A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes

Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8 + effector memory cells, in SNUC) and \u201cother cells\u201d: keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic \u3b2-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities

Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review [Sarcoma bifenotipico nasosinusale: case-series europeo multicentrico e revisione sistematica della letteratura]

Obiettivo: Il sarcoma nasosinusale bifenotipico (SNSB) è un raro tumore a basso grado, incluso a partire dalla 4° edizione WHO dei tumori testa-collo. L’obiettivo di questo studio è analizzare i tassi di sopravvivenza e i pattern di recidiva di questa neoplasia. Metodi: Revisione retrospettiva dei pazienti affetti da SNSB, trattati mediante approccio endoscopico in 6 centri di riferimento europei. È stata condotta inoltre una revisione sistematica della letteratura dal 2012 ad oggi, secondo le linee guida PRISMA. Risultati: . Sono stati inclusi 15 pazienti (approccio endoscopico endonasale in 7 casi, craniectomia endoscopica transnasale in 4 casi, approccio combinato transcranico in 4 casi). In 2 casi è stata somministrata radioterapia adiuvante. Dopo un periodo di follow-up medio di 27,3 mesi, è stato riscontrato un caso di metastasi a distanza; i tassi di 5-year Overall Survival e Disease-Free Survival erano 100% e 80 ± 17,9%, rispettivamente. Conclusioni: . Il SNSB è un tumore localmente aggressivo con un basso tasso di recidiva e tassi di sopravvivenza incoraggianti se trattato con asportazione chirurgica radicale con radioterapia adiuvante per casi selezionati. La chirurgia endoscopica ha dimostrato di essere sicura ed efficace come trattamento iniziale all’interno di un protocollo di cura multidisciplinare.Objective: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm. Methods: Retrospective review of patients affected by BSNS who were treated via an endoscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guidelines. Results: A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively. Conclusions: BSNS is a locally aggressive tumour with a low recurrence rate and encouraging survival outcomes if properly treated with surgical resection and free margins followed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol

Primary Ectopic Ethmoidal Craniopharyngioma

Craniopharyngiomas are benign but aggressive epithelial tumors usually originating in the anterior lobe of the pituitary gland from squamous remnants of an incompletely involuted craniopharingeal duct developing from the Rathke pouch. To the authors' knowledge only 1 patient of a primary isolated ethmoidal craniopharyngioma has been reported in the literature. The authors report the case of a 17-year-old boy with a primary extracranial ethmoidal craniopharyngioma. An endoscopic endonasal approach was employed to resect the tumor. After 2 years of clinical and radiological follow-up no recurrence of disease was observed. Primary ethmoidal craniopharyngiomas are rare entities and biopsy is necessary for diagnosis. However, a preoperative assessment by means of nasal endoscopy, computed tomography scan, and enhanced magnetic resonance imaging is mandatory to better evaluate the extension and characteristics of the tumor. The endoscopic endonasal technique is a safe and effective approach for the treatment of these lesions

COMPORTAMENTO ESPACIAL DA FUSARIOSE E DOS ATRIBUTOS DO SOLO NO CULTIVO DA PIMENTA-DO-REINO

A pimenta-do-reino é a especiaria mais consumida no mundo e o Brasil destaca-se como um dos maiores produtores. Um dos grandes limitantes no seu cultivo é a fusariose (Fusarium solani f. sp. piperis). Objetivou-se com a realização deste estudo caracterizar a variabilidade espacial da fusariose em pimenta-do-reino, verificando a existência de relação com os atributos físicos e químicos do solo. O estudo foi desenvolvido em uma lavoura localizada no município de São Mateus-ES, na qual foi estabelecida uma malha amostral irregular com 79 pontos, abrangendo uma área de um hectare.  Para a amostragem da fusariose foi realizado um levantamento, onde uma planta por ponto da malha amostral foi classificada em sadia, doente ou morta.  Os atributos do solo amostrados foram: pH em H2O, matéria orgânica, cálcio, magnésio, potássio e textura do solo. Os dados foram analisados através da estatística descritiva e ferramentas da geoestatística. Os semivariogramas ajustados apresentaram uma forte dependência espacial para as variáveis intensidade da fusariose, altimetria, matéria orgânica, textura do solo, pH, cálcio, magnésio potássio (89, 94, 92, 94, 93, 91, 100 e 85 % respectivamente). Os mapas gerados indicam que não há relação da intensidade da fusariose com os atributos do solo estudados no experimento.Palavra-chave: epidemiologia, Fusarium solani f. sp. piperis, geoestatística, Piper nigrum L. SPATIAL ANALYSIS OF FUSARIOSE AND SOIL ATTRIBUTES IN THE BLACK PEPPER CULTIVATION  ABSTRACT:Black pepper is the most consumed spice in the world, Brazil stands out as one of the largest producers. One of the major constraints in cultivation is fusariosis (Fusarium solani f. Piperis). The objective of this study was characterize the spatial variability of fusariosis in black pepper and verify the relationship of chemical attributes of the soil. The study was developed in a tillage located in the municipality of São Mateus - ES, which exist an irregular sampling network was established with 79 points, covering an area of one hectare. For the sampling of fusariosis intensity, the survey was performed, where one plant per point of the sample mesh was classified as healthy, symptomatic or dead. The attributes of the soil sampled were: pH in H2O, organic matter, nutrient content (calcium, magnesium, potassium) and soil texture. Data were analyzed through descriptive statistics and geostatistics tools. The adjusted semivariograms indicated a strong spatial dependence for the variables intensity of fusariosis, altimetry, organic matter, soil texture, pH, calcium, potassium magnesium (89, 94, 92, 94, 93, 91, 100 and 85%, respectively). The generated maps indicate that there is no relation between the incidence of fusariosis and the soil attributes studied in the experiment.Keywords: epidemiology, Fusarium solani f. sp. piperis, geostatistics, Piper nigrum L

COMPORTAMENTO ESPACIAL DA FUSARIOSE E DOS ATRIBUTOS DO SOLO NO CULTIVO DA PIMENTA-DO-REINO

A pimenta-do-reino é a especiaria mais consumida no mundo e o Brasil destaca-se como um dos maiores produtores. Um dos grandes limitantes no seu cultivo é a fusariose (Fusarium solani f. sp. piperis). Objetivou-se com a realização deste estudo caracterizar a variabilidade espacial da fusariose em pimenta-do-reino, verificando a existência de relação com os atributos físicos e químicos do solo. O estudo foi desenvolvido em uma lavoura localizada no município de São Mateus-ES, na qual foi estabelecida uma malha amostral irregular com 79 pontos, abrangendo uma área de um hectare.  Para a amostragem da fusariose foi realizado um levantamento, onde uma planta por ponto da malha amostral foi classificada em sadia, doente ou morta.  Os atributos do solo amostrados foram: pH em H2O, matéria orgânica, cálcio, magnésio, potássio e textura do solo. Os dados foram analisados através da estatística descritiva e ferramentas da geoestatística. Os semivariogramas ajustados apresentaram uma forte dependência espacial para as variáveis intensidade da fusariose, altimetria, matéria orgânica, textura do solo, pH, cálcio, magnésio potássio (89, 94, 92, 94, 93, 91, 100 e 85 % respectivamente). Os mapas gerados indicam que não há relação da intensidade da fusariose com os atributos do solo estudados no experimento.Palavra-chave: epidemiologia, Fusarium solani f. sp. piperis, geoestatística, Piper nigrum L. SPATIAL ANALYSIS OF FUSARIOSE AND SOIL ATTRIBUTES IN THE BLACK PEPPER CULTIVATION  ABSTRACT:Black pepper is the most consumed spice in the world, Brazil stands out as one of the largest producers. One of the major constraints in cultivation is fusariosis (Fusarium solani f. Piperis). The objective of this study was characterize the spatial variability of fusariosis in black pepper and verify the relationship of chemical attributes of the soil. The study was developed in a tillage located in the municipality of São Mateus - ES, which exist an irregular sampling network was established with 79 points, covering an area of one hectare. For the sampling of fusariosis intensity, the survey was performed, where one plant per point of the sample mesh was classified as healthy, symptomatic or dead. The attributes of the soil sampled were: pH in H2O, organic matter, nutrient content (calcium, magnesium, potassium) and soil texture. Data were analyzed through descriptive statistics and geostatistics tools. The adjusted semivariograms indicated a strong spatial dependence for the variables intensity of fusariosis, altimetry, organic matter, soil texture, pH, calcium, potassium magnesium (89, 94, 92, 94, 93, 91, 100 and 85%, respectively). The generated maps indicate that there is no relation between the incidence of fusariosis and the soil attributes studied in the experiment.Keywords: epidemiology, Fusarium solani f. sp. piperis, geostatistics, Piper nigrum L

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal-inverted papilloma to squamous cell carcinoma

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISP-associated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC

Methylation Drivers and Prognostic Implications in Sinonasal Poorly Differentiated Carcinomas

Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several epigenetic markers have been suggested to support the histopathological classification, predict prognosis, and guide therapeutic decision. Indeed, molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as separate entities. Identification of aberrant DNA methylation levels associated with these specific epigenetic driver genes could be useful for prognostic and therapeutic purpose

Sinonasal mucosal melanoma: A 12-year experience of 58 cases

Sinonasal mucosal melanoma is a rare malignancy with poor prognosis