[Primary ectopic intraosseous meningioma associated with multiple meningioma in a patient with central neurofibromatosis].

We present a case of multiple meningiomas (MM) as initial manifestation of central neurofibromatosis (NF2). A 19 y. o. woman was admitted with increasing signs of spinal cord compression at Th5-7 level. At CT assisted myelography, an entirely extradurally situated meningioma was detected and totally removed. Two years later increasing right-sided exophthalmos, without visual impairment was observed. The CT scan revealed thickening and abnormal shape of the sphenoid and the bony structures of the orbit. The retrobulbar space was narrowed and the optic nerve was shifted. At operation, ala parva of the sphenoid bone, the roof and the lateral orbital wall appeared thickened, laminated, fragile and exceedingly vascularized. The subdural space was found intact. The histopathological study revealed primary intraosseous meningioma of the sphenoid. There was no family history for neurofibromatosis (NF). The clinical findings at this time could not fulfil the criteria for NF2 and the case was considered as "true" multiple meningiomas occurring in different compartments of the neuraxis. The cytogenetical examination demonstrated a deletion of the long arm of the chromosome 22: 46 XX, del 22 (q 11.2). She was followed up and five years after the initial symptoms asymptotic bilateral vestibular schwannomas were found at CT and MRI. These findings finally led to the diagnosis NF2. There are no specific features distinguishing true MM from those associated with NF2, but we recall the importance of such manifestations for this diagnosis. We have not found any comparable case with these features in the medical literature.

Familial breast cancer. Part IV: survival of familial breast cancer in Bulgarian patients.

PURPOSE: The aim of part IV of this study was to register and compare the survival rates of sporadic and familial breast cancer, and to estimate the prognostic value of familial predisposition of the disease as a risk factor. PATIENTS AND METHODS: We investigated retrospectively 504 patients belonging to families with accumulation of the disease (study group, group I) and 300 patients with the sporadic form of breast cancer (control group, group II). All patients were diagnosed, treated, and followed-up at the Clinic of Thoracic Surgery, National Oncological Centre. For determination of the familial predisposition we used the Anderson's classification. The statistical significance of the difference between two groups and subgroups was evaluated by the x(2) Pearson's test and Student's paired t-test. RESULTS: Women with familial breast cancer were characterized by worse survival rates compared to the sporadic cases. Of the patients in group I 20.79% survived more than 5 years versus 76.74% in group II (p <0.0000). Group I patients with first degree of kinship had the lowest survival rates. Highly significant differences were found in survival, depending on stage: in group I stage IIA patients the survival was 42.86% versus 97.73% for group II; in IIB it was 14.17% versus 89.41%; and in IIIA it was 4.76% versus 75.00%, respectively. Tumor size, lymph nodes status, metastases and steroid receptors also showed a high statistical difference in survival between the 2 groups. Five-year survival in group I patients without metastases was 22.34%, while it was 80.71% in group II. In patients with metastases 4-year survival rates were 2.94% and 22.22%, respectively. Estrogen receptor (ER)-negative patients in groups I and II had 5-year survival of 17.41% and 72.06%, respectively. Progesterone receptor (PR)-negative patients in groups I and II had 5-year survival of 17.50% and 83.67%, respectively. Invasive lobular and invasive ductal carcinoma showed very poor survival in both groups (18.75% and 17.73% in group I versus 53.33% and 77.48% in group II, respectively). CONCLUSION: Familial breast cancer displays particular clinical characteristics that differ from the sporadic form of the disease in terms of clinical, histological and biochemical features. Our results show that patients with familial breast cancer have significantly lower survival rates in comparison with women with the sporadic form of the disease. The need for surveillance and diagnosis of the disease at an earlier stage is crucial for women with familial predisposition for breast cancer.

Familial breast cancer. Part II: Relationships with histology, staging, steroid receptors and serum tumor markers.

PURPOSE: To identify differences in clinical characteristics, histological features, hormone receptor status, and tumor marker expression between patients with sporadic and familial breast cancer. PATIENTS AND METHODS: As in the previous Part I of this study, two groups of women with breast cancer were compared. The first group (group I) included 504 patients with a family history of breast cancer. The second (control) group (group II) consisted of 300 patients not reporting such a history in their relatives. The examined parameters in this report were stage and axillary lymph node involvement at the time of the initial diagnosis, treatment methods, hormone receptor status, and serum levels of the tumor markers CEA and CA 15.3. The data were processed and analysed using the SPSS statistical package. The statistical significance of differences between groups and subgroups was evaluated by x(2) Pearson's test and Student's paired t-test. RESULTS: Compared to sporadic cases, patients with familial breast cancer were more often diagnosed at an advanced III or IV stage; metastatic involvement of the regional lymph nodes was more frequent in group I patients. In the same group more radical surgical procedures combined with chemotherapy and local irradiation were performed. In group I the percentage of negative hormone receptors was higher (35.3% versus 22.6%; p <0.0001) for estrogen receptors (ER), and 47.6% versus 32.6% (p <0.0001) for progesterone receptors (PR). Also, in group I raised serum levels of CA 15.3 were significantly more frequent compared with group II (48% versus 35.5%, p <0.0789), and this applied also for CEA values above 50 ng/ml (10.6% versus 1.5%, p <0.0002). CONCLUSION: Familial breast cancer displays particular clinical characteristics, distinguishing it from the sporadic type of the disease. Patients with familial breast cancer are usually diagnosed at an advanced stage. Commonly, the hormone receptors are negative and the serum concentrations of tumor markers elevated. The steroid receptor status represents the most reliable predictor of response to hormonotherapy and an important prognostic factor of the patient's outcome. As a result of their particular characteristics, these patients require more radical surgical techniques combined with pre- or postoperative local radiotherapy and systemic chemotherapy.

Familial breast cancer. Part III: Genome instability and cancer risk.

PURPOSE: The purpose of part III of this study was to direct our efforts towards more detailed genetic studies, which can be used in genetic counselling of patients with breast cancer and their relatives. PATIENTS AND METHODS: We investigated 52 patients, 25 with chromosomal fragility and 17 with spontaneous chromosomal aberrations, all with familial breast cancer (study group). The control group consisted of 10 healthy women without a history of proliferative diseases or breast cancer in their families. The chromosomal fragility and spontaneous chromosomal aberrations were studied in peripheral blood lymphocytes cultured for 72 and 48 hours, respectively, at 37 degrees C, following a standard procedure. RESULTS: In the patients with breast cancer the expression of chromosomal fragility was significantly higher (19.47%) compared to 11.61% in the control group (p<0.0001). In the patients with familial breast cancer the spontaneous chromosomal aberrations were significantly higher (6.72%) compared with those of the normal individuals (1.98%, p<0.0001). In the study group spontaneous breaks in a single lymphocyte were 0.15, while they were 0.05 in the control group (p<0.0001). CONCLUSION: The values of chromosomal fragility and chromosomal aberrations have some practical and theoretical importance in genetic services. The different variants in genomic stability are related with individual breast cancer development risk. Our results support the idea that the fragile sites and chromosomal aberrations may act as predisposing factors in carcinogenesis.