Solitary Fibrous Tumor of the External Auditory Canal.

Solitary fibrous tumors (SFTs) originating from the external auditory canal are uncommon; only few cases have been reported in the literature. In this article, we report a case of a 35-year-old man who presented with a 6-month history of a gradual swelling in the entrance of the left external auditory meatus associated with hearing loss. The tumor was surgically removed, and histological examination showed spindle-cell proliferation with a collagenous stroma. Immunohistochemically, the tumor cells were positive for CD34 confirming the diagnosis of an SFT. Although SFTs are benign, complications such as relapses and metastasis after excision were reported. Thus, a careful and long follow-up is recommended.

Predictive epidemiological and clinical factors of nasopharyngeal carcinoma diagnosis: Adult versus pediatric population.

OBJECTIVE: The objective of this study is to compare the clinical presentation and the cancer staging of nasopharyngeal carcinoma (NPC) between pediatric and adult populations to highlight the main characteristics of this disease within the two subgroups. MATERIEL AND METHODS: It is a retrospective study including all patients with a primary diagnosis of NPC over a period of 19 years. The pediatric group included patients aged less then 16 years old. RESULTS: A total of 80 patients were included. The pediatric population represented 22.5% of the cases. No difference in gender distribution was found (p˃.05). The most common presenting symptom was neck mass in children (77.8% vs. 48.4%, p = .02), and nasal obstruction in adult patients (64.5% vs. 16.7%, p < .01). The median time between the presenting symptom's onset and the diagnosis was 5 months. The diagnosis of NPC was delayed in pediatric patients compared to adults (<0.05). We noted a predominance of patients with stages III and IV (32.5% and 40%, respectively) with no difference between the two subgroups (p˃.05). CONCLUSION: Our study showed some differences in NPC clinical features between pediatric patients and adults. Neck mass was the most common symptom in children. The initial presentation is sometimes misleading. NPC was mainly diagnosed in advanced locoregional stages in both pediatric and adult patients. Efforts toward early diagnosis are of great importance.

Orbital complication of acute ethmoiditis: A Tunisian paediatric cross sectional study.

OBJECTIVE: The anatomical and developmental particularities of sinus cavities in paediatric population lead acute ethmoiditis to be the earliest form of sinusitis in children. Orbital complications are frequent and could lead to visual and neurological impairment. This study investigated the clinical, biological and radiological features of orbital complications. We identified the predictive factors of severe ophthalmological lesions and/or associated cerebral complications of acute ethmoiditis. DESIGN AND METHODS: This cross sectional study included all patients identified as having orbital extension of acute ethmoiditis in the database of a single academic paediatric care centre over a period of 14 years. All orbital and cerebral Scans of the included patients were reviewed and the cohort was classified using Chandler's classification as having less severe lesions (Chandler's 1 and 2) or more serious lesions (Chandler's 3, 4 and 5). RESULTS: In total, 16 patients (12 girls and 4 boys) were included among 39 consecutives cases of ethmoiditis recessed with a complication rate of 41%. Average consultation delay was 4.88 days. The mean age was 4.37 years. Fever was objectified in 13 cases (81%). Six patients (37.5%) had exophthalmos. Orbital extension spectrum was: stage I (n = 4, 25%), stage II (n = 4, 25%), stage III (n = 6, 37.5%), stage IV (n = 1, 6.5%), stage V (n = 1, 6.5%) and intra cranial extension was associated in two cases. Univariate analysis showed that fever, exophthalmos, ophthalmoplegia, positive CRP, age and white blood cells count were not associated with more severe lesions in the CT scan. Initially, all children received intravenous antibiotic treatment. Association of multiple antibiotics was prescribed in 75% of the cases. With 21.07 days ±â€¯5.51 days as a total treatment duration. Only Four patients underwent surgical treatment. CONCLUSION: Orbital complications of ethmoiditis are frequent. No clinical or biological criteria seem to predict the severity of orbital lesions. Both orbital and brain CT scan could help detect eventual complications on time to adapt antibiotic treatment and eventually bring forward surgical intervention.

A rare case of primary inverted papilloma of the middle ear.

Inverted papilloma (IP) of the middle ear as a primary lesion or as an extension of a sinonasal papilloma, is extremely rare. Only 23 cases of primary inverted papilloma of the middle ear have been reported in the literature. They are locally aggressive tumours, with a high rate of recurrence and associated malignancy. We present a rare case of a 59-year-old man presenting with unilateral otorrhoea, tinnitus, and hearing loss. Otoscopy revealed posterior perforation filled by irregular budding neoformation. The temporal CT scan showed tissue filling the tympanic cavity as well as the mastoid antrum without bone lysis. The patient underwent limited tympanoplasty. An intraoperative biopsy of polypoid tissue filling the tymapanic cavity was made and histopathology showed an IP. A recurrence occurred 4 months after surgery. We performed open tympanoplasty allowing complete resection of the lesions, with no recurrence after a follow-up of 30 months.

[Symptomatic vallecular cyst in adults: about 4 cases]. / Le kyste de la vallécule symptomatique chez l'adulte: à propos de 4 cas.

Symptomatic vallecular cyst is a rare benign lesion. These cysts are often asymptomatic in the adult. We here report 4 cases of symptomatic vallecular cyst in the adult. Three patients presented with mixed high dysphagia associated with dysphonia. The fourth patient complained of foreign body sensation in the throat. Laryngoscopy showed a cyst in left vallecular region in all cases. CT scan confirmed vallecular cyst. Treatment was based on marsupialisation of the cyst in two cases and endoscopic resection in two cases. This study suggests to clarify the diagnostic and therapeutic features of this disorder.

A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.

Hearing loss is the most common sensory deficit in humans. We show that a point mutation in DCDC2 (DCDC2a), a member of doublecortin domain-containing protein superfamily, causes non-syndromic recessive deafness DFNB66 in a Tunisian family. Using immunofluorescence on rat inner ear neuroepithelia, DCDC2a was found to localize to the kinocilia of sensory hair cells and the primary cilia of nonsensory supporting cells. DCDC2a fluorescence is distributed along the length of the kinocilium with increased density toward the tip. DCDC2a-GFP overexpression in non-polarized COS7 cells induces the formation of long microtubule-based cytosolic cables suggesting a role in microtubule formation and stabilization. Deafness mutant DCDC2a expression in hair cells and supporting cells causes cilium structural defects, such as cilium branching, and up to a 3-fold increase in length ratios. In zebrafish, the ortholog dcdc2b was found to be essential for hair cell development, survival and function. Our results reveal DCDC2a to be a deafness gene and a player in hair cell kinocilia and supporting cell primary cilia length regulation likely via its role in microtubule formation and stabilization.

Association of COL1A1 and TGFB1 polymorphisms with otosclerosis in a Tunisian population.

Otosclerosis is a condition characterized by an abnormal bone metabolism in the otic capsule, resulting in conductive and/or sensorineural hearing loss. Otosclerosis is a common disorder in which genes play an important role. Case-control association studies have implicated several genes in the abnormal bone metabolism associated with otosclerosis: COL1A1, TGFB1, BMP2, and BMP4. To investigate the association of these genes with otosclerosis in the Tunisian population, we examined nine single nucleotide polymorphisms (SNPs) in 159 unrelated otosclerosis patients and 155 unrelated controls. We found an association of rs11327935 in COL1A1 with otosclerosis that was shown to be sex specific. The coding polymorphism T263I in TGFB1 was also associated with otosclerosis in the Tunisian population. The effect sizes of both the associations were consistent with previous studies, as the same effect was found in all cases. The association of BMP2 and BMP4 was not significant. However, a trend towards association was found for the BMP4 gene that was consistent with earlier reports. In conclusion, this study replicates and strengthens the evidence for association between polymorphisms of COL1A1 and TGFB1 in the genetic aetiology of otosclerosis.

[Surgical treatment of secondary hyperparathyroidism in patients with chronic renal failure]. / Traitement chirurgical de l'hyperparathyroïdie secondaire chez l'insuffisant rénal chronique.

OBJECTIVE: To identify the indications for subtotal parathyroidectomy (PTX) in secondary hyperparathyroidism (SHPT) and report postoperative, early and late complications of PTX. PATIENTS AND METHODS: We conducted a retrospective study of subjects with chronic renal failure operated in Tunisian hospitals who received subtotal PTX over 10 years from January 1997 to December 2007. We analyzed the clinical, biological and radiological parameters pre- and postoperatively. RESULTS: We included 70 patients with average age of 39.4 years, 55.7% men and 44.3% in dialysis for 7.75 ± 4.8 years before PTX. The initial nephropathy was interstitial in 50% of cases. No cases of diabetic nephropathy have been reported. The clinical signs were bone pain (88.6%), muscle pain (85.6%), pruritus (81.4%). Radiological signs of osteitis fibrosa were observed in the majority of patients mainly resorption of extremities (92.9%), thinning of cortical (85.7%) and osteosclerosis (87.1%). The most common indication of PTX (85.7% of cases) was the persistence of serum PTH of more than 800 pg/ml associated with hypercalcemia and/or hyperphosphatemia refractory to medical treatment. A subtotal PTX (3/4 or 7/8) was performed after ultrasound and scintigraphy in the majority of cases. The histology of the parathyroid glands showed diffuse hyperplasia (51.4%), nodular hyperplasia (45.7%) and adenoma (2.8%). The postoperative evolution was marked by an improvement of the clinical and radiological criteria in 80% of cases. A PTH level of less than 15 pg/ml was rarely observed (10% of cases), and a PTH level of more than 300 pg/ml concerned 13% of patients. We noted a low morbidity and mortality (no cases laryngeal paralysis or cervical hematoma). CONCLUSION: Surgical treatment of SHPT in Tunisia is very effective in our experience. The biological results are comparable to treatment with calcimimetics, not available in Tunisia and whose price is higher. An early treatment of disorders of bone and mineral metabolism should reduce the incidence of SHPT.

Genetic variants in RELN are associated with otosclerosis in a non-European population from Tunisia.

Otosclerosis is a common form of conductive hearing loss, caused by an abnormal bone remodelling in the otic capsule. Both environmental and genetic factors have been implicated in the etiology of this disease. A recent genome wide association study identified two regions associated with otosclerosis, one on chr7q22.1, located in the RELN gene, and one on chr11q13.1. A second study in four European populations has replicated the association of the RELN gene with otosclerosis. To investigate the association of these loci with otosclerosis in a non-European population, we tested 11 SNPs from the two regions in 149 unrelated Tunisian patients and 152 controls. Four SNPs were significantly associated with otosclerosis. Three SNPs are located in the RELN region and the last one is located in the region on chromosome 11. We also observed a significant interaction with gender for rs3914132. This suggests an influence of sex on the association of RELN with otosclerosis. A meta-analysis showed that the disease-associated alleles in the Tunisian sample are the same as in all previously reported associations. Our study provides additional evidence implicating RELN in the development of otosclerosis. Additional functional studies should determine the role of RELN in the physiopathology of this disease.

Mutation in gap and tight junctions in patients with non-syndromic hearing loss.

Biallelic mutations in the GJB2, GJB3, GJB6 and CLDN14 genes have been implicated in autosomal recessive non-syndromic hearing impairment (ARNSHI). Moreover, a large number of GJB2 heterozygous patients was reported. The phenotype was in partly justified by the occurrence of two deletions including GJB6. We analysed GJB2, GJB6, GJB3 and CLDN14 in 102 Tunisian patients with ARNSHI. The deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) were also screened. The c.35delG in GJB2 was the most frequent mutation (21.57%). It was detected at heterozygous state in 2 patients. The del(GJB6-D13S1830) was identified in one case at heterozygous state. No other mutation in studied gap junction genes was detected in heterozygous patients. Several polymorphisms were identified in GJB3, GJB6 and CLDN14. Our study confirms the importance of GJB2 screening in ARNSHI and suggests that in consanguineous populations, a single DFNB1 mutant allele in individuals with HI is likely due to a coincidental carrier state.

Screening of the DFNB3 locus: identification of three novel mutations of MYO15A associated with hearing loss and further suggestion for two distinctive genes on this locus.

Recessive mutations of MYO15A are associated with nonsyndromic hearing loss (HL) in humans (DFNB3) and in the shaker-2 mouse. Human MYO15A has 66 exons and encodes unconventional myosin XVA. Analysis of 77 Tunisian consanguineous families segregating recessive deafness revealed evidence of linkage to microsatellite markers for DFNB3 in four families. In two families, sequencing of MYO15A led to the identification of two novel homozygous mutations: a nonsense (c.4998C>A (p.C1666X) in exon 17 and a splice site mutation in intron 54 (c.9229 + 1G>A). A novel mutation of unknown significance, c.7395 + 3G>C, was identified in the third family, and no mutation was found in the fourth family. In conclusion, we discovered three novel mutations of MYO15A, and our data suggest the possibility that there are two distinct genes at the DFNB3 locus.

TMC1 but not TMC2 is responsible for autosomal recessive nonsyndromic hearing impairment in Tunisian families.

Hereditary nonsyndromic hearing impairment (HI) is extremely heterogeneous. Mutations of the transmembrane channel-like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of nonsyndromic HI linked to the loci DFNA36 and DFNB7/B11, respectively. TMC1 is 1 member of a family of 8 genes encoding transmembrane proteins. In the mouse, MmTmc1 and MmTmc2 are both members of Tmc subfamily A and are highly and almost exclusively expressed in the cochlea. The restricted expression of Tmc2 in the cochlea and its close phylogenetic relationship to Tmc1 makes it a candidate gene for nonsyndromic HI. We analyzed 3 microsatellite markers linked to the TMC1 and TMC2 genes in 85 Tunisian families with autosomal recessive nonsyndromic HI and without mutations in the protein-coding region of the GJB2 gene. Autozygosity by descent analysis of 2 markers bordering the TMC2 gene allowed us to rule out its association with deafness within these families. However, 5 families were found to segregate deafness with 3 different alleles of marker D9S1837, located within the first intron of the TMC1 gene. By DNA sequencing of coding exons of TMC1 in affected individuals, we identified 3 homozygous mutations, c.100C-->T (p.R34X), c.1165C-->T (p.R389X) and the novel mutation c.1764G-->A (p.W588X). We additionally tested 60 unrelated deaf Tunisian individuals for the c.100C-->T mutation. We detected this mutation in a homozygous state in 2 cases. This study confirms that mutations in the TMC1 gene may be a common cause for autosomal recessive nonsyndromic HI.

Mutational analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in Tunisian patients with nonsyndromic hearing loss.

We explored the mitochondrial 12S rRNA and the tRNASer(UCN) genes in 100 Tunisian families affected with NSHL and in 100 control individuals. We identified the mitochondrial A1555G mutation in one out of these 100 families and not in the 100 control individuals. Members of this family harbouring the A1555G mutation showed phenotypic heterogeneity which could be explained by an eventual nuclear-mitochondrial interaction. So, we have screened three nuclear genes: GJB2, GJB3, and GJB6 but we have not found correlation between the phenotypic heterogeneity and variants detected in these genes. We explored also the entire mitochondrial 12S rRNA and the tRNASer(UCN) genes. We detected five novel polymorphisms: T742C, T794A, A813G, C868T, and C954T, and 12 known polymorphisms in the mitochondrial 12S rRNA gene. None of the 100 families or the 100 controls were found to carry mutations in the tRNASer(UCN) gene. We report here the first mutational screening of the mitochondrial 12S rRNA and the tRNASer(UCN) genes in the Tunisian population which describes the second family harbouring the A1555G mutation in Africa and reveals novel polymorphisms in the mitochondrial 12S rRNA gene.

A novel autosomal recessive non-syndromic deafness locus, DFNB66, maps to chromosome 6p21.2-22.3 in a large Tunisian consanguineous family.

Hereditary non-syndromic deafness is extremely heterogeneous. Autosomal recessive forms account for approximately 80% of genetic cases. Autosomal recessive non-syndromic sensorineural deafness segregating in a large consanguineous Tunisian family was mapped to chromosome 6p21.2-22.3. A maximum lod score of 5.36 at theta=0 was obtained for the polymorphic microsatellite marker IR2/IR4. Haplotype analysis defined a 16.5-Mb critical region between microsatellite markers D6S1602 and D6S1665. The screening of 3 candidate genes, COL11A2, BAK1 and TMHS, did not reveal any disease causing mutation, suggesting that this is a novel deafness locus, which has been named DFNB66. A search in the Human Cochlear EST Library for ESTs located in this critical interval allowed us to identify several candidates. Further investigations on these candidates are needed in order to identify the deafness-causing gene in this Tunisian family.

Incidental discovery of pulmonary metastases during I-131 scintigraphy after total thyroidectomy.

We report the case of a 40-year-old man with radiographically silent pulmonary metastases of papillary thyroid cancer discovered during I-131 scintigraphy following total thyroidectomy performed 10 years after unilateral lobectomy. The residual lobe was histologically normal. After a dose of 11.1 GBq (300 mCi), there was no I-131 uptake in the thyroid bed and lung metastases, and serum thyroglobulin became undetectable. Conservative therapy could be associated with a delay in the possibility of diagnosing and treating extrathyroidal metastases.