Mucosal melanoma of the nasal cavity and paranasal sinuses is a rare disease, but its incidence appears to be increasing. The mean age at diagnosis is between 65 and 70 years. Unilateral nasal obstruction and epistaxis are the most common presenting complaints. Melanoma arises in the septum or lateral wall of the nasal cavity in the great majority of cases. The histological diagnosis is based on specific immunohistochemical labelling and is usually established at an advanced stage of disease: stage T3 or T4 tumours according to the 7th edition of the American Joint Committee on Cancer (AJCC) classification of tumours. First-line treatment consists of surgery. The place of intranasal endoscopic surgery remains controversial due to the difficulty of controlling surgical margins and should be reserved for experienced teams. Adjuvant radiotherapy is usually performed due to its efficacy on local and regional disease control. Five-year overall survival of mucosal melanoma of the nasal cavity and paranasal sinuses in the most recent series does not exceed 40%. Local recurrence is observed in about 50% of cases and metastatic disease is common. The quality of initial tumour resection with negative surgical margins is the most important prognostic factor for tumours confined to the nasal cavity. Hopes for improvement of survival are based on early diagnosis, progress in radiotherapy techniques and cell and gene therapy that are currently under evaluation.

Malignant epithelial lacrimal sac tumors are rare cancers with significant recurrence rates. Correct diagnosis and appropriate therapy require a multidisciplinary management approach. Treatment of these malignant epithelial tumors is first and foremost complete surgical removal with wide excision.

BackgroundUsher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.MethodsWe sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).ResultsBiallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.ConclusionsBased on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

These results show that this option is valid for patients with a fixed footplate and unsuccessful previous surgeries or patients who cannot benefit from a stapedotomy for anatomic reasons. In some cases, access to the round window membrane could represent a limitation. However, these promising initial results establish the need for further works with regard to 3 issues: 1) clinical data studies are needed, including a greater number of patients to confirm these preliminary results; 2) a long-term follow-up must be performed to detect any possible cochlear adverse effects, in particular, on the basilar membrane; 3) the effect of fascia interposition and tip size has to be evaluated in experimental studies.

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