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The Oncologist Jun 2024This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with...
BACKGROUND
This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations.
METHODS
Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib.
RESULTS
Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (nâ=â7) and prior BRAF inhibitor therapy (nâ=â7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles.
CONCLUSION
There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035).
PubMed: 38873934
DOI: 10.1093/oncolo/oyae119 -
Oral Surgery, Oral Medicine, Oral... Mar 2024This study aimed to analyze the clinicoradiologic features and Ki-67 proliferation indices between the histopathologic variants of ameloblastomas (ABs) for possible...
OBJECTIVES
This study aimed to analyze the clinicoradiologic features and Ki-67 proliferation indices between the histopathologic variants of ameloblastomas (ABs) for possible associations.
STUDY DESIGN
The diagnosis and histopathologic variant were confirmed for all cases by experienced Oral and Maxillofacial Pathologists. Immunohistochemistry for Ki-67 was performed on the most representative formalin-fixed paraffin-embedded tissue block. Demographic, clinical data and radiologic features were analyzed from patient records and available radiographic examinations. The investigators were blinded to the histopathologic variant and proliferation index when the clinicoradiologic features were assessed.
RESULTS
The current study included 116 cases of AB in the final sample. The indolent behavior of the unicystic variant was supported by their low proliferation index and slow growth paired with low frequencies of cortical destruction, loss of teeth, root resorption, and encroachment on anatomical structures. In contrast, the comparatively high proliferation index of the plexiform variant correlated with their fast growth and pain. Furthermore, high radiologic frequencies of cortical destruction, loss of teeth, and encroachment of surrounding anatomical structures supported their more aggressive clinical course.
CONCLUSION
Statistically significant differences were noted between certain variants and Ki-67, location, borders, locularity, and cortical destruction, providing better insight into their biological behavior.
PubMed: 38871622
DOI: 10.1016/j.oooo.2024.03.007 -
Diagnostic Pathology Jun 2024Intravascular papillary endothelial hyperplasia (IPEH) represents an uncommon reactive endothelial hyperplastic proliferation. A 46-year-old man experienced increased... (Review)
Review
Intravascular papillary endothelial hyperplasia (IPEH) represents an uncommon reactive endothelial hyperplastic proliferation. A 46-year-old man experienced increased volume in the right maxilla, elevation of the nasal ala, and swelling of the hard palate with a reddish hue for 3 months. Computed tomography revealed an expansive hypodense region and cortical bone destruction associated with an impacted supernumerary tooth and an endodontically treated tooth. Under the differential diagnoses of a radicular cyst, dentigerous cyst, and ameloblastoma, an exploratory aspiration and incisional biopsy were performed. This revealed the formation of blood vessels of various diameters lined by endothelium, forming intravascular papillae positive for CD-34. The definitive diagnosis was IPEH, and the patient was treated by embolization and surgery. Histological analysis confirmed the presence of IPEH associated with an odontogenic cyst. After 12 months of follow-up, no recurrence was observed. Also, we reviewed case reports of IPEH affecting the maxilla and mandible. Fourteen intraosseous cases were reported in the maxilla and mandible, with a preference for males and affecting a wide age range. Complete surgical excision was the treatment of choice, and recurrences were not reported. The pathogenesis of IPEH is controversial and may originate from trauma or inflammatory processes. To the best of our knowledge, this is the first report of an association of IPEH with an odontogenic cyst. The importance of IPEH in the differential diagnosis of intraosseous lesions in the jaws is emphasized, and preoperative semiotic maneuvers are needed to prevent surgical complications.
Topics: Humans; Male; Middle Aged; Odontogenic Cysts; Hyperplasia; Diagnosis, Differential; Maxilla; Biopsy; Treatment Outcome; Tomography, X-Ray Computed; Maxillary Diseases; Embolization, Therapeutic
PubMed: 38867285
DOI: 10.1186/s13000-024-01505-1 -
Cureus May 2024Odontogenic fibromyxoma typically presents as painless swelling in the jaw, and clinically, it grows slowly, becoming benign and asymptomatic. It causes the cortical...
Odontogenic fibromyxoma typically presents as painless swelling in the jaw, and clinically, it grows slowly, becoming benign and asymptomatic. It causes the cortical plates to expand gradually, which leads to mobility and drifting of the teeth. Root resorption is also common. The tumor is locally aggressive in nature. It is also known to have a high recurrence rate. We present the case of a 30-year-old female patient who was diagnosed and treated for odontogenic fibromyxoma of the maxilla conservatively with enucleation. The radiograph showed a multilocular lesion, which can be confused with ameloblastoma, aneurysmal bone cyst, or odontogenic keratocyst. Hence, with proper clinical, radiographic, and histopathological examination, a correct diagnosis can be made and adequate treatment can be planned.
PubMed: 38846229
DOI: 10.7759/cureus.59763 -
International Journal of Surgery Case... May 2024Unicystic ameloblastomas are a rare variant of ameloblastomas, which are characterized by slow growth and being relatively locally aggressive, with the main site of...
INTRODUCTION
Unicystic ameloblastomas are a rare variant of ameloblastomas, which are characterized by slow growth and being relatively locally aggressive, with the main site of origin being the posterior portion of the mandible, it also refers to those cystic lesions that show clinical, radiographic, or gross features of a jaw cyst.
PRESENTATION OF CASE
A 27-year-old female patient presented with a chief complaint of extensive mass of mandible along with severe swelling and numbness of right lips and chin. The oral examination revealed a swelling in the molar region of the right mandible with buccal plate expansion. The radiographic and histopathologic features were consistent with the diagnosis of unicystic ameloblastoma. Consequently, the lesion was surgically removed, and no clinical or radiological recurrence was detected during 5 years post-operative follow-up.
DISCUSSION
While previous reports of unicystic ameloblastoma in the posterior portion of the jaw showed favorable prognosis lesions appeared as a unilocular entity, this case reports multilocular appearance and aggressive behavior of expansive unicystic ameloblastoma. Furthermore, while some studies linked the unilocular appearance of unicystic ameloblastoma to impacted tooth, our case suggests a possible traumatic link of preexisting lesion into multilocular unicystic ameloblastoma related to impacted tooth.
CONCLUSIONS
This case presents a rare multilocular unicystic ameloblastoma appearance, notably with impacted tooth involvement. It also indicates the potential transformation of solid ameloblastoma into unicystic ameloblastom.
PubMed: 38821006
DOI: 10.1016/j.ijscr.2024.109830 -
Bioinformatics and Biology Insights 2024Ameloblastoma (AM) is a benign tumor locally originated from odontogenic epithelium that is commonly found in the jaw. This tumor makes aggressive invasions and has a...
BACKGROUND
Ameloblastoma (AM) is a benign tumor locally originated from odontogenic epithelium that is commonly found in the jaw. This tumor makes aggressive invasions and has a high recurrence rate. This study aimed to investigate the differentially expressed genes (DEGs), biological function alterations, disease targets, and existing drugs for AM using bioinformatics analysis.
METHODS
The data set of AM was retrieved from the GEO database (GSE132474) and identified the DEGs using bioinformatics analysis. The biological alteration analysis was applied to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interaction (PPI) network analysis and hub gene identification were screened through NetworkAnalyst. The transcription factor-protein network was constructed via OmicsNet. We also identified candidate compounds from L1000CDS2 database. The target of AM and candidate compounds were verified using docking simulation.
RESULTS
Totally, 611 DEGs were identified. The biological function enrichment analysis revealed glycosaminoglycan and GABA (γ-aminobutyric acid) signaling were most significantly up-regulated and down-regulated in AM, respectively. Subsequently, hub genes and transcription factors were screened via the network and showed FOS protein was found in both networks. Furthermore, we evaluated FOS protein to be a therapeutic target in AMs. Candidate compounds were screened and verified using docking simulation. Tanespimycin showed the greatest affinity binding value to bind FOS protein.
CONCLUSIONS
This study presented the underlying molecular mechanisms of disease pathogenesis, biological alteration, and important pathways of AMs and provided a candidate compound, Tanespimycin, targeting FOS protein for the treatment of AMs.
PubMed: 38812739
DOI: 10.1177/11779322241256459 -
Journal of Oral and Maxillofacial... 2024Ameloblastoma is one of the major odontogenic neoplasms with an invasive and recurrence potential. Its tumourigenesis and proliferative capacity can be attributed to the...
Immunohistochemical evaluation of yes-associated protein molecule in the odontogenic epithelium of different histopathological variants of ameloblastoma and unicystic ameloblastoma.
BACKGROUND
Ameloblastoma is one of the major odontogenic neoplasms with an invasive and recurrence potential. Its tumourigenesis and proliferative capacity can be attributed to the activation or inactivation of certain molecular signalling pathways. Hippo signalling pathway is known to regulate diverse physiological processes related to mitosis and organ growth and is an emerging tumour suppressor pathway, the dysfunction of which is implicated in various diseases including cancers. Yes-associated protein1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the downstream effectors in the Hippo cascade, which on nuclear activation leads to cellular proliferation in various tumours.
AIM
The current study was undertaken to evaluate the expression of YAP in various histopathological variants of ameloblastoma and unicystic ameloblastoma.
MATERIALS AND METHODS
Fifty formalin-fixed paraffin-embedded tissue samples of histopathologically diagnosed cases of ameloblastoma, and 10 histopathologically diagnosed cases of unicystic ameloblastoma were obtained from the departmental archives to evaluate the immunohistochemical expression of YAP both manually and by software analysis.
RESULTS
More than 90% of cases of conventional ameloblastoma and unicystic ameloblastoma elicited positive expression of YAP. No statistical difference was found among different histopathological variants of conventional ameloblastoma. Significant difference between the means of all four quantitative score groups was observed.
CONCLUSION
In view of the modulating effect of YAP in tumourigenesis and its higher expression in ameloblastoma, further exploration of this molecule appears to be a promising area of research.
PubMed: 38800449
DOI: 10.4103/jomfp.jomfp_215_23 -
Journal of Oral and Maxillofacial... 2024Glucose uptake may be considered the rate-limiting step for the growth and metabolism of the cancer cell. Studies on GLUT1 have shown that GLUT1 is involved in cell...
CONTEXT
Glucose uptake may be considered the rate-limiting step for the growth and metabolism of the cancer cell. Studies on GLUT1 have shown that GLUT1 is involved in cell survival and proliferation in both healthy and pathological circumstances. GLUT1 expression is regarded as one of the crucial elements in the development of local aggressiveness, tumour invasiveness, and metastasis, particularly in malignant tumours. The role of glut1 in odontogenic cysts and tumours has remained uncertain.
AIM
The aim of the study is to assess the expression of Glut1 in dentigerous cysts, odontogenic keratocysts, and ameloblastoma.
SETTINGS AND DESIGN
The study was conducted in GSL Dental College. The study design was a resprospective immunohistochemical study.
METHODS AND MATERIAL
Formalin-fixed, paraffin-embedded blocks of histologically confirmed cases (n = 50), 10 cases of odontogenic keratocysts, dentigerous cysts, ameloblastomas solid, ameloblastomas unicystic, and dental follicles each. Brown colour staining was considered as positive staining for GLUT1. Quantitative analysis was performed by counting the number of labelled cells, and semi-quantitative analysis was conducted by assigning immunostaining intensity scores.
STATISTICAL ANALYSIS
Chi-square test was used to compare differences between the groups. A value of ≤0.05 was considered as statistically significant.
RESULTS
Odontogenic keratocysts and unicystic ameloblastoma showed ≥50% of label cells with strong intensity of staining. Odontogenic keratocysts and solid ameloblastoma showed sub-cellular localisation of staining in the cytoplasm and membrane. Dentigerous cysts exhibited combined nucleus, cytoplasm, and membrane sub-cellular localisation of staining.
CONCLUSIONS
The development of ameloblastomas, odontogenic keratocysts, and dentigerous cysts appears to be influenced by GLUT-1. Variation in its expression may aid in explanation of some of the differences in biological activity of these lesions.
PubMed: 38800443
DOI: 10.4103/jomfp.jomfp_455_23 -
Journal of Oral and Maxillofacial... 2024[This corrects the article on p. 727 in vol. 27, PMID: 38304525.].
[This corrects the article on p. 727 in vol. 27, PMID: 38304525.].
PubMed: 38800422
DOI: 10.4103/jomfp.jomfp_96_24 -
Prague Medical Report 2024Salivary 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...
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.
Topics: Humans; Male; Adenoma, Pleomorphic; Ameloblastoma; Diagnosis, Differential; Mandibular Neoplasms; Adult
PubMed: 38761048
DOI: 10.14712/23362936.2024.14