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1.
Toxicon ; 221: 106965, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36370827

RESUMO

This study investigated the antineoplastic effects of crotoxin isolated from snake venom of the South American Crotalus durissus terrificus in oral cancer cell lines and in an animal model of chemically induced oral cancer. We analyzed cell viability and death, clonogenic formation, DNA fragmentation, migration assay, and gene expression of MMP2, MMP9, COL1A1, and CASP3. In the animal model, after induction of oral cancer by 4-nitroquinoline-1-oxide carcinogen, mice were treated with crotoxin to investigate its effects on tumor development in tongue and oral mucosa. Crotoxin inhibited cell proliferation, viability, colony formation, and migration, favoring cell death. Furthermore, crotoxin increased caspase-3 expression, decreased Ki-67 protein and mRNA expression of MMP2, MMP9, and COL1A1. Mice treated with crotoxin at 10 µg/kg did not alter biochemical parameters total cholesterol, very-low-density lipoprotein, high-density lipoprotein, liver transaminases, glycemia, creatinine, and urea. Crotoxin treatment significantly reduced the frequency of oral squamous cell carcinoma lesions by 50%. Thus, this study highlights crotoxin as a promising chemotherapeutic substance, considering its effects on controlling the neoplastic cell population, reducing cell migration, and inhibiting tumor development. Clinical studies are necessary to understand better the impact of crotoxin as a potential adjuvant therapeutic agent for oral cancer patients.

4.
J Oral Pathol Med ; 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36116035

RESUMO

BACKGROUND: Chronic rhinosinusitis is a chronic inflammation of the nasal mucosa and nasal polyps are present in ~25%-30% of cases (chronic rhinosinusitis with nasal polyps [CRSwNP]). CRSwNP is associated with significant morbidity and decreased quality of life, making it clinically important. Inflammation leads to DNA damage and DNA mutations occur in some inflammatory diseases. Notably, mutations in KRAS, BRAF, and EGFR have been reported in different human benign and malignant neoplastic lesions. In addition, KRAS mutations have also been reported in non-neoplastic tissues under chronic inflammatory conditions. Importantly, KRAS mutations have been reported in oncocytic sinonasal papillomas and sinonasal squamous cell carcinoma associated with oncocytic sinonasal papilloma and EGFR mutations have been reported in sinonasal adenocarcinoma, inverted sinonasal papilloma, and sinonasal squamous cell carcinoma associated with inverted sinonasal papilloma. The molecular pathogenesis of nasal polyps remains unclear. Therefore, the present study aimed to investigate the presence of KRAS, BRAF, and EGFR pathogenic mutations in CRSwNP. METHODS: Fourteen chronic rhinosinusitis-associated nasal polyp samples were direct sequenced, targeting KRAS exons 2, 3, and 4 (encompassing important hotspot mutations, including codons 12, 13, 61 and 146), BRAF exons 11 and 15, and EGFR exons 19 and 20. RESULTS: No pathogenic mutations were detected in the sequenced regions of KRAS, BRAF, and EGFR genes. CONCLUSION: This finding suggests that mutations in these genes are not a frequent event in CRSwNP, and, if they occur, they might represent marginal events at best.

5.
Head Neck Pathol ; 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36169792

RESUMO

BACKGROUND: A recent systematic review published in Head and Neck Pathology found that 3.8% of dentinogenic ghost cell tumors harbor duct-like/ cribriform architecture. Herein we discuss this finding regarding the differential diagnosis of this tumor with adenoid ameloblastoma. METHODS: A critical review of some microscopic findings reported in a recent paper published in the Head and Neck Pathology Journal was done. RESULTS: Although there are overlapping microscopic features with dentinogenic ghost cell tumor, adenoid ameloblastoma is distinguished by the combination of duct-like structures and whorls/morules. In our opinion, at least some cases previously diagnosed as dentinogenic ghost cell tumors may now be more accurately classified as adenoid ameloblastoma. CONCLUSION: We conclude that a reassessment of dentinogenic ghost cell tumor cases using the diagnostic criteria proposed by the new WHO classification of Head and Neck Tumors (2022) is warranted.

6.
J Oral Pathol Med ; 51(8): 702-709, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36087273

RESUMO

BACKGROUND: Mitochondrial fission and fusion processes are known as mitochondrial dynamics and the occurrence of imbalances in the mitochondrial activity is related to the pathogenesis of many human cancers. However, the importance of mitochondrial dynamics in malignant salivary gland tumours remains unknown. Therefore, we aimed to investigate its prognostic significance in adenoid cystic carcinoma. METHODS: Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2 and OPA1 proteins. Clinical data were retrieved from the patients' medical files, including specific and disease-free survival data. RESULTS: It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, and 49.1%, 21.1%, 22.8% and 24.6% strongly positive for FIS1, MFN1, MFN2 and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumour. The higher expression of MFN2 was associated with solid microscopic pattern (p = 0.016). DRP1 overexpression showed a trend towards a shorter overall survival (p = 0.054), while negative/weak OPA1 showed a trend towards a lower disease-free survival (p = 0.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. CONCLUSION: In conclusion, mitochondrial dynamics markers do not seem to carry a prognostic significance for adenoid cystic carcinoma patients, but these proteins may play an important role in its pathogenesis.


Assuntos
Carcinoma Adenoide Cístico , Dinâmica Mitocondrial , Carcinoma Adenoide Cístico/metabolismo , Humanos , Mitocôndrias
7.
Head Neck Pathol ; 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36166159

RESUMO

BACKGROUND: Lymphomas affecting the sublingual glands are extremely rare and very few case reports are currently available. Therefore, the aim of the current study is to describe the clinicopathological features of a series of lymphomas involving the sublingual glands. METHODS: Cases diagnosed in four pathology services were assessed and the formalin-fixed paraffin-embedded tissue blocks were retrieved for diagnosis confirmation. Clinical data were obtained from patients' medical files. RESULTS: We obtained seven cases of lymphomas in the sublingual glands, representing two follicular lymphomas, two diffuse large B cell lymphomas not otherwise specified (DLBCL NOS), two extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas) and one mantle cell lymphoma (MCL). In all cases the tumor cells infiltrated the glandular parenchyma, although in two of them the neoplastic cells were located more superficially and permeated the glandular acini and ducts. Clinically, the tumors presented as asymptomatic nodules and two patients (affected by DLBCL NOS and MCL) died, while the other five patients remained alive at last follow-up. CONCLUSION: Lymphomas affecting the sublingual glands are usually of the mature B cell lineage, often represent low-grade subtypes and may clinically resemble other more common lesions in the floor of the mouth like salivary gland tumors.

8.
J Oral Pathol Med ; 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36169975

RESUMO

BACKGROUND: TERT promoter mutations increase telomerase activity, conferring cell immortality. The coexistence of TERT promoter mutations with BRAFV600E is associated with aggressiveness. Ameloblastoma and ameloblastic carcinoma are infiltrative neoplasms that harbor BRAFV600E; however, it remains unknown if these odontogenic tumors also show TERT promoter mutations. METHODS: Genomic DNA of paraffin-embedded ameloblastomas (n = 6) and ameloblastic carcinomas (n = 3) were Sanger-sequenced to assess the hotspot TERT promoter mutations C228T and C250T. BRAFV600E status was screened by TaqMan allele-specific quantitative polymerase chain reaction. RESULTS: None of the samples harbored TERT promoter mutations. The BRAFV600E mutation was positive in 3 of 6 of ameloblastomas and in 1 of 3 of ameloblastic carcinomas. CONCLUSION: The absence of TERT promoter mutation in the samples indicates that this molecular event is not relevant to the tumors' pathogenesis. Further studies are necessary to explore undefined genetic or epigenetic mechanisms related to TERT-upregulation in ameloblastoma, and the telomerase activity in ameloblastic carcinoma.

9.
J Oral Pathol Med ; 51(7): 603-610, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35822408

RESUMO

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.


Assuntos
Ameloblastoma , Carcinoma , Neoplasias Mandibulares , Tumores Odontogênicos , Ameloblastoma/patologia , Carcinoma/patologia , Humanos , Mandíbula/patologia , Neoplasias Mandibulares/patologia , Tumores Odontogênicos/patologia
10.
Mod Pathol ; 35(11): 1562-1569, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35840721

RESUMO

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.


Assuntos
Tonsila Faríngea , Ameloblastoma , Tumores Odontogênicos , Humanos , Masculino , Feminino , Ameloblastoma/genética , Ameloblastoma/patologia , beta Catenina/genética , beta Catenina/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Tonsila Faríngea/metabolismo , Tonsila Faríngea/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Tumores Odontogênicos/patologia , Mutação
11.
J Oral Pathol Med ; 51(7): 666-673, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35706152

RESUMO

BACKGROUND: Giant cell granuloma of the jaws are benign osteolytic lesions of the jaws. These lesions are genetically characterized by mutually exclusive somatic mutations at TRPV4, KRAS, and FGFR1, and a fourth molecular subgroup which is wild-type for the three mutations. Irrespective of the molecular background, giant cell granulomas show MAPK/ERK activation. However, it remains unclear if these mutations lead to differences in their molecular signaling in giant cell granulomas. METHODS: Metabolomics, proteomics, and phosphoproteomics analyses were carried out in formalin-fixed paraffin-embedded samples of giant cell granuloma of the jaws. The study cohort consisted of five lesions harboring mutations in FGFR1, six in KRAS, five in TRPV4, and five that were wild-type for these mutations. RESULTS: Lesions harboring KRAS or FGFR1 mutations showed overall similar proteomics and metabolomics profiles. In all four groups, metabolic pathways showed similarity in apoptosis, cell signaling, gene expression, cell differentiation, and erythrocyte activity. Lesions harboring TRPV4 mutations showed a greater number of enriched pathways related to tissue architecture. On the other hand, the wild-type group presented increased number of enriched pathways related to protein metabolism compared to the other groups. CONCLUSION: Despite some minor differences, our results revealed an overall similar molecular profile among the groups with different mutational profile at the metabolic, proteic, and phosphopeptidic levels.


Assuntos
Granuloma de Células Gigantes , Canais de Cátion TRPV , Granuloma de Células Gigantes/genética , Granuloma de Células Gigantes/metabolismo , Humanos , Arcada Osseodentária/metabolismo , Arcada Osseodentária/patologia , Metabolômica , Mutação , Proteômica , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
12.
Front Oral Health ; 3: 871107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619688

RESUMO

Background: The coronavirus disease 2019 (COVID-19) pandemic had quite an impact on dental health care. Concerns about the risk of SARS-CoV-2 transmission through contaminant fluids and droplet formation during several dental procedures highly impacted dental health care, drastically reducing the number of dental practices worldwide. To monitor SARS-CoV-2 contamination in dental clinics, a longitudinal study was carried out during the return of dental practice at university. Methods: Dental health care professionals [(DHCPs); teachers, undergraduate dental students, and dental assistants] and patients were screened for SARS-CoV-2 RNA in a dental school clinic environment from 11th January to 12th March 2021 (9 weeks). Serological testing was performed on DHCPs in two-time points. Additionally, samples with low Ct values were sequenced to identify the circulating SARS-CoV-2 variant and possible transmission clusters. Results: We found a low number of dental staff (5.8%), patients (0.9%), and environment sites (0.8%) positive for SARS-CoV-2. Most positive cases had asymptomatic to mild symptoms, and two asymptomatic DHCPs presented prolonged infection. In the first week after previous exposure to COVID-19, 16.2% of DHCPs had IgM or IgG antibodies against SARS-CoV-2, and 1/3 of them had undetected antibodies in the last weeks. The variant zeta (P.2) could be detected. No cross-infection was observed between participants. Conclusion: Our study suggests that dental practice can be safely executed when adequate control measures and biosafety protocols are applied. DHCP and patient testing, patient telemonitoring, proper use of personal protection equipment, and sanitization of surfaces are essential to avoid SARS-CoV-2 cross-infection in dental practice.

13.
Head Neck Pathol ; 16(3): 755-762, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35316511

RESUMO

Oral squamous cell carcinoma (OSCC) commonly affects older patients; however, several studies have documented an increase in its incidence among younger patients. Therefore, it is important to investigate if this trend is also found in different geographic regions. The pathology files of diagnostic and therapeutic institutions from different parts of the globe were searched for OSCC cases diagnosed from 1998 to 2018. Data regarding the sex, age, and tumor location of all cases, as well as the histologic grade and history of exposure to risk habits of cases diagnosed as OSCC in young patients (≤ 40 years of age) were obtained. The Chi-square test was used to determine any increasing trend. A total of 10,727 OSCC cases were identified, of which 626 cases affected young patients (5.8%). Manipal institution (India) showed the highest number of young patients (13.2%). Males were the most affected in both age groups, with the tongue and floor of the mouth being the most affected subsites. OSCC in young individuals were usually graded as well or moderately differentiated. Only 0.9% of the cases occurred in young patients without a reported risk habit. There was no increasing trend in the institutions and the period investigated (p > 0.05), but a decreasing trend was observed in Hong Kong and the sample as a whole (p < 0.001). In conclusion there was no increase of OSCC in young patients in the institutions investigated and young white females not exposed to any known risk factor represented a rare group of patients affected by OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Feminino , Humanos , Masculino , Encaminhamento e Consulta , Carcinoma de Células Escamosas de Cabeça e Pescoço
15.
J Oral Pathol Med ; 51(4): 405-412, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35103997

RESUMO

BACKGROUND: Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are the most common gnathic fibro-osseous lesions. These diseases exhibit remarkable overlap of several clinicopathological aspects, and differential diagnosis depends on the combination of histopathological, radiographic, and clinical aspects. Their molecular landscape remains poorly characterized, and herein, we assessed their proteomic and phosphoproteomic profiles. METHODS: The quantitative differences in protein profile of FD and COF were assessed by proteomic and phosphoproteomic analyses of formalin-fixed paraffin-embedded tissue samples. Pathway enrichment analyses with differentially regulated proteins were performed. RESULTS: FD and COF exhibited differential regulation of pathways related to extracellular matrix organization, cell adhesion, and platelet and erythrocytes activities. Additionally, these lesions demonstrated distinct abundance of proteins involved in osteoblastic differentiation and tumorigenesis and differential abundance of phosphorylation of Ser61 of Yes-associated protein 1 (YAP1). CONCLUSIONS: In summary, despite the morphological similarity between these diseases, our results demonstrated that COF and DF present numerous quantitative differences in their proteomic profiles. These findings suggest that these fibro-osseous lesions trigger distinct molecular mechanisms during their pathogenesis. Moreover, some proteins identified in our analysis could serve as potential biomarkers for differential diagnosis of these diseases after further validation.


Assuntos
Cementoma , Fibroma Ossificante , Displasia Fibrosa Óssea , Cementoma/diagnóstico , Cementoma/patologia , Diagnóstico Diferencial , Fibroma Ossificante/metabolismo , Displasia Fibrosa Óssea/patologia , Humanos , Proteômica
16.
Artigo em Inglês | MEDLINE | ID: mdl-35181256

RESUMO

Hyperparathyroidism is one of the most common endocrine disorders worldwide. In countries where routine biochemical screening is not common, symptomatic hyperparathyroidism predominates. Its manifestations include skeletal alterations, calcification of soft tissues, kidney stones, and functional alterations in other systems. Notably, jaw alterations can be the first clinical sign of hyperparathyroidism, including brown tumor, renal osteodystrophy, osteitis fibrosa, and leontiasis ossea, and knowing such conditions is of core importance for the multidisciplinary diagnosis and management of hyperparathyroidism. We aimed to perform a concise review, systematizing the concepts and mechanisms underlying hyperparathyroidism and associated gnathic alterations. In addition, a detailed description of the clinical aspects of the jaw manifestations is presented.


Assuntos
Calcinose , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Hiperostose Frontal Interna , Hiperparatireoidismo , Osteíte Fibrosa Cística , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Feminino , Humanos , Hiperostose Frontal Interna/patologia , Hiperparatireoidismo/complicações , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/patologia , Arcada Osseodentária/patologia , Masculino , Osteíte Fibrosa Cística/diagnóstico , Osteíte Fibrosa Cística/etiologia , Osteíte Fibrosa Cística/patologia
17.
Int J Exp Pathol ; 103(2): 65-69, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35225401

RESUMO

Previously, by employing 3D organotypic tissue culture and patient-derived xenograft (PDX) model, oral myxoma response to a MAPK/MEK inhibitor was observed. Gross examination of the tumour fragments obtained after 55 days of PDX grafting revealed increased capsule vascularization. Microscopic analyses showed blood capillaries intermixed with myxoma cells, but the origin of these capillaries, from mice or humans, was not established. This study aimed to investigate whether the endothelial cells observed in the myxoma PDX model are derived from the mouse or from the primary human tumour. Immunohistochemistry was performed on five tumour fragments from the PDX of myxoma after 55 days of implantation in mice. Immunopositivity for antibodies against human (HLA-ABC) and mouse (H2 Db/H2-D1) major histocompatibility complex class I (MHCI) was assessed in the endothelial cells. The endothelial cells in the PDX fragments revealed a membrane staining for the human MHCI protein in the PDX tumour and adjacent connective tissue capsule, indicating that capillaries were derived from the human tumour fragment. Considering the probable human origin of the endothelial cells from capillary blood vessels in the myxoma PDX, we conclude that this PDX model is an interesting model to study myxoma angiogenesis.


Assuntos
Células Endoteliais , Mixoma , Animais , Modelos Animais de Doenças , Xenoenxertos , Humanos , Camundongos , Neovascularização Patológica , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Artigo em Inglês | MEDLINE | ID: mdl-35153188

RESUMO

Adenoid ameloblastoma with dentinoid is an uncommon benign odontogenic neoplasm, and its unicystic variant seems to be even rarer. A 34-year-old man was referred for evaluation of an asymptomatic swelling in the posterior maxilla. Intraoral examination showed an expansive lesion, soft to palpation, covered by a normal color mucosa. Cone beam computed tomography revealed a well-defined unilocular hypodense tumor involving the left maxillary sinus. Histopathological examination of the surgically excised specimen showed a cystic tumor lined by an ameloblastic-like epithelium containing columnar basal cells with hyperchromatic and polarized nuclei. In some areas of the capsule, the tumor showed mural infiltration by sheets of cells containing central whirling structures. Dentinoid material was also observed in association with ameloblastic-like cells. The tumor was BRAF and KRAS wild-type. Collectively, these findings were consistent with the diagnosis of a unicystic variant of adenoid ameloblastoma with dentinoid.


Assuntos
Tonsila Faríngea , Ameloblastoma , Tumores Odontogênicos , Tonsila Faríngea/patologia , Adulto , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/genética , Ameloblastoma/cirurgia , Epitélio/patologia , Humanos , Masculino , Maxila/patologia
19.
J Oral Pathol Med ; 51(2): 206-216, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35048460

RESUMO

BACKGROUND: Central giant cell granulomas (CGCG) of the jaws are osteolytic lesions that may behave aggressively and respond poorly to surgery. Microscopically, in addition to giant cells, there is a mononuclear cell population composed of macrophage/monocytic cells and spindle-shaped cells of mesenchymal origin. Seventy two percent of these tumours harbour mutually exclusive TRPV4, KRAS and FGFR1 mutations. We aimed to assess the mutational status of mononuclear and giant cells and the osteogenic potential of stromal cells in vitro and in vivo. METHODS AND RESULTS: We screened CGCG for signature mutations and used laser-capture microdissection to demonstrate that the mutations are restricted to the mononuclear cells. Additionally, we established CGCG primary cell culture and observed that the cells retained the mutations throughout passages. By flow cytometry, we observed predominance of CD14- CD51- CD61- cells, consistent with the expected profile for stromal cells. Considering the mesenchymal origin of stromal cells, we assessed the osteogenic differentiation potential of CGCG cells in culture by cytochemistry (von Kossa and alizarin red staining), alkaline phosphatase (ALP) activity assay and gene expression of osteogenic markers. CGCG cells presented self-capacity to increase ALP levels in a time-dependent manner and under osteogenic induction presented increasing number of calcium deposits, and overall higher expression of osteocalcin, RUNX2, ALPL and osteopontin than cells without osteogenic induction. A patient-derived xenograft model for CGCG was established, and osteoid material deposition was observed. CONCLUSION: Collectively, the results confirm that the signature mutations are restricted to stromal cells in CGCG, and the in vitro and in vivo results support that these cells have the capacity to differentiate into osteoblasts, in line with the bone formation often observed in the stroma of these lesions.


Assuntos
Granuloma de Células Gigantes , Células-Tronco Mesenquimais , Fosfatase Alcalina , Diferenciação Celular , Células Cultivadas , Granuloma de Células Gigantes/genética , Humanos , Arcada Osseodentária , Mutação , Osteogênese/genética , Células Estromais
20.
Head Neck Pathol ; 16(1): 294-303, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34106410

RESUMO

Smooth muscle neoplasms represent an important group of lesions which is rare in the oral cavity. Leiomyoma (LM) is benign smooth muscle/pericytic tumor usually presenting as non-aggressive neoplasm, while leiomyosarcoma (LMS) represents its malignant counterpart. The rarity of these lesions, together with its unspecific clinical presentation and a variable histopathological appearance, lead to a broad list of differential diagnoses, hampering their diagnoses. Therefore, in this study we describe the clinical and microscopic features of a series of oral and maxillofacial LMs and LMSs. A retrospective search from 2000 to 2019 was performed and all cases diagnosed as LM and LMS affecting the oral cavity and gnathic bones were retrieved. Clinical and demographic data were obtained from the patients' pathology records, while microscopic features and immunohistochemistry were reviewed and completed when necessary to confirm the diagnoses. Twenty-two LMs and five LMSs were obtained. In the LM group, males predominated, with a mean age of 45.7 years. The upper lip was the most affected site, and 18 cases were classified as angioleiomyomas and four as solid LM. In the LMS group, females predominated, with a mean age of 47.6 years. The mandible was the most affected site. Diffuse proliferation of spindle cells, with necrosis and mitotic figures, were frequent microscopic findings. LMs and LMSs were positive for α-smooth muscle actin, HHF-35 and h-caldesmon. In conclusion, oral LM/LMS are uncommon neoplasms with the latter usually presenting as metastatic disease. H&E evaluation may be very suggestive of oral LMs, but h-caldesmon staining is strongly recommended to confirm LMS diagnosis.


Assuntos
Leiomioma , Leiomiossarcoma , Tumor de Músculo Liso , Neoplasias Uterinas , Biomarcadores Tumorais , Proteínas de Ligação a Calmodulina , Feminino , Humanos , Leiomioma/diagnóstico , Leiomioma/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tumor de Músculo Liso/patologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia
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