Giant Cell Granuloma of the Jaws and Keratin-Positive Giant Cell-Rich Tumor of Bone and Soft Tissue.

BACKGROUND: Different giant cell-rich tumors may occur in the jaws. Recently, a new condition known as keratin-positive giant-cell rich tumor harboring recurrent HMGA2::NCOR2 fusions has been described. Interestingly, the mononuclear cells of this tumor are immunoreactive with the AE1/AE3 keratin. Considering the similarities of central and peripheral giant cell granuloma of the jaws with the keratin-positive giant cell-rich tumor of the soft tissue and bone, we hypothesized whether the keratin-positive tumors could also occur in the maxillary bones. METHODS AND RESULTS: An immunohistochemical investigation of AE1/AE3 in a cohort of 16 cases of peripheral and central giant cell granuloma of the jaws was carried out. None of the cases was keratin-positive. CONCLUSIONS: Although no immunopositivity for keratin was observed in the present giant cell granulomas cohort, we cannot completely exclude the possibility of keratin-positive giant cell-rich tumors occurring in the jaws. Therefore, oral pathologists should be aware about this condition and further studies using cohorts from different laboratories are necessary.

The use of deep learning state-of-the-art architectures for oral epithelial dysplasia grading: A comparative appraisal.

BACKGROUND: Dysplasia grading systems for oral epithelial dysplasia are a source of disagreement among pathologists. Therefore, machine learning approaches are being developed to mitigate this issue. METHODS: This cross-sectional study included a cohort of 82 patients with oral potentially malignant disorders and correspondent 98 hematoxylin and eosin-stained whole slide images with biopsied-proven dysplasia. All whole-slide images were manually annotated based on the binary system for oral epithelial dysplasia. The annotated regions of interest were segmented and fragmented into small patches and non-randomly sampled into training/validation and test subsets. The training/validation data were color augmented, resulting in a total of 81,786 patches for training. The held-out independent test set enrolled a total of 4,486 patches. Seven state-of-the-art convolutional neural networks were trained, validated, and tested with the same dataset. RESULTS: The models presented a high learning rate, yet very low generalization potential. At the model development, VGG16 performed the best, but with massive overfitting. In the test set, VGG16 presented the best accuracy, sensitivity, specificity, and area under the curve (62%, 62%, 66%, and 65%, respectively), associated with the higher loss among all Convolutional Neural Networks (CNNs) tested. EfficientB0 has comparable metrics and the lowest loss among all convolutional neural networks, being a great candidate for further studies. CONCLUSION: The models were not able to generalize enough to be applied in real-life datasets due to an overlapping of features between the two classes (i.e., high risk and low risk of malignization).

Radiological aspects of lymphomas and leukaemias affecting the jaws: A systematic review.

BACKGROUND: This systematic review aimed to investigate the radiological features of lymphomas and leukaemias affecting the jaws. METHODS: A systematic literature review was conducted using the electronic databases of PubMed, Web of Science and Scopus. Articles that contained sufficient radiographic examinations (periapical, panoramic or computed tomography images) for individual cases were included. Additionally, either immunohistochemical or molecular confirmation was required prior to inclusion. Three authors evaluated and described the image quality and radiological features. RESULTS: From an initial 1079 articles screened, 129 cases were included, containing 88 tomographic, 76 panoramic and 26 periapical examinations. The quality of the majority of images was sufficient for evaluation. Diffuse large B-cell lymphoma, Burkitt lymphoma, leukemic infiltration, plasmablastic lymphoma and extranodal Natural killer (NK)/T-cell lymphoma, nasal type were the most common subtypes. Involved teeth presented with mobility in 37.2% of the cases and a provisional diagnosis of inflammatory/infectious dental disease was considered in 49.2% of cases. Computed tomography exams were available for 76% of the cases, with most presented with an osteolytic lesion with ill-defined borders. Periosteal reactions were uncommon. CONCLUSION: Lymphoma/leukaemia infiltrates of the jaw bones are usually of high-grade subtypes and rarely present with periosteal reactions.

Oral follicular lymphoma: a clinicopathologic and molecular study.

Follicular lymphoma is a hematolymphoid neoplasm that originates from germinal center B cells. It is made up of a combination of small cleaved centrocytes and a varying quantity of larger non-cleaved centroblasts to describe the clinical, microscopic, immunohistochemical, and molecular features of oral follicular lymphomas. Follicular lymphomas affecting the oral cavity were retrieved from pathology files. Immunohistochemistry was performed to confirm the diagnosis, and fluorescence in situ hybridization (FISH) was employed to detect rearrangements in BCL2, BCL6, and MYC genes. Clinical and follow-up data were obtained from the patient's medical and pathology files. Twenty cases were obtained. There was an equal sex distribution (10 males: 10 females) and a mean age of 60.9 years (range: 10-83 years-old). Lesions presented as asymptomatic swellings, usually in the palate (10 cases) and the buccal mucosa (7 cases). Five patients presented with concomitant nodal involvement. Microscopic evaluation depicted the follicular growth pattern with diffuse areas in six cases. Grades 1 and 2 follicular lymphomas represented 12 cases, while grade 3A neoplasms accounted for other 8 cases. Two cases showed rearrangements in MYC, BCL2, and BCL6 genes, while single BCL2 translocation was found in eight cases. Two cases had no translocation. Three patients deceased and the 2-year overall survival achieved 88%. Follicular lymphoma affecting the oral cavity is uncommon, usually affects the palate as a non-ulcerated swelling and the presence of a systemic disease most always be ruled out.

Expression of mitochondrial dynamic markers in adenoid cystic carcinoma.

BACKGROUND: Mitochondrial fission and fusion processes are known as mitochondrial dynamics and the occurrence of imbalances in the mitochondrial activity is related to the pathogenesis of many human cancers. However, the importance of mitochondrial dynamics in malignant salivary gland tumours remains unknown. Therefore, we aimed to investigate its prognostic significance in adenoid cystic carcinoma. METHODS: Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2 and OPA1 proteins. Clinical data were retrieved from the patients' medical files, including specific and disease-free survival data. RESULTS: It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, and 49.1%, 21.1%, 22.8% and 24.6% strongly positive for FIS1, MFN1, MFN2 and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumour. The higher expression of MFN2 was associated with solid microscopic pattern (p = 0.016). DRP1 overexpression showed a trend towards a shorter overall survival (p = 0.054), while negative/weak OPA1 showed a trend towards a lower disease-free survival (p = 0.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. CONCLUSION: In conclusion, mitochondrial dynamics markers do not seem to carry a prognostic significance for adenoid cystic carcinoma patients, but these proteins may play an important role in its pathogenesis.

Oral Squamous Cell Carcinoma Frequency in Young Patients from Referral Centers Around the World.

Oral squamous cell carcinoma (OSCC) commonly affects older patients; however, several studies have documented an increase in its incidence among younger patients. Therefore, it is important to investigate if this trend is also found in different geographic regions. The pathology files of diagnostic and therapeutic institutions from different parts of the globe were searched for OSCC cases diagnosed from 1998 to 2018. Data regarding the sex, age, and tumor location of all cases, as well as the histologic grade and history of exposure to risk habits of cases diagnosed as OSCC in young patients (≤ 40 years of age) were obtained. The Chi-square test was used to determine any increasing trend. A total of 10,727 OSCC cases were identified, of which 626 cases affected young patients (5.8%). Manipal institution (India) showed the highest number of young patients (13.2%). Males were the most affected in both age groups, with the tongue and floor of the mouth being the most affected subsites. OSCC in young individuals were usually graded as well or moderately differentiated. Only 0.9% of the cases occurred in young patients without a reported risk habit. There was no increasing trend in the institutions and the period investigated (p > 0.05), but a decreasing trend was observed in Hong Kong and the sample as a whole (p < 0.001). In conclusion there was no increase of OSCC in young patients in the institutions investigated and young white females not exposed to any known risk factor represented a rare group of patients affected by OSCC.

Oral lesions containing amyloid-like material.

During oral pathology daily practice, true amyloid may be identified in oral amyloidosis and several odontogenic tumors. However, histologic examination often reveals other oral and perioral diseases with similar eosinophilic, acellular, amorphous substances. These include extensive areas of collagenous sclerosis, fibrin deposition, elastic fiber degeneration, and dentinoid material, which may resemble amyloid under light microscopic examination. These materials are often termed "amyloid-like" due to their close histologic resemblance to true amyloid. The rarity of most of these conditions and their strong histologic similarity may hamper an accurate diagnosis. Definitive diagnosis of these lesions may require clinical correlation; laboratory evaluation; histochemical or immunohistochemical reactions; and, in some cases, genetic investigation. In this review, we describe the main clinicopathologic features of this group of diseases that may manifest in the oral and/or perioral regions and that have in common the presence of amyloid-like material deposition.

BRAF p.V600E status in epithelial areas of ameloblastoma with different histological aspects: Implications to the clinical practice.

BACKGROUND: BRAF p.V600E is reported in up to 80% of ameloblastomas. Despite the high frequency, the presence of this mutation in different histopathological areas of the tumour has not been investigated. This information has an important role in the use of BRAF p.V600E assessment as an auxiliary tool in the differential diagnosis between unicystic ameloblastoma and other odontogenic cystic lesions, especially when only incisional biopsies are available. Therefore, the purpose of the present study was to investigate BRAF p.V600E heterogeneity in unicystic ameloblastoma. METHODS: Five cases of ameloblastoma and two dentigerous cysts were analysed. The regions exhibiting different microscopic characteristics were selected from each ameloblastoma case and manually dissected. TaqMan allele-specific qPCR or Sanger sequencing was performed to determine BRAF p.V600E status. RESULTS: We screened the mutation in a small cohort of UA and no molecular heterogeneity was found. Four cases of ameloblastoma (80%) exhibited BRAF p.V600E in all different areas evaluated. One case did not harbour the mutation in any microscopic region analysed. The BRAF mutation was absent in the dentigerous cysts. CONCLUSION: Ameloblastomas appear to exhibit a homogeneous profile regarding the BRAF p.V600E no matter what histological feature is observed under light microscopy, suggesting that this molecular test may contribute to establish the correct diagnosis in cases microscopically resembling other odontogenic lesions.

Solitary fibrous tumour of the oral cavity: An update.

BACKGROUND: Solitary fibrous tumour is an unusual neoplasm of the oral cavity that is sometimes not clinically distinguishable from other lesions. The purpose of the present study was to review the clinical, microscopic and molecular aspects of malignant and benign solitary fibrous tumour of the oral cavity currently available in literature. METHODS: For our review, an electronic search was performed using PubMed, Scopus, Ovid/MedLine, Web of science and ProQuest Dissertations and Theses Global database. RESULTS: A total of 74 publications reporting 150 cases were included. Oral solitary fibrous tumours are most frequently described as submucosal, well-circumscribed, asymptomatic nodule, more prevalent in females in their fourth to fifth decades of life. Buccal mucosa is the most commonly affected site by the benign tumour variant, whereas the tongue is the most common location affected by the malignant form of the neoplasm. Most of the lesions were treated by conservative surgery. One recurrent malignant tumour and one metastasis are reported. CONCLUSION: Asymptomatic normal-coloured submucosal nodules located in the buccal mucosa and tongue in adult patients are suggestive of oral solitary fibrous tumour, but only a careful microscopic examination can differentiate benign from malignant variants and the use of immunohistochemistry (CD34, Bcl-2, CD99 and STAT6), and cytogenetic studies (NAB2-STAT6) contribute significantly to confirm the diagnosis of solitary fibrous tumour in difficult cases.

Prognostic importance of the lymphovascular invasion in head and neck adenoid cystic carcinoma: A systematic review and meta-analysis.

The presence of lymphovascular invasion is considered a prognostic determinant for different human neoplasms and is frequently taken into account by surgeons and oncologists to determine patients' treatment. However, the exact frequency of this microscopic event and its prognostic impact for patients affected by adenoid cystic carcinoma (AdCC) remains unclear. Therefore, the aim of this study was to carry out a systematic review and meta-analysis to address the prevalence and the prognostic potential of lymphovascular invasion in head and neck AdCC. A literature search on PubMed, Scopus, ClinicalTrials.gov, Web of Science and ProQuest databases was undertaken in January 2019. The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS). The relative frequency of lymphovascular invasion and its possible association with other clinicopathological parameters were addressed. A total of 22 studies and 2117 patients were included in this study. The frequency of lymphovascular invasion ranged from 5.2% to 72.5%. Lymphovascular invasion was associated with an increased likelihood of lymph node metastasis (OR = 2.58; 95% CI 1.61-4.12; p = 0.0001) and death (OR = 3.09; 95% CI 1.82-5.26; p = 0.0001), solid/higher-grade AdCC were more likely to present lymphovascular invasion (OR = 5.51; 95% CI 1.87-16-21; p = 0.002) and patients with this microscopic finding had a significantly lower OS (HR = 8.30; 95% CI 1.68-40.91; p = 0.009) and DFS (HR = 3.76; 95% CI 1.13-12.53; p = 0.03). In conclusion, lymphovascular invasion seems to be a significant predictor of poor prognosis for head and neck AdCC patients.