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Indian Journal of Dental Research :... 2022Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign... (Review)
Review
Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign ameloblastomas to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of ameloblastoma and BRAF V600E mutation in ameloblastoma. An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, EBSCO, and Web of Science for eligible studies published between 1975 and 2021. The systematic review is registered with INPLASY (INPLASY202260018). The review included 2 case series and 17 case reports. The histopathological type, anatomic location, expression of BRAF mutation, additional mutations, and molecular-targeted therapies of the 19 reviewed articles were summarized and tabulated. Interestingly, the majority of the primary site of ameloblastoma was located in the mandible (80.9%) compared to the maxilla (17%). The tumour size was reported in nine of the included studies. Most of the included studies in the review exhibited ameloblastoma with BRAF V600E mutations and responded to molecular-targeted therapies. Molecular therapies employing BRAF and/or MEK inhibitors in ameloblastoma with BRAF V600E mutations proved to be an appropriate treatment based on the limited available evidence. It is essential further to deepen our understanding at the clinical and molecular level to enhance the precision of management of ameloblastoma.
Topics: Humans; Ameloblastoma; Molecular Targeted Therapy; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 36656197
DOI: 10.4103/ijdr.ijdr_456_22 -
Cancers Jun 2024Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in... (Review)
Review
Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies.
PubMed: 38927880
DOI: 10.3390/cancers16122174 -
Journal of Oral Pathology & Medicine :... Aug 2022To investigate and compare the demographic data, occurrence of recurrence and metastasis, and survival prognosis between ameloblastic carcinoma (AC) and metastasizing... (Review)
Review
PURPOSE
To investigate and compare the demographic data, occurrence of recurrence and metastasis, and survival prognosis between ameloblastic carcinoma (AC) and metastasizing ameloblastoma (MA), based on appropriate and currently accepted eligible diagnostic criteria, in a systematic review of the literature.
METHODS
An electronic search was undertaken, last updated in December 2021. Eligibility criteria included publications having enough clinicopathological information to confirm the diagnosis of these tumors.
RESULTS
Seventy-seven publications reporting 85 ACs and 43 MAs were included. Both tumors were more frequent in mandible and showed different clinical profiles regarding patients' sex and age. There was no difference in the estimated cumulative survival between patients diagnosed with these tumors. Metastases mainly affected the lungs, followed by cervical lymph nodes. The mean time between the first metastasis and the last follow-up was higher for MA (p = 0.021). In addition, MA patients remained alive longer than AC patients after the first metastasis diagnosis (p = 0.041). Considering only the cases that metastasized, a higher ratio of AC patients died in comparison to MA patients (p = 0.003). The occurrence of recurrence was associated with a conservative primary treatment with both AC (p < 0.001) and MA tumors (p = 0.017). Multiple recurrent events were associated with conservative primary therapies with MA (p < 0.001) but not with AC (p = 0.121).
CONCLUSION
In addition to some demographic differences, ACs that metastasize present a worse prognosis than MA. As conservative procedures are associated with multiple recurrent events, this treatment modality should be avoided for both tumors.
Topics: Ameloblastoma; Carcinoma; Humans; Mandible; Mandibular Neoplasms; Odontogenic Tumors
PubMed: 35822408
DOI: 10.1111/jop.13334 -
Journal of Stomatology, Oral and... Apr 2020Odontogenic lesions have been described in several syndromes. Despite multiple reports of ameloblastoma's association with various syndromes, it has not been added to...
Odontogenic lesions have been described in several syndromes. Despite multiple reports of ameloblastoma's association with various syndromes, it has not been added to the diagnostic criteria for any syndrome. Thus, the aim of this systematic review was gathering such cases' data. An electronic search in PubMed Central's database was performed. The search strategy was limited to human studies (case reports and case series), full-text English articles published from first of January 1975 until the end of 2018. Irrelevant articles or articles with inadequate information were omitted. Associated syndrome, patients' age and sex, lesions' location, radiographic features, and treatment modality were collected and analyzed. Ameloblastoma was reported in association with Gorlin syndrome (6 cases), epidermal nevus syndrome (2 cases), Gardner syndrome (2 cases), Simpson-Golabi-Behmel syndrome (1 case), and Williams syndrome (1 case). The commonest associated syndrome was Gorlin syndrome (50%) with maxillary and female predilections. Both cases of epidermal nevus syndrome (ENS) were female with mandibular involvement. In syndromes that odontogenic lesions are one of the diagnostic criteria, it is important to rule out ameloblastic changes. Although the relationship between ameloblastoma and these syndromes is not well known, any related information may be helpful in understanding the pathogenesis and the nature of this neoplasm.
Topics: Ameloblastoma; Basal Cell Nevus Syndrome; Female; Gardner Syndrome; Gigantism; Humans; Mandible
PubMed: 31336213
DOI: 10.1016/j.jormas.2019.07.010 -
Frontiers in Oral Health 2021To perform a comprehensive and systematic critical appraisal of the genetic alterations reported to be present in adenomatoid odontogenic tumor (AOT) compared to...
To perform a comprehensive and systematic critical appraisal of the genetic alterations reported to be present in adenomatoid odontogenic tumor (AOT) compared to ameloblastoma (AM), to aid in the understanding in their development and different behavior. An electronic search was conducted in PubMed, Scopus, and Web of Science during March 2021. Eligibility criteria included publications on humans which included genetic analysis of AOT or AM. A total of 43 articles reporting 59 AOTs and 680 AMs were included. Different genomic techniques were used, including whole-exome sequencing, direct sequencing, targeted next-generation sequencing panels and TaqMan allele-specific qPCR. Somatic mutations affecting were identified in 75.9% of all AOTs, mainly G12V; whereas a 71% of the AMs harbored mutations, mainly V600E. The available genetic data reports that AOTs and AM harbor somatic mutations in well-known oncogenes, being KRAS G12V/R and BRAFV600E mutations the most common, respectively. The relatively high frequency of ameloblastoma compared to other odontogenic tumors, such as AOT, has facilitated the performance of different sequencing techniques, allowing the discovery of different mutational signatures. On the contrary, the low frequency of AOTs is an important limitation for this. The number of studies that have a assessed the genetic landscape of AOT is still very limited, not providing enough evidence to draw a conclusion regarding the relationship between the genomic alterations and its clinical behavior. Thus, the presence of other mutational signatures with clinical impact, co-occurring with background mutations or in wild-type cases, cannot be ruled out. Since BRAF and RAS are in the same MAPK pathway, it is interesting that ameloblastomas, frequently associated with BRAFV600E mutation have aggressive clinical behavior, but in contrast, AOTs, frequently associated with RAS mutations have indolent behavior. Functional studies might be required to solve this question.
PubMed: 35048068
DOI: 10.3389/froh.2021.767474 -
Oral Diseases Sep 2022The aim of this systematic review was to critically analyze available data on gene polymorphisms in odontogenic keratocysts (OKC) and ameloblastomas, including their... (Review)
Review
OBJECTIVES
The aim of this systematic review was to critically analyze available data on gene polymorphisms in odontogenic keratocysts (OKC) and ameloblastomas, including their possible relationship with clinical and histological features of these lesions.
MATERIALS AND METHODS
A comprehensive search of Web of Science Scopus, PubMed, Cochrane Central Register of Controlled Trials and EMBASE was conducted using relevant key terms and supplemented by a gray literature search. Quality assessment of included studies was performed using criteria from the Strengthening the Reporting of Genetic Association (STREGA) statement.
RESULTS
Ten studies were included in the final review. Survivin -31G/C, interleukin IL-1α -889 C/T, p53 codon 72 G/C, tumor necrosis factor TNF-α (-308G>A) and its receptor TNF-R1 (36A>G), glioma-associated oncogene homolog 1 rs2228224 and matrix metalloproteinase 2 rs243865 gene polymorphisms were reported to be associated with OKC. For ameloblastomas, p53 codon 72 G/C, X-ray repair cross-complementing protein 1-codons 194 and 399 and matrix metalloproteinase 9 rs3918242 gene polymorphisms were identified as risk factors. It was not possible to establish a relationship between specific polymorphisms and clinical and histological features of investigated lesions.
CONCLUSIONS
Several gene polymorphisms might be considered as a risk factor for the development of these lesions. Future studies should investigate whether these polymorphisms might be used to identify patients with increased risk of recurrence or aggressive disease.
Topics: Ameloblastoma; Humans; Matrix Metalloproteinase 2; Odontogenic Cysts; Odontogenic Tumors; Polymorphism, Genetic; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53
PubMed: 33793041
DOI: 10.1111/odi.13865 -
Annals of Maxillofacial Surgery 2023Odontogenic cysts have the potential to transform into neoplasms. However, the characteristics of those which transformed to neoplastic tissues have not been well... (Review)
Review
BACKGROUND
Odontogenic cysts have the potential to transform into neoplasms. However, the characteristics of those which transformed to neoplastic tissues have not been well described and the exact causes of that phenomenon are not yet clear.
OBJECTIVES
This study aims to describe characteristics of odontogenic cysts that transformed into neoplasms and to look for their potential etiologies.
DATA SOURCES
English-written studies indexed in PubMed, Science Direct, and Proquest were assessed using keywords verified by Medical Subject Headings: 'Odontogenic Cyst' and 'Neoplastic Cell Transformation'.
STUDY ELIGIBILITY CRITERIA
Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines were used as guidance.
PARTICIPANTS
Following steps in PRISMA guidelines, 19 articles were fully reviewed (three case series and 16 case reports) with 27 subjects of 16 males (59%) and 11 females (41%) from 15 to 86 years old.
RESULTS
Cystic origins were eight dentigerous cysts, four odontogenic keratocysts, two residual cysts, one radicular cyst, one calcifying odontogenic cyst, one follicular cyst, one glandular odontogenic cyst, and nine unspecified odontogenic cysts that transformed to ameloblastoma (3 cases) and carcinoma (24 cases).
LIMITATIONS
Neoplastic transformations of odontogenic cysts arose from epithelial remnants of inadequate odontogenic cyst removal and chronic inflammation due to infection. However, the exact causes of their transformations remain unclear.
CONCLUSIONS
Therefore, careful removal of odontogenic cysts and regular postoperative follow-ups are key to prevent recurrence and neoplastic transformation. Future studies are needed to investigate potential causes of neoplastic transformation of odontogenic cysts.
PubMed: 37711539
DOI: 10.4103/ams.ams_226_22 -
Plastic and Reconstructive Surgery.... Jan 2023Microsurgical advances have led to minimally invasive approaches for mandibular reconstruction. Currently, no resource compares all minimally invasive microvascular...
UNLABELLED
Microsurgical advances have led to minimally invasive approaches for mandibular reconstruction. Currently, no resource compares all minimally invasive microvascular mandibular reconstruction (MIMMR) treatment options.
METHODS
All known cases of MIMMR were identified following the Preferred Reporting Items for Systematic Reviews, Meta-Analyses guidelines, and our own surgical experience. Patient demographics, MIMMR type [submandibular (SM), modified facelift/retroauricular (MFL/RA), or intraoral (IO)], methodology, and clinical outcomes were analyzed with the Fisher exact and Kruskal-Wallis tests.
RESULTS
Forty-seven patients underwent MIMMR. Ameloblastoma was the most common pathology treated using all approaches, and MFL/RA was the only approach used to treat squamous cell carcinoma ( = 0.0103). Reconstruction was reported for large, bilateral defects only via the SM or IO approach ( = 0.0216). The iliac crest or fibula was used as a donor site. The facial artery was the most common recipient vessel using the IO and SM approaches, whereas the superior thyroid and external carotid vessels were the most common in the MFL/RA approach ( < 0.0001). Virtual planning was used in all cases performed via an IO approach, 80.0% of cases using an SM approach, and no MFL/RA cases ( < 0.0001). Good aesthetic and functional outcomes were reported for every patient, and there was no difference in complication rates ( = 0.2880).
CONCLUSIONS
Minimally invasive approaches are safe and effective treatment options for patients requiring mandibular microsurgery, usually in the setting of benign pathology. The IO and SM approaches usually rely on the facial vessels, whereas the MFL/RA approach permits access to the superior thyroid and external carotid vessels and cervical lymphadenectomy.
PubMed: 36699208
DOI: 10.1097/GOX.0000000000004733 -
Journal of Cranio-maxillo-facial... Dec 2021The odontogenic keratocyst (OKC) is a potentially aggressive odontogenic lesion and there is an ongoing debate regarding its biological behavior and classification. The... (Meta-Analysis)
Meta-Analysis Review
The odontogenic keratocyst (OKC) is a potentially aggressive odontogenic lesion and there is an ongoing debate regarding its biological behavior and classification. The present systematic review aims to assess the expression of the p53 protein in the odontogenic keratocyst in comparison to the dentigerous cyst and ameloblastoma. We searched MEDLINE, Web of Science and Scopus for immunohistochemical studies reporting OKC's, dentigerous cysts and solid/multicystic ameloblastomas. The Risk Difference between the lesions expressing the p53 was the effect measure and a P value < 0.05 was considered to provide evidence to the effect estimates. Results: The first hit retrieved 126 records. After duplicates removal, there were 84 articles, of which eighteen were assessed for eligibility. Thirteen articles were included in the meta-analysis, showing that OKC's have an estimated difference of 23% (P < 0.003) in the probability to express the p53 over dentigerous cysts, and an estimated difference of 4% (P = 0.28) in the probability to express the p53 over ameloblastomas. OKCs seem to behave more similarly to a tumor rather than an odontogenic cyst regarding its p53 expression and the classification of this lesion into Keratocystic Odontogenic Tumor should be carefully revaluated.
Topics: Ameloblastoma; Dentigerous Cyst; Humans; Jaw Neoplasms; Odontogenic Cysts; Odontogenic Tumors; Tumor Suppressor Protein p53
PubMed: 34620539
DOI: 10.1016/j.jcms.2021.09.015 -
Journal of Racial and Ethnic Health... Feb 2024Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and... (Meta-Analysis)
Meta-Analysis Review
Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Jaw Neoplasms; Treatment Outcome; Mutation
PubMed: 36596981
DOI: 10.1007/s40615-022-01500-6