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ObjectivesThis study sought to identify tumor characteristics that associate with regional lymph node metastases in squamous cell carcinomas originating in the upper gingiva.Materials and methodsData from 113 patients from Osaka University Dental Hospital were included. We measured each primary tumor's width, length, depth, and the extent of bone invasion. Additionally, tumor signal intensity for T1 and T2-weighted images as well as the center of the tumor's location and T classification was assessed, and a histopathological analysis was performed.ResultsTumor signal intensity was not found to be a significant prognostic factor. However, bucco-lingual width, histopathological classification as well as the tumor's location were significantly different between metastatic and non-metastatic groups in both univariate and multivariate analysis. Superior-inferior depth and T classification were significant only in the univariate (and not the multivariate) analysis.ConclusionsBucco-lingual width, histopathological grading as well as the tumor's location are likely to be important predictors for the occurrence of LN metastasis in upper gingival carcinoma patients and should be considered when managing care for these patients.

High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.

Angiogenesis plays an important role in cancer growth and metastasis, and it is considered a therapeutic target to control tumour growth following anti‐angiogenic therapy. However, it is still unclear when tissues initiate angiogenesis during malignant transformation from premalignant condition and whether this premalignant condition could be a therapeutic target of anti‐angiogenic therapy. In this study, we aimed to analyse the onset of angiogenesis by evaluating morphological and functional alterations of microvessels during oral multistep carcinogenesis using a 4‐nitroquinoline 1‐oxide (4NQO)‐induced oral carcinogenesis mouse model. In the study, we initially confirmed that with the use of 4NQO, oral lesions develop in a stepwise manner from normal mucosa through oral epithelial dysplasia (OED) to oral squamous cell carcinoma (OSCC). Evaluation of CD31‐immunostained specimens revealed that microvessel density (MVD) increases in a stepwise manner from OEDs. Histological and functional analyses revealed the structural abnormalities and leakage of blood vessels had already taken place in OED. Then we evaluated the expression profiles of Hif1a and Vegfa along with hypoxic status and found that OED exhibited increased Vegfa expression under hypoxic conditions. Finally, we tested the possibility of OEDs as a target of anti‐angiogenic therapy and found that anti‐VEGFR2 neutralising antibody in OED slowed the disease progression from OED to OSCC. These data indicate that an angiogenic switch occurs at the premalignant stage and morphological, and functional alterations of microvessels already exist in OED. These findings also elucidate the tumour microenvironment, which gradually develops along with carcinogenic processes, and highlight usefulness of the 4NQO‐induced carcinogenesis model in the study of epithelial and stromal components, which will support epithelial carcinogenesis. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Adenosquamous carcinoma (ASC) is a rare variant of squamous cell carcinoma (SCC). It is thought to be more aggressive with poorer prognosis than conventional SCCs. Therefore, accurate preoperative diagnosis is crucial for adequate treatment strategy. In this report, we will present a case of ASC arising in left mandibular gingiva of 76-year-old male. Histological examination revealed both SCC component and adenocarcinoma (AdC) component. Also, transition from AdC to short spindle-shaped and pleomorphic cells, which is known as sarcomatoid change, was observed. Immunohistochemical study revealed that SCC component was positive for p40 and negative for Cytokeratin 7 (CK7), whereas, AdC component was negative for p40 and positive for CK7. In area with sarcomatoid change, immunohistochemical analysis revealed that negative expression of both CK7 and E-cadherin but positive expression of Vimentin and nuclear Snail/Slug, indicating the possible role of epithelial-mesenchymal transition (EMT) in AdC to sarcomatoid transition. [ABSTRACT FROM AUTHOR]

Transcellular Mg(2+) transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified. Here, we show that CNNM4 is the basolaterally located Mg(2+) extrusion molecule. CNNM4 is strongly expressed in intestinal epithelia and localizes to their basolateral membrane. CNNM4-knockout mice showed hypomagnesemia due to the intestinal malabsorption of magnesium, suggesting its role in Mg(2+) extrusion to the inner parts of body. Imaging analyses revealed that CNNM4 can extrude Mg(2+) by exchanging intracellular Mg(2+) with extracellular Na(+). Furthermore, CNNM4 mutations cause Jalili syndrome, characterized by recessive amelogenesis imperfecta with cone-rod dystrophy. CNNM4-knockout mice showed defective amelogenesis, and CNNM4 again localizes to the basolateral membrane of ameloblasts, the enamel-forming epithelial cells. Missense point mutations associated with the disease abolish the Mg(2+) extrusion activity. These results demonstrate the crucial importance of Mg(2+) extrusion by CNNM4 in organismal and topical regulation of magnesium.

Background: Although cervical lymph node metastasis is an important prognostic factor for oral cancer, occult metastases remain undetected even by diagnostic imaging. We developed a learning model to predict lymph node metastasis in resected specimens of tongue cancer by classifying the level of immunohistochemical (IHC) staining for angiogenesis‐ and lymphangiogenesis‐related proteins using a multilayer perceptron neural network (MNN). Methods: We obtained a dataset of 76 patients with squamous cell carcinoma of the tongue who had undergone primary tumor resection. All 76 specimens were IHC stained for the six types shown above (VEGF‐C, VEGF‐D, NRP1, NRP2, CCR7, and SEMA3E) and 456 slides were prepared. We scored the staining levels visually on all slides. We created virtual slides (4560 images) and the accuracy of the MNN model was verified by comparing it with a hue–saturation (HS) histogram, which quantifies the manually determined visual information. Results: The accuracy of the training model with the MNN was 98.6%, and when the training image was converted to grayscale, the accuracy decreased to 52.9%. This indicates that our MNN adequately evaluates the level of staining rather than the morphological features of the IHC images. Multivariate analysis revealed that CCR7 staining level and T classification were independent factors associated with the presence of cervical lymph node metastasis in both HS histograms and MNN. Conclusion: These results suggest that IHC assessment using MNN may be useful for identifying lymph node metastasis in patients with tongue cancer. [ABSTRACT FROM AUTHOR]