An imaging­based diagnostic approach to vascular anomalies of the oral and maxillofacial region.

The accurate diagnosis of vascular anomalies (VAs) is considered a challenging endeavor. Misdiagnosis of VAs can lead clinicians in the wrong direction, such as the performance of an unnecessary biopsy or inappropriate surgical procedures, which can potentially lead to unforeseen consequences and increase the risk of patient injury. The purpose of the present study was to develop an approach for the diagnosis of VAs of the oral and maxillofacial region based on computed tomography (CT), magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI (DCE-MRI). In the present study, the CT and MR images of 87 VAs were examined, and the following imaging features were evaluated: Detectability of the lesion, the periphery of the lesion, the inner nature of the lesion, the density of the lesion on CT, the signal intensity of the lesion on MRI, the detectability of phleboliths and the shape of the lesion. A total of 29 lesions were further evaluated using the contrast index (CI) curves created from the DCE-MRI images. A diagnostic diagram, which is based on the imaging features of VAs and CI curve patterns, was subsequently extrapolated. The results obtained demonstrated that the VAs were detected more readily by MRI compared with CT, whereas the detectability of phleboliths was superior when using CT compared with MRI. VAs showed a propensity for homogeneous isodensity on CT, whereas, by contrast, they exhibited a propensity for heterogeneous hyperdensity on CE-CT. VAs also showed a propensity for homogeneous intermediate signal intensity when performing T1-weighted imaging (T1WI), heterogeneous high signal intensity when performing short tau inversion recovery MRI, and heterogeneous high signal intensity when performing fat-saturated CE-T1WI. The CI curves of VAs were found to exhibit a specific pattern: Of the 29 CI curves, 23 (79.3%) showed early weak enhancement, followed by a plateau leading up to 400-600 sec. An imaging-based diagnostic diagram was ultimately formulated. This diagram can act as an aid for radiologists when they are expecting to find a VA, and hopefully serve the purpose of simplifying the diagnostic process. Taken together, the findings of the present study indicated that DCE-MRI may be considered a useful tool for the diagnosis of VAs.

Dynamic contrast-enhanced MRI as a predictor of programmed death ligand-1 expression in patients with oral squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) are highly promising therapies for oral squamous cell carcinoma (OSCC). The assessment of PD-L1 expression may help predicting the therapeutic effect of ICIs and, thus, benefit patient selection. Contrast index (CI) parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been proven as efficient to assess microvessel density (MVD) in OSCC. The present study aimed to determine the correlation between DCE-MRI parameters and MVD and between DCE-MRI parameters and PD-L1 expression to determine whether DCE-MRI could be used non-invasively to evaluate PD-L1 expression in patients with OSCC. A total of 21 patients with primary OSCC who had undergone a 3T MRI scan, including DCE-MRI, were included in the present study, and CI curve-derived parameters were examined. The MVD and PD-L1 expression in the surgically resected specimens were analyzed using immunohistochemistry (IHC) staining for CD31 and IHC staining for PD-L1, respectively. The results demonstrated that the expression levels of these markers were correlated with DCE-MRI parameters. PD-L1 expression levels were found to be significantly correlated with the maximum CI (CI-max; P=0.007), peak CI (CI-peak; P=0.007), maximum CI gain (CI-gain; P=0.006) and MVD (P=0.001) values. The mean CI-max, CI-peak, CI-gain and MVD values were significantly higher in tumors with high PD-L1 expression (P<0.05). MVD levels were also significantly correlated with the time of CI-max (T-max; P=0.003) and CI-gain (P=0.037). The mean CI-gain was significantly increased, and the mean T-max was significantly shorter in high MVD tumors (P<0.05 and P<0.01, respectively). In summary, the findings from the present study confirmed the correlation between CI parameters, derived from DCE-MRI, and MVD, and suggested that these parameters may be correlated with PD-L1 expression in OSCC tumor cells.

Morphological characteristics of radicular cysts using computed tomography.

The purpose of this study was to evaluate computed tomography (CT) findings of radicular cysts with a focus on location, size, and condition of the surrounding bone. Subjects comprised 60 men and 86 women (mean age 47.2 years) with histopathologically confirmed radicular cysts who underwent CT examination between 2012 and 2014. Mesiodistal and buccolingual diameters were measured at the location where the lesion appeared to be largest on CT axial images. Of the 146 cases, 103 lesions were in the maxilla and 43 were in the mandible. Mesiodistal diameter of the maxillary lesions was significantly larger than that of the mandibular lesions. However, the ratio of mesiodistal diameter to buccolingual diameter in the mandible was significantly larger than that in the maxilla. Bone expansion was more significant in the maxilla than in the mandible. Mesiodistal and buccolingual diameters in only the maxilla and perilesional sclerotic radiolucency in images of both jaws were significantly associated with the severity of clinical symptoms. The findings suggest that radicular cysts in the maxilla are accompanied by bone expansion in the mesiodistal and buccolingual directions and those in the mandible progress in the mesiodistal direction without bone expansion. Clinical acute symptoms (pain and swelling) are correlated with lesion size in the maxilla; such a correlation is not clear for mandibular lesions, and discovery of mandibular lesions may, therefore, be delayed.

Fourth molar: A retrospective study and literature review of a rare clinical entity.

PURPOSE: The prevalence of supernumerary teeth has been reported to be between 0.1% and 3.8%. The aim of this study was to determine the prevalence, clinical significance, and associated pathologies of fourth molars based on a retrospective study and a literature review. MATERIALS AND METHODS: A 5-year retrospective prevalence study was conducted at the Department of Oral Diagnosis and Dentomaxillofacial Radiology of Okayama University Hospital, Okayama, Japan. The study involved extracting data from the digital records of patients from January 1, 2013 through December 31, 2017. The sampling frame included all patients who had panoramic radiographs, cone-beam computed tomography (CT), and multislice CT images during the period under review. RESULTS: A total of 26,721 cases were reviewed and 87 fourth molars were identified. The prevalence of fourth molars in the 5-year study at Okayama was calculated as 0.32%. The mean age of patients with a fourth molar was 30.43 years, and the male-to-female ratio was 1:0.98. The vast majority of cases were in the maxilla (92%) and had normal shapes (89.7%); furthermore, 82.8% of cases were unerupted. CONCLUSION: The prevalence of fourth molars in the study population was found to be 0.32%, and fourth molars occurred with approximately equal frequency in males and females. Fourth molars were more common in the maxilla and were predominantly unerupted and small.

A case of sublingual adenoid cystic carcinoma involving the mandible presenting as a "skip lesion".

Adenoid cystic carcinoma (ACC) is a slowly growing malignant neoplasm with a propensity for perineural invasion. Microscopic invasion of ACC often prevents its detection on computed tomography (CT) or magnetic resonance imaging (MRI). We herein report a rare case of sublingual ACC presenting as a "skip lesion" that rapidly infiltrated the mandible after tumor resection. A 64-year-old man presented to Okayama University Hospital with an 18-month history of swelling in the right floor of the mouth. Clinical examination displayed an ulcerated swollen mass in that region. An enhanced mass was detected in the right sublingual space on CT and MRI. Bone surface erosion was observed at the inferior border of the mandible, but continuity with the sublingual mass or mass around that lesion was not detected by imaging. Sublingual tumor resection and selective neck dissection were performed by the pull-through method. Histopathologically, the surgical margins were free of cancer cells, and the tumor was diagnosed as ACC. Continuity with the sublingual mass and mandibular bone was not detected intraoperatively. However, marked bone resorption was detected in the anterior mandible 3 months after the operation. Biopsy was performed, and the findings indicated the same histological type of sublingual ACC. This case suggests that a malignant tumor close to the jaw bone requires the clinician to consider the possibility of bone invasion and to observe a wide region surrounding the tumor using imaging examination.

Carcinogenic epithelial-mesenchymal transition initiated by oral cancer exosomes is inhibited by anti-EGFR antibody cetuximab.

Overexpression and increased signaling from the epidermal growth factor receptor (EGFR) often changes oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed the roles of OSCC-derived extracellular vesicles (EVs), including exosomes in the trafficking of cetuximab and in epithelial-mesenchymal transition (EMT) of epithelial cells. OSCC cells abundantly expressed EGFR, which was secreted from cells with OSCC-EVs upon EGF stimulations. The OSCC-EGFR-EVs were then able to enter into and transform epithelial cells leading to increased mesenchymal traits with increased vimentin and spindle-like shapes. EGF priming of OSCC cells further increased this EMT-initiating effect of the OSCC-EVs. The internalization and pro-EMT effects of the OSCC-EVs were largely blocked by cetuximab. Thus, OSCC-derived EVs transform normal epithelial cells into a mesenchymal phenotype and anti-EGFR therapeutic antibody cetuximab inhibits such a carcinogenic effect of the OSCC-EVs.

Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells.

The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10-35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.

Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition.

Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

The role of dentistry other than oral care in patients undergoing radiotherapy for head and neck cancer.

The usefulness of dental approaches, such as oral management, has gained recognition among patients treated for head and neck cancer. In particular, oral management plays a very important role before, during, and after treatment in patients undergoing radiotherapy, chemotherapy, or a combination of both. However, specialized dentistry knowledge and techniques that are useful for patients undergoing radiotherapy for head and neck cancer have yet to be reported. Therefore, in this review article, our aim is to introduce dental approaches in radiotherapy for patients with head and neck cancer that have been developed and are currently being used at our institute.

De novo myoepithelial carcinoma with multiple metastases arising from a submandibular salivary gland: A case report.

Salivary gland carcinomas are rare tumors, representing ~0.5% of all malignancies. Myoepithelioma is also uncommon, representing ~1% of all salivary gland tumors. Myoepithelial carcinoma (MC) is even rarer, representing 0.2 to 0.6% of all salivary gland tumors. We herein report a case of MC with multiple metastases arising from a submandibular gland in a 71-year-old male patient and present the associated imaging findings. The patient was considered to have a de novo type of myoepithelial carcinoma, which is reportedly associated with higher malignancy than the transformation type of the disease (i.e., a malignant change from pleomorphic adenoma or myoepithelioma). This was reflected in the multiple lung and bone metastases sites and strong positivity for p53 and Ki-67.

High-dose-rate brachytherapy using molds for lip and oral cavity tumors.

BACKGROUND: High-dose-rate (HDR) brachytherapy using the mold technique is a less invasive treatment for early lip and oral cavity cancer. However, limited reports exist regarding the feasibility of this method. In this retrospective study, we evaluated the outcome of this therapy and investigated its feasibility for lip and oral cavity tumors. METHODS: Between May 2002 and December 2010, 17 patients (median age, 80.0 years) with histologically confirmed squamous cell carcinoma of the lip or oral cavity were treated by means of HDR brachytherapy using the mold technique after external beam radiotherapy (EBRT). Tumor sites included the buccal mucosa in eight cases, the gingiva in three cases, the lips in two cases, the floor of the mouth in two cases, and the hard palate in two cases. For all patients, EBRT (30 Gy/15 fractions), was performed before HDR brachytherapy. Two 6-Gy fractions were delivered twice daily for 2 days a week with an interval of 6 hours between the fractions. The total HDR brachytherapy dose was 24 Gy. Prior to EBRT, two patients with neck metastasis underwent neck dissection, and one patient with an exophytic tumor underwent tumor resection. RESULTS: The median follow-up period was 53.4 (range, 4.8-83.4) months. Of the 17 patients, 14 (82.4%) achieved a complete response, and three (17.6%) displayed a partial response. The overall 3- and 5-year survival rates were both 68.8%, the 3- and 5-year disease-specific survival rates were both 86.7%, and the 3- and 5-year local control rates were both 54.1%. Seven patients developed local recurrence at a median time of 3.4 (range, 1.7-29.1) months after treatment. Nodal and lung metastases occurred separately in two patients. By the end of the follow-up period, two patients had died of the primary disease and four patients had died of other causes. CONCLUSIONS: Although there is a need to improve the technical aspects of the treatment protocol, HDR brachytherapy using the mold technique might be a therapeutic option for superficial lip or oral cavity tumors, especially in older patients who have a poor performance status or are in poor physical condition.

Primary intraosseous squamous cell carcinoma of the maxilla possibly arising from an infected residual cyst: A case report.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare type of odontogenic carcinoma arising from the jawbone. Odontogenic cysts are true cysts that arise from the dental epithelium, which is associated with tooth formation. The epithelial lining of odontogenic cysts has the potential to transform into various types of odontogenic tumor; however, this transformation from an odontogenic cyst to a malignant tumor is rare. The definitive diagnosis for PIOSCC generally requires the observation of either features of squamous cell carcinoma (SCC) within the jawbone that are distinct from direct invasion from the surface oral epithelium, or evidence of SCC arising from odontogenic epithelium and from tumors that have metastasized to the jawbone from distant sites. In the present study, a case of PIOSCC of the maxilla is presented, which, based on the results of computed tomography and the clinical course, was hypothesized to have originated from an infected residual cyst.

A new phantom and empirical formula for apparent diffusion coefficient measurement by a 3 Tesla magnetic resonance imaging scanner.

The aim of this study was to create a new phantom for a 3 Tesla (3T) magnetic resonance imaging (MRI) device for the calculation of the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI), and to mimic the ADC values of normal and tumor tissues at various temperatures, including the physiological body temperature of 37°C. The phantom was produced using several concentrations of sucrose from 0 to 1.2 M, and the DWI was performed using various phantom temperatures. The accurate ADC values were calculated using the DWIs of the phantoms, and an empirical formula was developed to calculate the ADC values of the phantoms from an arbitrary sucrose concentration and arbitrary phantom temperature. The empirical formula was able to produce ADC values ranging between 0.33 and 3.02×10-3 mm2/sec, which covered the range of ADC values of the human body that have been measured clinically by 3T MRI in previous studies. The phantom and empirical formula developed in this study may be available to mimic the ADC values of the clinical human lesion by 3T MRI.

Case series: conditions inhibiting eruption of permanent first molars.

PURPOSE: The purpose of this study was to evaluate the radiological and histopathological findings of 11 patients with unerupted first molars to verify the factors obstructing spontaneous eruption. METHODS: The patients' clinical, radiological, and histopathological data were evaluated retrospectively to determine histopathological diagnosis, radiographic findings, methods of surgical management, and postoperative course. RESULTS: This study involved 4 male and 7 female patients (mean age=9.5 years old). Nine cases involved the mandible. The patients' histopathological diagnoses included 3 odontogenic tumors, 2 odontogenic cysts, and 6 hyperplastic dental follicles. Radiographically, 10 cases showed characterless enlargement of the follicular space, while only 1 displayed radiopaque bodies. One patient with a tumor underwent enucleation, and 1 with a cyst underwent cystectomy and tooth extraction. The others underwent wide excision or partial excision of the surrounding tissue at the top of the impacted tooth. Tumor relapse was observed in 3 cases. CONCLUSION: Surgeons should perform aggressive treatment for patients with unerupted teeth because spontaneous eruption is rare in cases involving non-neoplastic lesions such as hyperplastic dental follicles.

Ossifying fibroma of the maxilla: a case report including its imaging features and dynamic magnetic resonance imaging findings.

Ossifying fibroma (OF), a rare nonodontogenic tumor, is defined as a bone-related jawbone lesion. The main histopathological feature of OF is the replacement of bone by benign connective tissue. Ossifying fibroma usually occurs in the second to fourth decades of life and shows a predilection for females. Ossifying fibroma most commonly occurs in the mandible, and OF arising from the anterior part of the maxilla is rare. Ossifying fibromas display various radiographic findings, including varying degrees of radiolucency and radiopacity, depending on the proportions of their soft and hard tissue components. Depending on their components, it can be difficult to distinguish OF from other fibroosseous lesions and some odontogenic tumors by using conventional radiographs, computed tomography, and magnetic resonance imaging (MRI). We report a case of OF in the anterior maxilla in a 56-year-old man, together with its histopathological and imaging findings including the dynamic MRI findings.

Solid-type primary intraosseous squamous cell carcinoma of the mandible: a case report with histopathological and imaging features.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant odontogenic tumor arising from odontogenic epithelial remnants within the jawbones. PIOSCC is histopathologically divided into 3 types: solid-type carcinoma, carcinoma derived from a keratocystic odontogenic tumor, and carcinoma derived from an odontogenic cyst. In this article, we report a case of solid-type PIOSCC involving reactive bone formation in the mandible in a 60-year-old female patient together with its histopathological and imaging findings.

Central odontogenic fibroma of the jawbone: 2 case reports describing its imaging features and an analysis of its DCE-MRI findings.

Odontogenic fibroma (OF) is a rare nonepithelial benign tumor arising from the odontogenic mesenchymal tissue in the jawbone. OFs are topographically categorized into 2 types, the central type and peripheral type, and are histopathologically divided into the epithelium-poor type and epithelium-rich type. The radiological findings of central OF commonly include a uni- or multilocular radiolucent area with a well-defined margin, which are similar to those of cysts and other benign tumors of the jawbone. Therefore, it is difficult to distinguish OF from these jawbone lesions on radiographs because of their noncharacteristic radiological findings. In this article, we report the cases of 2 patients with central OF who underwent magnetic resonance (MR) examinations and describe the usefulness of dynamic contrast-enhanced MR imaging for diagnosing OF.

Magnetic resonance imaging (MRI) and dynamic MRI evaluation of extranodal non-Hodgkin lymphoma in oral and maxillofacial regions.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI), especially dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), in extranodal non-Hodgkin lymphoma (NHL) of oral and maxillofacial regions. STUDY DESIGN: Thirteen cases with extranodal NHL were examined using MRI. T1-weighted images (T1WI) and T2-weighted images (T2WI) or short TI inversion recovery (STIR) images were obtained in all cases. Contrast-enhanced images and DCE-MRI were acquired in 10 and 7 cases, respectively. On DCE-MRIs, we analyzed the parameters as follows: contrast index at maximal contrast enhancement (CImax), maximum contrast index (CI) gain/CImax ratio, and washout ratios (WR(300), WR(600), and WR(900)) at 300, 600, and 900 seconds after contrast medium injection. RESULTS: The signal intensity of all lesions was hypointense to isointense on T1WIs and showed variable contrast enhancement patterns. On T2WIs and STIR images, the signal intensity was isointense to hyperintense in almost all cases. Analysis of DCE-MRI parameters in extranodal NHLs resulted in the identification of 4 types of CI curves according to CImax and WR: (1) CImax greater than 2.0 and WR(900) greater than 40%, (2) CImax greater than 2.0 and WR(900) less than 40%, (3) CImax less than 1.5 and WR(900) greater than 40%, and (4) CImax less than 1.5 and WR(900) greater than 40%. CONCLUSIONS: The signal intensities on MRI were not specific to extranodal NHL and resembled those of other tumor types. When CImax was less than 1.5 or WR900 was less than 40%, these parameters contributed to diagnosis in extranodal NHLs.

Two-piece customized mold technique for high-dose-rate brachytherapy on cancers of the buccal mucosa and lip.

OBJECTIVE: High-dose-rate (HDR) brachytherapy using a customized mold is a minimally invasive treatment for oral cancer; however, it is difficult to use this technique for buccal and lip cancers involving the commissura labiorum, owing to its anatomic form. The purpose of this study was to introduce an improved customized mold consisting of 2 pieces to allow the fixation of molds to these sites. STUDY DESIGN: Five patients with buccal carcinoma and 1 patient with lip carcinoma were treated with this technique after external beam radiotherapy. One patient with neck metastasis underwent both neck dissection and partial tumor resection before HDR brachytherapy. RESULTS: At the end of the follow-up period, 5 patients had no tumor recurrence, and 1 patient had suffered local recurrence. CONCLUSIONS: Our technique is a viable therapeutic option for patients with buccal and lip carcinomas for whom the therapeutic modalities are limited by age, performance status, and other factors.