Novel BRCA2 pathogenic variant c.5219 T > G; p.(Leu1740Ter) in a consanguineous Senegalese family with hereditary breast cancer.

BACKGROUND: Pathogenic variants associated with hereditary breast cancer have been reported for BRCA1 and BRCA2 (BRCA1/2) genes in patients from multiple ethnicities, but limited information is available from sub-Saharan African populations. We report a BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. METHODS: An index case from a consanguineous family and nineteen healthy female relatives were recruited after informed consent. Along with this family, 14 other index cases with family history of breast cancer were also recruited. For the control populations we recruited 48 healthy women with no cancer diagnosis and 48 women diagnosed with sporadic breast cancer without family history. Genomic DNA was extracted from peripheral blood. All BRCA2 exons were amplified by PCR and sequenced. Sequences were compared to the BRCA2 GenBank reference sequence (NM_000059.3) using Alamut Software. RESULTS: We identified a novel nonsense pathogenic variant c.5219 T > G; p.(Leu1740Ter) in exon 11 of BRCA2 in the index case. The pathogenic variant was also identified in three sisters and one daughter, but was absent in the controls and unrelated cases. CONCLUSIONS: This is the first report of a novel BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. This result confirms the diversity of hereditary breast cancer pathogenic variants across populations and extends our knowledge of genetic susceptibility to breast cancer in Africa.

[Extramammary myofibroblastoma affecting the pelvic region: a case report]. / Myofibroblastome extramammaire de localisation pelvienne: à propos d'un cas.

Mammary myofibroblastoma is a rare soft-tissue tumor. Extramammary myofibroblastomas are particularly rare. We here report the case of a 78-year-old man presenting with pelvic pain relieved by defecation or urination. Rectal examination showed a mass in front of the anterior rectal wall. The magnetic resonance imaging (MRI) showed a well-circumscribed and heterogeneous mass measuring 10 x 6 x 8cm located behind the bladder which was pushed forward in front of the rectosigmoid. Immunohistochemical analyses showed diffuse co-expression on CD34 cells and desmin, Rb expression on most cells, oestrogen receptor expression, intense and diffuse P16 expression and a ki67 proliferation index of 25%. The patient had no recurrence 8 months after radiotherapy followed by surgery. Breast myofibroblastoma is a rare and benign tumor. Recurrence is hardly observed after local treatment. This study highlights the supporting role of radiotherapy in the efficacy of surgery.

Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal.

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.

Embryonal rhabdomyosarcoma of the perineum in an adult: a case report.

BACKGROUND: We report the case of an adult patient with embryonal rhabdomyosarcoma of the perineum admitted to our practice at Joliot Curie Institute in Dakar. It is a rare tumor at this age and has a bad prognosis at this localization. CASE PRESENTATION: We describe the case of a 22-year-old African man admitted for a perineal mass that had evolved over 6 months. He complained of tenesmus, obstinate constipation, and dysuria. A clinical examination revealed perineal swelling spread over his anus, scrotum, penis, testicles, and inguinal lymph nodes. A perineal ultrasound and computed tomography scan showed a large mass driving his testicles forward with regional lymph node metastases. An ultrasound-guided biopsy showed embryonal rhabdomyosarcoma on histology and immunohistochemistry, with strong positivity of neural cell adhesion molecule and myogenin while results for cytokeratin AE1/AE3, cluster of differentiation 45, synaptophysin, and chromogranin were negative. Our patient was classified T2N1M1. Outcome was quickly marked by occlusive syndrome and colostomy. Our patient did not opt for chemotherapy and died after 6 months of follow-up. CONCLUSIONS: The embryonic RMS of the adult is a rare disease. Despite the sensitivity to chemotherapy and surgery. Localization to perineum remains poor prognosis.

Malignant chondroid syringoma in a West African cancer institute: A case report.

OBJECTIVE: To report a case of malignant chondroid syringoma, a rare skin tumor at Joliot Curie Cancer Institute in Dakar. RESULTS: We report a case of malignant chondroid syringoma of the deltoid and axilla in a 53year old patient. Malignant chondroid syringoma is an extremely rare tumor of the sweat glands. It is included in myoepithelial tumors of the skin. It has an epithelial component with eccrin or apocrin differentiation, and myoepithelial component. It preferentially seat at the extremities. We report an unusual case with deltoid presentation and axillary mass masqueriding as metastatic lymph node. Surgery is the main treatment. It has a poor prognosis.

[Synchronous bilateral breast cancer and pregnancy: about 3 cases at Joliot Curie institute of Dakar (Senegal)]. / Cancers du sein bilatéraux synchrones et grossesse a l'institut Joliot Curie de Dakar (Sénégal).

To describe our diagnostic and therapeutic strategy against synchronous, bilateral breast cancer during the pregnancy. Gestational age at diagnosis of cancer was 7; 21 and 25 weeks respectively. Patients had stage IV and IIIA of breast cancer in two and one case respectively. They all received chemotherapy, two cases during pregnancy (6TEC and 3AC) and one case after delivery. Bilateral mastectomy was performed in one case. One patient died. The others were alive but all metastatic. Fetal growth restriction was noted in one case. This association leads to delayed diagnosis of cancer. Surgery is feasible and the type of intervention is only determined by the cancer stage. Chemotherapy is feasible and is associated with less foetal complications in the last two quarters of pregnancy.

[Diagnosis and treatment of the epithelial ovarian cancer at the West African Cancer Center of Dakar]. / Prise en charge diagnostique et thérapeutique des tumeurs épithéliales malignes de l'ovaire dans le Centre Ouest-Africain de lutte Contre le Cancer de Dakar.

INTRODUCTION: Epithelial ovarian cancer are the most frequent of ovarian cancer, their prognosis is very bad. The aim of this study is to describe the diagnosis, the treatment and to assess the survival rate of the patients. METHODS: It was a retrospective study realized at the Cancer Institute of Dakar from December 2000 to January 2007. We have collected 117 patients with epithelial ovarian cancer. The mean age was 49 years. Patients were comprised: 22 stage I, 32 stage II, 35 stage III and 26 stage IV. Primary surgery was performed to 34 patients and the other patients were treated with chemotherapy and surgery. The survival rate was assessed by Kaplan-Meier method and the Logrank test had allowed to compare the survival among age and optimal surgery. RESULTS: Optimal surgery R0 was done in 20 cases and surgical resection R2 was performed in 45 cases. Pathological exam had found 65 serous cystadenocarcinoma, 28 mucinous cystadenocarcinoma and 21 endometrioid cystadenocarcinoma, one malignant tumor of Brenner. Overall survival at five years was 13.3%. The survival among optimal surgery was 16.3 and 2.3% for suboptimal surgery. There was no significant difference of the survival among patients who were less than 40 years old (P = 0.334). CONCLUSION: Prognosis of epithelial ovarian cancer is worse in Senegal as like as in the world. To improve the survival of our patients, we must detect the early diagnosis of these tumors and to introduce the neoadjuvant chemotherapy before optimal surgery.