOT) was classified by the World Health Organization as a mixed odontogenic tumor in 1992 and reclassified without a clear rationale as an epithelium-only tumor in 2005. The purpose of this study was to investigate if there was any evidence to suggest AOT might be a mixed odontogenic tumor.

Study Design: Immunohistochemical studies with nestin, dentin sialophosphoprotein (DSPP), cytokeratin, and vimentin were performed using 21 cases of AOT, and the staining results were analyzed according to the various morphologic patterns seen in AOT.

Non-calcifying Langerhans Cell Rich Variant of Calcifying Epithelial Odontogenic Tumor and Amyloid Rich Variant of Central Odontogenic Fibroma: A Unique Entity or a Spectrum?

Overlapping clinicopathological features of non-calcifying Langerhans cell rich variant of calcifying epithelial odontogenic tumor (NCLC-CEOT) and the amyloid rich variant of the central odontogenic fibroma (AR-COF) have been recognized recently. It is still under debate whether these two diseases are indeed one unique disease entity or belong to CEOT and COF, respectively. To clarify this issue, we have performed a literature review to compare the similarities and differences in clinicopathological features among NCLC-CEOT, AR-COF, classic CEOT, and classic COF.

Nucleostemin upregulation and STAT3 activation as early events in oral epithelial dysplasia progression to squamous cell carcinoma.

Most low-grade oral epithelial dysplasia remains static or regress, but a significant minority of them (4-11%) advances to oral squamous cell carcinoma (OSCC) within a few years. To monitor the progression of epithelial dysplasia for early cancer detection, we investigated the expression profiles of nucleostemin (NS) and phospho-STAT3 (p-STAT3) in rodent and human samples of dysplasia and OSCCs. In a 4NQO-induced rat oral carcinogenesis model, the number and distribution of NS and p-STAT3-positive cells increased in hyperplastic, dysplastic, and neoplastic lesions compared to normal epithelium.

Machine-Learning Assisted Discrimination of Precancerous and Cancerous from Healthy Oral Tissue Based on Multispectral Autofluorescence Lifetime Imaging Endoscopy.

Multispectral autofluorescence lifetime imaging (maFLIM) can be used to clinically image a plurality of metabolic and biochemical autofluorescence biomarkers of oral epithelial dysplasia and cancer. This study tested the hypothesis that maFLIM-derived autofluorescence biomarkers can be used in machine-learning (ML) models to discriminate dysplastic and cancerous from healthy oral tissue. Clinical widefield maFLIM endoscopy imaging of cancerous and dysplastic oral lesions was performed at two clinical centers.

Interobserver Variation in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma: Phase 2 Survey Study.

In a previous study, we found interobserver agreement among 88 board-certified pathologists evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) was fair, and participants most often used the following criteria: (1) tumor invading the perineurium, (2) tumor surrounding a nerve. In this study, we aimed to determine whether application of these most commonly used criteria may improve interobserver agreement. 512 pathologists were invited to participate in a web-based survey.

Down-regulation of the tumor suppressor miR-34a contributes to head and neck cancer by up-regulating the MET oncogene and modulating tumor immune evasion.

Background: MicroRNAs (miRs) have been shown to play an important role in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). The miR-34 family is thought to play a role in tumor suppression, but the exact mechanism of their action in HNSCC is not well understood. Moreover, the impact of chromosomal changes and mutation status on miR-34a expression remains unknown.

Dysbiosis of saliva microbiome in patients with oral lichen planus.

Background: Oral microbiota is not only important for maintaining oral health but also plays a role in various oral diseases. However, studies regarding microbiome changes in oral lichen planus (OLP) are very limited. To the best of our knowledge, there has been only two studies investigating salivary microbiome changes in OLP.

Radiographic manifestations of fibroblastic osteosarcoma: A diagnostic challenge.

Osteosarcoma is the most common primary bone tumor after plasma cell neoplasms. Osteosarcoma has diverse histological features and is characterized by the presence of malignant spindle cells and pluripotent neoplastic mesenchymal cells that produce immature bone, cartilage, and fibrous tissue. Osteosarcoma most frequently develops in the extremities of long bones, but can occur in the jaw in rare cases.

Salivary Sialadenoma Papilliferum Consists of Two Morphologically, Immunophenotypically, and Genetically Distinct Subtypes.

Papillary salivary gland neoplasms are rare tumors usually arising in the minor salivary glands of the oral cavity. Their classification has been historically confusing due to overlapping histologic features, but molecular analysis may clarify these entities. Sialadenoma papilliferum (SP) is a peculiar member of this group that demonstrates both an endophytic ductal and an exophytic squamous component.

Nanoparticle-based assay for detection of S100P mRNA using surface-enhanced Raman spectroscopy.

The focus of this work is toward the development of a point-of-care (POC) handheld technology for the noninvasive early detection of salivary biomarkers. The initial of focus was the detection and quantification of S100 calcium-binding protein P (S100P) mRNA found in whole saliva for use as a potential biomarker for oral cancer. Specifically, a surface-enhanced Raman spectroscopy (SERS)-based approach and assay were designed, developed, and tested for sensitive and rapid detection of S100P mRNA.

Spindle-cell variant of ameloblastic carcinoma: a report of 3 cases and demonstration of epithelial-mesenchymal transition in tumor progression.

Ameloblastic carcinoma is a rare odontogenic neoplasm that demonstrates the histologic characteristics of ameloblastoma, accompanied by the cytologic features of malignancy. The spindle-cell variant of ameloblastic carcinoma (SCAC) is exceptionally rare, with a total of 10 cases having been reported in the literature to date. Histologically, a prominent sarcomatoid cell population appears to originate from the epithelial (ameloblastic) component.

Endogenous Fluorescence Lifetime Imaging (FLIM) Endoscopy For Early Detection Of Oral Cancer And Dysplasia.

We have performed a pilot clinical study, in which multispectral endogenous fluorescence (or autofluorescence) lifetime imaging (FLIM) was performed on clinically suspicious oral lesions of 73 patients undergoing tissue biopsy for oral dysplasia and cancer diagnosis. The results from this pilot study indicated that mild-dysplasia and early stage oral cancer could be detected from benign lesions using a computed aided diagnosis system developed based on biochemical and metabolic biomarkers derived from the endogenous FLIM images. The diagnostic performance of this novel FLIM clinical tool was estimated using a leave-onepatient-out cross-validation approach, which reported levels of sensitivity >90%, specificity >85%, and Area Under the Receiving Operating Curve (ROC-AUC) >0.

Longitudinal clinicopathologic data of the progression of oral mucosal melanoma-report of 2 cases and literature review.

Oral mucosal melanoma (OMM) is notorious for having a poor prognosis. Recognition of the early features of OMM by both clinicians and pathologists can play an important role in improving survival. Therefore, the purpose of this report is to increase awareness of the early features of OMM, by presenting 2 cases with longitudinal clinical and histopathologic documentation showing progression of OMM from a deceptively bland premalignant (noninvasive) oral melanocytic lesion (POML).

An actionable test using loss of heterozygosity in identifying high-risk oral premalignant lesions.

Objectives: To develop an actionable test using fluorescence capillary electrophoresis (FCE) to assess loss of heterozygosity (LOH) of histologically similar low-grade lesions (LGLs) to identify high-risk lesions for oral cancer progression.

Study Design: To determine the cutoffs of LOH, the FCE results of 52 surgical margin samples were used to compare with the existing LOH results from the previously validated P-GE approach. Using the developed FCE workflow, an independent set of 102 LGLs with known progression status was used to determine the LOH molecular risk (MR) patterns and associated risk of progression.

Handheld tunable focus confocal microscope utilizing a double-clad fiber coupler for in vivo imaging of oral epithelium.

A reflectance confocal endomicroscope with double-clad fiber coupler and electrically tunable focus lens is applied to imaging of the oral mucosa. The instrument is designed to be lightweight and robust for clinical use. The tunable lens allows axial scanning through > 250 ?? ? m in the epithelium when the probe tip is placed in contact with tissue.

Interobserver Variation Among Pathologists in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma.

The aims of this study are as follows: (1) to assess variations among pathologists in evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC), (2) to survey PNI criteria used by pathologists and how they came to adopt those criteria. An electronic survey was sent to 363 oral and/or surgical pathologists. Eligibility criteria included pathology board certification.