Nasopharyngeal carcinoma with cutaneous metastases.

INTRODUCTION: Cutaneous metastases from nasopharyngeal carcinoma are extremely rare and associated with a poor prognosis. CASE REPORTS: We retrospectively reviewed 820 patients with nasopharyngeal carcinoma treated over a 20-year period in the radiotherapy department of Farhat Hached hospital in Sousse and Ibn Khaldoun Medical centre, Hammam Sousse. Two of these patients presented cutaneous metastases. The skin lesions appeared during radiotherapy and 3 months after treatment of the primary tumour. Cutaneous metastases present as multiple painless nodules and erythematous plaques. Cutaneous metastases were associated with other metastatic sites (liver, bone). One patient received chemotherapy. Both patients died in a context of rapidly progressive disease. DISCUSSION: Nasopharyngeal carcinoma with cutaneous metastases is a rapidly fatal disease. In the light of these two cases and a review of the literature, patients with this disease are aged between 30 and 63 years with a marked male predominance. Cutaneous metastases are correlated with a more advanced primary tumour. The main sites are the trunk and scalp. There is no standard treatment modality for this disease and survival does not exceed 9 months.

Undifferentiated carcinoma of nasopharyngeal type in children: Clinical features and outcome.

OBJECTIVES: To describe the epidemiology, clinical features and treatment of undifferentiated carcinoma of nasopharyngeal type in children. MATERIAL AND METHODS: Retrospective study of 40 patients under the age of 17 years managed for undifferentiated carcinoma of nasopharyngeal type in two oncology centres in the central region of Tunisia between 1995 and 2012. RESULTS: Patients had a median age of 14 years with a sex ratio of 1.3. The mean time to presentation was 5 months. The presenting complaint was cervical lymphadenopathy in 90% of cases. Thirty-seven patients received curative treatment, according to a sequential mode in 85% of cases, starting with chemotherapy followed by radiotherapy to the nasopharynx and cervical lymph nodes. The median dose delivered to the nasopharynx was 70.4Gy. Two cases of local recurrence and five cases of metastatic relapse (all involving bone), were observed during follow-up. After a mean follow-up of 80.5 months (range: 1 to 180), 29 patients (72.5%) were in complete remission, eight had died and three were lost to follow-up. The 5-year overall survival was 77.7%. CONCLUSION: Undifferentiated carcinoma of nasopharyngeal type in children represents 6% of all cases of UCNT managed in our institutions. It is often discovered at an advanced stage. Sequential treatment combining chemotherapy and radiotherapy achieves an excellent local control rate.

Bilateral Breast Cancer After Prophylactic Bilateral Pulmonary Irradiation.

The purpose of this article is to report a new case of a probably radio-induced bilateral breast cancer occurred after prophylactic bilateral pulmonary irradiation in the treatment of osteosarcoma. A 42-year-old woman, treated at the age of 12 years for osteosarcoma at the right lower limb with chemotherapy (methotrexate, adriamycin and cisplatin) followed by non-conservative surgery and adjuvant radiotherapy. Eighteen years after, she developed her first breast cancer, and five years later, her second contralateral breast cancer. The patient was treated for her two non-metastatic cancers and is currently in complete remission. This publication adds to several previous publications the very probable effect of ionizing radiation in the occurrence of secondary cancers.

[Primary osseous Hodgkin's lymphoma of the sacrum: A diagnostic and therapeutic challenge]. / Lymphome de Hodgkin primitif osseux de la région sacrée : un défi diagnostique et thérapeutique.

Primary osseous Hodgkin's lymphoma is a very rare entity. Cases reported in the literature are limited with often insufficient initial exploration. We report a new case of a 24 years old patient with a diagnosis of primary osseous Hodgkin lymphoma of the lumbosacral region with extension to the soft tissues, without simultaneous lymph node involvement confirmed both by conventional and metabolic imaging. The patient received a combination chemotherapy (two courses BEACOPP® and four courses ABVD) followed by radiotherapy of the lombosacral region at the dose of 40Gy in 20 fractions. Fifteen months after the end of treatment, the patient was in complete remission.

La radiothérapie postopératoire du cancer du larynx: Étude clinique et résultats thérapeutiques à propos de 164 cas

But:Étudier les caractéristiques épidémiologiques, cliniques et anatomopathologiques, ainsi que les résultats thérapeutiques des cancers laryngés traités par radiothérapie postopératoire.Méthodes: Une étude rétrospective a été menée entre Janvier 1995 et Décembre 2010 colligeant 164 patients atteints d'un cancer laryngé traités à Sousse (Tunisie).Résultats :L'âge médian était de 60 ans. La prédominance masculine était marquée avec un sex- ratio de 26,4. Il s'agissait d'un carcinome épidermoïde dans 98,2%. Tous les patients ont eu une laryngectomie totale ou partielle associée à un curage cervical uni ou bilatéral. Tous les patients ont eu une radiothérapie postopératoire. La dose totale délivrée variait de 50 à 74 Gy avec une fraction de 1,8- 2 Gy/ séance. Avec un recul moyen de 55 mois, 49,4 % des patients étaient en vie en situation de rémission complète. Les probabilités de survie globale à trois, cinq et dix ans étaient respectivement de 77 % et 73 %, 69%. Les facteurs pronostiques de survie globale et de survies sans récidive locorégionale retenus, en analyse uni-variée, étaient : La radicalité du curage ganglionnaire, l'atteinte ganglionnaire histologique et l'effraction capsulaire.Conclusion :Le cancer du larynx est un cancer fréquent occupant la première place des cancers des voies aéro-digestives chez l'homme en Tunisie. Notre étude présume que l'absence d'atteinte ganglionnaire, la sélectivité de l'évidement ganglionnaire et l'absence d'effraction capsulaire sont des facteurs pronostic favorables de survie globale et de contrôle local

Human papillomavirus genotypes and HPV-16 variants distribution among Tunisian women with normal cytology and squamous intraepithelial lesions.

BACKGROUND: Little is known about the epidemiological characteristics of papillomavirus (HPV) infection among North African countries. Herein, we conducted a molecular epidemiological study to investigate prevalence of HPV type and HPV-16 variants among cervical-screened unvaccinated Tunisian women. METHODS: Cross-sectional study was performed on 494 Tunisian women visiting Women's Healthcare Centers. HPV-DNA detection was carried out on cervical samples using real-time polymerase chain reaction. HPV genotyping and HPV-16 variants were characterized by direct sequencing of L1 viral capsid gene. RESULTS: The overall HPV prevalence was 34% (95% CI: 30-38%) with significantly higher prevalence among women with squamous intraepithelial lesions (SIL) than those with no intraepithelial lesions (NIL) 84% (95% CI: 76-92%) and 24.5% (95% CI: 20-29%) respectively. The distribution of HPV prevalence according to women's age shows a U-shaped curve and the highest HPV prevalence rates were observed among the youngest (≤25 years; 51.2%, 95% CI: 37-67%) and the oldest women (>55 years; 41.7%, 95% The HPV-16 prevalence was 32.8% (95% CI: 22-45%) among women with SIL and 9.2% (95% CI: 6-12%) among women with NIL. Whereas, the HPV-18 prevalence was 1.3% (95% CI: 0-5%) among women with SIL and 0.3% (95% CI: 0-1%) among women with NIL. Among HPV-16 positive women, European lineage (E) was identified as the predominant HPV-16 variant (85.7%, 95% CI: 76-95%). The frequency of E variant was lower among SIL than among NIL women (81%, 95% CI: 64-99%, and 88%, 95% CI: 77-100%, respectively). Conversely, the African-2 variant frequency was higher among SIL than among NIL women (18%, 95% CI: 1-36% and 6%, 95% CI: 2-14%, respectively). In multivariate analysis, young age was the only risk factor that is independently associated with HPV infection. Moreover, HPV infection and menopause were both found to be independently associated with SIL and HSIL. CONCLUSION: HPV DNA testing should be proposed to young and menopausal Tunisian women. Considering HPV prevalence, only 13% of the Tunisian women could be protected by the bivalent HPV vaccine. These results may be helpful for designing an adapted HPV testing and vaccination program in Tunisia.

[Uterine sarcoma in Tunisia: retrospective study about 14 cases]. / Les sarcomes utérins en Tunisie : étude rétrospective à propos de 14 cas.

OBJECTIVE: To report epidemiologic, anatomoclinical treatment and results about a Tunisian retrospective serie of 14 patients with uterine sarcoma (US). PATIENTS AND METHODS: A retrospective study of 14 cases of uterine sarcoma treated in the Radiotherapy Unit of Farhat Hached Hospital of Sousse between 1995 and 2008. Epidemiologic and anatomoclinical features were assessed. A complete work-up including abdominal ultrasonography and abdominopelvic CT scan were perfomed in 7 and 10 cases, respectively. RESULTS: The median age was 48.5 years (15 to 78) without previous medical history of irradiation or prolonged drug exposition. There were 3 cases of leimyosarcoma, 7 cases of mixed Mullerian tumor and 4 cases of endometrial stromal sarcoma. The diagnosis was made postoperatively in 6 patients and after curettage in 8 cases. According to the classification of the International Federation of Gynecology and Obstetrics (FIGO), 8 patients were in FIGO stage I, 3 in stage II and 3 in stage III. Hysterectomy was associated with annexectomy in 12 cases. Bilateral pelvic lymphadenectomy was performed in one patient. Eight of our 14 patients underwent postoperative pelvic radiotherapy, associated with adjuvant chemotherapy in 3 cases. The evolution was marked by the occurrence of local recurrence in 4 patients who did not have adjuvant therapy with lung metastases in one case and peritoneal carcinomatosis in another case. With a medium follow-up from 54 months, 7 patients are free from disease, 5 died of their disease (after a mean of 24 months) and 2 patients were lost to follow-up. DISCUSSION AND CONCLUSION: Uterine sarcomas are rare tumors with poor prognosis. Adjuvant therapy (radiotherapy and/or chemotherapy should be discussed due to the high risk of recurrence or metastases.

[Pineal metastasis of breast cancer: case report and review]. / Métastase pinéale d'un carcinome mammaire: à propos d'un cas et revue de la littérature.

Pineal metastases of solid tumors are rare. Primary cancer is generally absent at the diagnosis, for which a cerebral MRI is important. We report a case of pineal metastasis occurring in a 76-year-old woman treated for breast carcinoma in our department.

[Breast cancer in woman younger than 35 years in Tunisia: retrospective study about 124 cases]. / Cancer du sein chez la femme jeune de moins de 35 ans en Tunisie: étude rétrospective à propos de 124 cas.

OBJECTIVES: Our aim was to report the epidemiological and clinical characteristics of breast cancer in young women and to evaluate the therapeutic results in the central part of Tunisia. PATIENTS AND METHODS: We report the results of a retrospective study including 124 patients under 35years old treated for breast cancer between 1995 and 2007 in the Radiotherapy Department of CHU Farhat Hached, Sousse. RESULTS: The mean age of our patients was 31.3years. T2N0, node positive (N+), high grade (SBRII and III) and endocrine responsive tumors were the most frequent. Fourteen patients had metastatic disease. One hundred and fifteen patients underwent a surgical treatment, which was conservative in 35 cases and radical for the others followed by radiotherapy on 114 patients. Chemotherapy, especially based on the FEC protocol, was administrated to 89% of all patients. Forty-five patients received also hormonotherapy. After a median follow-up of 48.5months, 51 patients remained free of disease. The 5years overall survival was 67.7%, the 5years free disease survival was 58.2%. DISCUSSION AND CONCLUSION: The 5years overall survival of breast cancer in young women varies between 55 and 75%, it was 67.7% on our study. These results can be improved by early diagnosis, adapted treatment and nowadays with targeted therapies.

[Non-Hodgkin lymphoma of the nasopharynx: a report of four cases]. / À propos de quatre cas de lymphome malin non hodgkinien primitif du cavum.

We report four cases of non-Hodgkin lymphoma involving the nasopharynx. Clinical, radiological, histological and treatment modalities are described. The four patients were male and aged 20, 42, 71 and 77 years. The symptoms were nasal obstruction with epistaxis in three cases and a cervical node in the fourth case. The histological type was a non-Hodgkin lymphoma of phenotype B with large cells CD20+ in the four cases. The treatment consisted in radiotherapy and chemotherapy.

[Tunisian experience in the treatment of aggressive non Hodgkin's lymphoma in adults: about 337 patients]. / Expérience tunisienne dans la prise en charge des lymphomes agressifs de l'adulte: à propos de 337 patients.

From January 1997 to December 2005, 337 patients with aggressive non Hodgkin's lymphoma were treated with one of the two successive multicentric non randomized protocols established in Tunisia. The mean age was 53 years. Most patients had diffuse large cell lymphoma with B phenotype in 86% and T in 14%. The performance status was 2 or 3 in 34% of cases. The LDH were elevated in 74% of cases. Advanced disease (III or IV stage) was noted in 59% of cases and 10% had a tumoral mass greater than 10 cm. According to the international prognostic index (IPI) adjusted to age, we distinguish four groups: group 1 (0 factor and age < 70 years), group 2 (1-3 factors and age < or = 60 years), group 3 (1-3 factors and age between 61 and 70 years) and group 4 (1-3 factors and age > 70 years). The patients of group 1 (N = 47) received 3 courses of CHOP regimen followed by irradiation. The patients of group 2 (N = 160) received 4 courses of ACVBP regimen (+ rituximab for 21 patients) followed by consolidation (N = 92) or peripheral blood progenitor cell transplantation (N = 20). The patients of group 3 (N = 61) received 8 courses of CHOP regimen (+ rituximab for 20 patients). The patients of group 4 (N = 69) received 6 courses of mini-CEOP regimen (N = 48) or 6 courses CVP regimen (N = 21). The 4-year overall survival was 56% and the 4-year event free survival was 49%.

Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa.

BACKGROUND: The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known. METHODS: From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors. RESULTS: Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk. CONCLUSION: Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa.

Interleukin-10 and interferon-gamma gene polymorphisms in patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a multifactorial disease. Cytokines driving the immune response seem to be disturbed in NPC patients. Since interleukin-10 (IL-10) is known to reduce the production of interferon-gamma (IFN-gamma), we supposed that genetic differences in IL-10 and IFN-gamma expression could be a mechanism by which NPC cells escape antitumour immune response. As the production of each cytokine is affected by the genetic background, we investigated the possible association between single nucleotide polymorphisms in genes of IL-10 and IFN-gamma with NPC. Different IL-10 -1082 G/A and IFN-gamma+874 Tau/Alpha genotypes were determined in 160 patients with nasopharyngeal carcinoma and 197 healthy controls. No association was found either for each SNP studied alone or for the combined analysis for both IL-10 and IFN-gamma polymorphisms among NPC patients in comparison with controls. Compared with individuals from high incidence countries, we noted huge significant differences in genotype distribution between individuals from low and intermediate NPC incidence countries. Polymorphisms of the IL-10 and IFN-gamma do not appear to be associated with NPC risk in the Tunisian population. Nevertheless, we strongly believe that the relationship between cytokines polymorphisms and NPC susceptibility deeply depends on the ethnicity.

[Nasopharyngeal angiofibroma with intracranial extension: situating the chemotherapy-radiotherapy association]. / L'angiofibrome nasopharyngien avec extension intracrânienne : place de l'association chimiothérapie-radiothérapie.

Nasopharyngeal angiofibroma is a locally aggressive, although histologically benign, vascular neoplasm. This neoplasm accounts for 0.05% of head and neck tumours and affects almost exclusively male adolescents. Surgery is considered as the primary treatment of nasopharyngeal angiofibroma. Other treatment modalities such as radiotherapy and chemotherapy are still recommended for intracranial extension involving the cavernous sinus or the internal carotid artery. We report a rare case of nasopharyngeal angiofibroma, further complicated with a Kennedy syndrome in a 34 year-old women. The treatment consisted in a chemotherapy (adriamycine, decarbazine) followed by radiotherapy. We discuss the relevance and outcome of the association chemotherapy-radiotherapy in the treatment of nasopharyngeal angiofibromas with a consistent intracranial extension (stage III B of Arch Otolaryngol Head Neck Surg 122 (2003) 122-129).

[Radiation induced breast sarcoma: a case report]. / Sarcome radio-induit du sein: à propos d'un cas.

Radiation-induced breast sarcoma is a late complication of radiation treatment. We report a case of an undifferentiated sarcoma occurring 8 years after breast conserving treatment, which required mastectomy taking pectoralis major.

[Nasopharyngeal carcinoma. Recent data]. / Les carcinomes du nasopharynx: donnée actuelles.

Nasopharyngeal carcinoma (NPC) represents an interesting model in the field of head and neck cancers. This cancer is rare in occidental countries (<1/100,000) and relatively moderate to highly frequent in the Mediterranean area and south-east Asia. This disease is linked to Epstein-Barr virus with a latent infection starting in the oropharyngeal epithelium and involving not only both epithelial tumor cells but also B lymphocytes. This viral infection represents the early phase of carcinogenesis where Latent Membrane Protein-1 has an important role via the terminal part of the BARF-1 gene. There are also various chromosomal alterations reported in NPC concerning the regions of chromosomes 3p, 9p, 11q, 13q, 14q et 16q detected essentially in areas of suppressors genes. Allelic and antigenic specificities of class II and II HLA seems to be associated to an increased risk of NPC different according to the incidence areas. Anti-EBV serology is suggestive of for NPC with an elevated level of IgA EA (early antigen) and VCA (viral capsid antigen). Cyfra 21 represents a promising serum marker for NPC with a 80% sensitivity. Radiotherapy remains the base of loco-regional treatment with a more frequent and systematic use of systemic chemotherapy (primary or concomitant) for high-risk-patients (T3-4 and N2-3 disease).

[Metachronous cancers after treatment for undifferentiated nasopharyngeal carcinoma]. / Cancers métachrones après traitement des carcinomes indifférenciés du cavum.

OBJECTIVE: To collect second cancers occurring in the head and neck area after treatment by chemotherapy and/or radiotherapy for undifferentiated nasopharyngeal carcinoma in Tunisia. PATIENTS AND METHODS: This is a retrospective study of patients developing second cancers after treatment for nasopharyngeal UCNT by radiotherapy and/or chemotherapy. To be retained in this study, second tumour had to be histologically different from the initial UCNT, localised in the irradiated area and occurring after a minimal delay of 3 years. RESULTS: We collect 11 cases of second cancers occurring among 2346 patients treated from 1984 to 2001 in Tunisia (0.46%). Patients have been treated for nasopharyngeal UCNT mainly advanced T3-T4 (72%) or N2-N3 (63%). Median age was 20 years (11 to 48) with a sex-ratio of 0.3 (3 M/8 F). Treatment protocol included primary chemotherapy in 4 cases (adriamycin-cisplatin) or adjuvant (in 4) associated to the loco-regional irradiation at a mean dose of 72 Gy (70 to 75). Median delay of second cancer occurrence was 9 years (3 to 17). Tumors were epidermoid carcinomas in 4 cases, fibrosarcomas (2), osteosarcomas (2), glioblastoma (1) and basocellular carcinomas in 2. Second tumors have been treated by surgery alone in 4 cases and chemotherapy alone in 7 patients. No patient have been reirradiated. Median survival was 17 months, 4 patients died and 7 are still alive including 4 in complete remission (24+, 36, 36 and 48+ months) and 3 with progressing disease (8, 16 and 18 months). CONCLUSION: Even very rare, second cancers after treatment for UCNT need to be detected and have a poor prognosis.

Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma.

Glutathione S-transferase Theta1 and Mu1 (GSTT1 and GSTM1) are involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. Conversely, they contribute to tumour cell survival by detoxification of numerous products induced by cancer therapy. The authors designed a large study to investigate the susceptibility and prognostic implications of the GSTT1 and GSTM1 gene deletions in breast carcinoma. The authors used the polymerase chain reaction to characterise the variation of the GSTT1 and GSTM1 genes in 309 unrelated Tunisian patients with breast carcinoma and 242 healthy control subjects. Associations of the clinic-pathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) were assessed using univariate and multivariate analyses. A significant association was found between gene deletion of GSTT1 and the risk of early onset of breast carcinoma (OR=1.60, P=0.02). The lack of GSTT1 gene deletion was significantly associated with poor clinical response to chemotherapy (OR=2.29, P=0.03). This association was significantly higher in patients with axillary's lymph node-negative breast carcinoma (OR=12.60, P=0.005). The null-GSTT1 genotype showed a significant association with increased DFS in this selected population of patients. This association was even higher in patients carrying both null-GSTT1 and -GSTM1 genotypes. The gene deletion of GSTs may predict not only the early onset of breast carcinoma but also the clinical response to chemotherapy and the recurrence-free survival for patients with lymph node-negative breast carcinoma.