Endoscopic endonasal resection of adenoid cystic carcinoma of the sinonasal tract and skull base

Adenoid cystic carcinoma (ACC) is a locally aggressive salivary gland malignancy prone to perineural invasion and local recurrences. In the literature, few data exist to guide treatment when this tumor involves the paranasal sinuses and skull base. We report our experience in the management of sinonasal adenoid cystic carcinoma through an endoscopic endonasal approach

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

PAI-1 4G/5G repeat is a target in gastric carcinomas with microsatellite instability

Background: The plasminogen activator inhibitor-1 (PAL-1) plays an important role in the pathogenesis of cancer. The 4G/5G promoter polymorphism of PAI-1 is potentially involved in regulating gene transcription. Aims: To explore the role of the PAL-1 4G/5G repeat as target of microsatellite instability (MSI), 50 gastric carcinomas (GCs), characterized for MSI, were screened. Methods: PAI-1 4G/5G was analysed by direct sequencing. Results: Allelic imbalance was observed in 5 of the 50(10%) GCs. Specifically, 2 cases (40%) harboured a G deletion and 3(60%) a G insertion in tumour compared to normal DNA. These five cases were included in the subgroup of 20 GCs (25%) with high level of MSI (MSI-H). A statistically significant association emerged between PAL-1 mutations and MSI-H status (p = 0.0073). The frequency of PAL-1 mutations was also evaluated, together with other known target genes, by analysing MSI-H GCs for mutations at selected coding repeats within genes controlling cell growth, apoptosis and DNA repair. Overall, mutation frequency ranged from 56.3% to 5.3%. Conclusion: The frequency of PAL-1 mutations here reported in MSI-H GCs is, accordingly, comparable with values obtained for real targets. The relatively high incidence of PAL-1 mutations is suggestive of a positive pressure towards selection in MSI-H GCs. (C) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Endoscopic Endonasal Resection of Sinonasal and Nasopharyngeal Pleomorphic Adenomas: A Case Series

The aim of this study is to describe the clinicopathological characteristics of intranasal pleomorphic adenomas (PAs), as well as the role and outcomes of endoscopic endonasal resection. A retrospective review of the clinical data from patients with PA of the nasal cavity who were treated by the authors at three tertiary medical centers between June 1998 and December 2019. A total of five patients with PA were found. Three patients were male, two were female and their mean age was 62.2 years. All cases were resected "en bloc" with endoscopic endonasal approach. No evidence of disease was observed during a mean follow-up of 10.6 years. No case presented with malignant transformation into carcinoma ex-PA. PA of the sinonasal tract and the nasopharynx is difficult to diagnose due to nonspecific clinical and radiological findings. Endoscopic endonasal approaches can be considered the gold standard in the treatment of these tumors and provide excellent visual control of the surgical field and clear margins

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