Ahmed El May

Breast cancer in Tunisia in 2004 : a comparative clinical and epidemiological study

The aim of this study was to determine the epidemiological, clinical and anatomopathological aspects of breast cancer in Tunisia. We censored and analyzed all cases of breast cancer newly diagnosed in Tunisia during the year 2004. During that year, 1437 new cases of invasive breast cancer were diagnosed and 35 cases of non invasive breast cancer. There were 1408 women and 29 men. The accrual incidence was 27.1 and the standardized incidence was 28.5. The mean age for women was 51 years. The mean tumour size was 40.8 mm (32.3 mm and 42.5 mm for private and public sectors respectively). Tumour stage was T1 in 12.2% cases, T2 in 46.9% cases, T3 in 11.2% cases and T4 in 24.7% cases. Invasive ductal carcinoma was the most frequent (86,6%) with SBR II grade representing 54.5%. 27.7% of the patients had undergone conservative treatment. There was an unexpected increase of the incidence since 1994 where the standardized incidence was 16.9. We have noticed a moderate decrease of the tumour size of 8 mm during the last decade. This national epidemiological study on breast cancer showed an increase in the incidence of this cancer with a moderate decrease in the clinical tumour size. The relative young mean age of our patients may be explained by the age distribution in our population or by risk factors that may be particular to our country.

Association between HLA-A/-B Antigens and -DRB1 Alleles and Nasopharyngeal Carcinoma in Tunisia

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.

Head and neck liposarcomas A 32 years experience

OBJECTIVE The aim of this review is to study natural history, presentation, treatment and prognosis of head and neck liposarcomas. METHODS 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. RESULTS 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. CONCLUSION 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.

Inflammatory symptoms in breast cancer. Correlations with growth rate, clinicopathologic variables, and evolution

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 < 90 days), intermediate cases (DT between 90 and 180 days), and slow‐growing tumors (DT > 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.

Complementary determination of Epstein-Barr virus DNA load and serum markers for nasopharyngeal carcinoma screening and early detection in individuals at risk in Tunisia

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.

Descriptive analysis of molecular subtypes in Tunisian breast cancer

The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women.

Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer

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 (BRCA1c.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.

Expression profile of biomarkers altered in papillary and anaplastic thyroid carcinoma: Contribution of Tunisian patients

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.

Dubreuilh's melanosis or malignant lentigo

We report a 69 year-old man who presented with a 5-year history of pigmented lesion on the tip of the nose. Physical examination revealed a 2 cm, hyperpigmented lesion of the nose. The cervical and abdominal ultrasonographies were normal. A surgical resection of the tumor was performed. Grossly, the tumor was flat, black or dark brown, and measured 1.5 cm of diameter. Histological examination showed a confluent growth of melanocytes along dermo-epidermal junction with involvement of adnexal structures (Fig. 1). Some isolated or nested cells infiltrated papillary dermis and were surrounded by inflammatory and fibrous stroma (Fig. 2). The derm presented a significant solar elastosis and the epidermis was atrophic. These features confirmed the diagnosis of Dubreuilh’s melanosis. At 3 years of follow-up, the patient was asymptomatic and there was no recurrence.

Calcifying fibrous tumor of axillary region

We report a 17 year-old woman who presented with a 1-year history of left axillary palpable mass. At physical examination the lesion was firm, lipomatous. The breast ultrasonography showed a left voluminous axillary mass, measuring 54mm, hyperechoic and ill limited. A surgical resection of the mass was performed. Grossly, it was a white firm well-circumscribed and lobed mass measuring 15x10x6 cm. Histological examination showed a benign mesenchymal tumor. It consisted of abundant fibrosis with hyalinised vessels, containing mononuclear infiltrate and foci of psammomatous calcifications (Fig. 1). Lymphoid follicles were noted around vessels and psammomas (Fig. 2). The tumor did not show any features of malignancy. Immunohistochemically, the spindle cells were vimentin positive (Fig. 3) and vessels showed CD34 positivity. These features confirmed the diagnosis of Calcifying fibrous tumors. At 4 years of follow-up, the patient was asymptomatic and there was no recurrence.