Aggressive osteoblastoma with degeneration to secondary aneurysmal bone cyst / Osteoblastoma agressivo com degeneração secundária para cisto ósseo aneurismático

ABSTRACT A 4-year-old male patient presented with headaches that started 18 months ago and were associated with progressive loss of balance and difficulty walking. Magnetic resonance imaging (MRI) demonstrated an expansile extra-axial mass lesion in the posterior aspect of the posterior fossa on the left, compressing the adjacent brain, as well as the cerebellar hemispheres; it also distorts the fourth ventricle with severe obstructive hydrocephalus upstream. Histological evaluation diagnosed aggressive osteoblastoma with a secondary aneurysmal bone cyst of the skull. We report a case of aggressive osteoblastoma in which the lesion in the MRI was mimicking brain tumor or intracranial primary tumor rather than primary bone tumor.

RESUMEN Paciente masculino, de 4 años de edad, con cefalea de 18 meses asociada a pérdida progresiva de equilibrio y dificultad de deambulación. La resonancia magnética (RM) mostró una lesión espansiva extraaxial en la porción posterior de la fosa posterior a la izquierda, comprimiendo el tejido cerebral adyacente, así como los hemisferios cerebelares; aún deforma el cuarto ventrículo con hidrocefalia obstructiva severa. La evaluación histológica diagnosticó osteoblastoma agresivo con quiste óseo aneurismático secundario del cráneo. Reportamos un caso de osteoblastoma agresivo en lo cual la lesión visualizada con la RM estaba mimetizando tumor cerebral o tumor primario intracraniano y no un tumor óseo primario.

RESUMO Paciente do sexo masculino, 4 anos de idade, com cefaleia há 18 meses associada à perda progressiva do equilíbrio e à dificuldade de deambulação. A ressonância magnética (RM) demonstrou uma lesão expansiva extra-axial na porção posterior da fossa posterior à esquerda, comprimindo o cérebro adjacente, bem como os hemisférios cerebelares; ainda distorce o quarto ventrículo com hidrocefalia obstrutiva grave a montante. A avaliação histológica diagnosticou osteoblastoma agressivo com cisto ósseo aneurismático secundário do crânio. Relatamos um caso de osteoblastoma agressivo em que a lesão na RM estava mimetizando tumor cerebral ou tumor primário intracraniano em vez de tumor ósseo primário.

AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma.

Thyroid cancer is the fastest increasing cancer worldwide in all age groups. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in both adults and children. PTC genomic landscape has been extensively studied in adults, but information regarding sporadic pediatric patients is lacking. Although BRAF V600E mutation is highly prevalent in adults, this mutation is uncommon in pediatric cases. As adult and pediatric PTC is a mitogen-activated protein kinase-driven cancer, this altered pathway might be activated by different genetic events. The aim of this study was to investigate the occurrence of AGK-BRAF fusion gene, recently described in radiation-exposed pediatric PTC, in a cohort of exclusively sporadic pediatric PTC. The series consisted of 30 pediatric PTC younger than 18 years of age at the time of diagnosis and 15 matched lymph node metastases (LNM). Primary tumors and matched LNM were screened for the presence of the AGK-BRAF fusion transcript by RT-PCR. To confirm the identity of the amplified products, randomly selected samples positive for the presence of the fusion transcripts were sequenced. Moreover, BRAF dual-color, break-apart probes confirmed BRAF rearrangement. Overall, the AGK-BRAF fusion gene was detected in 10% (3/30) of primary tumors. For one of these cases, paired LNM was also available, which also shows the presence of AGK-BRAF fusion gene. This study described, for the first time, the presence of AGK-BRAF in sporadic pediatric PTC. Understanding the molecular events underlying pediatric PTC may improve preoperative diagnosis, allow molecular prognostication and define a therapeutic approach toward sporadic PTC patients.

Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF-ß1 as compared with healthy nasal mucosa.

OBJECTIVE: To evaluate TGF-ß1 expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-ß1 visualization. Then, the percentage of TGF-ß1 expression in stroma and epithelium was objectively quantified using UT Morph software. RESULTS: A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05). CONCLUSION: The lower percentage of TGF-ß1 expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.

Secular trends in the rate of low birth weight in Brazilian State Capitals in the period 1996 to 2010 / Tendência secular da taxa de baixo peso ao nascer nas capitais brasileiras de 1996 a 2010 / Tendencia secular de la tasa de bajo peso al nacer en las capitales brasileñas de 1996 a 2010

Secular trends in rates of low birth weight in Brazilian state capital cities were evaluated for the period 1996 to 2010 using joinpoint regression models. The rates were calculated using data from the Live Births Information System. Newborns weighing less than 500g were excluded. Only data for capital cities was included since under-registration of births in these cities is lower and new trends can be detected earlier. There was a significant increase in the rate of low birth weight in the Brazilian capitals of the North Region, Northeast Region, South Region and Southeast Region up to 2003/2004, stabilizing thereafter. In the capitals of the Center-west Region the rate increased throughout the whole study period. The rate of low birth weight was higher in the capitals of the more developed regions. The rate of multiple births increased significantly in all Brazilian capitals, while the stillbirth rate decreased and showed a negative correlation with the rate of low birth weight. The increase in the rate of low birth weight may be partially explained by the increase in multiple births, an increase in the birth of infants weighing 500 to 999g and by the reduction in the stillbirth rate.

A tendência secular da taxa de baixo peso ao nascer de 1996 a 2010 nas capitais brasileiras foi avaliada utilizando-se modelos de regressão joinpoint. As taxas foram calculadas a partir do Sistema de Informações sobre Nascidos Vivos, excluindo-se recém-nascido com peso < 500g. Foram incluídos apenas dados das capitais, onde o sub-registro é menor e novas tendências podem ser detectadas mais precocemente. A taxa de baixo peso ao nascer aumentou significantemente nas capitais brasileiras das regiões Norte, Nordeste, Sul e Sudeste até 2003/2004, tendo se estabilizado a partir de então. Nas capitais da Região Centro-oeste a taxa aumentou ao longo de todo o período. A taxa de baixo peso ao nascer foi maior nas capitais das regiões mais desenvolvidas. A taxa de partos múltiplos aumentou significantemente nas capitais brasileiras. A taxa de natimortalidade diminuiu e apresentou correlação negativa com a taxa de baixo peso ao nascer. Parte do aumento na taxa de baixo peso ao nascer pode ser explicado pelo aumento na taxa de nascimentos múltiplos e pelo nascimento de recém-nascido pesando de 500g a 999g e pela redução da taxa de natimortalidade.

La tendencia secular de la tasa de bajo peso al nacer de 1996 a 2010 en las capitales brasileñas se evaluó utilizando modelos de regresión joinpoint. Las tasas se calcularon a partir del Sistema de Información sobre Nacidos Vivos, excluyéndose recién nacidos con un peso < 500g. Fueron incluidos solamente datos de las capitales, donde el sub-registro es menor y las nuevas tendencias pueden ser detectadas más precozmente. La tasa de bajo peso al nacer aumentó significantemente en las capitales brasileñas de las regiones Norte, Nordeste, Sur y Sudeste hasta 2003/2004, habiéndose estabilizado a partir de entonces. En las capitales de la Región Centro-oeste la tasa aumentó a lo largo de todo el período. La tasa de bajo peso al nacer fue mayor en las capitales de las regiones más desarrolladas. La tasa de partos múltiples aumentó significantemente en las capitales brasileñas. La tasa de natimortalidad disminuyó y presentó una correlación negativa con la tasa de bajo peso al nacer. Una parte del crecimiento en la tasa de bajo peso al nacer puede ser explicada por el aumento en la tasa de nacimientos múltiple, por el nacimiento de recién nacidos pesando de 500g a 999g y por la reducción de la tasa de natimortalidad.

C-kit expression in human osteosarcoma and in vitro assays.

Biologic agents targeting oncogenes have encourage researchs trying to correlate the role of tyrosine kinase in the pathogenesis of tumours. Osteosarcoma is a high grade aggressive neoplasm with poor survival. Our aim was to investigate c-kit immunoexpression, its prognostic relevance for patients with osteosarcoma, and the effect of imatinib mesylate (STI571) on proliferation and invasion of the human osteosarcoma cell line.A retrospective immunohistochemical study was performed on archival formalin-fixed paraffin-embedded specimens from 52 patients with high-grade primary osteosarcoma of extremities treated at the Pediatric Oncology Institute (IOP, GRAAC) and archived in the Department of Pathology, Federal University of São Paulo. Only pre-chemotherapy specimens were analyzed. Strongly stained cytoplasm and membrane cells were taken as positive. Human osteosarcoma cells from line MG-63 were incubated and the inhibitory effect of imatinib mesylate (STI571) on cell proliferation and invasion was studied. In 24 cases (46.15%), c-kit was expressed by the cells and c-kit-positive tumors exhibited lower necrosis post-chemotherapy. No correlation was found between c-kit expression and overall and disease-free survival. Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but not the invasive capacity of these neoplastic cells. These data suggested that imatinib mesylate could be a therapeutic target of strategies against osteosarcoma tumors. Further studies are necessary to confirm this indication.

Large and round tumor nuclei in osteosarcoma: good clinical outcome.

Osteosarcoma is the most frequent primary malignant bone tumor. Distinct histological features are distinguishable based on the morphology of the tumor. Differences in nuclei size and shape are often observed in osteosarcoma reflecting its broad histopathological heterogeneity. This study explores the relevance of two nuclear parameters in osteosarcoma: large area and round shape. Computerized nuclear morphometry was performed in 56 conventional osteosarcoma preoperative biopsies. The mean patient follow-up time was 35.1 months. Based on the nuclear area, no significant difference (P = 0.09) in overall survival between patients with large (> 42.5 µm(2)) and small (< 42.5 µm(2)) tumor nuclei was found. However, when cases with large and round nuclei were analyzed jointly (> 42.5 µm(2) and coefficient of nuclear roundness > 0.7), these two parameters together were likely to be a predictive factor (P = 0.05). Osteosarcoma patients with large and round tumor nuclei had a better outcome than patients with small and polymorphic (ovoid or spindle-shaped) nuclei. In this study, nuclear morphometry proved to be a useful tool to shed light on the biology of osteosarcoma showing that some morphometric parameters can be easily applied to help identifying patients with a good prognosis.

Histologic analysis of zafirlukast's effect on capsule formation around silicone implants.

BACKGROUND: The most common complication experienced by patients who have undergone mammary implant surgery is capsular contracture. This matter concerns physicians and patients, but to date, there is no effective way to avoid this complication. Surgical intervention usually is required. In 2002, the use of zafirlukast, a leukotriene inhibitor (a drug used for asthma treatment), was reported for the treatment of capsular contracture, with good results. METHODS: For this study, 30 female Wistar rats were used. These animals received two silicone implants each: one with a smooth surface and one with a textured surface. All the animals received daily intraperitoneal injections for 90 days and were divided as follows: control group (C) receiving only saline solution, experimental group 1 (E-I) receiving 1.25 mg/kg/day of zafirlukast, and experimental group 2 (E-II) receiving 5 mg/kg/day of zafirlukast. Histologic analysis used hematoxilin and eosin to verify vessels, capsule thickness, and inflammatory cells. Immunoistochemical analysis with smooth muscle anti-actin antibody was used for myofibroblast verification. Picro-Sirius under polarized light was used for collagen analysis. RESULTS: Textured implant experimental groups presented smaller numbers of vessels, thinner capsules, lower collagen density, and smaller numbers of mastocytes and eosinophils than the control group. No significant differences were found in smooth surface implants, as compared with the control group. CONCLUSION: Zafirlukast reduced the occurrence of factors directly and indirectly connected with capsular contracture.

Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: prognostic factors and impact on survival.

PURPOSE: To evaluate the impact of chemotherapy and surgery on the outcome of osteosarcoma (OS) of the extremities and to identify prognostic factors in Brazilian patients. PATIENTS AND METHODS: A total of 225 patients with metastatic and nonmetastatic OS of the extremities were enrolled and assessed in two consecutive studies designed and implemented by the Brazilian Osteosarcoma Treatment Group. RESULTS: The 5-year survival and event-free survival rates for the 209 assessable patients were 50.1% and 39%, respectively; for the 178 patients with nonmetastatic disease at diagnosis, the rates were 60.5% and 45.5%, respectively. The multivariate analysis showed that the following variables were associated with a shorter survival: metastases at diagnosis (P < .001), necrosis grades 1 and 2 (P = .046), and tumor size (P = .0071). CONCLUSION: The overall 5- and 10-year survival rates were lower than the rates reported in North American and European trials. A pattern of advanced disease at diagnosis was often present, with a high proportion of patients having metastases (20.8%) and large tumor size (42.9%). However, these features were not necessarily associated with longer duration of prediagnostic symptoms. These findings were considered in the strategic planning of the current Brazilian cooperative study, with the aim of improving survival and quality of life of a large number of patients with OS.

Rhabdomyosarcoma of the oral tissues--two new cases and literature review.

Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm consisting of cells derived from the primitive mesenchyme that exhibit a profound tendency to myogenesis. About 35% of RMS arises in the head and neck, being classified as parameningeal and non-orbital non-parameningeal forms. Parameningeal tumors carry the worst prognosis. The use of contemporary, multi-agent chemotherapy, radiotherapy, and surgery has made treatment of the disseminated disease possible, and has significantly improved overall survival from 25% in 1970 to 70% in 1991. Here, we present the management of two cases of orofacial RMS in adolescents: an 18-year-old, white female that had a 9-month history of a nodule in the left buccal mucosa, and a 19-year-old, white male who had been aware of a nodule in the left, posterior maxillary ridge with progressive growth for 4 months. Before final diagnosis, both cases were previously treated as inflammatory lesions. Their clinicopathological aspects, treatment, and poor survival as a consequence of delays in diagnosis are discussed.