[Clinical aspects of brain metastases from nasopharyngeal carcinoma]. / Aspects anatomocliniques des métastases cérébrales des carcinomes nasopharyngés.

Metastasis to the central nervous system, either through a hematogenous route or through the cerebrospinal fluid, is extremely rare in nasopharynx cancer. We aim to expose clinical aspects, therapeutic features and prognosis of nasopharyngeal carcinoma with brain metastases. We retrospectively reviewed the medical history of about 420 patients with nasopharyngeal carcinoma treated during 17 years at the university hospital of Sfax (Tunisia). Among them, three patients had brain metastasis. We excluded patients with direct extension to the brain. Tumours of the nasopharynx were locally advanced. The first patient had brain metastases at the initial diagnosis. The two other patients had brain metastases at 10 and 16 months during the follow-up. Ocular signs were the symptoms. Lesions were unique in two patients. Synchronous bone metastases were recorded in the three cases. All patients had whole brain radiation therapy and palliative chemotherapy. All patients had a progression of the disease and died. Brain metastases in nasopharynx cancer represent a rare event. Prognosis is poor, depending on age, surgical excision and synchronous metastases. Survival does not exceed 6 months.

[Extramedullary plasmocytomas]. / Plasmocytomes extraosseux.

PURPOSE: To study the localization, treatment and prognosis of extramedullary plasmocytoma through a series of eight patients and a literature review. PATIENTS AND METHODS: Eight patients with extramedullary plasmocytoma were treated in the university's hospital of Sfax in Tunisia. The average age was 57.3 years. Female represented 75% of patients. The diagnosis of plasmocytoma was based on anatomo-pathology and immunohistochemistry of a biopsy or resected tumour. Extramedullary location was confirmed if biological and radiological exams and medullary biopsy were normal. The therapeutic decision was made after multidisciplinary meetings regarding tumour location and anterior treatment. RESULTS: Solitary extramedullary plasmocytoma was located in nasal cavity, cervical node, testis, ovary, bladder and the tongue. One patient was treated for three simultaneous locations of extramedullary plamocytoma (node, bowel, pleura) without evidence of myeloma. Radiotherapy was proposed in six cases but refused in one case (plasmocytoma of the bladder is currently receiving radiotherapy). Treatment consisted in chemotherapy in two cases. Evaluation after treatment revealed complete remission in 86% of the cases. Nodal recurrence was noted in two cases. These two patients were lost to follow up. The five other patients were in complete remission after a mean follow up of 5.7 years. No local recurrence or myeloma was noted. CONCLUSION: Extramedullary plasmocytoma is a rare affection. It can occur in any region of the body. Head and neck is most frequent localization. The treatment is irradiation or surgery in some localization. Progression to myeloma is the most important factor that influences the prognosis of the disease.

Refined mapping of the autosomal recessive non-syndromic deafness locus DFNB13 using eight novel microsatellite markers.

The locus for a type of an autosomal recessive non-syndromic deafness (ARND), DFNB13, was previously mapped to a 17-cm interval of chromosome 7q34-36. We identified two consanguineous Tunisian families with severe to profound ARND. Linkage analyses with microsatellites surrounding the previously identified loci detected linkage with markers corresponding to the DFNB13 locus in both families. Haplotype analyses assigned this locus to a 3.2-Mb region between markers D7S2468 and D7S2473. In order to refine this interval, we identified nine dinucleotide repeats in the 7q34 region. To investigate the polymorphism of these repeats, a population study of 74 unrelated individuals from different regions of Tunisia was carried out. Our results demonstrated that eight of the nine repeats are polymorphic. The average number of alleles at these informative loci was 9.12 with a polymorphism information content of 0.71. Little evidence for linkage disequilibrium between some marker pairs was found. Haplotype analysis using these microsatellites refined the DFNB13 interval to an area of 2.2 Mb between the D7S5377 and D7S2473. In order to identify the DFNB13 gene, we sequenced and eliminated three candidate genes. Other known and predicted genes are being screened for deafness-causing mutations.

Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness.

Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness. The audiometric tests showed a loss of hearing greater than 70 dB, in all affected individuals of both families. Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain. Both mutations were not found in 200 control Tunisian chromosomes. The detection of naturally-occurring TMPRSS3 missense mutations in deafness families identifies functionally important amino acids. Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity.

Contrasted frequencies of p53 accumulation in the two age groups of North African nasopharyngeal carcinomas.

EBV-associated nasopharyngeal carcinomas (NPCs) from Southeast Asia and North Africa have many common clinical and biological characteristics. However, they differ with regard to their age distribution. In Asia, NPC mainly affects patients in the 4th or 5th decade of their life, whereas in North Africa an additional peak of incidence is found between the ages of 10 and 20. The p53 gene is rarely mutated in NPC. However, several groups have reported a consistent accumulation of p53 in Asian NPCs. To determine whether p53 was also accumulated in North African NPCs, we investigated its expression, by immunohistochemistry, in a series of 90 Tunisian biopsies. Bc12 and CD95, two proteins involved in the regulation of cell survival and apoptosis, were investigated in the same study. We found accumulation of p53 in 81% of the cases for patients over 30 years of age, but in only 38% of specimens for younger patients (P = 0.00013). There was a trend toward a higher frequency of Bc12 detection in patients over 30, but it was not statistically significant. CD95 expression was detected in all biopsies, generally at a high level, even at advanced stages of the disease. The changing frequency of p53 accumulation, below and over 30, suggests that NPC cells often achieve malignant transformation through different pathways in both age groups.

Pendred syndrome: phenotypic variability in two families carrying the same PDS missense mutation.

Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. Recently, this autosomal recessive disorder was shown to be caused by mutations in the PDS gene, which encodes an anion transporter called pendrin. Molecular analysis of the PDS gene was performed in two consanguineous large families from Southern Tunisia comprising a total of 23 individuals affected with profound congenital deafness; the same missense mutation, L445W, was identified in all affected individuals. A widened vestibular aqueduct was found in all patients who underwent computed tomography (CT) scan exploration of the inner ear. In contrast, goiter was present in only 11 affected individuals, who interestingly had a normal result of the perchlorate discharge test whenever performed. The present results question the sensitivity of the perchlorate test for the diagnosis of Pendred syndrome and support the use of a molecular analysis of the PDS gene in the assessment of individuals with severe to profound congenital hearing loss associated with inner ear morphological anomaly even in the absence of a thyroid goiter.