Depth of invasion of oral squamous cell carcinoma in Nos2-knockout mice correlated to alterations in systemic inflammatory markers following 4NQO treatment.

BACKGROUND: Peripheral blood analysis is a non-invasive and low-cost technique of prognostic value for several diseases, including oral cancer. Considering the role of inducible nitric oxide synthase in tumor-associated inflammation, this study purposed to evaluate the influence of this enzyme on peripheral blood parameters and systemic inflammatory biomarkers during murine oral carcinogenesis. METHODS: A 50 µg/mL solution of 4-nitroquinoleine-N-oxide was provided to 15 C57BL/6J (Nos2+/+ ) and 16 B6.129P2-Nos2tm1Lau /J (Nos2-/- ) for 16 weeks. Animals were followed for 8 weeks after treatment. Blood samples and tongues were collected for hematological and histopathological analyses. Red blood cells, white blood cells, and platelet cell parameters were analyzed. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index were also calculated. The depth of invasion of all carcinomas was measured. RESULTS: Differences were found in several blood parameters. The depth of invasion in Nos2-/- was lower than in Nos2+/+ (p = 0.009), and strong correlations were found between depth of invasion and neutrophil count (ρ = -0.68, p = 0.017), lymphocyte count (ρ = 0.72, p = 0.011), neutrophil-to-lymphocyte ratio (ρ = -0.65, p = 0.025), platelet-to-lymphocyte ratio (ρ = -0.73, p = 0.013), and systemic immune-inflammation index (ρ = -0.67, p = 0.037) in Nos2-/- mice. CONCLUSION: Inducible nitric oxide synthase seems to have an important role in OSCC invasion and progression, which might be associated to alterations in immune-inflammatory cell dynamics evidenced by peripheral blood and systemic inflammatory biomarkers.

OralEpitheliumDB: A Dataset for Oral Epithelial Dysplasia Image Segmentation and Classification.

Early diagnosis of potentially malignant disorders, such as oral epithelial dysplasia, is the most reliable way to prevent oral cancer. Computational algorithms have been used as an auxiliary tool to aid specialists in this process. Usually, experiments are performed on private data, making it difficult to reproduce the results. There are several public datasets of histological images, but studies focused on oral dysplasia images use inaccessible datasets. This prevents the improvement of algorithms aimed at this lesion. This study introduces an annotated public dataset of oral epithelial dysplasia tissue images. The dataset includes 456 images acquired from 30 mouse tongues. The images were categorized among the lesion grades, with nuclear structures manually marked by a trained specialist and validated by a pathologist. Also, experiments were carried out in order to illustrate the potential of the proposed dataset in classification and segmentation processes commonly explored in the literature. Convolutional neural network (CNN) models for semantic and instance segmentation were employed on the images, which were pre-processed with stain normalization methods. Then, the segmented and non-segmented images were classified with CNN architectures and machine learning algorithms. The data obtained through these processes is available in the dataset. The segmentation stage showed the F1-score value of 0.83, obtained with the U-Net model using the ResNet-50 as a backbone. At the classification stage, the most expressive result was achieved with the Random Forest method, with an accuracy value of 94.22%. The results show that the segmentation contributed to the classification results, but studies are needed for the improvement of these stages of automated diagnosis. The original, gold standard, normalized, and segmented images are publicly available and may be used for the improvement of clinical applications of CAD methods on oral epithelial dysplasia tissue images.

Histopathological diagnosis in pediatric stomatology: A 43-year retrospective study of 1,480 cases from a Brazilian institution.

OBJECTIVES: the aim of this study was to analyze the prevalence of histopathological diagnoses in oral biopsied tissues obtained from a Brazilian pediatric population. METHODS: an analytical, cross-sectional retrospective study was performed with biopsy files of patients ≤14 years of age from a Brazilian oral pathology laboratory over a 43-year period. Data included sex, age, location, and diagnoses. The prevalence was calculated by means of relative frequency. Associations between sex, age groups and diagnoses were verified with Pearson's chi-square test. RESULTS: from 19,456 oral biopsies, 1480 (7.6%) were obtained from patients aged ≤14 years. Most children were 10-14 years of age (60.1%) and females (55.1%), with an overall M:F of 1:1.2. Children aged 0-9 years and males had a higher frequency of lesions of the oral mucosa, whilst the 10-14 year age group showed a higher frequency of cysts, odontogenic tumors, and salivary gland lesions. The latter was also significantly higher in females. Samples consisted mostly of soft tissue lesions (53%) obtained from the lower lip (30.7%). Intraosseous lesions showed a slight predilection for the mandible (21.2%). Salivary gland lesions (28.8%) was the most common diagnostic category, followed by reactive lesions (18.8%), and cysts (16.1%). Mucocele (33.5%), dentigerous cyst (6.7%), and fibrous hyperplasia (5.9%) were the top three histopathological diagnoses. Malignant lesions affected only 0.9% of this population. CONCLUSION: our results were similar to other retrospective studies. Due to the low frequency of oral biopsies in children, data on the prevalence of oral pathology in this population might aid in the clinical and histopathologic diagnoses.

A retrospective study of 30 basal cell adenomas of the salivary gland in a Brazilian population and literature review.

PURPOSE: The present study aimed to provide the clinicopathological data of Brazilian patients with basal cell adenoma (BCA). METHODS: Records of BCA cases were retrospectively gathered from the Brazilian National Cancer Institute database between 1996 and 2006. All cases were histopathologically reviewed, and the clinicopathological data were collected from the patients' medical files. In addition, an English literature review about this tumor is also presented. RESULTS: Of 1127 salivary gland tumors identified, 30 were BCAs (2.7%). Women were more affected than men (70.0% vs. 30.0%), and the majority (60.0%) were elderly (> 65 years old). The parotid gland was the most frequent location affected (93.3%), followed by the upper lip (3.3%) and submandibular gland (3.3%). Fine-needle aspiration was the main procedure applied to establish a preoperative diagnosis of tumor; however, the results were not always consistent. Histopathologically, the trabecular pattern was the most common type seen (50.0%) among our BCA samples. Most patients underwent superficial or partial parotidectomy. Frey's syndrome was reported only in one case during the follow-up. No recurrence was noted in the present series. The literature review revealed a total of 213 reported cases of BCA in the period investigated. CONCLUSIONS: This is the first case series of BCA reported in Brazil. As occurred in other previously reported series, the clinicopathological data of BCAs are similar and confirm that this type of tumor is rare, develops predominantly in the parotid gland, frequently affects older women, has an indolent behavior, and the affected patients have an excellent prognosis.

The role of the histones H3K9ac, H3K9me3, HP1γ, and H3K36me3 in oral squamous cell carcinoma loco-regional metastasis and relapse.

Molecular markers with unequivocal significance in predicting cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) has not yet been identified. Histones are DNA-binding proteins that can regulate gene expression, and some studies have shown that such proteins are implicated with tumor development and progression. This study aimed to investigate the expression of some histone modifications in OSCC and their roles in cervical lymph node metastasis. To address this goal, H3K9ac, H3K9me3, HP1γ, and H3K36me3 expression levels were investigated immunohistochemically in a retrospective metastatic and non-metastatic OSCC samples. We analyzed the association between these markers with clinical-pathological data and survival rates. Hyperacetylation of H3K9ac was associated with cervical lymph node metastasis and local relapse. High expression levels of H3K9m3 were related to age and symptomatology. Furthermore, it was also found a statistically significant association between high HP1γ-expressing tumors and tumor size. However, no markers were associated with reduced overall survival rate. Our results suggest that covalent histone modifications contribute to OSCC behavior, and H3K9ac may play a critical role in OSCC-derived cervical lymph node metastasis.

Unsupervised method for normalization of hematoxylin-eosin stain in histological images.

Histological images stained with hematoxylin-eosin are widely used by pathologists for cancer diagnosis. However, these images can have color variations that highly influence the histological image processing techniques. To deal with this potential limitation, normalization methods are useful for color correction. In this paper, a histological image color normalization is presented by considering the biological and hematoxylin-eosin properties. To this end, the stain representation of a reference image was applied in place of the original images representation, allowing the preservation of histological structures. This proposal was evaluated on histological images with great variations of contrast, and both visual and quantitative analyzes yielded promising results.

The importance of inducible nitric oxide synthase and nitrotyrosine as prognostic markers for oral squamous cell carcinoma.

BACKGROUND: The prognosis of human cancer depends on the deregulations of many molecular patterns. In recent years, a great interest in the intracellular signaling mechanisms related to nitric oxide (NO)-induced carcinogenesis has appeared, as one of the most preeminent prognostic markers for many types of neoplasms. In this study, we identify the levels of iNOS and nitrotyrosine in the sample of normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). METHODS: Quantitative polymerase chain reactions (qPCRs) were utilized to detect the NOS2 levels in fresh-frozen tissue samples of NOM (n = 6), OL (n = 20), and OSCC (n = 15). Moreover, the immunohistochemical method was used to examine the levels of iNOS and nitrotyrosine in 85 cases of OSCC (39 cases without metastases and 46 with metastases), 42 cases of OL, and 16 cases of NOM. RESULTS: There are rising tendencies in the iNOS mRNA and protein levels during human oral carcinogenesis. Similar findings were obtained in the nitrotyrosine staining. Furthermore, iNOS and nitrotyrosine immunostaining are associated with several clinical-pathological features of OSCC (site, presence of metastasis, staging, recidivism, and survival). CONCLUSIONS: The NO-signaling pathway plays a vital role in the development and progression of human oral dysplastic and neoplastic diseases. Nitrotyrosine was a significant marker for the discrimination of OSCC prognosis and survival.

Color normalization of faded H&E-stained histological images using spectral matching.

Histological samples stained with hematoxylin-eosin (H&E) are commonly used by pathologists in cancer diagnoses. However, the preparation, digitization, and storage of tissue samples can lead to color variations that produce poor performance when using histological image processing techniques. Thus, normalization methods have been proposed to adjust the color of the image. This can be achieved through the use of a spectral matching technique, where it is first necessary to estimate the H&E representation and the stain concentration in the image pixels by means of the RGB model. This study presents an estimation method for H&E stain representation for the normalization of faded histological samples. This application has been explored only to a limited extent in the literature, but has the capacity to expand the use of faded samples. To achieve this, the normalized images must have a coherent color representation of the H&E stain with no introduction of noise, which was realized by applying the methodology described in this proposal. The estimation method presented here aims to normalize histological samples with different degrees of fading using a combination of fuzzy theory and the Cuckoo search algorithm, and dictionary learning with an initialization method for optimization. In visual and quantitative comparisons of estimates of H&E stain representation from the literature, our proposed method achieved very good results, with a high feature similarity between the original and normalized images.

Computational normalization of H&E-stained histological images: Progress, challenges and future potential.

Different types of cancer can be diagnosed with the analysis of histological samples stained with hematoxylin-eosin (H&E). Through this stain, it is possible to identify the architecture of tissue components and analyze cellular morphological aspects that are essential for cancer diagnosis. However, preparation and digitization of histological samples can lead to color variations that influence the performance of segmentation and classification algorithms in histological image analysis systems. Among the determinant factors of these color variations are different staining time, concentration and pH of the solutions, and the use of different digitization systems. This has motivated the development of normalization algorithms of histological images for their color adjustments. These methods are designed to guarantee that biological samples are not altered and artifacts are not introduced in the images, thus compromising the lesions diagnosis. In this context, normalization techniques are proposed to minimize color variations in histological images, and they are topics covered by important studies in the literature. In this proposal, it is presented a detailed study of the state of art of computational normalization of H&E-stained histological images, highlighting the main contributions and limitations of correlated works. Besides, the evaluation of normalization methods published in the literature are depicted and possible directions for new methods are described.

Odontogenic carcinosarcoma: morphologic and immunohistochemical description of a case.

OBJECTIVES: The goal of this study was to describe an extremely rare case of odontogenic carcinosarcoma and compare the findings with those of a literature review. STUDY DESIGN: The clinical and pathologic data of an odontogenic carcinosarcoma affecting the posterior maxilla of a 42-year-old male patient was described. The lesion was immunostained for cell-cycle, cytokeratin, and mesenchymal markers. A review of literature from 1960 to 2017 was conducted in a search for similar well-documented case reports. Descriptive statistics were calculated to compare clinical and pathologic variables. RESULTS: In the reported case, the percentage of Ki-67-positive epithelial and mesenchymal cells was estimated as 40% and 25%, respectively. Epithelial cells were focally positive for cytokeratin 7, -8, -14, and -18, and diffusely positive for cytokeratin 19, p53, and p16. Mesenchymal cells were strongly positive for desmin, HHF-35, and vimentin. Our review showed that odontogenic carcinosarcoma is diagnosed mostly in the advanced stage. All patients with relapsed tumors had died as a result of the disease. CONCLUSIONS: Very few cases have been reported in the literature supporting that most odontogenic carcinosarcoma develop in the posterior mandible in a wide age range, without gender and racial predilections. Only one case of odontogenic carcinosarcoma in the maxilla other than the one described here has been reported. Until today, the best treatment remains unknown.

Pathologic significance of AKT, mTOR, and GSK3ß proteins in oral squamous cell carcinoma-affected patients.

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3ß activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3ß proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1Thr308, pAKTSer473, GSK3ß, pGSK3ßSer9, and pmTORSer2448 was analyzed by immunohistochemistry. The mean expression of GSK3ß, pGSK3ßSer9, total AKT, and pmTOR2448 was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTORSer2448, and pGSK3ßSer9 expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3ß expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3ß and pGSK3ßSer9 were significantly associated with CLN metastasis, but only GSK3ß remained an independent predictor of CLN metastasis. pGSK3ßSer9 and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3ßSer9 and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3ß itself may drive CLN metastatic spread of OSCC cells.

Evaluation of specific modified histones in lip carcinogenesis.

OBJECTIVE: Histones regulate chromatin density and therefore influence gene expression and cellular proliferation. These properties are modified by methylation, acetylation and phosphorylation of histones. The aim of this study was to investigate the variation of specific modified histones in actinic cheilitis (AC) and squamous cell carcinoma of the lip (SCCL). METHODS: Samples of non-neoplastic tissue of the lip (NNTL, n = 9), AC (n = 33), and SCCL (n = 27) were submitted to immunohistochemistry to detect the modified histones H3K36me3, H3K9ac, H4K12ac, and H3S10 ph. RESULTS: Reactivity for all of the modified histones was significantly decreased from NNTL to AC, but not from AC to SCCL. Dysplasia in AC or histological grade in SCCL were not related to the reactivity of any modified histones. CONCLUSIONS: Histone modifications are related to initial actinic damage, but not to malignant transformation in the lip.

Variation of Energy in Photobiomodulation for the Control of Radiotherapy-Induced Oral Mucositis: A Clinical Study in Head and Neck Cancer Patients.

Oral mucositis (OM) is a frequent and severe adverse effect of therapy against head and neck cancer. Photobiomodulation with the low-power laser is known to be effective against OM, but the diversity of protocols and the possibility of stimulating residual tumor cells are still obstacles. The present study aimed to compare two doses of laser energy delivered to the oral mucosa of patients under oncologic treatment for head and neck cancer, looking for differences in the control of mucositis, as well as in the frequency of tumoral recurrences. Fifty-eight patients undergoing radiotherapy were randomized into two groups, distinguished according to the energy delivered by laser irradiation, namely, 0.25 J and 1.0 J. The groups were compared according to frequency, severity, or duration of OM, as well as the frequency of tumoral recurrences. OM was significantly less frequent in patients receiving 1.0 J of energy, but the groups did not differ regarding severity or duration of OM. Tumoral recurrence also did not vary significantly between the groups. Photobiomodulation with a higher dose of energy (1.0 J versus 0.25 J) is associated with better control of radiotherapy-induced OM and does not significantly increase the risk of neoplastic recurrence.

Oral peripheral nerve sheath tumors: A clinicopathological and immunohistochemical study of 32 cases in a Brazilian population.

BACKGROUND: Oral peripheral nerve sheath tumors (OPNSTs) are reactive or neoplastic diseases that develop from proliferation of the nerve itself or their limiting sheaths. Here we describe the clinicopathologic data of OPNSTs observed in a sample of the Brazilian population and evaluate the expression of molecules associated with neural biology to determine their usefulness in the diagnosis. MATERIAL AND METHODS: Descriptive study of cases diagnosed as OPNSTs, from the Pathology Laboratory at the School of Dentistry/ Federal University of Uberlandia, followed by an immunohistochemical study of S-100, CD57, neurofilament protein (NFP) and epithelial membrane antigen (EMA). RESULTS: OPNSTs comprised 0.27% of all biopsies. There were eight patients with neurofibromas, eight with traumatic neuromas, seven with schwannomas, five with granular cell tumor (GCT), and four with palisaded encapsulated neuromas (PEN). Women were more frequently affected (60.6% of the cases). Tongue and lips prevailed as the most frequent sites. S-100 was reactive in 100% of the cases. Neural fibers evidenced by CD57 reactivity of their Schwann cells were always nested in bundles within neurofibromas and GCT, absent within schwannomas and dispersed within PEN. Reactivity for NFP was limited to axons and then followed the same pattern of CD57, though much less evident. Reactivity for EMA was observed in the capsular tissues and perineurium of nerve fascicles, and absent in parenchymal cells of GCT. CONCLUSIONS: This study showed that OPNSTs are rare, widely benign and often found in tongue and lips. OPNSTs evolve from a common origin to distinct histological patterns, with eventual overlapping in their clinical and morphologic features. The arrangement of reactive residual neural fibers for CD57 can be a useful staining in the differential diagnosis of OPNSTs. Key words:Peripheral nerve sheath tumors. Oral cavity. Differential diagnosis. Immunohistochemistry. CD57 antigens.

Ultrastructural evaluation of gingival connective tissue in hereditary gingival fibromatosis.

OBJECTIVE: To describe the ultrastructural features of hereditary gingival fibromatosis (HGF) in affected family members and compare microscopic findings with normal gingival (NG) tissue. STUDY DESIGN: Gingival tissue samples from nine patients with HGF from five unrelated families were evaluated by transmission electron microscopy. Nine NG tissue samples were used for comparison. RESULTS: Areas containing collagen fibrils forming loops and folds were observed in both groups, whereas oxytalan fibers were frequently identified in the HGF group. The diameter of collagen fibrils and the interfibrillar space among them were more uniform in the NG group than in the HGF group. Fibroblasts were the most common cells found in both the HGF and NG groups and exhibited enlarged, rough endoplasmic reticulum, mitochondria with well-preserved crests, conspicuous nucleoli, and euchromatic chromatin. Other cells, such as mast cells, plasma cells, and macrophages, were also observed. CONCLUSIONS: HGF tissues had ultrastructural characteristics that were very similar to those of NG tissues. Oxytalan fibers were observed more frequently in the HGF samples than in the NG samples. Other studies of HGF in patients from different families should be performed to better understand the pathogenesis of this hereditary condition.

Involvement of oral tissues by AL amyloidosis: a literature review and report of eight new cases.

OBJECTIVE: Amyloidosis is a term used to describe a group of diseases in which there is an extracellular deposition of amorphous fibrillar proteins known as amyloid. The aim of this study was to present clinicopathological data from eight oral amyloidosis-affected patients and a deep review of the literature about the disease. MATERIALS AND METHODS: A retrospective study was conducted based on the records of oral amyloidosis-affected patients diagnosed in our institution between 1978 and 2012. The clinicopathological features and immunohistochemical (IHC) staining with anti-kappa and anti-lambda light chain antibodies were carried out and analyzed. RESULTS: Eight patients were diagnosed with the disease; the tongue and women in their sixth decade of life were mostly affected. All lesions demonstrated apple-green birefringence and immunoreactivity for kappa-light chain, and four cases also showed lambda positivity. According to our series, four cases were diagnosed with localized amyloidosis and four with systemic amyloidosis. Prognosis for the systemic ones was gloomy, but good for the localized ones, which was characterized by a slow pattern of deposition without evolution to systemic involvement. CONCLUSIONS: This study reinforces our knowledge about predilections, outcomes, and the importance of making a correct and quick diagnosis of oral amyloidosis and shows the necessity of more studies detailing oral amyloidosis predilection on a global scale. The importance and utility of IHC in the typing of the biochemical nature of amyloid deposits are becoming increasingly necessary for proper management of the patient. Correct classification of the type of amyloid is important for treatment consequences. CLINICAL RELEVANCE: This article highlights the clinicopathological data of patients with amyloidosis affecting oral tissues and compare these new findings with other worldwide descriptions. Because of its rarity, such data are often unfamiliar to most clinicians and pathologists.

Adenoid ameloblastoma: clinicopathologic description of five cases and systematic review of the current knowledge.

OBJECTIVE: To describe the clinicopathologic and immunohistochemical features of five cases of adenoid ameloblastoma. STUDY DESIGN: Clinicopathologic data were gathered from medical records and compared with those compiled from a systematic review. Slides were also immunohistochemically stained for Ki-67, p16, p53, and cytokeratins (7, 8, 14, 18, and 19). RESULTS: There were 3 males (60%) and 2 (40%) females. The mean age was 44 ± 10 years. Of the five adenoid ameloblastomas, 4 (80%) occurred in the posterior maxilla. Patients typically complained of asymptomatic swelling. All patients received surgical resection as primary therapy; 1 (20%) patient also received adjuvant radiotherapy. Recurrence was diagnosed in all patients. Immunohistochemically, the tumors stained focally positive for CK7, 8, 14, and 18 and diffusely positive for CK-19, p16, and p53. The mean Ki-67-positive cells were 72.4 ± 24.9 positive cells per high-power field (range 53-111). CONCLUSIONS: To our knowledge, this is the largest series of adenoid ameloblastoma reported in the literature. Our data suggest that this entity demonstrates aggressive behavior characterized by a high likelihood of recurrence.

Clear cell odontogenic carcinoma: report of 7 new cases and systematic review of the current knowledge.

OBJECTIVE: The goal of this study is to describe 7 cases of clear cell odontogenic carcinoma among a Brazilian population and compare these data with a systematic review of the English-language literature. STUDY DESIGN: Descriptive statististics were used to compare the clinicopathologic data gathered retrospectively with those compiled from a review. Tumor sections were immunostained for Ki-67, p16, p53, and cytokeratins (CKs) 7, 8, 14, 18, and 19. Log-rank tests were performed for survival analysis. RESULTS: Most cases occurred in the posterior mandible (5/7, 71.4%), and recurrence was diagnosed in all treated patients. Metastatic disease occurred in 2 patients (28.6%). Tumors were focally positive for CKs 7, 8, 14, and 18 and diffusely positive for CK19, p53, and p16. The mean number of Ki-67-positive cells was 35.2 cells/high-power field. Our systematic review provided evidence that tumor size (P = .046), histologic pattern (P = .034), regional metastasis (P = .001), distant metastasis (P = .001), and local recurrence (P = .05) were of significant prognostic value. CONCLUSIONS: This study has contributed to improved characterization of clear cell odontogenic carcinoma, which is an aggressive odontogenic malignant neoplasm diagnosed mainly in the posterior mandible of middle-aged women and typically at an advanced stage. Radical surgical procedures remain the gold standard treatment.

Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours.

The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82 %) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83 %) unicystic, 7/9 (78 %) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36 %) malignant tumours, specifically, 3/8 (38 %) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a secondary genetic event in the ameloblastoma pathogenesis. Our findings support the possibility for personalised, molecular-targeted therapy for ameloblastomas and odontogenic carcinomas harbouring the BRAFV600E mutation.