RESUMEN
Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.
Asunto(s)
Carcinoma , Neoplasias del Seno Maxilar , Melanoma , Neoplasias Nasales , Senos Paranasales , Humanos , Carcinoma/diagnóstico , Neoplasias del Seno Maxilar/diagnóstico , Neoplasias del Seno Maxilar/patología , Cavidad Nasal/patología , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/epidemiología , Neoplasias Nasales/terapia , Senos Paranasales/patologíaRESUMEN
PURPOSE: Maxillary sinus carcinomas usually present as a locally advanced disease at the time of diagnosis and it is extremely unusual to have a second primary maxillary carcinoma on the contralateral side after many years of completion of treatment of the first malignancy. We present here a case report of a sphenopalatine artery (SPA) pseudoaneurysm mimicking the second primary maxillary carcinoma. METHODS: We reviewed the literature for SPA pseudoaneurysm. RESULTS/CASE REPORT: This report describes the case of a 90-year-old man with a background of adenoid cystic carcinoma of the right maxillary sinus, diagnosed and treated with surgery and radiotherapy 14 years ago, who presented with a history of multiple episodes of epistaxis. The radiological evaluation showed a heterogeneously enhancing mass with a central hemorrhagic component and surrounding bony erosions in the left maxillary sinus and the patient was planned for biopsy from the suspicious mass along with SPA ligation. However, on opening the maxillary antrum there was excessive bleeding and it was determined unsafe to proceed further. The patient was subsequently taken to interventional radiology for diagnostic angiography which revealed an SPA pseudoaneurysm that was subsequently embolized successfully. CONCLUSIONS: Sphenopalatine artery pseudoaneurysms should be considered as a differential for recurrent epistaxis in patients with a history of sinonasal malignancy. In such cases, endovascular embolization is a viable management option.
Asunto(s)
Aneurisma Falso , Humanos , Masculino , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/diagnóstico , Aneurisma Falso/terapia , Anciano de 80 o más Años , Diagnóstico Diferencial , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico por imagen , Neoplasias Primarias Secundarias/patología , Neoplasias del Seno Maxilar/diagnóstico , Neoplasias del Seno Maxilar/diagnóstico por imagen , Neoplasias del Seno Maxilar/patología , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/diagnóstico por imagen , Epistaxis/etiología , Arteria Maxilar/diagnóstico por imagenRESUMEN
Extranodal natural killer/T-cell lymphoma is a distinct subtype of non-Hodgkin lymphoma that originates from natural killer cells or cytotoxic T cells. Its diagnosis is challenging due to the rarity and lack of awareness, especially in cases where osteomyelitis of the jawbone is the initial symptom. This paper reports a case of extranodal natural killer/T-cell lymphoma presenting primarily with oral ulcers. Through analyzing the clinical and pathological characteristics, differential diagnosis, treatment and prognosis, and reasons for misdiagnosis of the disease, this study aims to provide references for clinical diagnosis and treatment.
Asunto(s)
Neoplasias del Seno Maxilar , Osteomielitis , Humanos , Osteomielitis/diagnóstico , Osteomielitis/diagnóstico por imagen , Diagnóstico Diferencial , Neoplasias del Seno Maxilar/patología , Neoplasias del Seno Maxilar/diagnóstico , Masculino , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/diagnóstico , Tomografía Computarizada por Rayos X , Enfermedades Mandibulares/diagnóstico por imagen , Enfermedades Mandibulares/diagnóstico , Enfermedades Mandibulares/patología , Úlceras Bucales/diagnóstico , Úlceras Bucales/patología , Persona de Mediana EdadRESUMEN
Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172K, R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the Gene Expression Omnibus database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sinonasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, showed the position of our sample to be within 1.02 standard deviation of the other IDH-mutant SNUCs. A molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.
Asunto(s)
Carcinoma , Metilación de ADN , Isocitrato Deshidrogenasa , Neoplasias del Seno Maxilar , Mutación , Humanos , Isocitrato Deshidrogenasa/genética , Metilación de ADN/genética , Carcinoma/genética , Carcinoma/patología , Neoplasias del Seno Maxilar/genética , Neoplasias del Seno Maxilar/patología , Masculino , Persona de Mediana Edad , Femenino , AncianoRESUMEN
OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.
Asunto(s)
Carcinoma , Neoplasias del Seno Maxilar , Humanos , Neoplasias del Seno Maxilar/terapia , Neoplasias del Seno Maxilar/patología , Carcinoma/patología , Terapia Combinada , Pronóstico , Estudios RetrospectivosRESUMEN
OPINION STATEMENT: The role of induction chemotherapy in sinonasal cancers is promising; however, prospective studies with higher grades of evidence are needed. With the currently available literature, the authors would advocate for the use of induction chemotherapy (IC) in locally advanced sinonasal squamous cell carcinoma (T3-T4) for organ preservation and potentially for improved survival outcomes. In sinonasal undifferentiated carcinoma (SNUC), IC should be considered in all patients given its tendency for aggressive invasion and poor outcomes. In SNUC, response to IC may direct the modality of definitive treatment to follow. In responders (partial or complete), chemoradiation therapy should be strongly considered. In non-responders or in those with progression of disease, surgical therapy is favored. For esthesioneuroblastoma, surgical resection with negative margins and adjuvant radiation therapy remains the gold standard. However, IC may be considered for locally advanced disease especially with orbital invasion or in recurrent/distant disease. There is no definite indication for IC in sinonasal adenoid cystic carcinoma or sinonasal adenocarcinoma. Recommendations are summarized in Table 1.
Asunto(s)
Neoplasias del Seno Maxilar , Neoplasias Nasales , Humanos , Quimioterapia de Inducción , Estudios Prospectivos , Neoplasias del Seno Maxilar/patología , Neoplasias del Seno Maxilar/terapia , Neoplasias Nasales/patología , Cavidad Nasal/patologíaRESUMEN
OBJECTIVE: The aim of this study was to determine the long-term efficacy of four steps of operation on the treatment of maxillary sinus (MS) inverted papilloma (IP). METHODS: 83 patients who were diagnosed with IP that originated from the MS, underwent four step procedure of attachment sites, including mucosal stripping, periosteum ablation, bone drilling and bone ablation and had postoperative follow-up of 3 years were enrolled. RESULTS: Of the 83 patients, 59 (71.1%) patients were primary surgery and revision surgery in 24 (28.9%), single attachment was in 31(37.3%) patients and multifocal attachments in 52 (62.7%).When the numbers were not mutually exclusive, the most common origin sites of IPs were the medial wall in 54 (37.2%), lateral wall in 29 (20.0%), anterior wall in 18 (12.4%), inferior wall in 22 (15.2%), posterior in 15 (10.3%), and superior wall in 7 (4.8%). Large MMA alone was performed in 5 (6.0%), MMA combined with medial maxillectomy 76 (91.6%), and MMA combined with Caldwell-Luc approach in 2 (2.4%). No major intra- or postoperative complications were observed. The average follow-up was 41 months (range, 37-61 months). CT and endoscope showed that tumor and symptom recurrence occurred in 2 patients (2.41%). In addition, although the opening of antrostomy was closed and CT revealed the uniform soft tissue shadow and hyperostosis of MS in 11(13.3%) patients, they didn't report any symptoms and showed well epithelization of middle meatus mucosa. CONCLUSION: The four steps of operations of attachment sites of MS IP, including mucosal stripping, periosteum ablation, bone drilling and bone ablation, may effectively prevent the recurrence of MS IP.
Asunto(s)
Neoplasias del Seno Maxilar , Papiloma Invertido , Humanos , Seno Maxilar/cirugía , Seno Maxilar/patología , Neoplasias del Seno Maxilar/cirugía , Neoplasias del Seno Maxilar/patología , Papiloma Invertido/cirugía , Papiloma Invertido/patología , Endoscopía/métodos , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer of the sinonasal tract and is often characterized by intracranial invasion. However, SNUC rarely metastasizes to the spine. In this paper, we present a case of extradural metastasis and invasion of the adjacent spine by SNUC. A 42-year-old man presented to our hospital with two-month history of anosmia and nosebleeds. Imaging studies showed a neoplasm of the ethmoid sinus with extension into the anterior cranial fossa. The patient underwent resection of the carcinoma and began chemoradiotherapy. After completing chemoradiotherapy the patient complained of neck pain radiating down the right arm, and imaging showed an extradural mass at the C5 vertebral level. The patient underwent laminectomy for debulking of this tumor. One month later, the patient complained of recurrent weakness and pain in the right shoulder and arm. Imaging showed an extradural tumor wrapping around the C7 and C8 nerve roots, as well as a separate tumor at C2 adherent to the dura. The extradural tumor at C2 was surgically resected. Further imaging showed multiple new soft tissue masses at the thoracic level. We present a case of SNUC metastasis to the extradural spine representing the second case reported in the literature. Peri-dural metastasis and resulting symptoms should be included in the differential diagnosis and assessment of patients with SNUC.
Asunto(s)
Carcinoma , Neoplasias del Seno Maxilar , Masculino , Humanos , Adulto , Carcinoma/cirugía , Carcinoma/patología , Neoplasias del Seno Maxilar/patologíaRESUMEN
BACKGROUND: Primary maxillary sinus carcinosarcoma (CS) is an extremely rare malignant tumor characterized by biphasic histologic components, lack of standardized treatment, high recurrence rate, and poor prognosis. This paper presents a case of primary maxillary sinus CS and its treatment. CASE PRESENTATION: A 39-year-old female patient complained of right facial pain and maxillary teeth numbness on March 21, 2018. Computed tomography examination revealed a malignant mass with osteolytic destruction. Preoperative biopsy suggested sarcomatoid carcinoma or CS. A total right maxillectomy under general anesthesia was performed on April 12, 2018. The final staging was T3N0M0 (ACJJ 2019). Postoperative radiotherapy and chemotherapy were performed. On May 26, 2018, the patient received the first cycle of doxorubicin plus ifosfamide. Two days before radiotherapy, the patient received an intra-oral prosthesis. From June 20, 2018, to August 22, 2018, the patient received concurrent chemoradiotherapy: radiotherapy (60 Gy in 30 fractions) and the second cycle of doxorubicin. Then, the patient received four cycles of doxorubicin plus ifosfamide. The patient was followed for 39 months with no evidence of disease. CONCLUSION: Using multidisciplinary therapy, clinical-stage T3N0M0 (ACJJ 2019) maxillary sinus CS may achieve a good prognosis.
Asunto(s)
Carcinosarcoma , Neoplasias del Seno Maxilar , Femenino , Humanos , Adulto , Seno Maxilar/diagnóstico por imagen , Ifosfamida/uso terapéutico , Estudios de Seguimiento , Neoplasias del Seno Maxilar/patología , Neoplasias del Seno Maxilar/cirugía , Carcinosarcoma/terapia , Carcinosarcoma/tratamiento farmacológico , Doxorrubicina/uso terapéuticoRESUMEN
SMARCB1(INI1)-deficient sinonasal carcinoma is a recently recognized entity with wide histomorphologic spectrum. The classification of sinonasal adenocarcinoma (SNAC) is complex and yet to be redefined, especially the category of high-grade non-intestinal-type SNAC. Recently SMARCB1(INI1)-deficient SNACs with an unique oncocytoid/rhabdoid cytomorphology and variable degrees of glandular formation have been reported. Here we described a rare case of SMARCB1(INI1)-deficient SNAC composed of mainly oncocytoid/rhabdoid cells with mixed solid and cribriform patterns. This case was originally diagnosed as non-intestinal-type SNAC and was reclassified due to complete loss expression of SMARCB1(INI1) by immunohistochemistry (IHC). The SMARCB1(INI1) stain provides a valuable tool for identification of this specific type of SNAC. We compared this case with other SNACs diagnosed in our department and reviewed relevant literature for this specific type of SNAC.
Asunto(s)
Adenocarcinoma , Neoplasias del Seno Maxilar , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Biomarcadores de Tumor/análisis , Carcinoma/diagnóstico , Carcinoma/patología , Femenino , Humanos , Hiperplasia , Inmunohistoquímica , Neoplasias del Seno Maxilar/diagnóstico , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , Proteína SMARCB1/análisisRESUMEN
Comprehensive molecular testing of individual tumors has led to the identification of novel molecularly defined cancer therapies and treatment indications. Given low frequencies of many molecular alterations, efficacy of therapies used to target them are often undefined, especially in the context of rare malignancies. Here we describe the first reported case of MET amplification in sinonasal undifferentiated carcinoma (SNUC), a rare cancer with a poor prognosis. The patient was treated with crizotinib, a tyrosine kinase inhibitor that targets c-MET, and experienced a complete response. Our report demonstrates the potential of employing precision oncology approaches in SNUC and other rare cancers.
Asunto(s)
Carcinoma/terapia , Crizotinib/farmacología , Neoplasias del Seno Maxilar/terapia , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Carcinoma/diagnóstico por imagen , Carcinoma/genética , Carcinoma/patología , Femenino , Amplificación de Genes/efectos de los fármacos , Humanos , Neoplasias del Seno Maxilar/diagnóstico por imagen , Neoplasias del Seno Maxilar/genética , Neoplasias del Seno Maxilar/patología , Terapia Molecular Dirigida , Tomografía Computarizada por Tomografía de Emisión de Positrones , Proteínas Proto-Oncogénicas c-met/genéticaRESUMEN
The novel coronavirus (SARS-CoV-2) pandemic has influenced the timeliness of care for patients with both common and rare conditions, particularly those affecting high-risk operative sites such as the upper aerodigestive tract. Sinonasal undifferentiated carcinoma (SNUC) represents a rare malignancy of the sinonasal tract, a unique subset of which has never been previously reported in the otolaryngology literature and is characterized by inactivation of the SMARCB (INI-1) tumor suppressor gene. This subtype exhibits a particularly poor prognosis and is characterized pathologically by its rhabdoid appearance. Here we present the case of an individual who was diagnosed with a sinonasal mass during the SARS-CoV-2 pandemic, which was ultimately found to be SMARCB (INI-1)-deficient sinonasal carcinoma. Advanced imaging was deferred in the interest of limiting the patient's exposure to the virus, and expedited operative management was performed which facilitated prompt referral for adjuvant chemoradiation. The SARS-CoV-2 pandemic presents unique challenges, but the work-up of high-risk lesions must be prioritized; this continues to be paramount as SARS-CoV-2 resurges in many cities across the USA.
Asunto(s)
COVID-19/epidemiología , Carcinoma/diagnóstico , Carcinoma/cirugía , Neoplasias del Seno Maxilar/diagnóstico , Neoplasias del Seno Maxilar/cirugía , Biopsia , Carcinoma/patología , Quimioradioterapia Adyuvante , Diagnóstico Diferencial , Endoscopía , Femenino , Humanos , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Sinonasal tumors that harbor neuroendocrine histologic features include olfactory neuroblastoma (previously known as esthesioneuroblastoma), sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. These tumors represent a diverse spectrum of clinical behavior and as such require histology-specific management. Herein, we review the management of these sinonasal tumors with neuroendocrine features and discuss fundamentals of multi-modality care for each histology. An emphasis is placed on olfactory neuroblastomas, given their relative frequency and skullbase origin. METHODS: A comprehensive literature review on contemporary management of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma was performed. RESULTS: Management of sinonasal tumors with neuroendocrine features can include surgical resection, radiation therapy, and/or chemotherapy. Due to their site of origin, these tumors can frequently involve the skullbase, which can require site-specific care. The optimal treatment modalities and the sequence in which they are performed are largely dependent on histology. In most cases, olfactory neuroblastoma is best managed with surgical resection followed by radiation therapy. Sinonasal neuroendocrine carcinomas represent a variety of histologic phenotypes (carcinoid, atypical carcinoid, small cell, and large cell), which determine the optimal treatment modality. Finally, sinonasal undifferentiated carcinoma is likely best managed by induction chemotherapy with subsequent therapy dictated by the initial response. CONCLUSIONS: A team approach to multi-modality care is essential in the treatment of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. Early biopsy, histologic diagnosis, and comprehensive imaging are critical to determining the appropriate management paradigm.
Asunto(s)
Carcinoma Neuroendocrino/terapia , Carcinoma/terapia , Estesioneuroblastoma Olfatorio/terapia , Neoplasias del Seno Maxilar/terapia , Neoplasias Nasales/terapia , Neoplasias de la Base del Cráneo/terapia , Animales , Carcinoma/patología , Carcinoma Neuroendocrino/patología , Terapia Combinada , Manejo de la Enfermedad , Estesioneuroblastoma Olfatorio/patología , Humanos , Neoplasias del Seno Maxilar/patología , Neoplasias Nasales/patología , Neoplasias de la Base del Cráneo/patologíaRESUMEN
BACKGROUND: Maxillary sinus squamous cell carcinoma (MSSCC) is a relatively rare head and neck cancer with poorly defined prognosis, and the present study aimed to investigate the outcomes for MSSCC according to different treatments. METHODS: Tianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 2007 to 2017, and 98 patients with pathologically confirmed MSSCC were enrolled. Retrospective analysis and follow-up were performed for each patient. Multivariate analysis of prognostic factors was performed using Cox's regression model. RESULTS: For all the 98 cases of MSSCC, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 31.0% and 29.3%, respectively. Among 98 patient, 33 patients were treated with systemic treatment (NON-SUR), 19 patients underwent neoadjuvant chemotherapy and/or radiotherapy followed by surgery (CT/RT+SUR), 38 patients received surgery followed by chemotherapy and/or radiotherapy (SUR+RT/CT), and 8 patients were performed surgery alone (SUR).The OS rate for each group was 27.3%, 57.9%, 30.6% and 37.5%, respectively, while the DFS was 21.2%, 36.8%, 31.6% and 25.0%, respectively. The OS rate of CT/RT+SUR was significantly higher than that of NON-SUR and SUR+CT/RT groups (P < 0.05). Multivariate analysis revealed that smoking, low differentiation, and advanced T stage were independent risk factors for OS, while low differentiation and advanced N stage for DFS. CONCLUSIONS: Surgery-based treatment is still the first-line therapeutic strategy for MSSCC. And neoadjuvant chemoradiotherapy followed by surgery is highly recommended for MSSCC patients, especially those with advanced tumors or requesting high quality of life.
Asunto(s)
Quimioradioterapia Adyuvante/estadística & datos numéricos , Neoplasias del Seno Maxilar/terapia , Procedimientos Quírurgicos Nasales/estadística & datos numéricos , Terapia Neoadyuvante/estadística & datos numéricos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia Adyuvante/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Seno Maxilar/patología , Seno Maxilar/cirugía , Neoplasias del Seno Maxilar/mortalidad , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , Procedimientos Quírurgicos Nasales/efectos adversos , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto JovenRESUMEN
The skull base is the location of a wide variety of malignant tumors. Among them is sinonasal undifferentiated carcinoma (SNUC), a highly aggressive sinonasal neoplasm that was recently reclassified into subgroups of high-grade carcinomas with unique genomic events (e.g., SMARC-deficient carcinoma, nuclear protein in testis NUT carcinoma). Other high-grade carcinomas in this location are neuroendocrine carcinomas, sinonasal adenocarcinomas, and teratocarcinosarcomas. Given the rarity of these tumors, little transcriptomic data is available. The aim of this study was to characterize the immune-oncology gene expression profile in SNUC and other high-grade sinonasal carcinomas. Next-generation sequencing was performed in 30 high-grade sinonasal carcinoma samples using the HTG EdgeSeq Precision Immuno-Oncology Panel. Ingenuity pathway analysis was performed to understand the immunobiology, signaling, and functional perturbations during tumor development. The samples were divided into 3 groups: 21 SNUCs and SMARC-deficient sinonasal carcinomas; 5 high-grade neuroendocrine carcinomas (HGNECs), with small cell and large cell variants; and 4 high-grade sinonasal carcinomas (HGSNCs) of mixed histology (1 NUT carcinoma, 1 teratocarcinosarcoma, and 2 sinonasal adenocarcinomas). PRAME and ASCL1 emerged as upregulated transcripts with strong protein validation for SNUC and HGNEC; other upregulated candidates EZH2 and BRCA1 offer consideration for alternative targeted therapy, and downregulation of major histocompatibility complex molecules and chemokines represent another hurdle in the development of effective immunotherapy. This immune-oncology gene expression analysis of 3 groups of high-grade sinonasal carcinoma with emphasis on SNUC identified a number of differentially expressed transcripts reflecting effects on tumorigenesis. Identification of immune pathways should be further investigated for possible integration of immunotherapy into a multidisciplinary approach to these cancers and personalized treatment.
Asunto(s)
Carcinoma/genética , Carcinoma/inmunología , Neoplasias del Seno Maxilar/genética , Neoplasias del Seno Maxilar/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma/patología , Femenino , Humanos , Masculino , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , Estudios Retrospectivos , TranscriptomaRESUMEN
Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy harboring IDH2 R172 mutations in >80% cases. We explored the potential of genome-wide DNA methylation profiling to elucidate tumor biology and improve the diagnosis of sinonasal undifferentiated carcinoma and its histologic mimics. Forty-two cases, including sinonasal undifferentiated, large cell neuroendocrine, small cell neuroendocrine, and SMARCB1-deficient carcinomas and olfactory neuroblastoma, were profiled by Illumina Infinium Methylation EPIC array interrogating >850,000 CpG sites. The data were analyzed using a custom bioinformatics pipeline. IDH2 mutation status was determined by the targeted exome sequencing (MSK-IMPACTTM) in most cases. H3K27 methylation level was assessed by the immunohistochemistry-based H-score. DNA methylation-based semi-supervised hierarchical clustering analysis segregated IDH2 mutants, mostly sinonasal undifferentiated (n = 10) and large cell neuroendocrine carcinomas (n = 4), from other sinonasal tumors, and formed a single cluster irrespective of the histologic type. t-distributed stochastic neighbor embedding dimensionality reduction analysis showed no overlap between IDH2 mutants, SMARCB1-deficient carcinoma and olfactory neuroblastoma. IDH2 mutants demonstrated a global methylation phenotype and an increase in repressive trimethylation of H3K27 in comparison to IDH2 wild-type tumors (p < 0.001). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed no difference in pathway activation between IDH2-mutated sinonasal undifferentiated and large cell neuroendocrine carcinomas. In comparison to SMARCB1-deficient, IDH2-mutated carcinomas were associated with better disease-free survival (p = 0.034) and lower propensity for lung metastasis (p = 0.002). ARID1A mutations were common in small cell neuroendocrine carcinoma but not among IDH2 mutants (3/3 versus 0/18 and p < 0.001). IDH2 mutations in sinonasal carcinomas induce a hypermethylator phenotype and define a molecular subgroup of tumors arising in this location. IDH2-mutated sinonasal undifferentiated carcinoma and large cell neuroendocrine carcinoma likely represent a phenotypic spectrum of the same entity, which is distinct from small cell neuroendocrine and SMARCB1-deficient sinonasal carcinomas. DNA methylation-based analysis of the sinonasal tumors has potential to improve the diagnostic accuracy and classification of tumors arising in this location.
Asunto(s)
Carcinoma/diagnóstico , Metilación de ADN , Isocitrato Deshidrogenasa/genética , Neoplasias del Seno Maxilar/diagnóstico , Proteína SMARCB1/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/genética , Carcinoma/patología , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Neoplasias del Seno Maxilar/genética , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
Undifferentiated sinonasal carcinoma (SNUC) is defined as a small round blue cell tumor that is immunohistochemically distinct from other sinonasal malignancies, such as lymphoma, mucosal melanoma, nasopharyngeal carcinoma, neuroendocrine carcinoma, and olfactory neuroblastoma. SNUCs are very aggressive malignancies, provoking quick destruction of the splanchnocranium structures. Being a very rare neoplasm, there are no prospective clinical trials assessing their treatment strategies, so lots of data are derived by small retrospective trials. Tri-modality treatments (namely those treatments which use together surgery, radiation therapy and chemotherapy) are now considered the best of care for this category of poor prognosis tumors, and whenever possible they should be employed. Despite the tri-modality treatments and the multidisciplinary management, SNUCs are characterized by poor prognosis with a median overall survival reaching 14 months. Ameliorating radiotherapy techniques and performing therapies adapted to the genetics of the disease could represent a promising strategy of therapy in the near future. In this report, we have presented our experience, describing the treatment and the prognosis of four patients seen at our Institution. Moreover, we have performed a review of the literature analyzing the now available therapy options and the possible future strategies.
Asunto(s)
Carcinoma/terapia , Neoplasias del Seno Maxilar/terapia , Anciano , Carcinoma/patología , Terapia Combinada , Manejo de la Enfermedad , Humanos , Masculino , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , PronósticoRESUMEN
Sinonasal carcinomas are head and neck tumours arising from the nasal cavity and paranasal sinuses characterized by unfavourable outcome, difficult treatment, diagnosis and prognosis. MicroRNAs are key molecules in the regulation of development and progression of cancer and their expression profiles could be used as prognostic biomarkers, to predict the patients' survival and response to treatment. In this study, we used quantitative realtime PCR with TaqMan® Advanced miRNA Assays to investigate the relative expression values of selected micro- RNAs in a unique set of formalin-fixed paraffin-embedded tissue samples obtained from 46 patients with sinonasal squamous cell carcinoma. Our results showed statistically significant up-regulation of three mature microRNAs: miR-9-5p (fold change: 6.80), miR-9-3p (fold change: 3.07) and let-7d (fold change: 3.93) in sinonasal carcinoma patients. Kaplan-Meier survival analysis and logrank test identified association between higher expression of miR-9-5p and longer survival of the patients (P = 0.0264). Lower expression of let-7d was detected in the patients with impaired survival, and higher expression of miR-137 was linked to shorter survival of the patients. We also identified several correlations between expression of the studied microRNAs and recorded clinicopathological data. Higher expression of miR-137 and lower expression of let-7d correlated with local recurrence (P = 0.045 and P = 0.025); lower expression of miR-9-5p and higher expression of miR-155-5p correlated with regional recurrence (P = 0.045 and P = 0.036). Higher expression of miR-9-3p correlated with occupational risk (P = 0.031), presence of vascular invasion (P = 0.013) and perineural invasion (P = 0.031). Higher expression of miR-155-5p was present in the samples originating from maxillary sinus (P = 0.011), cN1-3 classified tumours (P = 0.009) and G2-3 classified tumours (P = 0.017). In conclusion, our study supports the hypothesis of future prospect to use expression of miRNAs as prognostic biomarkers of squamous cell sinonasal carcinoma. In particular, miR-9-5p and miR-9-3p seem to be important members of the sinonasal cancer pathogenesis.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias del Seno Maxilar/genética , MicroARNs/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neoplasias del Seno Maxilar/patología , MicroARNs/metabolismo , Persona de Mediana Edad , Pronóstico , Análisis de RegresiónRESUMEN
Renal cell carcinoma accounts for more than 3% of all malignant diseases. Metastatic disease to the head and neck ranges from 15% to 30%. The 5-year survival rate after nephrectomy is 60% to 75%, but with multiorgan metastases the 5-year survival rate is significantly lower, 0% to 7%. The authors present the case of a patient with a progressive, painless right facial swelling over the maxillary area of 3-month's duration associated with a considerable decrease of right visual acuity. Cranial computed tomography scan and magnetic resonance imaging showed a maxillary sinus mass extending to the orbital cavity and 2 choroidal and retinal thickenings. The mass biopsy was performed by Caldwell-Luc procedure and pathology report suggested metastatic renal cell carcinoma. Following histological findings, a total body computed tomography scan showed a heterogeneous mass at the middle-lower portion of the right kidney measuring approximately 8â×â12â×â4âcm with associated ipsilateral renal vein thrombosis. The patient was referred to the Oncology Department for further treatment. Unfortunately, 3 months after the mass biopsy, the patient died due to complications of multiorgan failure. Although metastases of renal cell carcinoma to the head and neck are very rare, it should be first suspected when investigating a metastatic tumor in this region.
Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias del Seno Maxilar/diagnóstico por imagen , Neoplasias del Seno Maxilar/patología , Biopsia , Carcinoma de Células Renales/secundario , Resultado Fatal , Humanos , Neoplasias Renales/patología , Imagen por Resonancia Magnética , Masculino , Neoplasias del Seno Maxilar/secundario , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with limited treatment options and poor outcome. A morphological spectrum of 47 sinonasal tumours including 17 (36.2%) SNUCs was analysed at genomic level. Thirty carcinomas (cohort 1) were subjected to a hybridization exon-capture next-generation sequencing assay (MSK-IMPACTTM ) to interrogate somatic variants in 279 or 410 cancer-related genes. Seventeen sinonasal tumours (cohort 2) were examined only for the presence of IDH1/2 exon 4 mutations by Sanger sequencing. IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs, in two (20%) poorly-differentiated carcinomas with glandular/acinar differentiation, and in one of two high-grade neuroendocrine carcinomas, large cell type (HGNECs). No IDH2 mutation was detected in any of five olfactory neuroblastomas or in any of five SMARCB1-deficient carcinomas. Among 12 IDH2-mutated cases in cohort 1, five (41.7%) harboured co-existing TP53 mutations, four (33.3%) CDKN2A/2B loss-of-function alterations, four (33.3%) MYC amplification, and three (25%) had concurrent SETD2 mutations. AKT1 E17K and KIT D816V hotspot variants were each detected in one IDH2-mutated SNUC. The vast majority of SNUCs and variable proportions of other poorly-differentiated sinonasal carcinomas may be amenable to IDH2-targeted therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.