Enrichment of SOX2-Positive Cells in BRAF V600E Mutated and Recurrent Ameloblastoma

Ameloblastoma is the most common benign odontogenic neoplasm, but with an aggressive behavior and a high recurrence rate. Nowadays wide surgical resection is the current recommended treatment, which can cause further loss of function and esthetics. Recent studies point to the stem/progenitor cells as both initiators and propagators of the tumors. Elucidation of the cellular and molecular mechanisms underlying the tumor stem cells is of broad interest for understanding tumorigenesis and for developing effective targeted therapies. SRY related HMG box gene 2 (SOX2) is a transcription factor that plays important roles in development, stem cell renewal, and cancer formation. Few studies have revealed increased SOX2 expression in atypical ameloblastoma and ameloblastic carcinoma. For the development of personalized medicine for ameloblastoma, biomarkers that provide prognostic or predictive information regarding a tumor’s nature or its response to treatment are essential. Thus, in this study, we aimed to study if SOX2-positive cells exist in ameloblastomas and their correlation with the clinicopathologic parameters. Our data suggested BRAF(V600E) mutation might contribute to the expansion of SOX2-positive cells. The identification of BRAF(V600E) mutation and the amplification of SOX2-positive cells in ameloblastomas imply the possible benefit of applying BRAF and SOX2 inhibitors in recurrent and un-resectable ameloblastomas.

Genetic Study of BRAF V600E and SMO L412F Mutations in Japanese Patients with Ameloblastoma

Background and aim: Ameloblastoma is a benign, intraosseous, progressively growing, epithelial, odontogenic neoplasm. BRAF and SMO mutations have been reported in ameloblastoma. In this study, we evaluated BRAF V600E and SMO L412F mutations; and assessed the relationship between BRAF V600E mutant expression and the clinicopathological features in Japanese patients with ameloblastoma. Methods: We examined 24 formalin-fixed paraffin-embedded samples. All specimens were from patients with mandibular ameloblastoma: 20 were conventional ameloblastoma and 4 were unicystic ameloblastoma. The BRAF V600E mutation was assessed by Sanger sequencing and immunohistochemistry, and the SMO L412F mutation was assessed only by Sanger sequencing. Results: Twenty of the 24 (83%) ameloblastoma samples carried the BRAF V600E mutation; 22 of the 24 (92%) samples were immunohistochemically positive for BRAF V600E. However, the SMO L412F mutation was not detected in any of them. The BRAF V600E mutation status did not correlate with the clinicopathological features, such as age, sex, location, method, recurrence, and subtype. Conclusion: BRAF inhibitors could be a potential treatment option for Japanese patients with ameloblastoma, harboring the BRAF V600E mutation.

Innocuous presentation of ameloblastic carcinoma

Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits diverse clinical and radiological presentations. In fact there are several differential diagnoses during histopathological evaluation too. Lack of adequate reports could not establish the predominant demographic, clinical and radiological presentations. For the same reasons, the role of adjuvant radiotherapy and chemotherapy is also unsubstantiated yet. This case discusses the innocuous clinical and radiological presentation of ameloblastic carcinoma in a 55-year-old man where the diagnostic confirmation was achieved through histopathological evaluation. The differential diagnoses, treatment and follow-up details of this case are discussed in light of the previous published case reports and systematic reviews of case reports in an attempt to increase the sensitisation among dentists towards ameloblastic carcinoma.

Effectiveness of the Conservative Surgical Management of the Ameloblastomas: A Cross-Sectional Study

Ameloblastoma is a benign, but locally aggressive odontogenic neoplasm, whose appropriate therapeutic management remains highly debatable. The aim of this study was to evaluate the reliability and effectiveness of the two conservative surgical therapeutic protocols (curettage with peripheral ostectomy only and curettage plus cryotherapy) for the management of ameloblastomas. About 53 cases of the ameloblastomas treated in 9 years were retrospectively analyzed regarding their clinical, histopathologic, radiographic, and therapeutic data. The results and the postoperative complications related to both the therapeutic protocols were also statistically investigated. A slight female preponderance was seen (1.12:1.0) with a mean age of 27.1 years. The posterior mandible was the most affected site and dental involvement was frequently found. Multilocular lesions causing the alterations of the bone cortices were the most common radiographic findings. Recurrences were seen in 9.4% of the cases and although the patients submitted to curettage plus cryotherapy have shown an increased incidence of wound dehiscence, infection, and paresthesia, only bone sequestration proved to be significantly more frequent in this group compared to the patients treated by curettage with peripheral ostectomy only. The incidence of the recurrences following the conservative management is low and cryotherapy use as an adjuvant tool must be rationally considered.

A Case of Ectopic Odontogenic Ghost Cell Tumor: Histogenetic Features of a New Entity

Background: Odontogenic tumors arising from extra-alveolar sites are extremerly rare. Dentinogenic ghost cell tumor (DGCT) is an uncommon odontogenic neoplasm characterized by CTNNB1 mutation, ghost cell appearance, and dentinoid-like calcification. We present a case of an ectopic DGCT arising from a calcifying odontogenic cyst in the floor of the mouth. Case presentation: A 72-year-old man presented with a painless sublingual swelling. Imaging revealed a multi-lobulated, solid-cyst mass on the floor of the mouth. Cytology showed folded epithelial clusters composed of basaloid cells, keratinized material, and dentinoid matrix. Histology also revealed a multi-cystic, cribriform to solid nest. Immunohistochemically, CK19, CK5/6, bcl-2, and p63 were diffuse positive. CTNTTB1 mutation was detected, leading to the final diagnosis of an ectopic DGCT. There was no recurrence during a 6-month follow-up. Conclusion: This is the first report to comprehensively describe the clinicopathological features of an ectopic DGCT of odontogenic origin, developing similarly to that of a true odontogenic DGCT. Accurate diagnosis of this rare entity is necessary to avoid overtreatment.

Diagnostic Utility of Ki-67 for Histopathological Typing of Conventional Ameloblastoma, Proliferative Ameloblastoma and Ameloblastic Carcinoma – A Retrospective Study

BACKGROUND Ameloblastoma is a rare, benign odontogenic neoplasm which is locally aggressive and mostly present with a painless swelling. The enigma about the diagnosis of proliferative ameloblastoma and ameloblastic carcinoma is still a debate because the diagnostic criteria is not standardized or quantified which has a direct correlation on its biological behaviour and prognosis. Despite numerous studies, correlation between the histological patterns of ameloblastoma and tumour behaviour has not been consistently established. The present study was done to compare the expression levels of Ki-67 between conventional ameloblastoma, proliferative ameloblastoma and ameloblastic carcinoma and to assess the usefulness of these markers for diagnostic differentiation. METHODS A retrospective study of total of 18 cases of ameloblastoma were retrieved from the archives of Department of Oral and Maxillofacial Pathology, Saveetha Dental College from 2012 till 2019, which included conventional ameloblastoma, proliferative ameloblastoma and ameloblastic carcinoma. Immunohistochemical (IHC) analysis was done using the marker Ki-67 and labelling index were determined for the same. RESULTS The results of the current study showed that the cellular proliferative activity assessed using Ki-67 in follicular ameloblastoma was (55 %), 4 cases of plexiform ameloblastoma (22 %), 17 % of proliferative ameloblastoma and 6 % of ameloblastic carcinoma showed negative expression. CONCLUSIONS Immunophenotyping using the marker Ki-67 may be a useful tool for histological typing of ameloblastoma. KEY WORDS Ameloblastoma, Ki-67, IHC, Immunophenotyping

Cistos e tumores odontogênicos: estudo retrospectivo dos casos diagnosticados no período de 10 anos em um hospital no sul do Brasil

Introduction: odontogenic lesions (OLs) represent a heterogeneous group of oral and maxillofacial pathologies presenting distinct characteristics. The present study aimed to identify the clinical and pathological characteristics of OLs diagnosed in a southern Brazilian hospital. Materials and methods: a retrospective study was performed to evaluate cases with histopathological diagnosis of OLs identified in the period between 2007 and 2017. The patient's medical records were evaluated in order to obtain the clinical and pathological characteristics and the histopathological diagnosis from each case. Results: a total of 255 cases of OLs were identified. From these, 197 (77%) odontogenic cysts and 58 (23%) odontogenic tumors were surveyed, with only one case (0,39%) of a malignant odontogenic neoplasm. The most prevalent diagnosis were radicular cyst (32.5%) and dentigerous cyst (31.76%), followed by odontogenic keratocyst (10.98%), odontoma (10%) and ameloblastoma (10%). The majority of the cases affected the mandible (53.7%) with a slight preference by female individuals (51%). The mean age was 34±20.53 years old. Discussion: the presented data are in accordance with the literature regarding the rarity of the diagnosis of odontogenic tumors. Conclusion: the present study demonstrated the main clinical and pathological characteristics of OLs diagnosed in a southern Brazilian hospital, contributing to a better understanding of these injuries profiles.

Unusual Variant of Unicystic Ameloblastoma with CEOT-Like Areas: A Rare Case Report with Review of Literature

Ameloblastoma is an epithelial odontogenic neoplasm with clinical and histological diversity. They are locally invasive tumors with 3 clinical variants such as solid, unicystic, and peripheral ameloblastomas, and the unicystic variant constitutes only 13%. Histologically, it shows diverse microscopic patterns that may occur isolated or in combination with other patterns. The granular cell variant accounts for 3.5% of all ameloblastoma cases. The eosinophilic granules seen in the cytoplasm of the tumor are thought to be lysosomes and presumably contribute to the pathogenesis of the tumor. Although such a phenomenon is rare in unicystic ameloblastoma, granular cell differentiation in solid multicystic ameloblastoma is a well-established phenomenon. In this paper, we present a unique case of unicystic ameloblastoma with granular cell differentiation with a brief review.

Ossifying Fibroma of Non-odontogenic Origin: A Fibro-osseous Lesion in the Craniofacial Skeleton to be (Re-)considered

In the cranio-facial skeleton, a heterogeneous group of well characterized fibro-osseous lesions can be distinguished. Whereas fibrous dysplasia can affect any skeletal bone, ossifying fibroma and cemento-osseous dysplasia exclusively develop in the cranio-facial region, with most subtypes restricted to the tooth bearing areas of the jaws. Herein we present a series of 20 fibro-osseous lesions that developed mostly in the frontal bone and in the mandible, presenting as expansile intramedullary tumors with a unique histologic appearance and an indolent clinical course. We provide evidence that these tumors are distinct from the categories included in the WHO classification and are therefore currently unclassifiable. The definition of cemento-ossifying fibroma as an odontogenic neoplasm developing only in close proximity to teeth should be re-considered and incorporate also extragnathic lesions as shown here.

Metastatic mandibular ameloblastoma of the lung ten years after primary resection: A rare case report

Ameloblastoma is a rare odontogenic neoplasm of the jaw. It usually behaves as a benign, slow growing tumour of the oral cavity with a high recurrence rate, especially when it is inadequately resected. A small proportion of ameloblastomas metastasize to distant organs, with lungs representing the most common site of metastatic spread. In this report, we present the case of a middle-aged man with two pulmonary nodules and a history of mandibular ameloblastoma excised 10 years prior to this radiological finding. Following resection and histopathological analysis of the lung lesion, a diagnosis of metastatic ameloblastoma was confirmed. No local recurrence of the primary tumour was identified. At 1-year follow-up, the patient had no evidence of local or metastatic disease.