NUT carcinoma, an under-recognized malignancy: a clinicopathologic and molecular series of 6 cases showing a subset of patients with better prognosis and a rare ZNF532::NUTM1 fusion.

NUT carcinoma (NC) is a rare malignancy with aggressive clinical behavior, defined by rearrangements involving the NUTM1 gene locus. This entity is often under-recognized and its diagnosis may be challenging. In this study, we describe a subset of patients that, despite the molecularly proven diagnosis of NC, show improved outcomes. In addition, we describe one case with the novel ZNF532::NUTM1 fusion. All cases of NC diagnosed from 2013 to 2022 in our department were retrieved. FISH using dual color bring-together probes and next-generation sequencing assay were performed to characterize the fusions involving NUTM1. Among 6 patients identified, 5 were men with a median age of 35.6 years. Four patients had primary tumors in the head and neck region (2 ethmoid sinus, 1 parotid gland, and 1 lacrimal gland); 1 in the mediastinum, and another presented with a femoral bone tumor. In all cases, the initial diagnoses were not NC. The cases showed different morphological patterns, including monomorphic, rhabdoid, and pleomorphic appearances. One case showed a pseudopapillary pattern. By immunohistochemistry, all tumors showed squamous differentiation and ≥50% of neoplastic cells with nuclear positivity for NUT antibody. One case expressed WT1 (C-terminus) and other showed chromogranin positivity. Genetic study revealed a BRD4::NUTM1 fusion in all head and neck cases, BRD3::NUTM1 in mediastinum case, and ZNF532::NUTM1 fusion in the femur bone case. They were treated with surgical resection plus chemotherapy and radiotherapy. The median overall survival was 23.11 months (1.6-83.3 months) and the median disease-free survival was 14.86 months (0-54.4 months). The patients with longer overall survival were one with a lacrimal gland primary (83.3 months) and other with a parotid lesion (31.9 months). Both patients were primarily treated with complete surgical resection. Anatomic location may be directly related to the overall survival in NC cases. Resectability of the lesion is also an important factor related to survival. Pathologists should include NC in the differential diagnosis of any poorly differentiated and undifferentiated monomorphic malignancy, regardless of its anatomic location.

Endonasal endoscopic surgery for sinonasal squamous cell carcinoma from an oncological perspective.

Endonasal endoscopic surgery (EES) has been applied to the management of sinonasal (SN) tumors based on recent advances in endoscopic surgical techniques and technologies over the past three decades. EES has been mainly indicated for benign tumors and less aggressive malignant tumors. Notwithstanding this, EES has been gradually adopted for squamous cell carcinoma (SCC), which is the most common histology among SN malignancies. However, an analysis of the outcomes of EES for patients with SCC is difficult because most articles included SCC a wide range of different tumor histologies. Therefore, we herein review and clarify the current status of EES focusing on SCC from an oncological perspective. The oncologic outcomes and the ability to achieve a histologically complete resection are similar between endoscopic and open approaches in highly selected patients with SN-SCC. Surgical complications associated with EES are likely similar for SN-SCC compared to other sinonasal malignancies. The indications for a minimally invasive approach such as EES in the management of patients with SN-SCC should be stricter than those for less aggressive malignant tumors because of the aggressive nature of SCC. Also, it is important to achieve negative surgical margins with EES in patients with SCC. We believe that the indications for EES for SN-SCC are widening due to advances in diagnostic imaging, and endoscopic surgical techniques and technologies. However, while expanding the indications for EES for SN-SCC we must carefully confirm that the outcomes support this strategy.

Influence of cyclic AMP on facial nerve regeneration in rats.

UNLABELLED: Promoting facial nerve regeneration is a significant challenge. AIM: To evaluate the possible neurotrophic influence of cyclic AMP on facial nerve regeneration of Wistar rats. METHOD: The right facial nerve of thirty-two animals were completely transected and immediately sutured, followed by exposure or not to topical cyclic AMP. Behavioral and histometric analyses were done at 14 and 28 days. RESULTS: Statistical differences (p<0.05) were found in the behavioral and histometric analyses on the 14th day, suggesting an early regenerative response of the facial nerve to cAMP exposure. CONCLUSION: This study demonstrates a possible neurotrophic effect of cAMP on facial nerve regeneration in rats.

Influência do AMP cíclico na regeneração do nervo facial em ratos / Influence of cyclic AMP on facial nerve regeneration in rats

Estimular a regeneração do nervo facial é ainda hoje um desafio. OBJETIVO: Estudar a possível influência neurotrófica do nucleotídeo cíclico adenosina monofosfato (AMPc) na regeneração do nervo facial de ratos Wistar. MÉTODO: Trinta e dois animais foram submetidos à transecção completa com sutura imediata do nervo facial direito, sendo divididos em expostos ou não expostos à aplicação tópica de AMPc, com análises comportamentais (movimentação de vibrissas e fechamento da rima palpebral) e histométrica (contagem de fibras mielinizadas) em dois períodos, 14 e 28 dias após a lesão. RESULTADO: Encontramos diferenças estatísticas (p<0,05) nas análises comportamental e histométrica no 14º dia, sugerindo uma precocidade na regeneração do nervo facial exposto ao AMPc. CONCLUSÃO: Nosso estudo constatou uma possível ação neurotrófica do AMPc na regeneração do nervo facial em ratos.

Promoting facial nerve regeneration is a significant challenge. AIM: To evaluate the possible neurotrophic influence of cyclic AMP on facial nerve regeneration of Wistar rats. METHOD: The right facial nerve of thirty-two animals were completely transected and immediately sutured, followed by exposure or not to topical cyclic AMP. Behavioral and histometric analyses were done at 14 and 28 days. RESULTS: Statistical differences (p<0.05) were found in the behavioral and histometric analyses on the 14th day, suggesting an early regenerative response of the facial nerve to cAMP exposure. CONCLUSION: This study demonstrates a possible neurotrophic effect of cAMP on facial nerve regeneration in rats.

Vocal fold immobility after thyroidectomy with intraoperative recurrent laryngeal nerve monitoring.

CONTEXT AND OBJECTIVE: Intraoperative nerve monitoring has emerged as a valuable tool to facilitate recurrent laryngeal nerve identification during thyroid surgery, thereby avoiding its injury. The aim was to evaluate vocal fold mobility in patients who underwent thyroidectomy with intraoperative nerve monitoring. DESIGN AND SETTING: Cohort formed by a consecutive series of patients, at a tertiary cancer hospital. METHODS: The subjects were patients who underwent thyroidectomy using intraoperative laryngeal nerve monitoring, between November 2003 and January 2006. Descriptive analysis of the results and comparison with a similar group of patients who did not undergo nerve monitoring were performed. RESULTS: A total of 104 patients were studied. Total thyroidectomy was performed on 65 patients. Vocal fold immobility (total or partial) was detected in 12 patients (6.8% of the nerves at risk) at the first postoperative evaluation. Only six (3.4% of the nerves at risk) continued to present vocal fold immobility three months after surgery. Our previous series with 100 similar patients without intraoperative nerve monitoring revealed that 12 patients (7.5%) presented vocal fold immobility at the early examination, and just 5 (3.1%) maintained this immobility three months after surgery, without significant difference between the two series. CONCLUSION: In this series, the use of intraoperative nerve monitoring did not decrease the rate of vocal fold immobility.

Sigmoid sinus thrombosis associated to chronic otitis media.

UNLABELLED: Otogenous lateral sinus thrombosis (OLST) is a rare disease and presents a controversial treatment. AIM: Clinical aspects and treatment were reported based on our experience. METHODS: Retrospective study. Six cases of OLST were treated in our institution in the last ten years. Clinical and imaging data were analyzed. RESULTS: All six patients had the lateral sinus thrombosis detected during image evaluation for other symptoms related to chronic otitis media (COM) complications. Fever, headache and facial paralysis were the main clinical manifestation related to mastoiditis, meningitis and cerebellar abscess. We could not identify, in any case, specific features of lateral sinus thrombosis. In all cases a mastoidectomy was associated with large spectrum antibiotics maintained for 3 months. In three cases anticoagulation therapy was introduced and in three cases anticoagulation was not indicated. All cases presented a good clinical evolution, without sequelae. CONCLUSIONS: OLST is almost always associated with other complications of COM. It is diagnosed almost by accident during the investigative image study. We believe such disease is underestimated. In our experience, OLST presents a benign course, and mastoidectomy with antibiotics is the treatment of choice.

Vocal fold immobility after thyroidectomy with intraoperative recurrent laryngeal nerve monitoring

CONTEXT AND OBJECTIVE: Intraoperative nerve monitoring has emerged as a valuable tool to facilitate recurrent laryngeal nerve identification during thyroid surgery, thereby avoiding its injury. The aim was to evaluate vocal fold mobility in patients who underwent thyroidectomy with intraoperative nerve monitoring. DESIGN AND SETTING: Cohort formed by a consecutive series of patients, at a tertiary cancer hospital. METHODS: The subjects were patients who underwent thyroidectomy using intraoperative laryngeal nerve monitoring, between November 2003 and January 2006. Descriptive analysis of the results and comparison with a similar group of patients who did not undergo nerve monitoring were performed. RESULTS: A total of 104 patients were studied. Total thyroidectomy was performed on 65 patients. Vocal fold immobility (total or partial) was detected in 12 patients (6.8 percent of the nerves at risk) at the first postoperative evaluation. Only six (3.4 percent of the nerves at risk) continued to present vocal fold immobility three months after surgery. Our previous series with 100 similar patients without intraoperative nerve monitoring revealed that 12 patients (7.5 percent) presented vocal fold immobility at the early examination, and just 5 (3.1 percent) maintained this immobility three months after surgery, without significant difference between the two series. CONCLUSION: In this series, the use of intraoperative nerve monitoring did not decrease the rate of vocal fold immobility.

CONTEXTO E OBJETIVO: A monitorização intra-operatória de nervos surgiu como uma ferramenta valiosa para facilitar a identificação do nervo laríngeo recorrente durante a cirurgia de tireóide, evitando a sua lesão. O objetivo foi avaliar a mobilidade das pregas vocais em pacientes submetidos a tireoidectomia com monitorização intra-operatória do nervo laríngeo recorrente. TIPO E LOCAL DO ESTUDO: Coorte de uma série consecutiva de pacientes em um hospital terciário de tratamento de câncer. MÉTODOS: Pacientes foram submetidos à cirurgia de tireóide usando a monitorização intra-operatória do nervo laríngeo recorrente, entre novembro de 2003 e janeiro de 2006. Uma análise descritiva dos resultados e uma comparação com um grupo similar de pacientes que não foram submetidos a monitorização dos nervos foram realizadas. RESULTADOS: Um total de 104 pacientes foi estudado. Tireoidectomia total realizada em 65 pacientes. Imobilidade de pregas vocais (parcial ou total) foi detectada em 12 pacientes (6.8 por cento dos nervos sob risco) na primeira avaliação pós-operatória. Apenas 6 (3.4 por cento dos nervos sob risco) permaneceram com imobilidade de prega vocal três meses após a cirurgia. Nossa série prévia com 100 pacientes similares sem a monitorização intra-operatória revelou que 12 pacientes (7.5 por cento) apresentaram imobilidade de prega vocal na avaliação precoce, e apenas 5 (3.1 por cento) mantiveram a imobilidade três meses após a cirurgia, sem diferença significativa entre as séries. CONCLUSÃO: Nesta série, o uso da monitorização intra-operatória do nervo laríngeo recorrente não diminuiu a taxa de imobilidade de prega vocal.

Trombose do seio sigmóide associada à otite média crônica / Sigmoid Sinus thrombosis associated to chronic otitis media

A trombose séptica do seio sigmóide (TSSS) é uma doença rara de tratamento controverso. OBJETIVO: Relatarmos nossa experiência, ressaltando os aspectos clínicos e terapêuticos. MATERIAL E MÉTODO: Estudo retrospectivo de seis casos de TSSS tratados nos últimos 10 anos. O diagnóstico foi confirmado através de angiorressonância com acompanhamento de seis meses a seis anos. RESULTADOS: O diagnóstico da TSSS só foi suspeitado durante a análise de imagem solicitada para avaliação de outras complicações de otite média crônica. Febre, cefaléia e paralisia facial foram as principais manifestações clínicas relacionadas aos diagnósticos de mastoidite, meningite e abscesso cerebelar. Não foi possível identificar nenhum sintoma específico de trombose do seio sigmóide. Em todos os pacientes foi realizado mastoidectomia com antibioticoterapia de largo espectro sendo mantido por três meses. Em três casos foi realizada anticoagulação e nos outros três não foi indicado este tipo de terapia. Todos os pacientes evoluíram bem sem seqüelas. CONCLUSÃO: O diagnóstico de TSSS tem sido realizado inesperadamente em pacientes com otites médias crônica com outras complicações associadas. Acreditamos que esta doença esteja sendo subdiagnosticada. Apesar de grave, o prognóstico clínico tem sido bom, apenas com mastoidectomia e antibioticoterapia.

Otogenous lateral sinus thrombosis (OLST) is a rare disease and presents a controversial treatment. AIM: Clinical aspects and treatment were reported based on our experience. METHODS: Retrospective study. Six cases of OLST were treated in our institution in the last ten years. Clinical and imaging data were analyzed. RESULTS: All six patients had the lateral sinus thrombosis detected during image evaluation for other symptoms related to chronic otitis media (COM) complications. Fever, headache and facial paralysis were the main clinical manifestation related to mastoiditis, meningitis and cerebellar abscess. We could not identify, in any case, specific features of lateral sinus thrombosis. In all cases a mastoidectomy was associated with large spectrum antibiotics maintained for 3 months. In three cases anticoagulation therapy was introduced and in three cases anticoagulation was not indicated. All cases presented a good clinical evolution, without sequelae. CONCLUSIONS: OLST is almost always associated with other complications of COM. It is diagnosed almost by accident during the investigative image study. We believe such disease is underestimated. In our experience, OLST presents a benign course, and mastoidectomy with antibiotics is the treatment of choice.

Modelo experimental comportamental e histológico da regeneração do nervo facial em ratos / Behavioral and histologic experimental model of facial nerve regeneration in rats

O estabelecimento de modelos experimentais é o passo inicial para estudos de regeneração neural. OBJETIVO: Estabelecer modelo experimental de regeneração do nervo facial. MATERIAIS E MÉTODOS: Ratos Wistar com secção completa e sutura do tronco do nervo facial extratemporal, com análise comportamental e histológica até 9 semanas. FORMA DE ESTUDO: Estudo prospectivo experimental. RESULTADOS: Progressiva recuperação clínica e histológica dos animais. CONCLUSÃO: Estabelecemos um método aceitável para o estudo de regeneração do nervo facial em ratos.

To setup an experimental model is the first step to study neural regeneration. AIM: Setting up an experimental model on facial nerve regeneration. MATERIAL AND METHODS Wistar rats with complete sectioning and suturing of the extratemporal facial nerve trunk; with a behavioral and histological analysis for 9 weeks. STUD DESIGN: Experimental prospective study. RESULTS: Progressive clinical and histological recovery of the animals. CONCLUSION: Our method is acceptable to study facial nerve regeneration in rats.

Voice and vocal self-assessment after thyroidectomy.

BACKGROUND: Voice alterations after thyroidectomy can be found even with preserved function of laryngeal nerves. The purpose of this study was to evaluate voice before and after thyroid surgery and the role of orotracheal intubation on voice changes. METHODS: We conducted a prospective nonrandomized study of patients who underwent thyroid surgery and compared the results with a control group of patients who underwent breast surgery. Subjects underwent a videolaryngoscopic exam, a subjective and an objective voice analysis and a Voice Handicap Index (VHI) questionnaire before and after surgery. RESULTS: A total of 100 patients who underwent thyroidectomy and 30 who underwent breast surgery were studied. Both groups were similar in demographic, clinical, and surgical variables. Postoperative videolaryngoscopy showed larynx alterations in 28% of the thyroidectomized patients, without significant alterations in the control group. There were subjective voice changes in 29.7% of the patients without vocal fold immobility after thyroid surgery and no statistically significant changes after breast surgery. Acoustic analysis showed significant increased values in the voice turbulence index (VTI) parameter in both groups, although higher in the thyroid one. In the VHI assessment, voice complaints were more frequently registered in the thyroid group rather than in the control group. CONCLUSIONS: Voice alterations are frequent after thyroidectomy even with preserved vocal fold mobility. Such alterations were more frequently detected in that group than in patients who underwent breast surgery. Orotracheal intubation is just one of the multiple factors involved.

Behavioral and histologic experimental model of facial nerve regeneration in rats.

UNLABELLED: To setup an experimental model is the first step to study neural regeneration. AIM: Setting up an experimental model on facial nerve regeneration. MATERIAL AND METHODS: Wistar rats with complete sectioning and suturing of the extratemporal facial nerve trunk; with a behavioral and histological analysis for 9 weeks. STUDY DESIGN: Experimental prospective study. RESULTS: Progressive clinical and histological recovery of the animals. CONCLUSION: Our method is acceptable to study facial nerve regeneration in rats.

Fatores clínicos, etiológicos e evolutivos da audição na surdez súbita / Clinical, etiological and progression factors of hearing in sudden deafness

Existem várias terapias preconizadas para o tratamento da surdez súbita, algumas apresentam riscos significativos necessitando inclusive de internação hospitalar. OBJETIVO: Este estudo prospectivo analisa aspectos clínicos, etiológicos e evolutivos nos casos de surdez súbita (SS) em pacientes tratados ambulatorialmente com medicação oral. FORMA DE ESTUDO: clínico com coorte transversal. MATERIAL E MÉTODO: 40 pacientes com perda súbita da audição submeteram inicialmente a avaliação clínica otorrinolaringológica, testes audiométricos, análise hematológica e ressonância magnética. Confirmado o diagnóstico de SS, todos os pacientes receberam inicialmente prednisona e pentoxifilina sendo acompanhados por pelo menos um ano. RESULTADO: 45 por cento (n=18) apresentaram normalização dos limiares auditivos, 40 por cento (n=16) apresentaram melhoras auditivas, 15 por cento (n=6) mantiveram os mesmos limiares iniciais. Nove casos (22,5 por cento) apresentaram manifestações clínicas que justificaram a perda auditiva (infecção viral, fatores imunomediados, alterações vasculares e outros), três (7,5 por cento) apresentaram tumores na região do ângulo ponto-cerebelar. A evolução auditiva nestes 12 casos com etiologia presumida não apresentou diferença estatística significante em relação aos 28 casos sem etiologia definida. O tratamento clínico instituído nos primeiros sete dias de instalação da perda auditiva, nos pacientes que obtiveram melhora, foi o único parâmetro estatisticamente significante dos fatores prognóstico avaliado. CONCLUSÃO: A pesquisa exaustiva etiológica deve ser realizada em qualquer caso de perda auditiva neurossensorial aguda. A presença de 7,5 por cento de tumores localizados na região do ângulo ponto-cerebelar nos casos de SS juntamente com outras causas tratáveis justifica a investigação clínica nestes pacientes. Nossos pacientes apresentaram uma boa melhora auditiva em 67,5 por cento dos casos, independentemente da etiologia. O início da terapia nos primeiros sete dias de instalação da perda auditiva foi o único fator de melhora significante dos limiares auditivos.

Clinical, etiological and progression factors of hearing in sudden deafness.

UNLABELLED: Out of the many forms of therapy for sudden deafness, some require hospitalization and present significant risks. AIM: This prospective study analyzes etiology and evolution in cases of sudden deafness (SD) where outpatient oral treatment was used. STUDY DESIGN: Clinical with transversal cohort. MATERIAL AND METHOD: Forty cases of sudden hearing loss were followed for at least one year. All were submitted to initial clinical evaluation, auditory tests, routine blood analysis, and magnetic resonance imaging. All received initial treatment with pentoxifylline and prednisone. RESULTS: 45% (n=18) presented normal auditory thresholds, 40% (n=16) showed some improvement in hearing, 15% (n=6) maintained initial hearing level. Nine cases (22.5%) presented clinical conditions possibly implicated in hearing loss (viral infection, immunomediated hearing loss, vascular disorders, and so on); three (7.5%) had cerebellopontine tumors. Evolution of hearing in these 12 cases with presumed etiology presented no differences from hearing in the 28 cases without any known etiological factor. Clinical treatment within the first seven days was the only statistically significantly different condition in patients who improved hearing. CONCLUSIONS: An objective search for etiological bases should be conducted in any case of acute sensorineural hearing loss. The presence of cerebellopontine tumors in 7.5% of cases of SD, among other treated causes, justifies a thorough clinical investigation in these patients. Overall good evolution of hearing was observed in 67.5% of cases of SD, regardless of its etiology. Therapy within the first seven days of SD was significantly related to better outcomes in hearing.

Disacusia neurossensorial imunomediada / Immunomediated sensorineural hearing loss

A disacusia neurossensorial imunomediada (DNSI) é caracterizada geralmente por uma disacusia neurossensorial bilateral, progressiva e assimétrica, acompanhada ou näo por outros sintomas da orelha interna. Três pacientes com DNSI cujo quadro clínico e audiométrico eram sugestivos de doença auto-imune, e apresentaram resposta positiva à terapia imunossupressora ou pesquisa positiva de anticorpo anti hsp-70 68kD, foram estudados com relaçäo às características clínicas, testes diagnósticos, alternativas terapêuticas e evoluçäo da doença. Dois pacientes apresentaram quadro de disacusia neurossensorial rapidamente progressiva, associado a quadro vestibular, e outro, quadro de surdez súbita unilateral. Nenhum paciente apresentou positividade às provas reumatológicas, e apenas um paciente apresentou aumento na velocidade de hemossedimentaçäo. Nenhum paciente obteve resposta adequada sustentada à corticoterapia, mas dois deles melhoraram com outras terapias imunossupressoras. O diagnóstico da DNSI é clínico e baseado na resposta positiva ao teste terapêutico com imunossupressores. A pesquisa de anticorpo anti-hsp70 de 68 kD pelo Western Blot é o único exame laboratorial específico para seu diagnóstico, possuindo sensibilidade de 42 por cento e especificidade de 90 por cento. Apenas 1 paciente apresentou positividade para este teste e näo respondeu à terapia imunossupressora. Os dois pacientes com teste negativo responderam satisfatoriamente ao tratamento. A baixa sensibilidade do Western Blot e seu alto custo dificultam sua difusa utilizaçäo em nosso meio. A introduçäo precoce do tratamento é de suma importância por auxiliar no diagnóstico e por proporcionar um melhor prognóstico auditivo

Medida do nível de ruído produzido por aparelhos eletrodomésticos / Measurement of the noise level produced by household appliances

A Pedra Auditiva Induzida Por Ruído (P.A.I.R.) é definida como qualquer alteração dos liminares auditivos do tipo neurossensorial, decorrente da exposição sistemática a níveis elevados de pressão sonora. Neste trabalho, foram medidos os níveis de intensidade de ruído de 11 aparelhos eletrodomésticos. O resultado evidenciou que alguns dos aparelhos apresentam níveis de ruído que podem comprometer a audição.