RESUMO
We report 2 primary renal sarcomas demonstrating BCOR-CCNB3 gene fusions that have recently been identified in undifferentiated round cell sarcomas of bone and soft tissue. These neoplasms occurred in male children aged 11 and 12 years, and both were cystic as a result of entrapment and dilatation of native renal tubules. Both cases were composed of variably cellular bland spindle cells with fine chromatin set in myxoid stroma and separated by a branching capillary vasculature. Both neoplasms demonstrated immunoreactivity for BCOR, cyclin D1, TLE1, and SATB2 in the spindle neoplastic cells and negativity in the prominent capillary vasculature. One case was extensively cystic and had hypocellular areas that simulated cystic nephroma; this neoplasm recurred 3 years later as a solid, highly cellular spindle cell sarcoma in the abdominal cavity. The morphology and immunoprofile of these renal neoplasms was compared with a control group of other sarcomas with BCOR genetic abnormalities, including clear cell sarcoma of the kidney (CCSK), infantile undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy, and bone/soft tissue sarcomas with BCOR-CCNB3 gene fusion; along with primary renal synovial sarcoma. Our findings show that the renal sarcomas with BCOR-CCNB3 gene fusion overlap with CCSK. These results are in keeping with a "BCOR-alteration family" of renal and extrarenal neoplasms which includes CCSK and undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy (which typically harbor BCOR internal tandem duplication), and BCOR-CCNB3 sarcomas, all of which are primarily driven by BCOR overexpression and have overlapping (but not identical) clinicopathologic features.
Assuntos
Biomarcadores Tumorais/genética , Ciclina B/genética , Fusão Gênica , Neoplasias Renais/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Sarcoma de Células Claras/genética , Sarcoma/genética , Biomarcadores Tumorais/análise , Biópsia , Criança , Ciclina B/análise , Diagnóstico Diferencial , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/química , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Fenótipo , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/análise , Proteínas Repressoras/análise , Sarcoma/química , Sarcoma/patologia , Sarcoma/cirurgia , Sarcoma de Células Claras/química , Sarcoma de Células Claras/patologiaRESUMO
This article reports a rare case of a temporomandibular joint (TMJ) chondrosarcoma in a child. Chondrosarcoma is a malignant cartilaginous neoplasm that resembles synovial chondromatosis. In the head and neck region, chondrosarcoma is uncommon, corresponding to 6.4% to 12% of all reported cases. The majority of patients with chondrosarcoma are in the third to fourth decades of life. A Pubmed search showed that 20 TMJ chondrosarcoma cases had been reported up to 2008. The present case was of an 11-year-old girl referred to an Oral Disease Center and presenting with a preauricular swelling on the right side and normal ENT evaluation. The patient was healthy. Discrete pain and mild limitation of mouth opening were observed. A panoramic radiograph as well as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI) revealed an osteolytic lesion in the right TMJ. The skull base and adjacent spaces were preserved but adjacent anatomic structures were displaced. After an incisional biopsy, the patient underwent high condylectomy. Microscopic findings showed a tumor exhibiting cartilaginous tissue proliferation with cellular pleomorphism, nuclear hyperchromasia, and mixoid changes in the matrix. The immunohistochemical analysis of the expression of Ki-67 and Cyclin B1 proteins (cellular proliferation markers) revealed a very low proliferative cell index. The 3.5 years of clinical and imaging follow-up have shown no evidence of recurrence or metastasis, but signs of myofascial disorders could be observed. It is concluded that cartilaginous lesions in the jaws must be regarded with suspicion, since benign and malignant lesions may show similar clinical features. This case emphasized the importance of interdisciplinary approaches to minimize the possibility of misdiagnosis.
Assuntos
Condrossarcoma/patologia , Transtornos da Articulação Temporomandibular/patologia , Criança , Condrossarcoma/química , Ciclina B/análise , Ciclina B1 , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Côndilo Mandibular/patologia , Articulação Temporomandibular/patologiaRESUMO
OBJECTIVE: Although the genetic program for reinitiating DNA synthesis exists in post-mitotic cardiomyocytes, and it was reported that in human acute myocardial infarction (AMI) a significant proportion of myocytes enter mitosis, the rule is that the lost tissue is replaced by a collagen scar. The purpose of this study was to search for the basis of this discordance in order to devise future strategies to induce division of myocytes into daughter cells that may replace the lost tissue with contractile cells. METHODS: In 15 human hearts with 1- to 21-day-old infarcts, the expression of the cell cycle proteins Ki67 antigen, cyclins D, A, and B1, the presence of mitotic bodies, and the ploidy status were investigated with immunoenzymatic methods, light and laser confocal microscopy, and densitometry in the myocytes surrounding the infarct area. RESULTS: In 7- to 13-day-old infarcts, 11.61+/-6.94% of the myocytes presented Ki67+ nuclei, and a lower proportion presented cyclins D, A, and B. At earlier and later times, the proportion of Ki67+ myocytes was significantly lower. Although under confocal microscopy and fluorescent labels, some of the Ki67+ myocytes appeared to be in different stages of mitosis, with Nomarski optics and hematoxylin counterstaining, the condensed chromosomes, although arranged in metaphase and anaphase plates or split in sister chromatids, were always located within a preserved nuclear envelope, indicating the presence of endomitosis. Conventional mitosis was exceptionally observed. In the 14- and 21-day-old infarcts, the ploidy of the myocytes adjacent to the infarct was significantly higher than in distant zones. CONCLUSION: These observations indicate that in human infarcts, entrance of cardiomyocytes into the cell cycle is transient and that endomitosis, leading to polyploidy, rather than mitosis, leading to karyokinesis, is the final fate of cycling cells. Both observations may account for the discordance between the regenerative ability of myocytes and the lack of an efficient reparative process in human AMI.
Assuntos
Proteínas de Ciclo Celular/análise , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/química , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Ciclina A/análise , Ciclina B/análise , Ciclina B1 , Ciclina D , Ciclinas/análise , Feminino , Humanos , Antígeno Ki-67/análise , Masculino , Microscopia Confocal , Microscopia de Fluorescência , Pessoa de Meia-Idade , Mitose , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , PoliploidiaRESUMO
Caterpillar nuclei (CN) are characterized by their peculiar morphology, with chromatin distributed in clusters and running along the longitudinal axis of the nucleus. They can be observed in normal hearts of fetuses as well as in hearts of children and adults with rheumatic heart disease. This study has demonstrated by means of ploidy studies with digital image analysis that in the fetal heart (20.5+/-1.8 weeks) the CN (diploid = 5.6+/-8.4%; tetraploid = 46.2+/-24.2%; hypertetraploid = 46.9+/-26.3%) present higher DNA content than non-caterpillar myocyte nuclei (diploid = 89.4+/-6.2%; tetraploid = 10.0+/-4.1%; hypertetraploid = 1.5+/-1.3%) (P=0.000001, 0.00013, and 0.000038, respectively). Expression of proliferation cell nuclear antigen (PCNA; 30.6+/-11.7% in CN and 13.4+/-7.3% in non-caterpillar myocyte nuclei; P=0.0115) and cyclin B1 (2.8+/-3.8% and 12.6+/-15.6%, respectively; P=n.s.) was also positive in these nuclei. In conclusion, these results suggest that there exists a relationship between CN morphology and myocyte replication phenomena.
Assuntos
Núcleo Celular/ultraestrutura , Ciclina B/análise , DNA/análise , Coração Fetal/ultraestrutura , Antígeno Nuclear de Célula em Proliferação/análise , Ciclina B1 , Feminino , Coração Fetal/química , Humanos , Masculino , PloidiasRESUMO
The localisation of cyclin B throughout in vitro maturation of pig oocytes was determined by indirect immunofluorescence using a monoclonal antibody specific for an epitope of the human cyclin B. Maturation of pig oocytes was induced by addition of Pergonal (2 UI/ml of FSH/LH) and beta-oestradiol to the medium where isolated ovarian follicles were cultured for up to 72 h. Immature gametes with an intact germinal vesicle were observed during the first 30 h of culture. Only 10% were competent to reinitiate meiosis and showed germinal vesicle breakdown (GVBD) after 36 h. However, after 48-72 h, 60% of the oocytes accomplished their maturation and showed metaphase chromosomes. Immature oocytes showed cyclin B immunofluorescent staining in the cytoplasm, whereas mature oocytes showed the immunofluorescent label concentrated in the nucleus. Metaphase chromosomes showed an intense immunofluorescence. The migration of cyclin B to the nucleus and its association with metaphase chromosomes in pig oocytes able to progress through meiosis resembled the subcellular localisation of cyclin B and the distribution of maturation promoting factor (MPF) in mitotic dividing cells.