Novel pathogenic mutations and further evidence for clinical relevance of genes and variants causing hearing impairment in Tunisian population.

Introduction: Hearing impairment (HI) is characterized by complex genetic heterogeneity. The evolution of next generation sequencing, including targeted enrichment panels, has revolutionized HI diagnosis. Objectives: In this study, we investigated genetic causes in 22 individuals with non-GJB2 HI. Methods: We customized a HaloplexHS kit to include 30 genes known to be associated with autosomal recessive nonsyndromic HI (ARNSHI) and Usher syndrome in North Africa. Results: In accordance with the ACMG/AMP guidelines, we report 11 pathogenic variants; as follows; five novel variants including three missense (ESRRB-Tyr295Cys, MYO15A-Phe2089Leu and MYO7A-Tyr560Cys) and two nonsense (USH1C-Gln122Ter and CIB2-Arg104Ter) mutations; two previously reported mutations (OTOF-Glu57Ter and PNPT1-Glu475Gly), but first time identified among Tunisian families; and four other identified mutations namely WHRN-Gly808AspfsX11, SLC22A4-Cys113Tyr and two MYO7A compound heterozygous splice site variants that were previously described in Tunisia. Pathogenic variants in WHRN and CIB2 genes, in patients with convincing phenotype ruling out retinitis pigmentosa, provide strong evidence supporting their association with ARNSHI. Moreover, we shed lights on the pathogenic implication of mutations in PNPT1 gene in auditory function providing new evidence for its association with ARNSHI. Lack of segregation of a previously identified causal mutation OTOA-Val603Phe further supports its classification as variant of unknown significance. Our study reports absence of otoacoustic emission in subjects using bilateral hearing aids for several years indicating the importance of screening genetic alteration in OTOF gene for proper management of those patients. Conclusion: In conclusion, our findings do not only expand the spectrum of HI mutations in Tunisian patients, but also improve our knowledge about clinical relevance of HI causing genes and variants.

ENT mucormycosis. Report of 4 cases.

OBJECTIVES: Mucormycosis is an opportunist infection usually affecting immunocompromised patients. It is rare and often fatal. The pathogen is filamentous fungus of the mucorales order. Studies discuss the clinical, diagnostic and therapeutic aspects of ENT mucormycosis, insisting on early clinical diagnosis, laboratory data not being contributive within satisfactory time limits. MATERIAL AND METHODS: A retrospective study included 4 patients with ENT mucormycosis diagnosed over a 13-year period, from January 2000 to December 2012. RESULTS: The study included 2 male and 2 female patients, aged from 3 to 77 years. Two patients were diabetic. There were 2 cases of sinonasal mucormycosis and 2 of otologic involvement. Diagnosis was founded on anatomopathologic and mycologic examination. A fatal issue occurred in 1 case with otocerebral involvement. CONCLUSIONS: Otorhinolaryngologic mucormycosis is a rare fungal infection, which needs to be borne in mind. Rhinocerebral lesions are the most common clinical manifestations. Involvement of the ear is very rare. Diagnosis is often difficult, but should be as early as possible. Treatment, initiated urgently, associates antifungal treatment, surgical resection and control of risk factors. The prognosis remains in all cases severe.

Epstein-Barr virus-associated lymphoepithelial carcinoma of the larynx.

INTRODUCTION: Lymphoepithelial carcinoma is a rare tumour, named after its histological resemblance to undifferentiated nasopharyngeal carcinoma. The pathogenesis of lymphoepithelial carcinoma remains unknown. This tumour has been described in several organs, but the larynx remains an exceptional site. CASE REPORT: The authors report the case of a 73-year-old man who consulted for longstanding dysphonia and rapidly deteriorating dyspnoea requiring emergency tracheotomy. Endoscopic examination demonstrated a tumour of the left hemilarynx with fixed vocal cords. Histological examination and immunohistochemistry demonstrated lymphoepithelial carcinoma of the larynx. Screening for Epstein-Barr Virus (EBV) by immunohistochemistry and in situ hybridization was positive. Treatment consisting of neoadjuvant chemotherapy followed by surgical resection and then external beam radiotherapy achieved cure with a follow-up of 18months since completion of treatment. DISCUSSION: Lymphoepithelial carcinoma of the larynx is rare. Immunohistochemical examination is essential for the positive diagnosis. Epstein-Barr virus-associated lymphoepithelial carcinoma has been exceptionally reported. The radiosensitivity of this tumour allows conservative first-line treatment.

Myoepithelioma of the vallecula: a case report.

Myoepitheliomas are rare and generally benign neoplasms that account for fewer than 1% of all salivary gland tumors. A myoepithelioma neoplasm is almost entirely composed of myoepithelial cells and is most frequently located in the parotid gland and in the minor salivary glands of the hard palate. We report an extremely rare case of myoepithelioma of the vallecular region in a 65-year-old woman and describe this tumor's clinical peculiarity, diagnostic and therapeutic considerations, and prognosis.

[Cervico-facial hydatidosis. Report of 17 cases]. / L'hydatidose cervico-faciale. A propos de 17 cas.

BACKGROUND: Cervico-facial hydatid cyst is rare. It accounts for 1 % of echinococcosis locations. AIM: To describe the epidemiological, clinical and therapeutic aspects of cervico-facial hydatid cysts based on our clinical experience and data in the literature. METHODS: A retrospective study was made concerning 17 patients with cervico-facial hydatid cyst treated surgically over a 25-year period from 1982 to 2006. RESULTS: Mean patient age was 27 years (range 2-79). Hydatid cyst localization was: cervical muscle (7 cases), thyroid gland (5 cases), parotid gland (2 cases), cervico-thoracic (1 case), larynx (1 case) and cheek (1 case). Hydatic origin of the cyst was suspected for 6 patients (35.3 %) preoperatively. Surgical treatment was used in all cases and adapted to each case. Diagnosis was always confirmed by macroscopic aspects and pathology. CONCLUSION: Hydatid cysts are rarely found in the cervico-facial region, even in highly endemic zone. The manifestation of symptoms depends on the location and the size of the cyst. Positive diagnosis can be difficult during preoperative period. Exclusively surgical treatment is indicated, ideally for total pericystic resection without rupture.

Therapeutic approaches to complicated cholesteatoma of the external auditory canal: a case of associated facial paresis.

Spontaneous cholesteatoma of the external auditory canal (EAC) is an uncommon condition that is difficult to diagnose. In a patient with such a possibility, serious clinical investigation along with radiologic and histologic exploration should be performed early on because a delay in treatment can lead to severe complications. Given the rarity of EAC cholesteatoma, no therapeutic consensus has emerged. The type of management depends on the extensiveness of invasion and bone erosion and the status of the neighboring structures. The primary therapeutic objectives are to eradicate the cholesteatoma and then to fill in the residual cavity, which in our opinion can be best accomplished with a muscle flap and EAC reconstruction. Postoperative follow-up should be carried out to look for infections, stenosis, and recurrence. We report a new case of spontaneous EAC cholesteatoma, and we review its diagnostic and therapeutic challenges.

Rosai-Dorfman disease of the nasal cavities: A CO(2) laser excision.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare nonneoplastic histiocytic proliferative disorder characterized by painless massive lymphadenopathy. Extranodal manifestations frequently occur in the head and neck area. METHODS: We report the clinical and histological features of nasal cavities and cervical lymph node RDD in a 72-year-old woman, who complained of major nasal obstruction and hyposmia. RESULTS: Nasal endoscopy revealed polypoid masses arising from the turbinates; the septum was intact. Immunohistochemical analysis revealed staining for S-100 protein, CD68, and alpha-1 antitrypsin. The presence of the Epstein-Barr virus was revealed by serology and also by in situ hybridization. The general examination and systemic evaluation did not find other extranodal localization. CONCLUSION: Because the disease is known for not responding to local or systemic steroids, CO(2) laser excision was used to clear the nasal obstruction with a satisfactory result. This is, to the best of our knowledge, the first description of the use of laser excision for nasal cavities RDD.

[Fungal necrotizing external otitis]. / Otites externes nécrosantes d'origine mycosique.

OBJECTIVE: Fungal necrotizing otitis externa is rare, although its frequency has increased over the last few years. We report four cases, which to our knowledge make up the largest series published and discuss the main diagnostic problems and the management of this infection. OBSERVATIONS: Our study investigated two men and two women, all diabetics, aged between 69 and 74 years. All four patients were first treated for bacterial necrotizing otitis externa. Diagnosis was reviewed after a lack of response to antibiotic therapy. Aspergillus flavus and Candida parapsilosis were the fungal agents isolated in each of the two patients. Diagnosis was established based on the pathological specimen for one patient. The last patient was treated without identifying the causal fungus. Two patients developed facial paralysis during disease progression. Treatment was based on intravenous amphotericin B and oral itraconazole. Three patients are now free of disease after a three- to six-month course of antifungal therapy; one patient was not followed up. CONCLUSION: Fungal necrotizing otitis externa should be suspected in cases where there is no response to antipseudomonal antibiotic therapy. Deep biopsies from the external auditory canal or the mastoid are usually needed to confirm the diagnosis.

Papillary carcinoma arising in a thyroglossal duct cyst: case report and discussion of management modalities.

A case of papillary carcinoma arising in the wall of a thyroglossal duct cyst is described. These cancers are very rare and rather adult-specific. Preoperative diagnosis may be enhanced using fine-needle aspiration cytology and computing tomography findings. The standard treatment of thyroglossal duct cyst carcinoma is the sistrunk procedure. The concept of prognostic risk groups should be used to identify patients who would additionally undergo total thyroidectomy.

[Primary non-Hodgkin's lymphoma of the thyroid. A case report and review of the literature]. / Lymphome non hodgkinien primitif de la thyroïde. A propos d'une observation et revue de la littérature.

The authors report an observation of a non-Hodgkinien primitive lymphoma of the thyroid, developed on Hashimoto's thyroiditis. The 61 years old woman was operated on a total thyroidectomy for a multinodular goiter with dysphagia. The non-Hodgkinien high-grade lymphoma infiltrated the perithyroidal tissues. The extension' assessment was negative and the lymphoma was classified stage IE. The treatment was supplemented by 6 cures of standard chemotherapy CEOP. Based on this observation and on a literature' review, we will discuss the clinical and therapeutic characteristics of this thyroid cancer.

[Diagnostic and surgical strategy for parathyroid adenoma]. / Stratégie diagnostique et chirurgicale de l'adénome parathyroïdien.

From a retrospective study carrying on 8 patients operated for sporadic parathyroid adenoma, we underline the place of medical imagery which allowed the detection of parathyroid adenoma in 7 cases. For all our patients the exploration of thyroid space was bilateral, seeking parathyroid glands. The authors discuss the stages and the various processes of the surgical strategy for parathyroid glands' exploration.