Identification of BRCA2 Cis Double Heterozygous Breast Cancer Cases Using Whole Exome Sequencing: Phenotypic Expression and Impact on Personalized Oncology.

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity (Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors.

Coexistence of invasive ductal breast carcinoma and fibroadenoma.

Fibroadenomas are the most common breast disease that occurs usually in young. The coexistence of an invasive ductal carcinoma and a fibroadenoma in the ipsilateral breast is extremely rare. We present the case of a 52 years woman, presented to us for an upper-outer breast lump. Breast imaging concluded to tow contiguous lesions, one of them was suspicious. She had a conservative surgery. Histology concluded to a fibroadenoma and an invasive ductal carcinoma.

Fertility sparing surgery for ovarian sex cord stromal tumors: a nine case series.

Ovarian Sex Cord Stromal Tumors (SCST) are a rare disease carrying a good prognosis. They generally affect young women; therefore fertility preservation is a critical issue. Fertility Sparing Surgery (FSS) showed promising results in both oncologic safety and fertility preservation. A retrospective case series involving 9 patients diagnosed with SCST and treated with fertility sparing surgery at our institution was conducted between January 2000 and May 2015. The median age was 24 years old (10 to 39). The main clinical manifestation was pelvic pain seen in seven patients. Five patients complained about menstrual cycle disorders. The nine patients went through fertility sparing surgery; seven had conservative staging and the other two had a unilateral salpingo-oophorectomy. Three patients out of nine had a pelvic unilateral lymphadenectomy. Two patients received adjuvant chemotherapy. Only two patients presented locoregional recurrence that occurred respectively after 7 and 192 months. The treatment combined chemotherapy and surgery based on mass resection. One patient achieved a natural pregnancy after the treatment. FSS seems to be a suitable approach for SCST. However, more case series and meta-analysis should be conducted.

[Epithelioid leiomyosarcoma of the uterine cervix: two cases]. / Lilomyosarcome épithélioïde du col utérin: a propos de deux cas.

BACKGROUND: The epithelioid leiomyosarcoma of the uterine cervix is a rare tumor. Usually, the presenting symptoms are vaginal bleeding and pelvic pain. Surgery is the standard treatment. AIM: To present the characteristic of this rare pathology by mean of two cases handled in the Institute Salah Azaiz. CASES REPORT: Two patients, aged 51 and 42 years, were referred to our institute for vaginal bleeding. Tumors were classified stage II proximal and II distal (FIGO classification modified by Gustave Roussy Institute). The patients had total hysterectomy with pelvic lymph node dissection. Histological exams confirmed the diagnosis of epithelioid leiomyosarcoma of the uterine cervix. Adjuvant external radiotherapy was performed. At 12 and 36 months, the patients are alive with no evidence disease.