-
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 -
Biomedical Reports Apr 2024Ameloblastoma (AM) is a prominent benign odontogenic tumor characterized by aggressiveness, likely originating from tooth-generating tissue or the dental follicle (DF)....
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.
PubMed: 38476605
DOI: 10.3892/br.2024.1752 -
Eplasty 2024Ameloblastoma is a rare odontogenic tumor most commonly located within the mandible. These tumors can grow to massive proportions and result in malocclusion. Segmental...
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.
PubMed: 38476514
DOI: No ID Found -
Journal of the American Veterinary... May 2024
PubMed: 38467107
DOI: 10.2460/javma.24.01.0031 -
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 -
Turkish Archives of Pediatrics Mar 2024Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each...
OBJECTIVE
Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each other.
MATERIALS AND METHODS
The demographic characteristics as well as cutaneous and extracutaneous findings of consecutive Gorlin syndrome patients diagnosed during 23 years were evaluated retrospectively. The relationship between palmoplantar pitting and basal cell carcinoma (BCC) in this localization and the relationship between odontogenic keratocysts (OKCs) and epidermoid cysts were investigated.
RESULTS
A total of 30 patients were diagnosed with Gorlin syndrome of whom 36.7% were children. BCC was the most common finding (90%) followed by OKCs (83.3%), skeletal system anomalies (76.7%), and palmoplantar pitting (76.7%). While classical BCC (63.3%) lesions were the predominant clinical subtype among all patients, acrochordon-like or small-sized papular BCCs were seen in 45.4% of pediatric patients. Three patients, 2 of whom were children, had BCC lesions in the palmoplantar region in association with palmoplantar pitting. Epidermoid cysts presenting clinically as solitary (n = 12) or a few nodules (n = 4) without punctum, located more commonly in acral areas (n = 10) were seen in 16 (53.3%) patients of whom 7 were children. Epidermoid cysts were seen in 60% of patients with OKCs, and the relationship between epidermoid cysts and OKCs was not statistically significant (P = .15). Extracutaneous tumors such as medulloblastoma (n = 3), cardiac fibroma (n = 1), and ameloblastoma (n = 1) were also recorded.
CONCLUSION
The awareness of papular or acrochordon-like BCCs, palmoplantar BCCs, and acral epidermoid cysts without punctum may facilitate early diagnosis of Gorlin syndrome in children.
PubMed: 38454226
DOI: 10.5152/TurkArchPediatr.2024.23231