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Modern Pathology : An Official Journal... Jun 2024Calcifying odontogenic cyst (COC), once called calcifying cystic odontogenic tumor, is classified under the category of odontogenic cysts. However, the proliferative...
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, is classified under the category of odontogenic cysts. However, the proliferative capacity of the lesional epithelium and consistent nuclear β-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 calcifying cystic odontogenic tumor were included in this study. The growth patterns of the lesional epithelium were analyzed histologically in all cases. β-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 β-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 β-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.
Topics: Humans; Female; Male; Odontogenic Cyst, Calcifying; Adult; Wnt Signaling Pathway; Mutation; Middle Aged; beta Catenin; Ameloblastoma; Adolescent; Young Adult; Jaw Neoplasms; Biomarkers, Tumor; Odontogenic Tumors; Aged; Child
PubMed: 38574817
DOI: 10.1016/j.modpat.2024.100484 -
Journal of Stomatology, Oral and... Jun 2024Oral and maxillofacial tumors pose a significant clinical challenge due to their tendency to recur, despite advancements in surgical removal techniques. The jaw's... (Review)
Review
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.
Topics: Humans; Proto-Oncogene Proteins B-raf; Mutation; Ameloblastoma; Imidazoles; Oximes; Pyridones; Pyrimidinones; Antineoplastic Agents; Mouth Neoplasms; Neoadjuvant Therapy; Molecular Targeted Therapy
PubMed: 38556167
DOI: 10.1016/j.jormas.2024.101846 -
Journal of Dentistry (Shiraz, Iran) Mar 2024Periapical cyst and granuloma are inflammatory endodontic lesions. Periapical granuloma usually heals spontaneously after endodontic treatment; however, periapical cyst...
STATEMENT OF THE PROBLEM
Periapical cyst and granuloma are inflammatory endodontic lesions. Periapical granuloma usually heals spontaneously after endodontic treatment; however, periapical cyst mostly needs to be removed via surgical approaches. Although some clinicians believe that microscopic examination of periapical lesions is unnecessary, it is proved that some of them has non-endodontic nature that need critical consideration.
PURPOSE
The purpose of this study was to assess the disagreement between clinico-radiographic and microscopic diagnosis of periapical cysts and granulomas in a major center of oral pathology service in Iran.
MATERIALS AND METHOD
In this retrospective, descriptive cross-sectional study, the archives of the oral and maxillofacial pathology department of Shahid Beheshti University of Medical Sciences served as the source of the material during an 18-year-period for this retrospective, descriptive cross-sectional study. The reports of all patients whose initial clinical diagnosis was a periapical cyst/granuloma were extracted.
RESULTS
In the present study, 474 cases were diagnosed with a periapical cyst/granuloma clinico-radiographically, of which 61 cases (12.86%) received a microscopic diagnosis of a non-endodontic pathology. The most frequent lesion was odontogenic keratocyst (n= 12, 19.67%) followed by infected odontogenic cyst (n= 12, 19.67%). About 21.31% of diagnoses were non-cystic lesions and 4.9% were malignancies. The most odontogenic tumors that were diagnosed as periapical cyst/granuloma in clinico-radiography were the ameloblastoma variants (n= 4, 6.55%).
CONCLUSION
A wide variety of microscopic diagnoses, including aggressive lesions such as ameloblastoma, as well as other malignant lesions was noted in this study. These misdiagnoses can lead to an inappropriate treatment plan. It is important to microscopically examine all lesions removed from the jaw.
PubMed: 38544772
DOI: 10.30476/dentjods.2023.96819.1967 -
BMC Oral Health Mar 2024Ameloblastoma (AM) is the most common benign odontogenic tumor, which is more often detected in the mandible than maxilla, especially the mandibular body and mandibular...
BACKGROUND
Ameloblastoma (AM) is the most common benign odontogenic tumor, which is more often detected in the mandible than maxilla, especially the mandibular body and mandibular angle. Pediatric AM is a rare disease, especially in patients aged 10 and younger. Compared with the mainstream osteotomy and reconstructive surgery for adult ameloblastoma, there is more room for discussion in the treatment of pediatric ameloblastoma. The postoperative functional and psychological influence can not be ignored. Especially for children in the period of growth and development, an osteotomy is often challenging to be accepted by their parents. We report two patients with ameloblastoma under 10 years old who are treated with curettage and fenestration, which is a beneficial method for children with ameloblastoma.
CASE PRESENTATION
We present two cases of classic ameloblastoma in children. We describe in detail the patients' characteristics, treatment processes, and follow-up result. The bone formation and reconstruction in the lesion area after fenestration decompression and curettage are recorded at every clinic review. The surgical details and principles of curettage and decompression are also described and discussed. The two patients have good bone shape recovery and no recurrence.
CONCLUSIONS
Children are in the growth and development period and possess an extremely strong ability of bone formation and reconstruction. Based on the principles of minimally invasive and functional preservation, we believe that curettage combined with decompression can be the first choice for treating AM in children, especially for mandibular lesions.
Topics: Child; Humans; Ameloblastoma; Curettage; Decompression; Mandible; Mandibular Neoplasms
PubMed: 38519948
DOI: 10.1186/s12903-024-04126-8 -
Head and Neck Pathology Mar 2024Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors.... (Observational Study)
Observational Study
BACKGROUND
Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas.
METHODS
This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%.
RESULTS
Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24-73.89), favoring radical treatment.
CONCLUSION
BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.
Topics: Humans; Male; Female; Disease-Free Survival; Ameloblastoma; Proto-Oncogene Proteins B-raf; Syndecan-1; Retrospective Studies; Mutation
PubMed: 38504068
DOI: 10.1007/s12105-024-01621-w -
Shanghai Kou Qiang Yi Xue = Shanghai... Dec 2023To investigate protein and genetic status of BRAF V600E in ameloblastomas, ameloblastic carcinomas and cysts, and to explore if recurrence and malignant transformation...
PURPOSE
To investigate protein and genetic status of BRAF V600E in ameloblastomas, ameloblastic carcinomas and cysts, and to explore if recurrence and malignant transformation of ameloblastomas depends on BRAF status.
METHODS
Twenty cysts, 25 primary ameloblastomas, 25 recurrent ameloblastomas and 8 ameloblastic carcinomas were analysed by immunohistochemistry, and 2 cysts, 5 primary ameloblatomas, 5 recurrent ameloblastomas, 3 atypical ameloblastomas and 6 ameloblastic carcinomas were analysed by quantitative real-time PCR(qPCR). SPSS 26.0 software package was used for data analysis.
RESULTS
There was no correlation between BRAF V600E expression and recurrence. Cysts and carcinomas had lower frequencies of BRAF V600E mutations than ameloblastomas. There was a concordance between positive staining of BRAF V600E protein and BRAF V600E mutation.
CONCLUSIONS
BRAF V600E mutation may be useful in the differential diagnosis of ameloblastomas with cysts and ameloblastic carcinomas. Immunohistochemistry may be a beneficial method to screen for BRAF V600E mutation in ameloblastoma.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Odontogenic Tumors; Cysts; Carcinoma
PubMed: 38494972
DOI: No ID Found -
Journal of Oral Pathology & Medicine :... Apr 2024The 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...
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.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Prospective Studies; Mutation; Cell-Free Nucleic Acids
PubMed: 38494749
DOI: 10.1111/jop.13529 -
The American Journal of Case Reports Mar 2024BACKGROUND Adamantinoma is a rare low-grade malignant bone tumor, usually found in the tibial diaphysis and metaphysis, with histological similarities to mandibular...
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.
Topics: Female; Humans; Young Adult; Adamantinoma; Ameloblastoma; Bone Neoplasms; Indazoles; Pyrimidines; Sulfonamides; Tibia
PubMed: 38486378
DOI: 10.12659/AJCR.941248 -
The British Journal of Oral &... Apr 2024Ameloblastoma (AM) is characterised by local aggressiveness and bone resorption. To our knowledge, the proteomic profile of bone adjacent to AM has not previously been... (Comparative Study)
Comparative Study
Ameloblastoma (AM) is characterised by local aggressiveness and bone resorption. To our knowledge, the proteomic profile of bone adjacent to AM has not previously been explored. We therefore looked at the differential proteins in cancellous bone (CB) adjacent to AM and normal CB from the mandible. CB proteins were extracted, purified, quantified, and analysed by liquid chromatography-mass spectrometry (LC-MS) using samples from five patients with AM. These proteins were further investigated using gene ontology for additional functional annotation and enrichment. Proteins that met the screening requirements of expression difference ploidy > 1.5-fold (upregulation and downregulation) and p < 0.05 were subsequently deemed differential proteins. Immunohistochemical staining was performed to confirm the above findings. Compared with normal mandibular CB, 151 differential proteins were identified in CB adjacent to the mandibular AM. These were mainly linked to cellular catabolic processes, lipid metabolism, and fatty acids (FA) metabolism. LC-MS and immunohistochemistry showed that CD36 was one of the notably decreased proteins in CB bordering the AM compared with normal mandibular CB (p = 0.0066 and p = 0.0095, respectively). CD36 expression in CB correlates with bone remodelling in AM, making CD36 a viable target for therapeutic approaches.
Topics: Humans; Ameloblastoma; Bone Remodeling; Proteomics; CD36 Antigens; Mandibular Neoplasms; Chromatography, Liquid; Cancellous Bone; Lipid Metabolism; Adult; Female; Male; Mandible; Mass Spectrometry; Fatty Acids; Middle Aged; Proteome
PubMed: 38461076
DOI: 10.1016/j.bjoms.2024.01.001 -
The British Journal of Oral &... Apr 2024Odontogenic cysts are bony lesions in the jaws that can reach large sizes. Decompression, a technique that helps in their surgical treatment, aims to reduce their size....
Odontogenic cysts are bony lesions in the jaws that can reach large sizes. Decompression, a technique that helps in their surgical treatment, aims to reduce their size. We aimed to conduct a systematic review of the main types of device used for the decompression of odontogenic cysts and to analyse the indications, types, advantages, and disadvantages of the devices used. We searched PubMed, Science Direct, LILACS, EMBASE, and Web of Science until February 2023, with no time restriction. We considered studies with a minimum of 10 patients published only in English, those that reported cases and case series, randomised clinical trials of the decompression of odontogenic cysts, and the types of devices used during the decompression period. All reported odontogenic cysts had to have been confirmed by biopsy in their respective publications. We found 713 articles in the selected databases. After removing duplicates, 499 remained. After reading the titles and abstracts, we excluded 461 articles so 38 remained. Nine studies were selected for the review, totalling 244 patients. A total of 206 lesions were identified and confirmed by anatomopathological examination: 123 keratocysts, 40 dentigerous cysts, 34 radicular cysts, one cyst of epithelial origin but without specification, and eight unicystic ameloblastomas. Although we did not find out which device is best for the decompression of odontogenic cysts, our findings show that those that are most effective should be as comfortable as possible and should remain in place. They should have stability in the oral cavity and be easy for the patient to clean.
Topics: Humans; Decompression, Surgical; Mouth; Odontogenic Cysts
PubMed: 38458909
DOI: 10.1016/j.bjoms.2023.12.015