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Objectives: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored. In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. Methods: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. Results: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival ( P = .081) and long disease-free-survival ( P = .016) with a low rate of recurrence ( P = .006) than HPV– patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression ( P = .043). Conclusion: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.

The aim of this study was to describe the clinico-epidemiological and histopronostic characteristics of triple negative breast cancer (TNBC) and to evaluate the therapeutic results in tunisian women.We reported the results of a retrospective study including 90 patients treated for TNBC between Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis.TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was 53.67 years. Family history of breast cancer was reported in 10% of cases.The majority of tumors were classified as T2 (41%) and associated with invasive ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node metastases were detected in 44% of patients.Among operated patients, 46% of patients underwent conservative surgery and 54% radical surgery. Chemotherapy and postoperative radiotherapy were given in97% and 80%of patients, respectively. After a median follow-up of 33.51 months, 61% of patients remained free of disease, 12% hadloco-regional recurrence, 9% had disease progression during chemotherapy and 21% developed systemic disease.TNBC diagnosis is often made in the advanced stage and has a tendency to recur after treatment. The variable responseto chemotherapy is due to the molecular tumor heterogeneity. The development of targeted therapies is necessary to improve outcome of chemoresistant TNBC.

The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle.To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker.We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method.Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score.Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.

Mucinous carcinoma is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. It accounts for 1 to 7% of all breast cancers. We propose in this work to study at first the clinic-pathological characteristics and the evolution of 48 cases of mucinous carcinomas. Secondly, we propose to identify through a review of recent literature, the therapeutic management of these carcinomas.This is a retrospective study, conducted in Salah Azaiez carcinological institute, interesting 48 cases of mucinous carcinoma collected over 19 years. Clinical, radiological and pathological information were collected from medical records.The mean age of our patients was 57 years. The tumor was single in 41 cases and in 7 cases bifocal. Mammographic aspects were favor of malignancy in 33 cases (75%). It was mixed subtype in 14 cases and pure in 34 cases. Lymph node involvement was noted in 14 cases. The number of metastatic lymph nodes ranged from 1 to 11 with an average of 3. Hormone receptors were positive in 35 tumors (73%). The HER2 showed overexpression in 5 cases. Surgery consisted of a radical treatment for thirty-two patients (66%). Overall survival at 5 years was 75.3% and 59.3% at 10 years. Disease-free survival was 74% at 5 years and 58% at 10 years.Mucinous carcinoma consists of two distinct subtypes: pure and mixed with different prognosis. Larger data samples with longer follow-up are necessary to achieve an improved understanding of this particular tumor.

Summary Aims The objective of this study was to compare the protein expression profile between well-differentiated (papillary) and undifferentiated (anaplastic) thyroid carcinoma in Tunisian patients. Methods This first Tunisian retrospective study concerned data of 38 thyroid cancer cases (19 papillary carcinoma PTC and 19 anaplastic carcinoma ATC) collected at Salah Azaiez Institute of Tunisia. Immunohistochemistry was used to evaluate tumor expression of different molecular markers (p53, Ki67, E-cadherin, cyclin D1, bcl2, S100 and Her-2). The molecular expression was correlated with the clinicopathological characteristics of the tumors. Results There were 6 differentially expressed markers when comparing anaplastic thyroid carcinoma ATC with papillary thyroid carcinoma PTC. Expression of p53 and Ki67 were significantly increased in 16 and 18 ATC cases respectively, the Ki67 expression was lost in PTC. Cyclin D1, E-cadherin, bcl2 and S100 were overexpressed in PTC tumors; however, they were significantly decreased in ATC. The last marker, Her-2 was expressed in one case of PTC only. Conclusion Our results, similar with findings of other ethnic groups, showed alteration in expression of molecular markers associated with tumor dedifferentiation, indicating loss of cell cycle control with increased proliferative activity in ATC carcinoma. These data support the hypothesis that ATC may derive from dedifferentiation of preexisting PTC tumor.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.

Background In the Tunisian population, as yet a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer. These mutations are located in a few exons of BRCA1/2 . The aim of the present study was to search for these mutations in 66 unrelated patients with hereditary breast and/or ovarian cancer in order to assess the interest in such a targeted approach for genetic testing in Tunisia. Materials and Methods Blood specimens from the 66 Tunisian patients, with family history of breast and/or ovarian cancer, were collected at the Salah Azaiz Cancer Institute of Tunis. The exons 5, 20 and part of exon 11 of BRCA1 as well as part of exons 10 and 11 of BRCA2 were analyzed by Sanger sequencing. Results 12 patients had deleterious mutations in the BRCA1 or BRCA2 genes (18%), including a novel frame-shift mutation of BRCA1 (c.3751dup; 3780insT). Four distinct BRCA1 mutations were detected eight patients: c.5266dup (5382insC) and c.211dup (330insA) each in three patients, c.3751dup (3870insT) and c.4041_4042del (4160delAG) each in one patient. The four remaining cases all carried the same BRCA2 mutation, c.1310_1313del (1538delAAGA). Besides these deleterious mutations, eight polymorphisms and unclassified variants were detected, one of them being never reported ( BRCA1 c.3030T>G, p.Pro1010Pro). Conclusion In this study, we show that targeting relevant exons in BRCA1 and BRCA2 genes allows detection of a substantial percentage of mutations in the Tunisian population. Therefore such an approach may be of interest in genetic testing of high-risk breast and ovarian cancer families in Tunisia.

Many researchers have focused on the preventive and curative effects of garlic (Allium sativum), particularly on cardiovascular diseases and cancer. However, its impacts on the male reproductive system have not been clearly defined. In this study, the effect of chronic consumption of two garlic fractions was tested: one soluble in water (aqueous solution obtained by grinding and centrifugation) and the other one precipitated by ethanol (alcoholic precipitate obtained by precipitation of the aqueous solution), on different variables of male rats' reproductive functions. These two fractions were targeted to try to identify the nature of the active garlic compounds responsible for the different modifications observed on testicular parameters. The observation of seminiferous tubules of rats treated with garlic fractions showed an increased number of tubules deprived of spermatozoa. In addition, garlic fractions induced apoptosis of testicular germ cells (TdT-mediated dUTP-X nick-end labeling [TUNEL] approach) and a decrease of serum testosterone levels and seminiferous tubule DNA concentrations. In summary, our histological and molecular results suggest that one or several substances, soluble in water and precipitated by alcohol, impaired spermatogenesis.

The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women.This retrospective study concerned data of 966 breast cancer cases collected from 2007 to 2009 at Salah Azaiz Institute of Tunis. These cases were classified by an immunohistochemistry test for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) status in the four molecular subtypes, namely luminal A, luminal B, HER2+ and triple negative. The molecular classifications were correlated with the clinicopathological characteristics of the tumors.Luminal A (50.7% of cases) was the most common subtype, with triple negative subtype 22.5%, luminal B 13.4% and HER2+ 13.4%. Triple negative and HER2+ subtypes were significantly associated with large tumor size (5 cm, P 0.001), younger age (40 years, P 0.03) and high grade (P 0.001). Conversely, there was no correlation with the lymph node status.Our data demonstrated that the luminal A subtype, associated with a favorable prognosis, was the most frequent subtype in the Tunisian population; however the triple negative subtype occurred at a high incidence in Tunisia compared to Western countries. The molecular subtypes are correlated to the tumor size, histological grade and patient's age.

Le mélanome muqueux primitif de la fosse nasale est une tumeur maligne très agressive, rare, constituant 1% de l'ensemble des mélanomes. Sa symptomatologie est non spécifique et son diagnostic est anatomo-pathologique, appuyé par l'immunohistochimie. Son traitement est essentiellement chirurgical basé sur une résection large de la tumeur. Le pronostic est défavorable, caractérisé par des récidives et des métastases fréquentes et un taux de survie bas. Nous rapportons dans ce travail un nouveau cas de mélanome malin primitif de la fosse nasale, tout en précisant les caractéristiques de cette tumeur.

Inflammatory myofibroblatic tumor is a recently caracterized solid mesenchymal tumor. They are frequently localised in the lung. However, the head and neck forms are uncommon.To report a new case of inflammatory myofibroblastic tumor of the larynx.This 47-year old man presented with dysphonia without dyspnea. Laryngoscopy showed a tumor of anterior vocal cord. CT scan of larynx confirmed diagnosis. The patient had a cordectomy. Histology concluded to the diagnosis of inflammatory myofibroblastic tumor. No relapses have been noted after 4 months.Only a few cases of laryngeal inflammatory myofibroblastic tumor have been reported in the literature. Clinical presentation depends of tumor location. Radiological images are not specific and diagnosis is based on histology. The expected course is essentially marked by the risk of local recurrences. Surgical excision seems to be the treatment of choice.

Swyer syndrome is a distinct type of pure gonadal dysgenesis characterized by a 46 XY karyotype in female phenotypic patients. It shows an abnormality in testicular differentiation. It is usually revealed by primary amenorrhea. The tumor that usually develops in Swyer syndrome is gonadoblastoma. Although gonadoblastoma is considered benign, the risk of malignant germ cell tumor development is high.The aim of this report is to stress on the risk of occurrence of malignant germ cell tumors on these dysgenesic gonads.We present the clinical, sonographic and endocrine findings in the case of a 13 year-old phenotypic young girl with a 46 XY karyotype and gonadal dysgenesis. The patient underwent surgery for adnexal torsion. An examination of the gonads revealed gonadoblastoma associated to dysgerminoma. The treatment and the follow up are detailed.The presence of Y chromosome in the karyotype of a patient presenting a gonadal dysgenesis must lead to prophylactic bilateral gonadectomy in order to avoid a malignant transformation. Gonadectomy must be followed by a hormone replacement therapy.

Oral tongue cancer remains an aggressive tumour in Tunisia, and patients often present with locally advanced disease, leading to high mortality. The molecular pathway of its tumorigenesis is not yet understood. This study aimed to assess the biologic significance of p53, heat shock protein 70 (Hsp70), Ki67, and CD34 and their influence on survival in patients with tongue cancer.Archival tissues from 68 patients with squamous cell carcinoma of the tongue were examined for p53, Hsp70, Ki67, and CD34 by immunohistochemistry and correlated with 5-year survival.p53 and Ki-67 were detected in 55% and 77% of tumours, respectively; a significant association between p53 and Ki67 expression was found (p = .038). Forty-seven percent of cases of tongue cancer expressed Hsp70, and only 9% of tumours expressed CD34 angiogenic factor. No significant correlation was noted between survival and expression of p53, Hsp70, Ki67, and CD34 in patients.None of the markers p53, Hsp70, Ki67, and CD34 demonstrated prognostic significance for 5-year survival in patients with squamous cell carcinoma of the tongue.

The aim of this review is to study natural history, presentation, treatment and prognosis of head and neck liposarcomas.We carry a retrospective study about 15 patients diagnosed and treated in our department between 1969 and 2001. Therapeutic modalities included surgery, radiotherapy and chemotherapy.Tumors were mostly localized at the neck (4 cases) and the scalp (3 cases). Cervical lymphadenopathy was found in 1 case. Chest X-ray found showed metastases in 2 cases. Histological types of liposarcomas were the following: myxoid (5 cases), well differentiated (4 cases), pleomorphic (4 cases), round cell (1 case) and dedifferentiated (1 case). Twelve patients underwent surgery. Complete excision was performed in 7 cases. In the other 5 cases, exeresis was incomplete and 4 of them received postoperative radiotherapy. Three patients were not operated because of vascular involvement (1 case) or metastasis (2 cases), and they all received radiotherapy alone. After initial treatment, complete remission was achieved in 7 cases (46.7%). A recurrence occurred in 8 cases (53.3%). Two of these patients were reoperated and another one received chemotherapy. In the other 5 cases, the tumor was uncontrollable and no additional treatment has been proposed. Five-year survival rate was 87% for patients who underwent surgery alone, 75% for those who underwent surgery and postoperative radiotherapy, and 0% for those treated by radiotherapy alone.The mainstay of treatment of head and neck liposarcomas is surgical excision and the prognosis is largely determined by the histological grade and the clinical stage.

Seborrheic keratosis are one of the most common benign epidermal tumors encountered in clinical practice. Malignant transformation is exceptional. It may occur by the involvement of human papilloma virus. We report two cases of seborrheic keratosis in respectively 58 and 60-years-old women, which, on biopsy, revealed the presence of Bowen's disease for the former and Squamous cell carcinoma for the later.

primary squamous cell carcinoma (scc) of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. Cases of papillary carcinoma merging in association with squamous cell carcinoma are extremely rare.the characteristics of such association will be studied herein through a review of literature.we report a case of an 87-year-old patient presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically, malignancy was suspected. Histopathologic diagnosis was a well-differentiated scc associated with areas of papillary carcinoma. Exhaustive clinical, endoscopic and radiological examinations did not reveal any primary site of scc or any contiguous spread from neighboring structures. Surgery was followed by radiotherapy, but the patient died 6 months later.the coexistence of epidermoide and papillary carcinomas in the thyroid gland must be known because of its prognostic impact.

Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined.The purpose of this study was to investigate P53 expression in breast cancer and to examine the relationship between P53 overexpression and the degree of angiogenesis.A total of 52 paraffin-embedded tumors were evaluated immunohistochemically for expression of P53 and CD34 angiogenesis factor.The majority of P53 positive cases (82%) demonstrated high level of microvessel density (MVD); 18% demonstrated no CD 34 expression. In contrast there was no variation of CD34 expression among P53 negative tumors.This data suggests that microvessel density is promoted by P53 overexpression in breast cancer, and is correlated with high histologic grade.

Male breast cancer is rare compared to its female counterpart representing less than 1% of cancer in men. The objective of our retrospective study is to report the epidemiologic and clinical profile and to analyse the therapeutic results and prognostic factors in a Tunisian population collected during a period of 20 years at a single institution. We collected from 1979 to 1999, all the histological confirmed male breast cancers treated at our institution. We analyse the following data: age, clinical presentation and features, therapeutic protocol, results and prognostic factors. Survival was done with the Kaplan-Meier method and comparison with the log-rank test. 123 cases of male breast carcinoma were collected with a median age of 65 years. Most patients (62.2%) have an advanced T4 disease with bilateral lesions in 4 cases. Infiltrating ductal carcinoma represent 91% of all tumours. 85% of tumours expressed hormonal receptor. The treatment consisted in a radical mastectomy in 93 cases (84%) followed by radiotherapy, chemotherapy and in many cases by hormonotherapy. After a median follow up of 26 month, 22 patients presented loco regional recurrence and 41 metastases. Estimated 5-year survival rate was 62%. The presence of metastasis, nodal involvement, advanced disease, and grade affected survival. Male breast cancer represent at our institution 1 % of the male cancers treated comparable to the literature data. T4 tumours represent a higher rate, the treatment approach is the standard applicable in breast cancer; prognostic factors are the classical one like breast cancer in women.

We report the case of a special form of rhabdomyosarcoma called "lymphadenopathic" which was reported only two times in the literature. This lymphadenopathic alveolar RMS shows lymph nodes as clinical manifestation mimicking lymphoma with an unknown primary neoplasm. In the case we report, clinical examination, and radiological studies revealed superficial and deep located lymph nodes in association with bilateral pleural effusion. Conventional histological examination showed lymph node infiltration by a metastatic tumour having alveolar pattern. Some of tumour cells were round with multilobed off-centred nucleus and eosinophilic cytoplasm containing fibril material with longitudinal and transverse striation indicating a muscle nature of the tumour proliferation. The immunohistochemical study showed intense and diffuse immunoreactivity of tumour cells for vimentin and a discreet immunostaining by desmin. These findings were compatible with the diagnosis of lymph node metastasis by alveolar rhabdomyosarcoma.

Clear cell carcinoma is the most frequent cancer of the kidney (60-80% of cases). This tumour has a great propensity to metastasis. Metastasis lesions appear 15 to 20 years after nephrectomy and differential diagnosis with can be difficult to establish. We report an exceptional case of renal cell carcinoma metastasis to the tongue in a 63-years-old male patient who had a nephrectomy 20 years previously. To our knowledge, this is the second case reported in the literature.

The sarcoma of the penis is a very rare tumor more exceptional is the Leiomyosarcoma of the penis for which the diagnosis required an immunohistochemical study. The prognosis for this tumor is poor. We report a case, which arise to a 53 year-old-man in this instance we did a review of the medical literature.

Using serologic and molecular methods, 45 nasopharyngeal carcinoma (NPC) patients were typed for HLA class I and class II and were compared to 100 unrelated normal Tunisians. Our results showed that the antigen frequency of HLA-B13 and allelic frequencies of DRB1*03, DRB1*15 were significantly higher in the NPC patients than in the control group (15.5 vs. 4; 26.4 vs. 11.5, and 14.4 vs. 6.5%, respectively) probably indicating a positive association with NPC. Moreover, we observed that HLA-A23 was absent in our NPC sample and was present in 18% of normal controls, and HLA-DRB1*11 was less frequent among the patients compared to the controls (5.5 vs. 14%) suggesting a protective effect of this association with NPC.

Conflicting opinions exist concerning clinical and pathological presentation, as well as evolution and prognosis, of breast cancer in young women. The roles of associated pregnancy and lactation on these parameters is also unclear. These two conditions are studied in the present work through the comparison of two breast cancer patient age groups: patients under the age of 30 (Group A) and premenopausal patients aged 45–49 (Group B). Rapidly growing and/or inflammatory breast cancer (rapidly progressing breast cancer: RPBC) — a special form of Breast Cancer with a poor prognosis very frequent in the Tunisian breast cancer population — was more often present among Group A patients. This difference is a consequence of the more frequent association of this breast cancer group with pregnancy or lactation; nearly all the cases of breast cancer associated with pregnancy or lactation are RPBC. For breast cancer without the pregnancy/lactation association, the younger group generally shows poorer histological grading and more severe evolution. The number of patients in our study is not really sufficient to allow statistically significant conclusions, but it does seem clear that young age and associated pregnancy/lactation are aggravating factors in Tunisian breast cancer patients.

Based on two pretreatment evaluations, doubling time (DT) was calculated in 75 cases of invasive breast cancer (BC). The cases studied were more or less equally distributed between three DT groups: fast-growing tumors (DT less than 90 days), intermediate cases (DT between 90 and 180 days), and slow-growing tumors (DT greater than 180 days. A correlation was found to exist between DT and patient age and, to an even greater extent, between DT and pathologic prognostic indicators such as histologic grading and nuclear grade. Inflammatory symptoms were not associated with DT, but were closely related to the size of the tumor and regional lymph node involvement. The date of detection of distant metastases depended heavily on the DT of the BC:BC with shorter DT = earlier metastatic spread. The presence of inflammatory signs was also decisive: within each DT category, inflammatory BC metastases were both more frequent and precocious.