Application of machine learning in the preoperative radiomic diagnosis of ameloblastoma and odontogenic keratocyst based on cone-beam CT.

OBJECTIVES: Preoperative diagnosis of oral ameloblastoma (AME) and odontogenic keratocyst (OKC) has been a challenge in dentistry. This study uses radiomics approaches and machine learning (ML) algorithms to characterize cone beam computed tomography (CBCT) image features for the preoperative differential diagnosis of AME and OKC and compares ML algorithms to expert radiologists to validate performance. METHODS: We retrospectively collected the data of 326 patients with AME and OKC, where all diagnoses were confirmed by histopathologic tests. A total of 348 features were selected to train six ML models for differential diagnosis by a five-fold cross-validation. We then compared the performance of ML-based diagnoses to those of radiologists. RESULTS: Among the six ML models, XGBoost was effective in distinguishing AME and OKC in CBCT images, with its classification performance outperforming the other models. The mean precision, recall, accuracy, F1-score, and area under the curve (AUC) were 0.900, 0.807, 0.843, 0.841, and 0.872, respectively. Compared to the diagnostics by radiologists, ML-based radiomic diagnostics performed better. CONCLUSIONS: Radiomic-based ML algorithms allow CBCT images of AME and OKC to be distinguished accurately, facilitating the preoperative differential diagnosis of AME and OKC. ADVANCES IN KNOWLEDGE: ML and radiomic approaches with high-resolution CBCT images provide new insights into the differential diagnosis of AME and OKC.

Calcifying Odontogenic Cyst Demonstrates Recurrent WNT Pathway Mutations and So-Called Adenoid Ameloblastoma-like Histology: Evidence Supporting Its Classification as a Neoplasm.

Calcifying odontogenic cyst (COC), once called calcifying cystic odontogenic tumor (CCOT), is classified under the category of odontogenic cysts. However, the proliferative capacity of the lesional epithelium and consistent nuclear ß-catenin expression raise questions about its current classification. This study aimed to determine whether COC would be better classified as a neoplasm in the histologic and molecular context. Eleven odontogenic lesions diagnosed as COC or CCOT were included in this study. The growth patterns of the lesional epithelium were analyzed histologically in all cases. ß-catenin immunohistochemistry and molecular profiling using Sanger sequencing and whole-exome sequencing were performed in 10 cases. Of the 11 cases studied, histologic features reminiscent of so-called adenoid ameloblastoma were observed in 72.7% (8/11), and small islands of clear cells extended into the wall in 36.4% (4/11). Intraluminal and/or mural epithelial proliferation was found in 72.7% of the cases (8/11). Nuclear ß-catenin expression was observed focally in all 10 cases studied, mainly highlighting epithelial cells forming morules and adjacent to dentinoid. CTNNB1 hotspot mutations were detected in 60.0% of the cases (6/10). All the remaining cases had frameshift mutations in tumor suppressor genes involved in the WNT pathway, including APC and NEDD4L. Recurrent WNT pathway mutations leading to nuclear translocation of ß-catenin and distinct epithelial growth patterns found in COC are the neoplastic features shared by its solid counterpart, dentinogenic ghost cell tumor, supporting its classification as a tumor rather than a cyst.

Intraoral Basal Cell Carcinoma of Soft Palate: A Diagnostic Dilemma and Review of Literature.

Basal cell carcinoma is the most common cancer worldwide. Most of basal cell carcinoma can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, intramucosal BCC is a very rare clinical entity. We hereby present a rare case report of pigmented BCC on soft palate and review the literature of this entity.

A Retrospective Analysis of 129 Ameloblastoma Cases: Clinical and Demographical Trends from a Single Institution.

Ameloblastomas are benign neoplasms of the jaw, but frequently require extensive surgery. The aim of the study was to analyze the demographic and clinicopathological features of ameloblastoma cases at a single Oral and Maxillofacial Surgery group in the United States. STUDY DESIGN: A retrospective chart review of patients evaluated for ameloblastoma between 2010 and 2020 at a single tertiary care center. Age, race, sex, tumor size, tumor location, and histological subtypes were recorded. RESULTS: A total of 129 cases of ameloblastoma were recorded with a mean patient age of 42 ± 18.6 years (range 9-91 years old), male to female ratio 1.08:1. Ameloblastoma presenting in the mandible outnumbered maxilla in primary (118 to 8, respectively) and recurrent cases (8 to 1, respectively). There was a higher prevalence of ameloblastoma in Black patients (61.3%) with mean age of Black patients occurring at 40.5 years and the mean age of White patients occurring at 47.8 years and mean tumor size trended larger in the Black patients (15.7 cm2) compared to White patients (11.8 cm2). CONCLUSION: Data suggests a strong influence of racial factors on the incidence of ameloblastoma, with regards to size, Black patients with ameloblastoma trended higher and more data is needed to clearly elucidate any relationship between the tumor size and race, as other factors may influence the size (such as time to discovery).

L-cysteine contributes to destructive activities of odontogenic cysts/tumor.

BACKGROUND: Odontogenic cysts/tumor can cause severe bone destruction, which affects maxillofacial function and aesthetics. Meanwhile, metabolic reprogramming is an important hallmark of diseases. Changes in metabolic flow affect all aspects of disease, especially bone-related diseases. At present, the researches on pathogenesis of odontogenic cysts/tumor are mainly focused on the level of gene regulation, but the effects of metabolic alterations on odontogenic cysts/tumor have still underexplored. MATERIALS AND METHODS: Imaging analysis was used to evaluate the lesion size of different odontogenic lesions. Tartrate resistant acid phosphatase (TRAP) and immunohistochemistry (IHC) assays were utilized to detect the differences in bone destruction activity in odontogenic cysts and tumors. Furthermore, metabolomics and weighted gene co-expression network analysis (WGCNA) were conducted for the metabolomic features and key metabolite screening, respectively. The effect of ferroptosis inhibition on bone destruction was confirmed by IHC, immunofluorescence, and malondialdehyde colorimetric assay. RESULTS: The bone destruction activity of ameloblastoma (AM) was the strongest and the weakest in odontogenic cysts (OC). High-throughput targeted metabolomics was used to map the metabolomic profiles of OC, odontogenic keratocyst (OKC) and AM. WGCNA and differential analysis identified L-cysteine in OKC and AM. Cystathionine γ-lyase (CTH) was further screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The functions of L-cysteine were further validated. Finally, we confirmed that CTH affected destructive activities by regulating the sensitivity of epithelial cells to ferroptosis. CONCLUSION: High-throughput targeted metabolomics performed on diseased tissue confirmed the unique alteration of metabolic profiles in OKC and AM. CTH and its metabolite L-cysteine are the key factors regulating destructive activities.

Expression of Calretinin Expression in Odontogenic Cysts and Odontogenic Tumors - Original Research.

Aim: The present study was conducted for assessing variability in calretinin expression among odontogenic cysts as well as tumor cases. Materials and Methods: Fifteen cases were included in the present research consisting of cases like - dentigerous cyst, odontogenic keratocyst, apical radicular cyst along with tumors like ameloblastoma, ameloblastic carcinoma, adenomatoid odontogenic tumor. Calretinin antibody was used for immunohistochemical staining. The amount of expression of this calretinin was statistically analyzed with the help of Chi-square test where P < 0.05 was considered noteworthy statistically. Results: Most cases of ameloblastomas were highly positive for calretinin expression as compared to other cysts and tumors. Therefore, the correlation of this variation of expression of calretinin was statistically noteworthy (P = 0.00). Conclusion: In this study, we concluded that for ameloblastomas, calretinin can be a specific marker immunohistochemically and can help in identifying the amount of aggressive spread of various odontogenic tumors.

An Unusual Case Report of Unicystic Ameloblastoma of the Mandible.

There are plenty of benign lesions that can result in swelling of the mandible, and these can be classified as odontogenic and non-odontogenic lesions. Among the categories of odontogenic lesion, ameloblastoma is the most occurring lesion that takes origin from the epithelial cellular elements and dental tissues in their different stages of development. Ameloblastoma is the most serious odontogenic neoplasm due to its prevalence and clinical characteristics. Ameloblastoma is a broad class which encompasses 80% of solid multicystic type of ameloblastoma with unicystic ameloblastoma (UA) variant included as vital clinicopathological form claiming the rest 20% along with peripheral ameloblastoma variant. UA refers to cystic lesions that seem like jaw cysts clinically, radiographically, or grossly but are lined by typical ameloblastomatous epithelium, with or without luminal and/or mural tumor development, on histologic investigation. Around 5-15% of all ameloblastic lesions do not have a propensity to metastasis, and this is UA. Unicystic mural form, although slow growing overall, is very invasive locally and has a high recurrence rate. As UA tumors show very close features with dentigerous cyst, a very sharp differential diagnosis protocol need to be executed to exclude the other unicystic odontogenic lesions considering the clinical, radiological, and biological characteristics along with proper follow-up and seeing any recurrence of the lesion taking place. Here, we report the case of a twenty-one year male patient with UA of the mandible and review of the literature.

Primary Mandibular Tuberculous Osteomyelitis Mimicking Ameloblastoma: A Case Report and Literature Review of Mandibular Tuberculous Osteomyelitis.

Primary tuberculous osteomyelitis involving the mandible represents less than 2% of skeletal locations. In this paper, we report a case of mandibular tuberculosis (TB) detected after histopathological analysis of the surgically resected specimen during surgical management of a suspected case of ameloblastoma. A 14-year-old male patient presented to us with history of right-sided chin swelling. The clinical examination revealed a swelling, involving right body and parasymphysis of mandible, measuring approximately 6 cm in length and 2 cm in width, extending from right lateral incisor till the first molar. Radiological scans revealed a large multiloculated osteolytic expansive lesion measuring 52 × 20 × 18 mm. Excision of the lesion was performed and reconstruction was done with iliac bone grafting. The histopathological findings revealed a granulomatous lesion, suggestive of tuberculous osteomyelitis. The patient was successfully treated with standard multidrug therapy. One year after completion of therapy, there were no signs of recurrence. Primary mandibular TB is an extremely rare entity. Its clinical presentation is not specific. Radiologically, TB has no characteristic appearance. The positive diagnosis is based on histology. Primary mandibular TB is rare and should be kept among differential diagnoses in susceptible population and in endemic areas.

Malignant transformation of primary ameloblastoma of skull: case report and review of current literature.

Background: Since 1964, there has been a scarcity of reported cases of primary ameloblastoma (AM) or ameloblastic carcinoma (AMCa) of the skull. The clinical presentation and distinctive features of this uncommon condition at specific anatomical sites remain unclear. We report a case of malignant transformation of a primary AM of the skull situated in the frontal-temporal-parietal region and highlight its similarities to other cases reported in the literature. Clinical presentation: A 53-year-old female patient presented with a 20-day history of headaches and bilateral lower limb weakness for 10 days. Physical examination revealed slow and unsteady gait. An occupying lesion was observed in the right frontal-temporal-parietal region of the skull on the Cranial imaging. A right cranial bone tumor margin expansion resection was performed. The patient's motor functions recovered normally after surgery. Postoperative imaging examinations showed10 tumor resection. Follow-up imaging examinations showed tumor recurrence. The patient underwent resection of the recurrent tumor. Postoperative pathological analysis revealed malignant transformation of the AM.Follow-up imaging examinations showed tumor recurrence again. The patient was admitted for stereotactic radiotherapy. Follow-up imaging examinations demonstrated no evidence of tumor recurrence and subsequent chest CT revealed no signs of metastasis. Conclusion: Primary AM or AMCa of the skull is increasingly being described in the literature, but detailed reports on the malignant transformation of primary AM of the skull are lacking. The pathogenesis of this condition remains unclear. Aggressive treatment and close follow-up may be crucial for preventing disease recurrence and malignant transformation.

Desmoplastic histological subtype of ameloblastoma in 16 dogs.

Ameloblastoma in dogs most often has a highly conserved acanthomatous cell morphology and is recognized as canine acanthomatous ameloblastoma (CAA) while conventional ameloblastoma (CA) makes up a smaller yet morphologically diverse group of epithelial odontogenic tumors. In humans, a rare desmoplastic histological subtype has distinctive clinical, radiological, and microscopic features. Desmoplastic ameloblastoma (DA) has not previously been described in dogs, although it has been rarely referenced in the veterinary literature. This is the first thorough description of a case series of DA in dogs and describes clinical presentation, diagnostic imaging findings, histopathological features for diagnosis, and treatment outcome. Clinically, DA most often presents as a mass or swelling in the rostral mandible or maxilla of middle age to older dogs. On diagnostic imaging, the lesion has a radiolucent or mixed pattern with well-defined borders and variable loculation. As a solid, fibrous tumor with obscured odontogenic epithelium, DA is challenging to diagnose histologically and can mimic several other oral tumors, both benign and malignant. As an ameloblastoma, the biological behavior of DA is locally destructive yet benign and prognosis is favorable following surgical excision.

Surgical Resection and Reconstruction of Ameloblastoma: A 13-Year Retrospective Review.

BACKGROUND: Ameloblastoma is a locally aggressive, benign tumor presenting in the maxilla and mandible prone to recurrence. Resection greatly limits recurrence; however, reconstruction becomes critical to preserve patients' functionality and esthetics. PURPOSE: The aim of this study was to describe surgical resection and reconstructive approaches in the treatment of ameloblastoma and compare clinical outcomes to conservative methods of treatment. STUDY DESIGN, SETTING, SAMPLE: A retrospective case series was completed through analysis of patient records. The study population was composed of patients treated for ameloblastoma at the Royal Brisbane Hospital (Queensland, Australia) in the Oral and Maxillofacial Surgery Unit from January 1, 2008, to December 31, 2020. Patients without histological confirmation of intraosseous ameloblastoma were excluded from the study sample. PREDICTOR VARIABLE: Not applicable. Main Outcome Variable(s): The primary outcome variable was time to recurrence. Secondary outcome variables included any surgical complications incurred. COVARIATES: The covariate variables collected included age at diagnosis/treatment, gender, ethnicity, location of lesion and site(s) of involvement, tumor extent, alveolar expansion, histopathological growth pattern, and soft tissue involvement. ANALYSES: Descriptive statistics were computed for each study variable. RESULTS: A total of 48 cases of histologically confirmed ameloblastoma were identified (41 mandibular, 7 maxillary) involving 50 excisional operations (44 resections, 6 enucleations). Of these cases, 44 were followed up > 12 months, with a mean length of follow-up time of 65.6 months. No recurrence was detected for resected lesions. One enucleated lesion recurred at 25 months. Thirty-seven reconstructive procedures were undertaken, including 32 immediate free flaps. All reconstructive flaps and grafts survived, and no major complications were recorded. CONCLUSION AND RELEVANCE: Resection of ameloblastoma limits recurrence and should be considered curative. Immediate microvascular free flap reconstruction of maxillary and mandibular defects from resection of ameloblastoma is safe and predictable.

Unusual Association of Calcifying Cystic Odontogenic Tumor with Compound Odontoma and Ameloblastoma: Case Report and Review of the Literature.

Calcifying cystic odontogenic tumor (CCOT) is a rare odontogenic cyst accounts for <2% of all odontogenic cysts. Simple unicystic CCOT is commonly encountered accounts for 65%, whereas other forms of CCOT are <3%. CCOT is associated with two or more odontogenic tumors, it is called combined odontogenic lesions or hybrid lesions. The aim of the present article is to report a rare case of CCOT and highlighting the clinical feature and treatment aspects of combined lesions. A 25-year-old female complained of pain and swelling in the left maxilla for 6 months. Examination revealed diffuse swelling in the maxilla, firm in consistency, and tender on palpation. Panoramic radiograph showed impacted canine with multiple radiopaque structures and well-defined lesion in the maxillary sinus. The lesion was surgically removed and histopathologically diagnosed as CCOT with compound odontoma and ameloblastoma. Pub Med database search from 1978 to June 2020 revealed only three case reports of combined odontogenic tumors associated with CCOT.

Cholesterol Granuloma From a Developmental Odontogenic Cyst: A Report of a Rare Case and a Literature Review.

Dentigerous cysts are the second most common developmental odontogenic cysts that develop around the crown of unerrupted teeth with the maxillary canine region being one of the common sites of occurrence. The cystic lining of this lesion has been shown to develop into ameloblastoma, Muco epidermoid carcinoma, and squamous cell carcinomas. However, the development of cholesterol granuloma (CG) in the cystic lining of a dentigerous cyst is extremely rare. CG is a histological observation distinguished by the presence of a conglomeration of connective tissue and granulation tissue. The condition is predominantly seen in the field of otolaryngology, with very few cases reported in the maxillofacial region, most of which are associated with the maxillary sinus. This article presents the findings of a CG in a 39-year-old male patient that developed within the dentigerous cyst and discusses the possible etiopathogenesis, surgical management, and histological presentation.

It was not possible to detect BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma: A diagnostic accuracy study.

BACKGROUND: The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma. METHODS: This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated. RESULTS: Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%. CONCLUSION: Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.

Virtual Surgical Planning in Condyle Reconstruction of Posterior Mandibulectomy Defects.

Background: Ameloblastoma is a rare odontogenic tumor most commonly located within the mandible. These tumors can grow to massive proportions and result in malocclusion. Segmental mandibulectomy and reconstruction with an osteocutaneous free flap are frequently required. Virtual surgical planning (VSP) aids the surgeon in creating precise anatomic reconstruction when there is preoperative malocclusion due to tumor size. In this study we seek to further examine reconstruction of posterior mandibulectomy defects inclusive of condylar resection. Methods: Retrospective review of patients treated for giant ameloblastoma (tumor >4 cm) was examined; 3 patients with posterior tumors requiring ramus and condylar resection were included. Reconstruction in all patients was performed using fibula free flaps and VSP custom-made mandibular reconstruction plates. In these patients the reconstructed ramus was shortened and precise contouring done with a burr to recreate the native condylar surface. Intermaxillary fixation was used to maintain occlusion for 1 month postoperatively. Inferior alveolar nerve repair with allograft and nerve connectors was performed for all 3 patients. Results: All patients underwent successful mandibular reconstruction with preservation of mandibular function and improved occlusion postoperatively. Inferior alveolar nerve repair using nerve allograft allowed for neurosensory recovery in the mandibular division of trigeminal nerve distribution in 2 of the 3 patients. Conclusions: Giant ameloblastoma involving the mandibular condyle can be successfully treated with the fibula free flap utilizing mandible reconstruction plates and VSP. This technique allows for excellent restoration of occlusion and neurosensory recovery when paired with reconstruction of the inferior alveolar nerve at time of reconstruction.

Exploring protein profiles and hub genes in ameloblastoma.

Ameloblastoma (AM) is a prominent benign odontogenic tumor characterized by aggressiveness, likely originating from tooth-generating tissue or the dental follicle (DF). However, proteomic distinctions between AM and DF remain unclear. In the present study, the aim was to identify the distinction between AM and DF in terms of their proteome and to determine the associated hub genes. Shotgun proteomics was used to compare the proteomes of seven fresh-frozen AM tissues and five DF tissues. Differentially expressed proteins (DEPs) were quantified and subsequently analyzed through Gene Ontology-based functional analysis, protein-protein interaction (PPI) analysis and hub gene identification. Among 7,550 DEPs, 520 and 216 were exclusive to AM and DF, respectively. Significant biological pathways included histone H2A monoubiquitination and actin filament-based movement in AM, as well as pro-B cell differentiation in DF. According to PPI analysis, the top-ranked upregulated hub genes were ubiquitin C (UBC), breast cancer gene 1 (BRCA1), lymphocyte cell-specific protein-tyrosine kinase (LCK), Janus kinase 1 and ATR serine/threonine kinase, whereas the top-ranked downregulated hub genes were UBC, protein kinase, DNA-activated, catalytic subunit (PRKDC), V-Myc avian myelocytomatosis viral oncogene homolog (MYC), tumor protein P53 and P21 (RAC1) activated kinase 1. When combining upregulated and downregulated genes, UBC exhibited the highest degree and betweenness values, followed by MYC, BRCA1, PRKDC, embryonic lethal, abnormal vision, Drosophila, homolog-like 1, myosin heavy chain 9, amyloid beta precursor protein, telomeric repeat binding factor 2, LCK and filamin A. In summary, these findings contributed to the knowledge on AM protein profiles, potentially aiding future research regarding AM etiopathogenesis and leading to AM prevention and treatment.

Rare Case of Recurrent Adamantinoma of the Tibia: Limited Efficacy of Pazopanib as a Standalone Treatment.

BACKGROUND Adamantinoma is a rare low-grade malignant bone tumor, usually found in the tibial diaphysis and metaphysis, with histological similarities to mandibular ameloblastoma. The most effective treatment of recurrent adamantinoma is not yet clear. This report is of a 22-year-old woman with recurrent tibial adamantinoma treated with the tyrosine kinase inhibitor pazopanib. CASE REPORT We report the case of a 22-year-old woman who was referred to our center for a suspicious bone lesion in the right tibia. Bone biopsy findings were consistent with an adamantinoma. En bloc resection was completed successfully, with no postoperative complications. Five years later, a positive emission tomography scan revealed mildly increased tracer uptake near the area of the previous lesion and in the right inguinal lymph node. Biopsies of the lesion and inguinal lymph node confirmed recurrence of the adamantinoma. Due to abdominal and pelvic metastasis, the patient underwent surgical debulking, along with an appendectomy, right salpingo-oophorectomy, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Subsequently, the patient was placed on pazopanib for 4 months; however, her tumor continued to worsen after 4 months of chemotherapy. Currently, the patient is receiving gemcitabine and docetaxel as second-line medical therapy. CONCLUSIONS This report showed that pazopanib as standalone treatment does not appear to have promising role on patient outcomes. To the best of our knowledge, this is the second report of pazopanib in the treatment of adamantinoma.