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Background: Ameloblastic carcinoma (AC) is the most common odontogenic malignancy, constituting approximately 30% of cases in this category. Literature is sparse on malignant odontogenic neoplasms, with a large proportion of current knowledge derived from case reports or small case series. Methods: A systematic review of case series/case reports of AC was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) Statement guidelines. Demographic and clinical information, including duration of the lesion, location, clinical presentation and radiologic features, were analysed. Additionally, the origin of the lesion (primary/secondary), Ki‐67 proliferation index, treatment performed, metastasis, tumour recurrence and prognosis were collected for analysis. Results: A total of 126 studies, including 285 individual cases of AC, were included in this review. Patients presented with a near‐equal distribution of painless and painful swellings. ACs presented at a median age of 45 years, with a male‐to‐female ratio of 1:2. The mandible was most frequently involved, with rare cases extending to involve more than one region, including crossing the midline. Although most lesions presented with poorly‐demarcated borders (52.6%), unilocular lesions with well‐demarcated borders (47.4%) comprised a substantial number in the sample. The proliferation index was only reported in 27 cases, with a mean score of 42% and a wide range. The probability of tumour recurrence increased, and the survival probability decreased with prolonged follow‐up duration. Conclusion: This study provides more comprehensive, up‐to‐date descriptive data on these rare odontogenic malignancies, aiding clinicians and Pathologists with the diagnosis and surgeons in their management of cases. [ABSTRACT FROM AUTHOR]

Background: Tongue cancer is associated with debilitating diseases and poor prognostic outcomes. The use of imaging techniques like ultrasonography to assist in the clinical management of affected patients is desirable, but its reliability remains debatable. Therefore, the aim of this study is to investigate the importance of ultrasound use for the clinicopathological management of tongue cancer. Methods: A scoping review was carried out using specific search strategies in the following electronic databases: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Collected data included bibliographical information, study design, ultrasound equipment, the aim of the ultrasonography use, the timing of ultrasound use during oncological treatment (pre‐, trans‐, and/or post‐operatively), and the advantages and disadvantages of the use of the ultrasound. Results: A total of 47 studies were included in this review after following the selection process. The majority of the studies investigated the use of ultrasound pre‐operatively for the investigation of lymph node metastases or to determine the tumor thickness and depth of invasion. The sensitivity, specificity, and accuracy of ultrasound to determine clinical lymph node metastases ranged from 47% to 87.2%, from 84.3% to 95.8%, and from 70% to 86.2%, respectively. The sensitivity and specificity to determine the microscopic depth of invasion were 92.3% and from 70.6% to 82.1%, respectively. Conclusion: Ultrasonography seems to be a reliable imaging technique for the investigation of important prognostic parameters for tongue cancer, including depth of invasion and lymph node metastases. [ABSTRACT FROM AUTHOR]

Background: The purpose of the current study was to report on the clinical presentation and radiologic features of 155 cases of ameloblastoma (AB), representing a detailed, large, single‐centre radiologic study. Methods: Histologically confirmed cases were reviewed over 11 years. Demographic and clinical data were retrieved from the patient's records. Radiologic information was analysed from available radiographs. The radiologic features of ABs were assessed according to the mean age of presentation and the mean duration of the lesion. The distinguishing radiologic features between adults/children and sex were also evaluated. Results: A statistically significant correlation existed between loss of border demarcation and advanced mean age. Multilocular lesions were markedly more common in adults compared to children. Multilocular ABs were associated with increased lesion duration and advanced mean age. Radiologic signs of reactive bony changes associated with the tumour presented at the highest mean duration of all bony effects. Bony expansion and cortical destruction were statistically correlated with lesion duration. Tooth impaction was more common in children. Some mandibular lesions reached a significant size, resulting in impingement of the maxillary sinus, zygoma, orbit and pterygoid plates. Conclusion: Due to unfortunate healthcare access constraints, ABs grow to significant sizes and exhibit features not often reported in the literature. The findings of this analysis highlighted the radiologic features of ABs expressed through the mean age and duration of the lesion. This emphasises the significance of timely management of these lesions. [ABSTRACT FROM AUTHOR]

Background: Amyloidosis exhibits a variable spectrum of systemic signs and oral manifestations that can be difficult to diagnose. This study aimed to characterize the clinical, demographic, and microscopic features of amyloidosis in the oral cavity. Methods: This collaborative study involved three Brazilian oral pathology centers and described cases with a confirmed diagnosis of amyloidosis on available oral tissue biopsies. Clinical data were obtained from medical records. H&E, Congo‐red, and immunohistochemically stained slides were analyzed. Results: Twenty‐six oral biopsies from 23 individuals (65.2% males; mean age: 59.6 years) were included. Oral involvement was the first sign of the disease in 67.0% of cases. Two patients had no clinical manifestation in the oral mucosa, although the histological analysis confirmed amyloid deposition. Amyloid deposits were distributed in perivascular (88.0%), periacinar and periductal (80.0%), perineurial (80.0%), endoneurial (33.3%), perimuscular (88.2%), intramuscular (94.1%), and subepithelial (35.3%) sites as well as around fat cells (100.0%). Mild/moderate inflammation was found in 65.4% of cases and 23.1% had giant cells. Conclusions: Amyloid deposits were consistently found in oral tissues, exhibiting distinct deposition patterns. Oral biopsy is less invasive than internal organ biopsy and enables the reliable identification of amyloid deposits even in the absence of oral manifestations. These findings corroborate the relevance of oral biopsy for the diagnosis of amyloidosis. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Objective: Oral malignant infiltrations (OMI) are relevant for the diagnosis and prognosis of leukemia/lymphoma. This study analysed the oral health status and OMI of individuals with leukemia/lymphoma. Materials and Methods: A retrospective analysis (2010–2021) of data from individuals seen at a specialized hospital‐based dental service in Brazil. Results: A total of 781 cases of leukemia/lymphoma were surveyed. Acute lymphoblastic leukemia (30.1%), acute myeloid leukemia (AML; 26.0%), and non‐Hodgkin lymphoma (22.2%) were the most common diagnoses. The first (21.3%) and second (19.3%) decades of life were the most affected. Overall, dental caries (36.7%) and periodontal changes (34.6%) were the most frequent oral conditions. OMI occurred in 25 (3.2%) individuals. Lesions mainly involved the gingiva (80%) and patients diagnosed with AML (64%). Death (p < 0.001) and worse periodontal condition (p = 0.036) were more frequent among adults with OMI than among those without OMI. Death (p = 0.002) was more frequent among paediatric individuals with OMI than among those without OMI. When controlling for underlying disease, no association was observed between OMI and these outcomes. Conclusion: Oral status of individuals with leukemia, particularly those with acute leukemia or lymphoma, should be closely monitored since one or multiple conditions may occur, including OMI, which may influence disease outcomes. [ABSTRACT FROM AUTHOR]

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty‐eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Unicystic ameloblastoma is an encapsulated odontogenic neoplasm with a single cyst cavity. The conservative or aggressive surgical approaches used to treat the tumor directly affect recurrence rates. However, there is a lack of a standard protocol that can guide its management. Study Design: We retrospectively reviewed the clinicopathological findings and therapeutical procedures of 12 unicystic ameloblastoma cases treated by the same surgeon during the past 20 years. Methods: All cases of unicystic ameloblastoma diagnosed by biopsy and treated by the same surgeon between 2002 and 2022 were reviewed. Eligibility criteria were patients with completely filled‐out charts containing the follow‐up period and confirmation of the diagnoses based on the microscopic findings of the whole excised specimens. Data collected were categorized into clinical, radiographic, histological, surgical, and recurrence aspects. Results: There was a female predilection (2:1), and ages ranged between 18 and 61 years (mean: 27.25, ±12.45). Almost all (92%) affected the posterior mandible. Radiographically, the mean length of the lesions was 46.14 mm ± 14.28 mm which 92% were unilocular and 8.3% multilocular. Root resorption (n = 7, 58%), tooth displacement (n = 9, 75%), and cortical perforation (n = 5, 42%) were also observed. The mural histological subtype corresponded to 9 (75%) of the cases. The same conservative protocol was performed in all cases. The follow‐up period ranged between 12 and 240 months (~62 ± 65) and recurrence occurred in only one patient (8%). Conclusion: Our findings suggest a conservative approach should be the first option for unicystic ameloblastoma treatment, even for those with mural proliferation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Throughout the centuries, the world's outstanding scientists and research groups have gathered their efforts to characterise the initiation and progression of malignant neoplasms. The temporal dissection of tumourigenesis provided by phylogenetic studies is one of the milestones in understanding cancer; however, some black boxes are still unsolved. Currently, there is no consensus regarding the development of oral squamous cell carcinoma (OSCC), the leading cancer of the head and neck region. Oral epithelial dysplasia (OED) may precede oral cancer and, occasionally, be clinically evident as white, red or mixed mucosal lesions, called oral potentially malignant disorders (OPMD). In a stepwise view of oral carcinogenesis, OED and OPMD have been considered harbingers of oral cancer. Nevertheless, the malignant transformation of OPMD is a rare event. Most of these disorders remain benign and can even regress, making it challenging to formulate evolutionary hypotheses for OSCC initiation. Deciphering OED evolution is vital to highlight the potential drivers of oral carcinogenesis and molecular targets for OSCC preventative and therapeutic strategies. This narrative review synthesises the main concepts of evolutionary theories and discusses which of them better explains OED development and malignant transformation. [ABSTRACT FROM AUTHOR]

Oral potentially malignant disorders represent precursor lesions that may undergo malignant transformation to oral cancer. There are many known risk factors associated with the development of oral potentially malignant disorders, and contribute to the risk of malignant transformation. Although many advances have been reported to understand the biological behavior of oral potentially malignant disorders, their clinical features that indicate the characteristics of malignant transformation are not well established. Early diagnosis of malignancy is the most important factor to improve patients' prognosis. The integration of machine learning into routine diagnosis has recently emerged as an adjunct to aid clinical examination. Increased performances of artificial intelligence AI‐assisted medical devices are claimed to exceed the human capability in the clinical detection of early cancer. Therefore, the aim of this narrative review is to introduce artificial intelligence terminology, concepts, and models currently used in oncology to familiarize oral medicine scientists with the language skills, best research practices, and knowledge for developing machine learning models applied to the clinical detection of oral potentially malignant disorders. [ABSTRACT FROM AUTHOR]

Objectives: Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. Materials and Methods: The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin‐embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at −196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real‐time PCR (qPCR) assay. The ameloblastoma paraffin‐embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage. Results: There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. Conclusion: Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma. [ABSTRACT FROM AUTHOR]

Purpose: To investigate and compare the demographic data, occurrence of recurrence and metastasis, and survival prognosis between ameloblastic carcinoma (AC) and metastasizing ameloblastoma (MA), based on appropriate and currently accepted eligible diagnostic criteria, in a systematic review of the literature.Methods: An electronic search was undertaken, last updated in December 2021. Eligibility criteria included publications having enough clinicopathological information to confirm the diagnosis of these tumors.Results: Seventy-seven publications reporting 85 ACs and 43 MAs were included. Both tumors were more frequent in mandible and showed different clinical profiles regarding patients' sex and age. There was no difference in the estimated cumulative survival between patients diagnosed with these tumors. Metastases mainly affected the lungs, followed by cervical lymph nodes. The mean time between the first metastasis and the last follow-up was higher for MA (p = 0.021). In addition, MA patients remained alive longer than AC patients after the first metastasis diagnosis (p = 0.041). Considering only the cases that metastasized, a higher ratio of AC patients died in comparison to MA patients (p = 0.003). The occurrence of recurrence was associated with a conservative primary treatment with both AC (p < 0.001) and MA tumors (p = 0.017). Multiple recurrent events were associated with conservative primary therapies with MA (p < 0.001) but not with AC (p = 0.121).Conclusion: In addition to some demographic differences, ACs that metastasize present a worse prognosis than MA. As conservative procedures are associated with multiple recurrent events, this treatment modality should be avoided for both tumors. [ABSTRACT FROM AUTHOR]

Background: IgG4‐related disease is a fibroinflammatory and immune‐mediated condition, which has extremely variable clinical manifestations. In this study, we aim to investigate the clinicopathological features of IgG4‐related disease involving the oral and maxillofacial region. Methods: Cases of IgG4‐related disease manifesting in the oral and maxillofacial region were retrieved from three Brazilian institutions. Clinical and serological data were obtained from the patients' medical charts, while microscopic and immunohistochemical findings were revised by oral pathologists. Diagnosis followed the American College of Rheumatology/European League against Rheumatism criteria. Results: Seven patients diagnosed with IgG4‐related disease were included in this study. Women were affected in all analysed cases, with a mean age of 55.4 years. Two patients presented with the clinical involvement of more than one oral and maxillofacial anatomic site. Therefore, our sample comprised nine oral and maxillofacial anatomic sites affected by IgG4‐related disease. The submandibular gland was affected in four cases, the tongue and the parotid gland in two cases each, and the palate in one case. In a few cases, exploratory lower lip biopsy was used as a diagnostic approach. A moderate‐to‐severe lymphoid infiltrate containing plasma cells and lymphocytes, with an increased IgG4/IgG ratio, was common. Treatment varied and steroids were the most frequently used (57.4%). Six patients remained alive, while one died from unknown causes. Conclusion: Although major salivary glands are commonly affected by IgG4‐related disease, the oral cavity can also be involved, and lower lip biopsy may be an auxiliary diagnostic tool. [ABSTRACT FROM AUTHOR]

Background: Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of OM in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection. Aim: To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo‐HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment. Design: Medical data and OM presentation were retrieved retrospectively from all patients younger than 18 years who received allo‐HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters. Results: Forty‐nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM‐free survival rates. Conclusions: A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients. [ABSTRACT FROM AUTHOR]

Background: Hybrid odontogenic lesions combine histopathological characteristics of two or more odontogenic cysts and/or tumours. The aim of this study was to evaluate the available data on hybrid odontogenic lesions (HOL) and to analyse their epidemiological/clinical features and biological behaviour. Methods: An electronic search was done in January 2021 using multiple databases. Eligibility criteria encompassed publications with sufficient clinical and histological information to confirm the tumours' diagnoses. Results: A total of 147 articles were included in this study, comprising 203 cases. Calcifying odontogenic cyst associated with odontoma (COC/OD) (37/18.2%) was the most common HOL. Females were more affected with a mean age of 24.9 years. Lesions presented as asymptomatic swellings, with a mean evolution time of 8.2 months (0.3–96), and mean tumour size of 4.8 cm (0.3–7). Radiographic aspects frequently showed radiolucent (139/68.4%) and unilocular (52/25.6%) images with well‐defined limits (48/23.6%). The lesions mostly affected mandibular pre‐molars (69/34%) and mandibular molars (69/34%) regions. Enucleation (89/43.8%) and surgical excision (59/29%) were the most common treatment modalities. The mean follow‐up time was 33.8 months (0.5–216 months) and recurrences were observed in four cases (1.9%), all of which were central odontogenic fibroma associated with central giant cell granuloma (COF/CGCG). Conclusion: COC/OD is the most common HOL and recurrence is a rare event, being usually associated with the diagnosis of COF/CGCG. [ABSTRACT FROM AUTHOR]

Background: Adenoid ameloblastoma is a rare epithelial neoplasm, histologically characterized by the presence of ameloblastoma‐like features, duct‐like structures, epithelial whorls, and cribriform architecture. Dentinoid material is usually present. Some advocate adenoid ameloblastoma is an ameloblastoma variant. However, there are overlapping features not only with ameloblastoma, but also with adenomatoid odontogenic tumor. Most ameloblastomas are characterized by the presence of BRAF p.V600E mutations and adenomatoid odontogenic tumors harbor signature KRAS mutations. The molecular features of adenoid ameloblastoma remain unknown. Methods: Nine adenoid ameloblastoma cases were screened by TaqMan allele‐specific qPCR to assess BRAF p.V600E, ameloblastoma signature mutation, and KRAS p.G12V and p.G12R, adenomatoid odontogenic tumor signature mutations. Results: BRAF and KRAS mutations were not detected in any of the adenoid ameloblastoma cases. Conclusion: The molecular results support adenoid ameloblastoma as an entity distinct from adenomatoid odontogenic tumor and ameloblastoma. [ABSTRACT FROM AUTHOR]

Senescence is a common denominator in wound healing, fibrosis, and cancer. Although, senescence is transiently antifibrotic, when prolonged, promotes fibrosis and malignant transformation. Eligible studies indexed in MEDLINE, Embase and Web of Science were searched to understand the role of cellular senescence in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation. The senescence‐associated secretory phenotype (SASP) components like IL‐1, IL‐6, and GRO‐α induce double‐strand DNA breaks in keratinocytes and drive genetic instability. SASP derived from myofibroblasts induces epithelial–mesenchymal transition in OSF and facilitates cancer progression. The use of senolytics has been shown to eliminate senescent cells from the areas of fibrosis, thereby preventing malignancy. Naturally occurring agents such as apigenin and kaempferol inhibit SASP. Mechanistic insight into the emerging role of senescence in the pathogenesis of OSF and modalities to inhibit senescence‐associated antiapoptotic pathways as a supplementary therapy to prevent malignant transformation of OSF is underlined. [ABSTRACT FROM AUTHOR]

Background: The aim of the present systematic review was to analyze the available data regarding acinic cell carcinoma of the oral and maxillofacial region.Methods: A search strategy was performed using PubMed, Web of Science, Scopus, and Embase electronic databases.Results: Available data revealed a slight female preference (54.73%) and a mean age at diagnosis of 47.51 ± 19.85 years. The parotid glands (67.72%) were most frequently affected, and most cases were asymptomatic (69.54%). A microcystic histopathological pattern was reported in 21.56% of the cases, and the Periodic acid-Schiff was the staining method most frequently used, after the hematoxylin and eosin staining, in the tumors analyzed. The lesions were mainly treated by surgical removal (72.32%). Recurrence was reported in 81 cases (27.83%) and metastasis in 100 (42.91%). Statistical data analysis revealed that tumors located in major salivary glands and exhibiting high-grade histology were associated with local recurrence (P = .01). In addition, the patients older than 57 years, lesions with bone involvement, the high-grade tumors and the cases with a history of recurrence and metastasis were associated with a lower overall survival (P < .05).Conclusion: By assembling all eligible cases in the literature, the present systematic review determined the most common clinicopathological profile of acinic cell carcinoma and the most relevant prognostic factors in a distinctly representative sample. The survey demonstrated the importance of considering the histopathological grading in order to better define the treatment for each case. [ABSTRACT FROM AUTHOR]

Background: Plasmablastic lymphoma (PBL) is an aggressive neoplasm that commonly develops in HIV‐positive patients, usually affecting the oral cavity. EBV is present in the majority of cases, therefore, playing an important role in the pathogenesis of this neoplasm. Methods: PBL diagnosed from 2000 to 2020 were retrieved from the archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria, South Africa. The patients' clinical information including gender, age, tumour location and HIV status was obtained from the original histopathology request forms. A morphological description was assessed using H&E‐stained slides, with diagnoses confirmed by immunohistochemistry, and EBV detection performed via in situ hybridisation. Results: During the 20 years period investigated, 113 PBL were found. Males outnumbered females (M:F ratio of 3:1), with a median age of 41 years (range 8–62). The gingiva (50 cases or 44.2%) and the palate (23 cases or 20.4%) were the most affected sites. All cases with available information were HIV positive. The tumours were composed of a diffuse proliferation of immunoblasts or plasmablasts in all cases. A starry‐sky pattern, tissue necrosis, cellular pleomorphism and mitotic figures were common microscopic findings. IHC for CD3 and CD20 were negative in all cases, while positivity for CD38, CD138 and MUM1 was observed in 70.2%, 79.2% and 98.9%, respectively. EBV was present in 100% of the cases. Conclusion: PBL is a frequent diagnosis in South Africa, due to the country's HIV burden, where it usually affects the oral cavity and is always associated with EBV infection. [ABSTRACT FROM AUTHOR]

Immunosuppressed patients may be affected by a wide range of lymphoproliferative disorders (LPDs) ranging from self‐limiting disorders to malignant lymphoid proliferations. These LPDs may be associated with systemic immune disorders, develop following organ transplantation or occur in the background of other forms of iatrogenic immunosuppression. Lymphotropic viruses, including Epstein‐Barr virus (EBV) and human herpesvirus‐8 (HHV8), have been associated with the pathogenesis of distinct LPDs. The resulting classification of this group of disorders is very complex and inconsistent, with several new and emerging entities. Consequently, the diagnosis of an LPD, especially in an immunosuppressed patient, and its subsequent clinical management usually represent an important pitfall in daily clinical and pathology work. Therefore, the aim of this review was to use the available literature to describe the clinicopathological features of the most important benign LPDs that may be diagnosed in the head and neck region of immunosuppressed patients. Original clinical and microscopic images were used to illustrate some of these entities. [ABSTRACT FROM AUTHOR]

Background: Hydroa vacciniforme‐like lymphoproliferative disorder (HVLPD) is a chronic Epstein‐Barr virus (EBV)‐positive lymphoproliferative disease which may either present as an indolent condition or progress to a systemic T‐cell lymphoma. Methods: All HVLPD diagnosed over a 10‐year period were retrieved, and clinical data regarding sex, age, oral and systemic manifestations, and clinical follow‐up were obtained. Immunohistochemistry was done in order to characterize the lymphoid cells, and in situ hybridization was used to demonstrate the presence of EBV. Results: Eleven cases were included, with a male predominance and a mean age of 25.1 years. Buccal mucosa and the lips were the most affected oral sites, appearing as painful ulcers. All patients exhibited facial oedema, usually affecting the lips, nose and periorbital region. The clinical course was gradual but progressive, with four patients having fever and 3 showing lymphadenopathies. All cases showed a moderate to severe lymphocytic infiltrate with angiotropism, angiocentricity and epidermotropism. Two cases affecting the lip skin exhibited a periappendageal lymphocytic infiltrate. Few large pleomorphic cells were found, surrounded by smaller and medium‐sized lymphoid cells, as well as reactive plasma cells, macrophages, neutrophils and eosinophils. All lesions exhibited a cytotoxic T‐cell (CD8+) phenotype with a variable proliferative index. All cases were associated with EBV, and all patients died due to complications of the disease. Conclusions: HVLPD is a rare disease that may show oral involvement with a cytotoxic T‐cell phenotype, and is strongly associated with EBV. As shown in this series, HVLPD may show aggressive clinical behaviour. [ABSTRACT FROM AUTHOR]

Background: Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). Methods: Paraffin‐embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed and follow‐up status were retrieved from the pathology reports. Results: Fifty‐two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumours usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5 years of follow‐up was 26.6%. Conclusion: Plasma cell neoplasms are aggressive tumours with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations. [ABSTRACT FROM AUTHOR]

Background: Although uncommon, mature small B‐cell lymphomas may arise in the oral/maxillofacial area and oral pathologists must be aware of the key characteristics of these neoplasms to perform an accurate diagnosis. In this manuscript, we attempted to integrate the currently available data on the clinicopathological features of follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT‐L), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) affecting these anatomical regions. Methods: An updated descriptive literature review was carried out and a detailed electronic search was done in multiple databases to gather all cases affecting the oral/maxillofacial region and palatine tonsils. Results: We observed that MALT‐L was the most frequently reported subtype, followed by FL, MCL, and CLL/SLL. The palate was affected in a high proportion of cases and the most usual clinical presentation was an asymptomatic swelling. MALT‐L and CLL/SLL neoplastic cells were strongly associated with small salivary glands. FL showed no gender preference, while MCL and CLL/SLL were more prevalent in males and MALT‐L in females. Overall, cases were more common in elderly individuals. Patients' treatment and outcome varied, with MCL being the most aggressive neoplasm with a dismal prognosis in comparison to FL and MALT‐L. Conclusion: Despite the poor documentation in many of the cases available, especially regarding the microscopic and molecular features of tumors, this review demonstrated that the oral mature small B‐cell lymphomas investigated share similar clinical presentation, but carry different prognostic significance, demanding an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background: Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma with three variants (endemic, sporadic, and immunodeficiency‐associated), presenting with specific epidemiological and clinical features. Burkitt lymphoma affects the head and neck region (BLHN) in approximately 10% of cases. The aim of this study was to undertake a comparative analysis of the clinicopathologic and immunohistochemical (IHC) features of BLHN diagnosed in patients from Africa, Guatemala, and Brazil. Methods: Cases diagnosed as BLHN were collected from the files of six oral pathology laboratory services (Brazil, South Africa, and Guatemala) and one Brazilian pediatric oncology hospital from 1986 to 2020. Clinicopathological and IHC data, and Epstein‐Barr virus (EBV) status by in situ hybridization data for each case were reviewed and described. Results: Of the 52 cases, BLHN was predominant in pediatric patients [43 (82.69%)] and males [43 (82.69%)], with a mean age of 11.26 ± 9.68 years (range, 1‐39 years). Neck and cervical lymph nodes [14 (26.92%)], and involvement of both maxilla and mandible [8 (15.38%)], were the most common anatomical sites. Clinically, tumor/swelling [40 (31.25%)], cervical lymphadenopathy [14 (10.94%)], pain [12 (9.38%)], and bone destruction [12 (9.38%)] were frequent findings. All cases showed typical morphological characteristics of BL. IHC profiles included positivity for CD20 [52 (100%)], CD10 [38 (79.17%)], Bcl6 [29 (87.88%)], and c‐Myc protein [18 (81.82%)]. EBV was positive in 18 cases (62.07%). The Ki‐67 index ranged from 90 to 100%. Conclusion: The clinicopathological and EBV profile of BLHN in South African, Guatemalan, and Brazilian patients is similar. [ABSTRACT FROM AUTHOR]

Background: CD30 is variably expressed in diffuse large B‐cell lymphoma (DLBCL), but its prognostic potential for the affected patients remains debatable and unclear. Therefore, we aimed to determine the frequency of CD30 expression in DLBCL and its potential for prognostic determination. Methods: An electronic systematic review was performed using multiple databases, followed by a quantitative meta‐analysis to assess the frequency of CD30 expression with positivity cut‐off values of >0% and >20%, and to determine its association with clinicopathological features and patients' survival. Results: Using a cut‐off value >0%, we observed that 3.5%–59.1% of the cases were considered positive for CD30. There was a significant association of the protein expression with a lower number of extra‐nodal sites affected by the neoplasm, with Ann Arbor advanced stage, the absence of B‐symptoms, the lack of MYC and BCL2 translocations, and a lower ECOG performance. Using a cut‐off value >20%, we observed that 2.5%–36.7% of the cases were considered positive for CD30, being significantly associated with a lower number of extra‐nodal sites affected by the neoplasm, Ann Arbor stages III/IV, non‐GCB tumours, the lack of MYC and BCL2 translocations, and a lower ECOG value. CD30 expression was significantly associated with a better survival rate, regardless of what cut‐off parameter was used. Conclusion: Despite variations in the cut‐off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to integrate the available data published on leukaemic infiltration in the oral and maxillofacial region into a comprehensive analysis of its clinical manifestations, imaginological characteristics, management and survival. Materials and methods: An electronic search with no publication date restriction was undertaken in October 2020 in the following databases: PubMed, Web of Science, Scopus and Embase. Overall survival was calculated by survival analysis with the Kaplan‐Meier test. A critical appraisal of included articles was performed using the Joanna Briggs Institute tool. Results: A total of 63 studies including 68 patients were selected for data extraction. The most common haematologic diagnosis was acute myeloid leukaemia (47%). The most affected individuals were 40 to 49 years old (20.9%). The male‐to‐female ratio was 1.2:1. The gingiva was the most affected site (37%). Swelling/mass/oedema (33.7%) and enlargement/hyperplasia/hypertrophy (25.5%) were the main clinical findings. Osteolytic lesions with bone destruction were the main imaginological characteristics among the reported cases. Follow‐up was available for 36 patients. Overall, within the 21‐month follow‐up, the survival probability dropped to 14.3%. Conclusion: A considerable number of studies reported oral manifestations mainly in individuals with the acute form of leukaemia. Children and adults were affected, but the fifth decade of life was the most common. Dentists should be vigilant since these manifestations may be important for a diagnosis and for the monitoring of the treatment response and recurrence of haematological neoplasia. [ABSTRACT FROM AUTHOR]

Objective: Odontogenic keratocyst (OKC) is a benign lesion that tends to recur after surgical treatment. In an attempt to clarify the molecular basis underlining the OKC pathobiology, we aimed to analyze its proteomic profile. Materials and Methods: We compared the proteomic profiles of five OKC and matched normal oral mucosa by using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Then, we performed enrichment analysis and a literature search for the immunoexpression of the proteomics targets. Results: We identified 1,150 proteins and 72 differently expressed proteins (log2 fold change ≥ 1.5; p <.05). Twenty‐seven peptides were exclusively detected in the OKC samples. We found 35 enriched pathways related to cell differentiation and tissue architecture, including keratinocyte differentiation, keratinization, desmosome, and extracellular matrix (ECM) organization and degradation. The immunoexpression information of 11 out of 50 proteins identified in the enriched pathways was obtained. We found the downregulation of four desmosomal proteins (JUP, PKP1, PKP3, and PPL) and upregulation of ECM proteases (MMP‐2, MMP‐9, and cathepsins). Conclusions: Proteomic analysis strengthened the notion that OKC cells have a similar proteomic profile to oral keratinocytes. Contextual investigation of the differentially expressed proteins revealed the deregulation of desmosome proteins and ECM degradation as important alterations in OKC pathobiology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Brain‐derived neurotrophic factor (BDNF) and neurotrophin receptors have been recognized as fundamental regulators of normal brain development, homeostasis, and plasticity. They have also been studied in the behavior of central nervous system tumors. Here, we studied the pattern of BDNF, TrkB and p75NTR immunoexpression in peripheral benign and malignant neural lesions in head and neck. Methods: This cross‐sectional analytical study included 79 cases of head and neck neural lesions. Nineteen cases of traumatic neuromas (TN), 20 cases of granular cell tumors (GCT), 16 cases of neurofibromas (NF), 20 cases of schwannomas (SC), and 4 malignant peripheral nerve sheath tumor (MPNST) were submitted to immunohistochemistry with BDNF, TrkB, and p75NTR antibodies. A semi‐quantitative analysis was performed. Results: The analysis of BDNF demonstrated a high percentage of positive cells in TN, GCT and SC with a decrease in cases of NF and MPNST. TrkB presented a lower significant immunoexpression in GCT in relation to the TN, NF, SC, and MPNST (P <.0001); and TN showed less percentage of positive cell compared to SC (P =.0017). Regarding p75NTR, the percentage of positive cell was significantly reduced in MPNST compared GCT (P =.009), NF (P =.0138) and SC (P =.0069). Also, a decrease in TN compared to GCT (P =.007) was observed. Conclusions: Our results showed the immunoreactivity of BDNF, TrkB, and p75NTR in head and neck peripheral neural lesions. Reduction of BDNF and p75NTR in MPNST might suggest down‐regulation during the acquisition of malignant phenotype. [ABSTRACT FROM AUTHOR]

Objective: In the present study, we aimed to investigate the prognostic value of RUNX1 expression in 76 patients with adenoid cystic carcinoma (ACC). Materials and Methods: All cases were arranged in tissue microarray blocks and submitted to immunohistochemistry against RUNX1. These results were statistically correlated with clinicopathologic features, including age, gender, tumour site, tumour size, lymph node status, AJCC clinical stage, distant metastasis, treatment, recurrences, follow‐up, histologic pattern, vascular and neural invasion, all of which obtained from patient's medical records. Results: RUNX1 was expressed in the nuclei of tumour cells, with a mean of 18.1% of positivity. Nuclear RUNX1 expression was significantly associated with AJCC clinical stage (p <.0001), solid histologic pattern (p <.0001), vascular invasion (p <.0001) and presence of local recurrence (p <.0001). Using univariate and multivariate analyses, RUNX1 nuclear expression was significantly associated with a lower disease‐free survival (p <.0001 and p =.028, respectively) and disease‐specific survival (p <.0001 and p =.018, respectively) rates. Conclusion: In summary, RUNX1 nuclear expression may represent an indicator of unfavourable outcome for patients affected by head and neck ACC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the molecular pathogenesis of implant‐associated peripheral giant cell granuloma (IA‐PGCG). Methods: A convenience sample of 15 IA‐PGCG cases was selected. Hotspot mutations of KRAS, FGFR1, and TRPV4 genes, previously reported in conventional giant cell lesions of the jaws, were investigated by Sanger sequencing. As these mutations could activate MAPK/ERK pathway, the expression of phospho‐ERK1/2 was also evaluated by immunohistochemistry. Results: KRAS mutations were detected in 8/15 (53.4%) samples. Similar to conventional peripheral giant cell granuloma, the KRAS mutations most frequently occurred in codon 146 (p.A146V, n = 3), followed by codon 12 (p.G12A and p.G12D, n = 1 each) and codon 14 (p.V14L, n = 1). Variants of unknown significance (VUS) were also detected in two cases, affecting codons 37 (p.E37K) and 127 (p.T127I). All samples showed wild‐type (WT) sequences for FGFR1 and TRPV4 genes. Consistent with MAPK/ERK pathway activation, all mononuclear cells of the lesion showed strong staining for phospho‐ERK1/2 protein in the immunohistochemical analysis. Conclusions: KRAS mutations and activation of the MAPK‐ERK signaling pathway occur in IA‐PGCG. This is the first study to demonstrate cancer‐associated gene mutations in a non‐neoplastic reactive condition associated with dental implants. [ABSTRACT FROM AUTHOR]

Introduction: Toombak is a form of smokeless tobacco that is not well known in Western Society but is widely used by the Sudanese population and many others in the sub-Sahara region. However, unlike other smokeless tobacco products, information on the carcinogenic potential of toombak is scarce. The present review explored any potential epidemiological association between the use of toombak and oral leukoplakia and oral squamous cell carcinoma (OSCC).Methods: Databases including the Web of Science, SCOPUS, EMBASE and PubMed were searched for literature on the potential association between toombak and oral leukoplakia and OSCC. The search also included grey literature. The search period extended from 1990 to 2018. Following data mining, the study selection was conducted by two reviewers independently.Results: Eight studies that satisfied the inclusion criteria were included. Based on these results, there was a threefoldto sevenfold increased risk of developing the oral leukoplakia and oral squamous cell carcinoma among toombak users compared with non-users.Conclusion: Based on the results of the systematic review, there is a strong epidemiological evidence to suggest toombak to be a major risk factor for both oral leukoplakia and OSCC. Further studies are necessary to evaluate the molecular pathway of toombak-induced oral carcinogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the expression of brain‐derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB), and two downstream targets of this pathway, Akt and ribosomal protein S6 (RPS6), in normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC) and correlate this expression with OSCC patients' outcomes, cell senescence, and "stemness" profile. Materials and Methods: Ten cases of NOM, 32 OL, and 72 primary OSCC were included. Immunohistochemical analysis for BDNF, TrkB, p‐TrkB, p‐Akt, and p‐RPS6 was performed. Cell senescence and stemness profile of OSCC were evaluated through p16 and BMI‐1 immunohistochemical expression, respectively. The slides were scanned into high‐resolution images and quantified through digital analysis. Results: Oral squamous cell carcinoma presented increased expression of BDNF/TrkB/Akt pathway compared to NOM and OL. OSCC diagnosed in advanced clinical stages presented an upregulation of BDNF and p‐TrkB. BDNF and p‐Akt were identified as predictors of poor disease‐specific survival. The increase in stemness profile was correlated with a decrease in p‐TrkB and p‐Akt expression. Conclusions: BDNF/TrkB/Akt pathway is significantly increased in malignant cells from OSCC. Moreover, BDNF and Akt represent biomarkers capable to predict a poor prognosis of OSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: To establish a predictive clinical index of malignancy risk in palatal salivary gland tumors (PSGT). Materials and methods: One hundred cases of PSGT were evaluated. Clinical data were retrieved from the patient's files. Representative clinical photographs of each tumor were evaluated to identify clinical features suggestive of a malignant tumor. Features significantly associated with malignancy were included in a binary logistic regression model. Results: Malignant tumors were more common in the hard palate, in women and in older patients. Features associated with a malignant diagnosis included pain (p =.017), irregular surface (p =.004), bluish/purple coloration (p <.001), ulceration (p =.005), and telangiectasia (p =.015). After multivariate logistic regression, pain (OR: 4.017; 95% CI: 1.198–13.471; p =.024) and color alteration (OR: 7.243; 95% CI: 2.068–25.363; p =.002) were independently associated with malignancy. Including these factors in a predictive index, the proportion of malignant tumors in patients presenting none, one and two factors were 25% (95% CI: 0.13–0.40), 67% (95% CI: 0.48–0.83), and 85% (95% CI: 0.42–0.99), respectively. Conclusion: Pain and color alteration might be independent predictors of malignancy in PSGT, which could support the decision to perform an incisional or excisional biopsy. [ABSTRACT FROM AUTHOR]

Introduction: Transcriptomes in saliva can be used as potential biomarkers for both diagnostic and response to treatment in oral squamous cell carcinoma (OSCC). In this review, we explored their application in this increasingly common disease.Materials and Methods: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 to May 2017 were searched. Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of nine studies were included. Three studies showed increased expression of DUSP1, IL8, IL1B, OAZ1, SAT1, S100P and two showed increased expression of miRNA-31 among study groups compared to normal healthy controls. The sensitivity ranged from 14% to 100%, while the specificity ranged from 38% to 100%. miRNA-27b had the highest AUC (write in full) of 0.9643 and DUSP1 had the minimum AUC of 0.41.Conclusion: Salivary transcriptomics may play an effective role as a robust and non-invasive biomarker sighting tool for the diagnosis and management of OSCC. [ABSTRACT FROM AUTHOR]

The presence of a translocation involving MYB and NFIB genes have been described in adenoid cystic carcinoma (AdCC) from different anatomical regions. However, the exact frequency of this genetic event and its prognostic impact for patient survival remain obscure. The aim of this study was to carry out a systematic review to address the prevalence and the prognostic potential of t(6;9)(MYB‐NFIB) in head and neck AdCC. Quantitative analysis was done to determine the prevalence of the translocation. A total of 1,107 articles were initially retrieved with 36 remaining for data extraction. The prevalence of t(6;9)(MYB‐NFIB) varied significantly (16%–100%), especially due to methodological heterogeneity among studies. A total of 11 studies attempted to determine the prognostic importance of the translocation, but no study found any significant association with survival rates; only three studies observed a significant association with age, sex, tumour location and the presence of recurrences and metastases. The prevalence of t(6;9)(MYB‐NFIB) in head and neck AdCC varies according to the laboratorial methods used, and the best evidence available demonstrates that t(6;9)(MYB‐NFIB) does not seem to be a prognostic determinant. [ABSTRACT FROM AUTHOR]

Background: Oral Lichen Planus is a chronic inflammatory disorder that affects the oral mucosa, with the reticular and erosive forms representing the primary clinical variants of the disease. Previous studies have shown that metabolic alterations may well be involved in the pathogenesis of the disease; however, the molecular mechanisms related to the clinicopathological differences between erosive and reticular forms remain unknown.Methods: A comparative metabolomic analysis was performed on formalin-fixed and paraffin-embedded tissue samples of erosive (n = 6) and reticular (n = 10) oral lichen planus using gas chromatography-mass spectrometry.Results: The metabolomic analysis showed a distinct profile between the two clinical variants. Five metabolites (cyclohexanamine, glycine, mannitol/sorbitol, methyl palmitate and trehalose) were significantly diminished in erosive oral lichen planus as compared to the reticular form.Conclusions: Reticular and erosive forms of oral lichen planus have a distinct metabolic profile. However, further studies using a large number of fresh tissue samples are necessary to confirm this data. [ABSTRACT FROM AUTHOR]

Background: Ameloblastoma is a locally infiltrative, aggressive epithelial odontogenic neoplasm. BRAF-V600E mutation is frequently found in this tumor and has a pivotal role in its pathogenesis, but the consequences of this alteration need to be addressed. An untargeted metabolomics approach was applied to verify whether metabolic disturbances are related to tumor biology and whether BRAF-V600E mutation contributes to these alterations.Methods: Formalin-fixed and paraffin-embedded tissue specimens from thirteen ameloblastoma and six dental follicles were included in this study. BRAF mutational status was determined by competitive allele-specific real-time PCR. Metabolite extracts were analyzed using gas chromatography coupled to mass spectrometry. Univariate and multivariate statistical methods were employed to compare the metabolic profiles of the samples.Results: The abundance of eleven metabolites was significantly higher in ameloblastoma in relation to dental follicles, including amino acids, fatty acids, carbohydrates, inorganic acids, and organoheterocyclic compounds. The presence of BRAF-V600E mutations in ameloblastoma was related to decreased levels of glycerol in comparison with tumors carrying only wild-type alleles of this gene. No metabolic differences were observed between recurrent and primary manifestations of ameloblastoma.Conclusions: Ameloblastoma exhibits a distinct metabolic profile from normal odontogenic epithelium. BRAF-V600E may contribute to metabolic alterations in ameloblastoma. Collectively, our findings suggest that metabolic alterations might play a role in tumor pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma, NOS (DLBCL NOS) is the commonest extranodal non-Hodgkin lymphoma diagnosed in the oral and maxillofacial region. However, few studies are currently available and its prognostic determinants remain undefined.Purpose: To analyse the available data on oral DLBCL NOS and to describe its clinicopathological features, identifying potential prognostic factors.Methods: An electronic systematic search was performed using multiple databases with a specific search strategy in April 2018. All reports describing DLBCL NOS involving the oral cavity and jaw bones with sufficient clinicopathological information were assessed.Results: Sixty-three publications were included in the study, comprising 122 cases. Oral DLBCL NOS was found predominantly in elderly males (61.5%), and most often presented as an asymptomatic swelling of the gingiva. Patients commonly were HIV-negative (36.1%), with few reports describing EBV-positive cases (four cases/3.3%). Only eight cases presented B symptoms and most cases were classified as stage I or II (48.4%). CHOP therapy was the main treatment option (24.5%) and the overall 5-year survival rate achieved 83%. Males and advanced Ann Arbor stage patients presented significantly lower survival rates in the univariate analysis, but no significance was found in the multivariate model.Conclusion: Oral DLBCL NOS is an aggressive malignancy, but with a high survival rate. [ABSTRACT FROM AUTHOR]

Fibrous dysplasia is a non-neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune-Albright syndrome, Jeffe-Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management. [ABSTRACT FROM AUTHOR]

Background: Plasmablastic lymphoma (PBL) is a high-grade lymphoma that often affects the oral cavity of HIV-positive patients; however, its prognostic determinants remain unknown.Purpose: To integrate the available data on oral PBL to determine its clinicopathological features and to identify potential prognostic factors.Methods: An electronic systematic review was performed using multiple databases with a specific search strategy in February 2018. Inclusion criteria comprised cases diagnosed as PBL affecting the oral cavity and gnathic bones with sufficient data to confirm the diagnoses.Results: A total of 70 publications were included, representing 153 cases. Oral PBL predominantly affected HIV-positive males (76.4%). EBV was observed in 63.4% of the cases. The gingiva was the most involved site and the lesion usually presented as an asymptomatic swelling. Most cases were classified as stage I (21.6%), and chemotherapy alone was applied in 28.8% of the cases. There was a significant association between HIV and EBV infections, and cases affecting HIV-negative patients were more common in older individuals. Cumulative survival of the patients achieved 42.4% and 33.5% after 2 and 5 years, respectively. Although there were no statistically significant clinicopathological parameters in the univariate analysis, the multivariate Cox regression model demonstrated that EBV-positive status, presence of B-symptoms, and chemotherapy alone were independent prognostic determinants of a poor prognosis.Conclusion: Oral PBL is an aggressive neoplasm with low survival rates, which is influenced by the presence of EBV, presence of B-symptoms, and with the use of chemotherapy only. [ABSTRACT FROM AUTHOR]

Aim: Langerhans cell histiocytosis (LCH) is an unusual proliferative disorder of bone marrow-derived histiocytes (Langerhans cells) that can produce focal or systemic manifestations. Oral manifestations of LCH can present as single or multiple lesions and can be a challenge in clinical practice. The aim of this paper is to present the clinicopathological features of a series of nine patients with oral involvement.Methods and Results: The patient's age ranged from 2 to 63 years being five males and four females. The most common oral site involvement was the hard-palate mucosa. Ulceration was the main clinical feature. Only two patients showed clearly jawbone involvement. In eight out of nine patients, the diagnosis of LCH was established because of the oral manifestations.Conclusion: The recognition of the clinical features of LCH oral manifestation is important to avoid misdiagnosis and to the establishment of the correct treatment. Thus, dentists can play a vital role in the diagnosis of LCH since oral lesions may be the earliest manifestation and sometimes the only sign of the disease. Furthermore, oral lesions may be the early signs of disease reactivation or a multisystem disease indication. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the commonest subtype of oral cancer, mainly affecting older patients. It used to be a rare disease among individuals younger than 40 years, but recently increased incidences in this age group are being reported worldwide. The pathogenesis of OSCC affecting young patients remains controversial, and the well-known etiological factors for oral cancer, tobacco, and alcohol use are believed to play a minor role in the carcinogenesis of the neoplasm, suggesting that the etiology and the molecular basis of OSCC may differ between younger and older patients. Although several molecular markers and chromosomal abnormalities have been demonstrated to differ between both groups, most of the studies have failed to find significant differences. Moreover, divergent results have also been obtained regarding the presence of high-risk human papillomavirus infection in OSCC of young patients. Given these contradictory results and the limited methodological approaches of the majority of the studies, the exact difference between both age groups remains to be fully established. In this review, we evaluate the available data to establish the current evidence that might support the hypothesis that the molecular basis of OSCC in young patients (especially those under 40 years) differ from the older patients. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have been investigated in different human neoplasms and were shown to play important roles in the pathogenesis of these diseases; however, very few are known regarding their prognostic importance in the context of ameloblastoma. Therefore, the aim of this study was to investigate whether the expression of FGF2 and FGFR1 is associated with ameloblastoma clinical behavior.Methods: Fifty-eight cases of ameloblastoma arranged in tissue microarray were submitted to immunohistochemistry against FGF2 and FGFR1. Clinicopathological parameters regarding sex, age, tumor size, duration and location, treatment, recurrences, radiographic features, cortical disruptions, and follow-up data were obtained from patients' medical records and correlated with the molecules expression. Univariate and multivariate Cox regression analyses were used to investigate the prognostic potential of the biomarkers.Results: Forty-four cases (75.9%) exhibited cytoplasmic positivity for FGF2 in central and peripheral epithelial cells, 46 of 58 (79.3%) showed FGFR1 cytoplasmic positivity predominantly in the columnar peripheral cells, and 43 cases (74.1%) were positive for both. Expression of FGF2 and FGF2 + FGFR1 was associated with tumor recurrences (P = .05). However, univariate and multivariate analyses did not demonstrate a significant influence of FGF2, FGFR1, or FGF2 + FGFR1 in the 5-year disease-free survival (DFS) rate (P = .27, P = .33, and P = .25, respectively).Conclusion: Cytoplasmic expression of FGF2 and FGF2 + FGFR1 is associated with ameloblastoma recurrence, but FGF2 and FGFR1 are not determinants of a lower DFS. [ABSTRACT FROM AUTHOR]

Background: We have evaluated the rationale of existing grading and staging schemes of oral submucous fibrosis (OSMF) based on how they are categorized. A novel classification and staging scheme is proposed.Methods: A total of 300 OSMF patients were evaluated for agreement between functional, clinical, and histopathological staging. Bilateral biopsies were assessed in 25 patients to evaluate for any differences in histopathological staging of OSMF in the same mouth. Extent of clinician agreement for categorized staging data was evaluated using Cohen's weighted kappa analysis. Cross-tabulation was performed on categorical grading data to understand the intercorrelation, and the unweighted kappa analysis was used to assess the bilateral grade agreement. Probabilities of less than 0.05 were considered significant. Data were analyzed using SPSS Statistics (version 25.0, IBM, USA).Results: A low agreement was found between all the stages depicting the independent nature of trismus, clinical features, and histopathological components (K = 0.312, 0.167, 0.152) in OSMF. Following analysis, a three-component classification scheme (TFM classification) was developed that describes the severity of each independently, grouping them using a novel three-tier staging scheme as a guide to the treatment plan.Conclusion: The proposed classification and staging could be useful for effective communication, categorization, and for recording data and prognosis, and for guiding treatment plans. Furthermore, the classification considers OSMF malignant transformation in detail. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), all of them treated with epidermal growth factor (EGF) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 protein.Material and Methods: Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17-AAG and EGF.Results: Treatment with EGF resulted in increased levels of Akt, PTEN and p53 in all cell lineages. The expression of Mdm2 was constant in HN30 and HN6 lineages, while in HN19 showed slightly decreased expression. Under the action 17-AAG, in HN6 and HN19, the expression of PTEN and p53 proteins was suppressed, while Akt and Mdm2 expression was reduced. Finally, in the HN30 cell lineage were absolute absence of expression of Akt, Mdm2 and p53 and decreased expression of PTEN.Conclusion: These data allow us to speculate on the particular utility of 17-AAG for HNSCC treatment through the inhibition of Akt protein expression, especially in the cases that retain the expression of PTEN protein. [ABSTRACT FROM AUTHOR]