RESUMO
OBJECTIVE: The biallelic inheritance of an expanded intronic pentamer (AAGGG)exp in the gene encoding replication factor C subunit 1 (RFC1) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome. STUDY DESIGN: A retrospective descriptive study from an ataxia database comprising 500 patients. SETTING: The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain. METHODS: Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing. RESULTS: Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)exp in RFC1. CONCLUSION: A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.
Assuntos
Vestibulopatia Bilateral/diagnóstico , Vestibulopatia Bilateral/genética , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Expansão das Repetições de DNA/genética , Proteína de Replicação C/genética , Idoso , Bases de Dados Factuais , Diagnóstico Diferencial , Feminino , Testes Genéticos , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Avaliação de Sintomas , SíndromeRESUMO
Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Classe I de Fosfatidilinositol 3-Quinases/genética , Reparo do DNA/genética , Reparo do DNA/fisiologia , Genes BRCA1/fisiologia , Humanos , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores de LDL/genéticaRESUMO
PURPOSE: The aim of this study was to determine the prevalence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), characterizing this condition, both in its objective dimension and in terms of quality of life (QoL). METHODS: A cross-sectional study was developed in 11 patients diagnosed of CANVAS. In all patients, clinical records were reviewed and the Eating assessment tool 10 (EAT-10) was performed as screening of oropharyngeal dysphagia. To evaluate the QoL impairment secondary to dysphagia, we applied the swallowing quality of life questionnaire (SWAL-QOL) and the MD Anderson Dysphagia Inventory (MDADI). To evaluate the deglutition mechanisms impaired, two objective-instrumental studies were performed: the volume-viscosity swallow test (V-VST) and the fiberoptic endoscopic evaluation of swallowing (FEES). RESULTS: 82% of the patients presented an abnormal EAT-10 score. A correlation was found between the EAT-10 and MDADI and between both QoL questionnaires. After the FEES and V-VST analysis, all 11 patients presented some degree of swallow effectiveness impairment, and most of them safety alterations as well. CONCLUSION: CANVAS remains an underestimated and underdiagnosed condition and the prevalence of swallowing disorders in those patients is higher than expected. Despite the possibility that EAT-10 works as a useful screening test to predict the results in the QoL questionnaires, the absence of correlation between QoL test and instrumental results suggests that to properly evaluate the patients swallowing status, objective instrumental procedures must be conducted.
Assuntos
Vestibulopatia Bilateral , Ataxia Cerebelar , Transtornos de Deglutição , Ataxia Cerebelar/complicações , Ataxia Cerebelar/epidemiologia , Estudos Transversais , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Humanos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
The stereocilia of the inner ear sensory cells contain the actin-binding protein radixin, encoded by RDX. Radixin is important for hearing but remains functionally obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to visualize stereocilia motion while measuring electrical potential amplitudes during acoustic stimulation. Radixin inhibition decreased sound-evoked electrical potentials. Other functional measures, including electrically induced sensory cell motility and sound-evoked stereocilia deflections, showed a minor amplitude increase. These unique functional alterations demonstrate radixin as necessary for conversion of sound into electrical signals at acoustic rates. We identified patients with RDX variants with normal hearing at birth who showed rapidly deteriorating hearing during the first months of life. This may be overlooked by newborn hearing screening and explained by multiple disturbances in postnatal sensory cells. We conclude radixin is necessary for ensuring normal conversion of sound to electrical signals in the inner ear.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Células Ciliadas Auditivas Externas/metabolismo , Proteínas de Membrana/metabolismo , Estereocílios/metabolismo , Estimulação Acústica , Alelos , Animais , Arsenicais/farmacologia , Pré-Escolar , Proteínas do Citoesqueleto/genética , Modelos Animais de Doenças , Feminino , Imunofluorescência , Expressão Gênica , Variação Genética , Genótipo , Cobaias , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Humanos , Mecanotransdução Celular/genética , Proteínas de Membrana/genética , Modelos Biológicos , Linhagem , Estereocílios/efeitos dos fármacosRESUMO
INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications.
Assuntos
Perda Auditiva Neurossensorial/genética , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Criança , Pré-Escolar , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Lactente , Projetos PilotoRESUMO
BACKGROUND: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. METHODS: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations. RESULTS: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion). CONCLUSIONS: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.
Assuntos
Genômica , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação INDEL , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenótipo , Espanha , Adulto JovemRESUMO
BACKGROUND: Patients with intestinal-type sinonasal adenocarcinoma (ITAC) have an unfavorable prognosis and new therapeutic approaches are needed to improve clinical management. METHODS: Genetic analysis of 96 ITACs was performed by microarray comparative genomic hybridization and immunohistochemistry and correlated to previously obtained mutation, methylation, and protein expression data, and with pathological characteristics and clinical outcome. RESULTS: Seven copy number alterations (CNAs) were significantly associated with unfavorable clinical outcome: gains at 1q22-23, 3q28-29, 6p22, and 13q31-33, and losses at 4p15-16, 4q32-35, and 10q24. Unsupervised cluster analysis resulted in 5 subgroups of ITAC with significantly distinct genetic signatures and clinical outcomes, independently of disease stage or histological subtype. CONCLUSION: These data may guide studies to identify driver genes and signaling pathways involved in ITAC. In addition, the subclassification of genetic subgroups of patients with distinct clinical behavior can aid therapeutic decision making and may ultimately lead to personalized therapy with targeted inhibitors.
Assuntos
Adenocarcinoma/genética , Variações do Número de Cópias de DNA , Neoplasias dos Seios Paranasais/genética , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Hibridização Genômica Comparativa , Feminino , Perfil Genético , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias dos Seios Paranasais/mortalidade , Prognóstico , Análise de SobrevidaRESUMO
INTRODUCTION: Chromosomal translocations at 2p23 cause overexpression of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in signalling pathways that regulate cell proliferation. This translocation occurs in 5% of lung adenocarcinoma and has been demonstrated to be useful as a therapeutic target for crizotinib. sinonasal adenocarcinomas (SNAC) are histologically similar to lung adenocarcinomas; the aim of this study was to evaluate the presence of ALK alterations in SNAC. METHOD: Break-apart fluorescent in-situ hybridization was used to analyse the presence of ALK translocations in 96 tumour samples. In addition, ALK protein expression was studied by immunohistochemistry. RESULTS: The samples of SNAC did not show ALK translocation. Moreover, ALK protein expression was absent in all cases. CONCLUSIONS: These results suggest that ALK is not involved in SNAC.
Assuntos
Adenocarcinoma/genética , Cromossomos Humanos Par 2/ultraestrutura , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Nasais/genética , Neoplasias dos Seios Paranasais/genética , Receptores Proteína Tirosina Quinases/genética , Translocação Genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Cromossomos Humanos Par 2/genética , Crizotinibe , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Neoplasias Nasais/química , Neoplasias Nasais/metabolismo , Neoplasias Nasais/patologia , Neoplasias dos Seios Paranasais/metabolismo , Neoplasias dos Seios Paranasais/patologia , Pirazóis , Piridinas , Receptores Proteína Tirosina Quinases/biossínteseAssuntos
Seio Etmoidal/anormalidades , Imunoglobulina G/análise , Seio Maxilar/anormalidades , Pseudotumor Orbitário/etiologia , Diplopia/etiologia , Seio Etmoidal/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Seio Maxilar/diagnóstico por imagem , Pessoa de Meia-Idade , Músculos Oculomotores/patologia , Músculos Oculomotores/cirurgia , Pseudotumor Orbitário/diagnóstico por imagem , Pseudotumor Orbitário/imunologia , Pseudotumor Orbitário/cirurgia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION AND OBJECTIVES: The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. PATIENTS AND METHOD: This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. RESULTS: 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. CONCLUSIONS: Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used.
Assuntos
Neoplasias Faríngeas/epidemiologia , Adenoma Pleomorfo/epidemiologia , Adenoma Pleomorfo/cirurgia , Adenoma Pleomorfo/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Criança , Pré-Escolar , Traumatismos dos Nervos Cranianos/etiologia , Feminino , Humanos , Lactente , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Paraganglioma/epidemiologia , Paraganglioma/cirurgia , Paraganglioma/terapia , Neoplasias Faríngeas/cirurgia , Neoplasias Faríngeas/terapia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/terapia , Adulto JovemRESUMO
OBJECTIVE: To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data. STUDY DESIGN: Retrospective study. SETTING: Academic research hospital. SUBJECTS AND METHODS: The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data. RESULTS: Gene methylation was observed in 50% of all tumors. Recurrent methylated genes in SNSCC were RASSF1 and CDH13 (for both, 6 of 32 cases), CHFR (4 of 32 cases), and TIMP3 (2 of 32 cases). None of these genes showed significant correlation to clinicopathologic features or overall survival. In ITAC, recurrent methylated genes were CDH13 (18 of 50 cases), ESR1 (13 of 50 cases), APC (7 of 50 cases), TIMP3 (5 of 50 cases), CASP8 (3 of 50 cases), and HIC1 and RASSF1 (for both, 2 of 50 cases). Papillary and colonic ITAC subtypes carried a mean of 1.26 gene methylations per tumor versus 0.63 in solid and mucinous subtypes. Methylation of TIMP3 was associated with a significantly worse survival in ITAC patients. CONCLUSION: ITAC carries a higher number and a different profile of gene methylations as compared with SNSCC. Gene methylation plays a greater role in papillary and colonic ITAC subtypes, which may indicate a different tumorigenic pathway for these ITAC subtypes. These findings could be used as prognosticators and may have implications for future individualized therapies based on epigenetic changes.
Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Análise Mutacional de DNA/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Neoplasias dos Seios Paranasais/genética , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/terapia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Integration of HIV infant testing into immunization sessions is one of the strategies designed to increase coverage of early infant diagnosis. OBJECTIVE: To determine the evidence on the outcomes of such integration. METHODS: A systematic review of peer-reviewed and grey literature was undertaken from electronic sources such as MEDLINE, Google Scholar, websites of international agencies, past conferences and ministries of health reports published between year 2002 and 2013. Randomized controlled trials, observational and qualitative studies were searched and those meeting selection criteria were selected and relevant information extracted using structured tool. Statistical pooling was not possible owing to the heterogeneity of the study designs and outcome measures. RESULTS: Of the nine articles which met the selection criteria, none used a randomized controlled design. Of these, five articles measured mother's acceptability of their infants being tested for HIV during its first pentavalent or DPT vaccination visit, and 89·5-100% accepted. Four articles reported the proportion of mothers who returned for HIV test results, ranging from 56·8% to 86·0%. Increased uptake of HIV testing following integration was confirmed by two articles. Only one study in Tanzania determined the uptake of vaccinations following integration, with urban facilities showing stable or slight increase of monthly vaccine uptake while decreases were observed across the rural sites. In two articles, stigma was perceived by service-providers and mothers as the potential risk following integration, particularly in rural settings. DISCUSSION: Despite the limited number of articles, the findings in this systematic review suggest that HIV testing during immunization clinic visits is acceptable and feasible as a possible model for service delivery. However, the impact on vaccination uptake needs further study.
Assuntos
Infecções por HIV/diagnóstico , Programas de Imunização , Programas de Rastreamento/organização & administração , Humanos , LactenteRESUMO
BACKGROUND: Despite therapeutic improvements, patients with sinonasal squamous cell carcinoma (SCC) still face an unfavorable prognosis and there is great need for alternative treatments. METHODS: SCCNC4 cells, originally derived from a T2N1M0 primary and untreated sinonasal SCC, were inoculated in the maxillary sinus of immunodeficient mice. Histology, invasive behavior, and genetic features were evaluated and compared with the original primary tumor. RESULTS: The mice developed tumors that invaded bone, surrounding tissues, and brain, showing the same poor differentiation as the original primary tumor. Genetic analysis revealed an almost identical pattern of copy number alterations, except for the deletion and loss of expression of the genes CDKN2A and PTEN. CONCLUSION: This article shows the feasibility of an orthotopic mouse model of SCC of the maxillary sinus. Completed by genome-wide genetic profiling data, this model will be useful for preclinical testing of specific gene-targeted anticancer drugs.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias do Seio Maxilar/patologia , Animais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Inibidor p16 de Quinase Dependente de Ciclina/genética , Estudos de Viabilidade , Humanos , Neoplasias do Seio Maxilar/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Experimentais , PTEN Fosfo-Hidrolase/genética , PrognósticoRESUMO
Background: Integration of HIV infant testing into immunization sessions is one of the strategies designed to increase coverage of early infant diagnosis. Objective: To determine the evidence on the outcomes of such integration. Methods: A systematic review of peer-reviewed and grey literature was undertaken from electronic sources such as MEDLINE, Google Scholar, websites of international agencies, past conferences and ministries of health reports published between year 2002 and 2013. Randomized controlled trials, observational and qualitative studies were searched and those meeting selection criteria were selected and relevant information extracted using structured tool. Statistical pooling was not possible owing to the heterogeneity of the study designs and outcome measures. Results: Of the nine articles which met the selection criteria, none used a randomized controlled design. Of these, five articles measured mother's acceptability of their infants being tested for HIV during its first pentavalent or DPT vaccination visit, and 89·5-100% accepted. Four articles reported the proportion of mothers who returned for HIV test results, ranging from 56·8% to 86·0%. Increased uptake of HIV testing following integration was confirmed by two articles. Only one study in Tanzania determined the uptake of vaccinations following integration, with urban facilities showing stable or slight increase of monthly vaccine uptake while decreases were observed across the rural sites. In two articles, stigma was perceived by service-providers and mothers as the potential risk following integration, particularly in rural settings. Discussion: Despite the limited number of articles, the findings in this systematic review suggest that HIV testing during immunization clinic visits is acceptable and feasible as a possible model for service delivery. However, the impact on vaccination uptake needs further study.
RESUMO
Desmoplastic small round cell tumor (DSRCT) is a rare malignancy with poor prognosis that generally involves the peritoneum. Only rare cases occur outside the abdomen. Its diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. We describe a case of a 61-year-old man referred to our department with a primary sinonasal tumor. The DSRCT diagnosis was confirmed by the presence of a polyphenotypic immunoprofile (positive for cytokeratin, desmin, and neuronspecific enolase) and the characteristic EWS-WT1 gene fusion resulting from the t(11;22)(p13;q12) reciprocal translocation. This reported case of DSRCT draws attention to the importance of including DSRCT in the differential diagnosis of sinonasal tumors.
Assuntos
Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico , Neoplasias dos Seios Paranasais/diagnóstico , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Diagnóstico Diferencial , Fusão Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/patologiaRESUMO
Sinonasal carcinomas are rare tumours with an unfavourable prognosis whose management is difficult and complex, leading to high morbidity and mortality despite improvements in the field of surgery and radiotherapy. An elevated number of these tumours can be attributed to occupational exposure. In comparison with other head and neck malignancies, studies of molecular changes in these tumours are infrequent. This review was focused on findings about the epidemiology and molecular and phenotypic characterisation of sinonasal carcinomas, which can potentially be useful for diagnosis and treatment. The increasing knowledge about the molecular biology that underlies their carcinogenesis may help to identify precursor lesions, prognostic markers and markers that predict chemoradiotherapy response and, finally, to identify potential molecular targets that will expand treatment options.
Assuntos
Neoplasias dos Seios Paranasais , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/etiologia , Neoplasias dos Seios Paranasais/genéticaRESUMO
INTRODUCTION: Anterior craniofacial resection (CFR) is a standardised procedure for the treatment of tumours involving the anterior skull base. We present our experience in the endoscopic treatment of these tumours. MATERIAL AND METHOD: A retrospective analysis was performed of patients treated by endoscopic anterior CFR in our Department from 2004 until 2011. RESULTS: Thirty-two patients were analysed. Mean follow-up was 28 months (range: 6-84 months). The most frequent pathological entity was adenocarcinoma (60%), followed by undifferentiated carcinoma (13%). According to TNM classification, malignant epithelial tumour staging was T3 in 9%, T4a in 53% and T4b in 19% of the malignant epithelial tumours. The complication rate was 6% and the resection was complete in 91% of cases. During follow-up, 9% of patients developed recurrence. The 5-year overall survival rate was 70% and the 5-year disease-free survival rate was 85% CONCLUSION: These results seem to indicate that properly planned endoscopic CFR may be a valid alternative to traditional open approaches for the management of malignancies of the anterior skull base.
Assuntos
Endoscopia/métodos , Ossos Faciais/cirurgia , Neoplasias da Base do Crânio/cirurgia , Crânio/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: The increasing expertise of transnasal endoscopic surgery has recently expanded its indications to include the management of tumours affecting the skull base. We report our experience with endoscopic management of these tumours, emphasising the indications and surgical technique used. MATERIAL AND METHOD: A retrospective analysis was performed of patients treated by an endoscopic endonasal approach (EEA) in our department from 2004 until 2011. RESULTS: Sixty-three patients were analysed. We performed an endoscopic craniofacial resection in 32 patients (51%), an expanded EEA in 22 (35%), a transclival approach in 6 (9%) and a transpterygoid approach in 3 (5%). The most frequent benign tumour was nasopharyngeal angiofibroma (24%), while adenocarcinoma (30%) was the most common among malignancies. Mean follow-up was 26 months (range: 6 to 84 months). The complication rate was 5% and resection was complete in 56 cases (89%). The 5-year overall-survival was 71% in patients with malignant tumours and the effectiveness was 100% in benign tumours. CONCLUSION: Our results support that endoscopic surgery, when properly planned, represents a valid alternative to standard surgical approaches for the management of skull base tumours.
Assuntos
Adenocarcinoma/cirurgia , Angiofibroma/cirurgia , Endoscopia/métodos , Neoplasias Nasofaríngeas/cirurgia , Neoplasias da Base do Crânio/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiofibroma/terapia , Quimioterapia Adjuvante , Criança , Terapia Combinada , Intervalo Livre de Doença , Embolização Terapêutica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Neoplasias Nasofaríngeas/terapia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Base do Crânio/terapia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The management of juvenile angiofibroma (JA) has changed during the last decades but it still continues to be a challenge. The objective of this study was to review the used treatment and our outcomes. METHODS: From 1992 to 2010, 48 cases of JA were treated at our department. Charts were reviewed for standard demographic, tumour size and location, vascular supply and results of embolization, surgical approach, operative results, adjuvant therapies, recurrence and postoperative follow-up. RESULTS: Most tumours were Andrews-Fisch stages III and IV and surgery was used as the main treatment in all cases. We used an open surgical approach in 37 (77%) patients and 11 (23%) were treated endoscopically. The most common open approach used in this series was the subtemporal-preauricular approach. Until 1995, all tumours were operated on by a conventional open approach. Afterwards, early-stage tumours were operated on through an endoscopic approach. Ten patients were treated through surgery followed by radiosurgery. Two (4%) patients had recurrent disease. CONCLUSIONS: These tumours should be treated at centres with expertise in skull base surgery to achieve complete surgical resections with low morbidity. Radiosurgery after surgery seems to be a valuable option in the long-term control of some extended JAs.