Central Pleomorphic Adenoma of Mandible Mimicking Ameloblastoma - A Rare Case Report.

Salivary gland neoplasms account for 3% of all head and neck tumours. Pleomorphic adenoma (PA) is the most common salivary gland tumour that mainly occurs in the parotid gland, followed by minor salivary glands of the oral cavity, however, the occurrence of PA inside the jaw bones is exceedingly rare and very few cases have been reported in the literature. Inside jaw bones these lesions tend to imitate large osteolytic lesions encompass a diagnostic challenge. An exhaustive review of the literature revealed only 10 cases of central pleomorphic adenoma. We present a rare case of primary PA that occurred inside the mandible and was provisionally diagnosed as ameloblastoma.

Exploiting BRAF mutations in the therapeutic approach towards oral and maxillofacial tumors.

Oral and maxillofacial tumors pose a significant clinical challenge due to their tendency to recur, despite advancements in surgical removal techniques. The jaw's intricate structure further complicates treatments and affects patient quality of life. Consequently, emphasis has shifted towards pharmacological interventions, to potentially reduce invasive surgical procedures. One promising approach targets BRAF mutations, specifically the common V600E mutation. BRAF, a critical protein kinase, regulates cell growth and differentiation via the RAS-RAF-MEK-ERK-MAP kinase pathway. A specific nucleotide change at position 1799, swapping Thymine (T) for Adenine (A), results in the V600E mutation, causing unchecked cell growth. This mutation is common in certain oral and maxillofacial tumors like ameloblastoma. A recent neoadjuvant therapy targeting BRAF, involving the use of dabrafenib and trametinib, has showcased a promising, safe, and effective strategy for organ preservation in the treatment of mandibular ameloblastoma. This convergence of molecular insights and targeted therapies holds the key to managing BRAF-mutated oral and maxillofacial tumors effectively, promising improved patient outcomes.

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.

Adenoid ameloblastoma with dentinoid: A rare hybrid odontogenic tumor.

BACKGROUND: Adenoid ameloblastoma with dentinoid (AAD) is a hybrid odontogenic tumor comprising histopathological presentation of ameloblastoma (AM) and adenomatoid odontogenic tumor (AOT) along with extracellular dentinoid material. CASE PRESENTATION: A 35-year-old female reported an asymptomatic swelling in the left mandibular posterior region. Histopathological examination revealed composite features of AM with AOT along with dentinoid material, which stained positively with Van Gieson and trichrome stains. CONCLUSION: The present case report serves to add further to the modicum of literature reports pertaining to AAD, which may gain recognition as a distinct entity in future World Health Organization (WHO) classification of odontogenic tumors.

DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

Comparison of diagnostic methods for detection of BRAFV600E mutation in ameloblastoma.

BACKGROUND: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E-inhibitor therapy The study objective was to identify a sensitive low-cost test for BRAFV600E-positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin-fixed paraffin-embedded tissues for BRAFV600E mutation is a low-cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. METHODS: Tissues from 40 ameloblastoma samples were retrieved from either formalin-fixed paraffin-embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre-fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System-PCR and immunohistochemistry (IHC). RESULTS: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System-PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (𝜒2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64-0.90) and 0.9 (95% CI: 0.75-0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System-PCR detection method were 0.7 (95% CI: 0.53-0.80) and 0.9 (95% CI = 0.67-0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). CONCLUSION: Low-cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E-inhibitor therapies.

Transformation of an odontogenic keratocyst into a solid variant of odontogenic keratocyst/keratoameloblastoma during long­term follow­up: A case report.

Keratoameloblastoma (KA) and solid variant of odontogenic keratocyst (SOKC) are rare odontogenic lesions, and their relationship and differences are unclear. The present study described a case that started as an odontogenic keratocyst (OKC) and transformed to SOKC/KA upon recurrence. Briefly, a 26­year­old man presented with swelling in the right cheek and was referred to the Department of Oral and Maxillofacial surgery, Hiroshima University Hospital (Hiroshima, Japan). At the initial visit, unicystic bone permeation was observed extending from the right canine to the molar, maxillary sinus and nasal cavity. After the biopsy, the patient underwent excisional surgery and was diagnosed with OKC. Thereafter, the lesion recurred six times over a period of 13 years and showed different histopathological features from those of the primary lesion, all consisting of numerous cysts with keratinization, which were diagnosed as SOKC/KA. The Ki­67 positivity rate was ~10%, which was higher than that of the primary lesion, but there was no atypia. Genetic analysis of the recurrent lesion revealed mutations in adenomatous polyposis coli and Kirsten rat sarcoma viral oncogene homolog. This case originated from OKC, and the morphological features of OKC and KA were mixed upon recurrence, supporting the commonality and association between the two. However, multiple mutations different from those of OKC and ameloblastoma were detected, suggesting an association of SOKC/KA with increased proliferative activity and a high recurrence rate.

Utility of BRAF V600E immunohistochemistry in the diagnosis of mandibular ameloblastomas.

Ameloblastoma, odontogenic keratocyst (OKC), and dentigerous cyst (DC) can have similar radiographic and histological appearances. The purpose of this study was to determine the utility of BRAF immunohistochemistry in discerning mandibular ameloblastomas from OKCs and DCs. This retrospective cohort study included patients treated between 1998 and 2018. Inclusion criteria include incisional biopsy-proven mandibular ameloblastoma, OKC, or DC, and sufficient tissue for immunohistochemistry. The primary predictor variable was the type of lesion. The primary outcome variable was the presence/absence of BRAF V600E immunoreactivity. The cohort consisted of 43 patients (19 female, 24 male; mean age 48 ± 17 years). There were 22 ameloblastomas, 11 OKCs, and 10 DCs. Among ameloblastomas, 68.2% (15/22) stained positive for BRAF V600E; no OKC or DC was positive (P < 0.001). By subtype, the majority of the follicular (83.3%), unicystic (83.3%), desmoplastic (66.7%), and acanthomatous (100%) subtypes were positive, but only 33.3% of the plexiform subtype were positive. BRAF immunohistochemistry may be a useful adjunct in the differentiation of ameloblastoma from OKCs and DCs on incisional biopsies. It may be particularly useful for small samples with a prominent cystic component or equivocal histopathology. Mandibular lesions that are BRAF immunohistochemistry positive are unlikely to be DCs or OKCs.

Maxillary Ameloblastoma in an Asiatic Black Bear (Ursus thibetanus).

An approximately 30-year-old intact female Asiatic black bear (Ursus thibetanus) was presented for annual examination and a history of ptyalism. A large 9.5 cm × 5 cm × 5 cm, firm, round mass was identified attached to the hard palate on physical examination. A computed tomography scan was performed, and the heterogeneous, mineral-attenuating mass was seen arising from the right aspect of the palatine bone and extending rostrally to the level of the last maxillary molars, caudally into the oropharynx, and dorsally into the nasal choana. Surgical debulking was performed to remove the portion of the mass within the oral cavity. Histopathologic analysis was consistent with a keratinizing ameloblastoma. Nine months postoperatively, the patient was asymptomatic for the tumor. The patient was euthanized 23-months postoperatively, and severe diffuse pustular dermatitis, growth of the ameloblastoma on the hard palate, and various degenerative and aging changes were noted on necropsy at that time. This is the first report of an ameloblastoma in a member of the Ursidae family.

Epidemiological and Clinicopathological Analysis of Odontogenic Tumors: A 20-Year Study

ABSTRACT Objective: To perform the epidemiological and clinicopathological analyses of odontogenic tumors in Kerman for 20 years. Material and Methods: The present study investigated collected records from pathology departments of the Faculty of Dentistry, Bahonar, and Shafa teaching-medical hospitals for 20 years. Data on odontogenic tumors was recorded based on age, sex, and tumor location in the information forms. The statistical t-test and the Kappa coefficient computer codes were utilized for data analysis. Results: 38 samples of odontogenic tumors were considered in the present study. The mean age of participants was 31.7± 10.3 years. The frequency of tumors was higher in women (63.2%) and in the lower jaw) 78.9%). Among various tumors, ameloblastoma (63.1%) and odontoma (18.4%) were the most common tumors, respectively. The correlation between clinical and histopathologic diagnoses was 71.8% using the kappa coefficient. Conclusion: Ameloblastoma is the most common odontogenic tumor. The incidence of lesions was higher in the mandible, and odontogenic tumors were higher in women. Since the diagnosis of odontogenic tumors is based on radiographic and histologic appearances, clinical physicians and pathologists should collaborate for the definitive diagnosis of the disease.

Giant Mandibular Ameloblastoma with Rare Hypercalcemia: A Case Report and Literature Review.

Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common paraneoplastic syndrome that is commonly observed in patients with malignancies but rarely encountered in patients with benign tumors. Thus far, not many cases of ameloblastoma with hypercalcemia have been reported, and the pathogenic mechanism has not been studied in depth. This paper presents a case report of a 26-year-old male diagnosed with giant ameloblastoma of the mandible, accompanied by rare hypercalcemia. Additionally, a review of the relevant literature is conducted. This patient initially underwent marsupialization, yet this treatment was not effective, which indicated that the selection of the appropriate operation is of prime importance for improving the prognosis of patients with ameloblastoma. The tumor not only failed to shrink but gradually increased in size, accompanied by multiple complications including hypercalcemia, renal dysfunction, anemia, and cachexia. Due to the contradiction between the necessity of tumor resection and the patient's poor systemic condition, we implemented a multi-disciplinary team (MDT) meeting to better evaluate this patient's condition and design an individualized treatment strategy. The patient subsequently received a variety of interventions to improve the general conditions until he could tolerate surgery, and finally underwent the successful resection of giant ameloblastoma and reconstruction with vascularized fibular flap. No tumor recurrence or distance metastasis was observed during 5 years of follow-up. Additionally, the absence of hypercalcemia recurrence was also noted.

Pediatric Odontogenic Tumors.

Odontogenic tumors are rare tumors of the jaws that arise from remnants of the tooth forming apparatus. Some odontogenic tumors demonstrate strong predilection for pediatric patients including the unicystic ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma, ameloblastic fibro-odontoma, odontoma, and primordial odontogenic tumor. In this review, we discuss the clinical, radiographic, histopathologic, and molecular characteristics of select odontogenic tumors that demonstrate pediatric predilection and review management.

Papilliferous Keratoameloblastoma: Systematic review.

Papilliferous keratoameloblastoma (PKA) is a rare entity, and not much is known about its clinicodemographic features or biological nature. This review aimed to provide clarity regarding the characterisation of the demographic, clinical, radiological and histopathological features of PKA. Case reports of PKA were identified through a systematic search across multiple databases. The search yielded a total of 10 cases, half of which were of Indian origin. All the cases invariably occurred in the mandibular posterior region and involved the right side; only one case primarily involved the left side of the mandible. PKA should be considered a variant of the conventional ameloblastoma that is towards the more aggressive end of the spectrum. It tends to occur in older individuals (in their fifth decade or older), with a marked propensity to occur in the right mandibular posterior region. Surgical resection with diligent follow-up is warranted in the treatment of PKA.

Adenoid 'ameloblastoma': Clinicopathological description of 4 additional BRAF-negative cases.

OBJECTIVE: Adenoid ameloblastoma (AA) is an epithelial odontogenic tumor that was recognized as a separate entity in the last odontogenic classification of WHO in 2022. The etiology is unknown, and the pathogenesis remains controversial. The objective of this study is to contribute the clinicopathological features of 4 additional BRAF-negative cases to the existing literature, aiming to enhance the molecular understanding of this unique tumor in the forthcoming classification. MATERIALS AND METHODS: This study consists of a case series of four patients diagnosed with AA. The patients' demographic and clinical information were collected from the universities' medical achieves. Histopathologically, all cases were reexamined according to the latest update of the WHO odontogenic tumor classification. In addition to H&E and immunohistochemical stains, cytogenetics was also evaluated. RESULTS: Well-defined unilocular radiolucent lesions were observed in all cases. Ameloblastoma-like components exhibited reserved nuclear polarity, suprabasal stellate reticulum-like epithelium, duct-like structure, whorls/morules, and cribriform architecture were common features. Variable immunoreactivity to CK7, CK19, CK14, p63, and p40 were determined, and proliferative activity was greater than 15%. The BRAF molecular study revealed no mutations. CONCLUSIONS: When diagnosing AA, the essential histopathological characteristics must be rigorously applied, and a significant portion of the lesion should contain these features. Additionally, despite limited molecular data, since the BRAF mutation commonly observed in ameloblastomas is not present in the majority of AA cases, we propose changing the term "ameloblastoma" to "ameloblastic" and referring to it as "adenoid ameloblastic tumor" in the forthcoming classification.

Metastasising ameloblastoma or ameloblastic carcinoma? A case report with mutation analyses.

BACKGROUND: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis. CASE PRESENTATION: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet. CONCLUSIONS: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses.

Diagnostic significance of NM23 protein in ameloblastoma and ameloblastic carcinoma: An immunohistochemical study.

BACKGROUND: Clinico-histopathologic assessment of patients with ameloblastoma and ameloblastic carcinoma remains the best diagnostic modality for the tumors. However, in cases where the criteria for arriving at a definitive diagnosis are not clearcut, the pathologist is faced with a dilemma and thus an imperative need for adjunct diagnostic methods. OBJECTIVES: To evaluate/compare the immunohistochemical expression of NM23 in classical, borderline (atypical) ameloblastoma and ameloblastic carcinoma and to assess usefulness of NM23 in closing diagnostic gaps between ameloblastoma and ameloblastic carcinoma. METHODS: Twenty-four (24) cases of ameloblastoma, 10 ameloblastoma with classical histopathologic features, 8 with nonclassical histopathology [atypical], and 6 cases of ameloblastic carcinoma were selected from cases seen at the Oral Pathology Laboratory of the Lagos State University College of Medicine, Nigeria. NM23 immunostaining protocol was done on the selected tissue blocks and evaluated using Sinicrope method. Analysis was done using R language. RESULTS: Positive NM23 staining was observed in all cases of ameloblastoma and ameloblastic carcinoma, with more intense staining observed in the stellate reticulum-like areas than in the ameloblast-like areas. Ameloblastic carcinoma stained intensely with NM23 (100%) compared with atypical cases (37.5%) and ameloblastoma (20.0%; p = 0.04). The mean aggregate score was also significantly higher in AC (11 ± 2.4; p = 0.01). The mean aggregate score was also significant amongst growth pattern of ameloblastoma (p = 0 0.02). CONCLUSIONS: The findings in this study reveal the usefulness of NM23 in differentiating ameloblastoma from ameloblastic carcinoma; a more comprehensive study with a larger sample size is recommended to corroborate or refute the findings in this study.

Ameloblastoma uniquístico con patrón plexiforme: revisión de la literatura a propósito de un caso clínico / Unicystic ameloblastoma with a plexiform pattern: literature review regarding a clinical case

En 1827 el médico James William Cusack describió una lesión tumoral expansiva con características clínicas similares al ameloblastoma. Para el 2017 la Organización Mundial de la Salud lo clasificó como un tumor odontogénico benigno de origen epitelial. En la actualidad hemos aceptado la teoría de su etiología asociada con una mutación en el biomarcador BRAF-V600E, donde se presentan claras heterogeneidades extra/intratumorales en el metabolismo de la tumorogénesis; la mutación en BRAF genera cambios en la regulación de la odontogénesis, en conjunto con el gen CDC73 presente en el cromosoma 1 q25-q32, lo que produce un cambio en la proteína parafibromina que inhibe la proliferación celular durante el crecimiento y la división celular, esto afecta en conjunto al gen p53 y su homólogo p63 presentes en el cromosoma 17, por lo que se tiene como resultado la expresión de quistes y tumores dentales como el ameloblastoma. La presente obra muestra el caso clínico de un paciente femenino de 11 años de edad con aumento de volumen en la región submandibular izquierda de 7 × 4 cm, con seis años de evolución; de tal manera que fue diagnosticado con ameloblastoma uniquístico y tratado de forma conservadora mediante enucleación, posteriormente fue valorada anualmente hasta que la paciente cumplió los 18 años de edad (AU)

In 1827, physician James William Cusack described an expansive tumor lesion with clinical characteristics similar to ameloblastoma. For 2017, the World Health Organization classified it as a benign odontogenic tumor of epithelial origin. Currently, we have accepted the theory of its etiology associated with a mutation in the BRAF-V600E biomarker, where there are clear extra/intratumoral heterogeneities in the metabolism of tumorigenesis; the BRAF mutation generates changes in the regulation of odontogenesis, together with the CDC73 gene present on chromosome 1 q25-q32, producing a change in the parafibromin protein that inhibits cell proliferation during cell growth and division, which together it affects the p53 gene and its p63 homolog is present on chromosome 17, resulting in the expression of dental cysts and tumors such as ameloblastoma. This work provides the clinical case of an 11-year-old patient with an increase in volume in the left submandibular region of 7 × 4 cm of 6 years of evolution. Being diagnosed as a unicistic ameloblastoma and treated conservatively by enucleation, it is subsequently evaluated annually until the patient reaches 18 years of age (AU)

Transformation of ameloblastoma to ameloblastic carcinoma in a 10-year-old child.

Ameloblastic carcinoma (AC) is a rare odontogenic malignant epithelial neoplasm of maxillofacial skeleton with a distinct predisposition of the mandible. It can occur in a wide range of age groups, with a sex predilection in males. It can arise either as a de novo lesion or from preexisting ameloblastoma. AC has a high propensity for local recurrence as well as distant metastasis (chiefly lungs), thus requiring an aggressive surgical approach and a strict surveillance. Owing to the rarity of publications describing AC, little is known about this entity in pediatric patients. We report a case of transformation of ameloblastoma into AC in a 10-year-old child.