Abdelmoneem Ghorbel

Les sarcomes de la tête et du cou

INTRODUCTION Head and neck sarcomas comprise a heterogeneous and biologically diverse set of rare neoplasms. The difficulty treating the disease requires multidisciplinary consultation to improve outcome. In an effort to clarify the clinical behavior of head and neck sarcomas and evaluate treatment, we present our experience and review the relevant literature. PATIENTS AND METHODS This is a retrospective analysis of 15 patients with histologically proven head and neck sarcoma treated in the ENT department between 1998 and 2007. All cases were confirmed by histologic exam with immunohistochemical analysis. RESULTS Nine women and six men were included in the study. The mean age was 38.4 years (range: 6-73 years). Computed tomography and MRI were done in 66.7% and 60% of the patients, respectively, to evaluate tumor extension. Metastases were demonstrated in three cases. Curative treatment in eight cases was based on different combinations of chemotherapy, radiotherapy, and surgery. Complete remission was obtained in eight cases. Local recurrence was noted in two cases. Two patients died from tumor metastasis. Two patients were lost to follow-up. CONCLUSION Head and neck sarcomas present diverse rare neoplasms. They make up 5%-20% of all soft tissue sarcomas. All age groups can be affected by this neoplasm, with no predominance in one sex or the other. The most common histologic type is rhabdomyosarcoma, especially in children. Because of the potential for systemic metastasis, extension must be assessed. Treatment is based essentially on the association of surgery, radiotherapy, and chemotherapy to optimize therapeutic results. Five-year survival varies between 44% and 80%.

Segregation of a new mutation in SLC26A4 and p.E47X mutation in GJB2 within a consanguineous Tunisian family affected with Pendred syndrome

OBJECTIVE Recessive mutations of the SLC26A4 (PDS) gene on chromosome 7q31 can cause sensorineural hearing loss with goiter (Pendred syndrome) or non-syndromic autosomal recessive hearing loss (DFNB4). Furthermore, mutations in the GJB2 gene results in autosomal recessive (DFNB1) and dominant (DFNA3) non-syndromic hearing loss. The aim of the present study was to characterize a family with Pendred syndrome affected by severe to profound HL and presenting goiter. METHODS Affected members underwent detailed audiologic examination and characterization. DNA samples from family members were genotyped with polymorphic microsatellite markers and sequencing of the SLC26A4 and GJB2 genes was performed. A total of 25 families with non-syndromic hearing loss were screened for the common p.E47X mutation in the GJB2 gene by direct dideoxy sequencing. RESULTS Genetic microsatellite analysis showed linkage to the 7q22-q31 chromosomal region and mutation analysis revealed a novel frameshift mutation (c.451delG) in the SLC26A4 gene. Screening of the GJB2 gene in one patient, displayed a homozygous p.E47X mutation, together with a heterozygous c.451delG mutation. Screening of 25 families with HL showed frequent segregation of the p.E47X mutation, which was homozygous in five of these families. Haplotype analysis using microsatellite markers and single nucleotide polymorphisms (SNPs) closely flanking the GJB2 gene, revealed the presence of two disease-associated-haplotypes suggesting the presence of at least, two founder effects carrying the p.E47X non-sense mutation in the Tunisian population. CONCLUSIONS The segregation of both SLC26A4 and GJB2 mutations in the family illustrates once again the unexpected intra-familial genetic heterogeneity in consanguineous families and highlights the difficulty of genetic counselling in such families. In addition, our results disclose the existence of founder effects in the Tunisian population.

Un cas de métastase intrathyroïdienne d’un primitif inhabituel

Nasopharyngeal carcinoma affects preferentially young adults and is characterized by a high rate of node and visceral metastases that explains a part of therapeutic failure. We report a case of thyroid metastasis of a nasopharyngeal carcinoma. A 50-year-old patient had been treated of a nasopharyngeal carcinoma (T4 N2M0). Four years after a concomitant chemoradiotherapy, he presented with a compressive mass in the thyroid loge associated to cervical nodes. He underwent a total thyroidectomy and the definitive result concluded to an carcinome indifférencié de type nasopharyngé (UCNT) thyroid metastasis. A new concomitant chemoradiotherapy was delivered and consequently the tumor disappeared. Secondly, several node recurrences occurred. Metastasis of UCNT in thyroid gland is exceptional. Several problems are related to its aetiopathogenesis and to its treatment that is not systematized in the literature. The prognosis like for all metastatic forms of nasopharyngeal cancer is unfavorable.

Late Toxicities after Conventional Radiotherapy for Nasopharyngeal Carcinoma: Incidence and Risk Factors

Background. To determine the incidence and analyze the factors affecting late toxicity for nasopharyngeal carcinoma patients treated with conventional radiotherapy. Patients and Methods. Retrospective analysis was performed on 239 NPC patients treated between 1993 and 2004 in our institution. One hundred and fifty-seven patients were treated with conventional fractionation (2 Gy per fraction, 5 fractions per week) and eighty-two patients with hyperfractionated radiotherapy (1.6 Gy per fraction twice a day, 5 days per week). One hundred fifty nine patients underwent neoadjuvant cisplatin based chemotherapy. Late toxicity was evaluated according to the RTOG/EORTC score. Results. Xerostomia was the most common related complication (98.7%). Neoadjuvant chemotherapy and hyperfractionated radiotherapy did not increase late toxicities. Multivariate analyses showed that radiation dose was a significant factor for hearing impairment, younger age for trismus, initial node status for neck fibrosis, and initial dental hygiene for dental complications. Female gender was associated with significantly higher incidence of trismus and hearing impairment. Conclusion. Conventional radiotherapy was associated with a high rate of late toxicities which affect patients’ quality of life. With the development of three-dimensional conformal radiotherapy and intensity modulated radiotherapy, a reduced incidence of radiation related complications could be expected.

Résultats thérapeutiques du cancer du cavum : y a-t-il une différence entre enfants et adultes ?

PURPOSE To compare therapeutic results of nasopharyngeal carcinoma between adults and children. PATIENTS AND METHODS Three hundred and seventy seven patients with nasopharyngeal carcinoma received a radiotherapy between 1993 and 2007. Sixty-nine of them were 20years old or less. Two hundred and sixty eight patients received a chemotherapy (neoadjuvant or concomitant). RESULTS Overall survival and disease-free survival at 5 years were 67 % and 59.4 % in all patients, respectively. Overall survival rates at 5 years in children and adults were 66 % and 64 %, respectively (P=0.17), disease-free survival rates at 5 years were 66 % and 57 %, respectively (P=0.17). Local failures occurred more frequently in adults than in children (1.4 % versus 14 %). However, metastatic events were frequently seen in children. Late toxicities were important in children, xerostomia was the most common one. CONCLUSION Despite locally advanced disease in children, therapeutic results were better than in adults but not statistically significant. The use of treatment combination (chemotherapy and radiotherapy) in juvenile nasopharyngeal carcinoma may explain our findings.

Pneumosinus dilatans frontal associé à des méningiomes cérébraux multiples

UNLABELLED Pneumosinus dilatans is rare. It is defined as an expansion of one of paranasal sinuses. We discuss the etiopathogenic hypothesis of pneumosinus dilatans, its epidemiologic and clinical characteristics, and its therapeutic approaches. OBSERVATION A man, 50 years old, presented frontal pneumosinus dilatans associated with multiple cerebral meningiomas, one of which was appended in the nasal cavity revealed by frontal deformation and nasal obstruction. CT and MRI confirmed the diagnosis. The patient was operated in the neurosurgery department, via the bicoronal approach, allowing the removal of meningioma and osteodural repair of the skull base. DISCUSSION Pneumosinus dilatans is a rare pathology with an unknown etiology. It mainly affects the frontal sinus. Its association with cerebral meningioma has been described in the medical literature. Treatment is surgical and is recommended for cases with aesthetic problems.

Mélanomes primitifs des muqueuses nasosinusiennes: à propos de cinq cas

IntroductionPrimitive melanomas of the nasosinusal mucosa are rare. They only represent 0.5 to 2% of melanoma and usually cause unilateral nasal obstruction and nasal bleeding. The diagnosis is histological, achieved via immunohistochemistry analysis. Their prognosis remains poor in spite of surgical treatment associated with post-surgical chemoradiotherapy. Our objective is to discuss the epidemiological, clinical and pathological data relating to primary melanoma of the nasosinusal mucosa and to study their development potential and prognostic features.Patients and methodsWe report five cases of primary melanoma of the nasal fossae over a period of seven years (2000–2006).ResultsThere were three men and two women ranging in age from 22 to 76 years (mean: 55 years). The most frequent symptoms at presentation were nasal obstruction and epistaxis. The histological examination revealed a proliferation of globular, epithelioid or spindle cells with enlarged nucleus and prominent nucleolus. An immunohistochemical test for anti-vimentin, protein S100 andHMB45 antibodies was carried out. The treatment was essentially surgical, with or without associated radiotherapy.ConclusionPrimary melanomas of the nasosinusal mucosa are rare. The new therapeutic approaches based on biotherapy and immunotherapy could influence the survival rate.RésuméIntroductionLes mélanomes primitifs des muqueuses nasosinusiennes sont rares, mais très agressives, ils représentent seulement 0,5 à 2 % des mélanomes et se manifestent souvent par un syndrome tumoral obstructif unilatéral, volontiers hémorragique. Le diagnostic histologique de certitude est aisé depuis l’apport de l’immunohistochimie. Leur pronostic reste cependant défavorable. L’objectif de notre travail est de discuter les données épidémiologiques et anatomocliniques des mélanomes primitifs des muqueuses nasosinusiennes et de dégager leurs potentiels évolutifs et les éléments pronostiques.Patients et méthodesNous rapportons cinq observations de mélanomes primitifs des fosses nasales diagnostiqués durant sept ans (2000–2006).RésultatsIl s’agissait de trois hommes et deux femmes ayant un âge moyen de 55 ans, hospitalisés pour obstruction nasale unilatérale et/ou épistaxis récidivantes. À l’étude histologique, il s’agissait d’une prolifération de cellules globuleuses, épithélioïdes ou fusiformes, à noyau volumineux macronucléolé. Une étude immunohistochimique pour les anticorps antivimentine, protéine S 100 et HMB45 était réalisée. Le traitement était essentiellement chirurgical, associé ou non à une radiothérapie.ConclusionLes mélanomes primitifs des muqueuses nasosinusiennes sont rares; l’amélioration de leur pronostic est particulièrement conditionnée par un diagnostic précoce et un choix thérapeutique adapté et pluridisciplinaire.