PDGFRA, KIT, and KDR Gene Amplification in Glioblastoma: Heterogeneity and Clinical Significance.

Glioblastoma (GBM) is the most frequent tumor of the central nervous system, and its heterogeneity is a challenge in treatment. This study examined tumoral heterogeneity involving PDGFRA, KIT, and KDR gene amplification (GA) in 4q12 and its association with clinical parameters. Specimens from 22 GBM cases with GA for the 4q12 amplicon detected by FISH were investigated for homogeneous or heterogeneous coamplification patterns, diffuse or focal distribution of cells harboring GA throughout tumor sections, and pattern of clustering of fluorescence signals. Sixteen cases had homogenously amplification for all three genes (45.5%), for PDGFRA and KDR (22.7%), or only for PDGFRA (4.6%); six cases had heterogeneous GA patterns, with subpopulations including GA for all three genes and for two genes - PDGFRA and KDR (13.6%), or GA for all three and for only one gene - PDGFRA (9.1%) or KIT (4.6%). In 6 tumors (27.3%), GA was observed in focal tumor areas, while in the remaining 16 tumors (72.7%) it was diffusely distributed throughout the pathological specimen. Amplification was universally expressed as double minutes and homogenously stained regions. Coamplification of all three genes PDGFRA, KIT, and KDR, age ≥ 60 years, and total tumor resection were statistically associated with poor prognosis. FISH proved effective for detailed interpretation of molecular heterogeneity. The study uncovered an even more diverse range of amplification patterns involving the 4q12 oncogenes in GBM than previously described, thus highlighting a complex tumoral heterogeneity to be considered when devising more effective therapies.

Clinical and Molecular Characterization of Adult Glioblastomas in Southern Brazil.

We investigated 113 adult Brazilian patients with glioblastoma (GBM) for comparison with patients from distinct geographical areas and evaluation of suitability for novel targeted therapies. Patients were assessed for clinical features and tumor genomic characteristics such as ROS1 and NTRK1 rearrangements, KIT, PDGFRA, and KDR amplification, and RB1 deletion using multicolor fluorescence in situ hybridization. The majority of patients were male (53%), over 40 years (94%), with tumor located in single site (64%), in the right cerebral hemisphere (60%), and underwent partial resection (71%); 14% presented complications after surgery. The main clinical sign at diagnosis was focal abnormality (57%); frontal (31%); and temporal (20%) regions were most commonly affected. Median hospitalization time was 20 days, median survival was 175 days. One tumor was positive for rearrangement in NTRK1 and another in ROS1 (0.9% each). PDGFRA was amplified in 20% of cases, often co-amplified with KDR (>90%) and KIT (>60%). RB1 was deleted in 16% of patients. There was no association between these molecular abnormalities and patient survival. However, older age, complications after surgery, and right-sided tumors were independent variables associated with patient survival. This study contributes information on the molecular profile of glioblastomas in Latin America possibly supporting new target therapies.

Hirschsprung disease and hepatoblastoma: case report of a rare association / Doença de Hirschsprung e hepatoblastoma: relato de caso de uma associação rara

ABSTRACT CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.

RESUMO CONTEXTO: A doença de Hirschsprung é uma desordem do desenvolvimento do sistema nervoso entérico, que é caracterizada pela ausência de células ganglionares no intestino distal, ocorrendo em cerca de 1 a cada 500.000 nascimentos. O hepatoblastoma é uma neoplasia maligna do fígado que geralmente ocorre em crianças de 6 meses a 3 anos, com prevalência de 0,54 casos por 100.000. RELATO DE CASO: Um menino com diagnóstico de atresia intestinal na primeira semana de vida evoluiu com diagnóstico concomitante de doença de Hirschsprung. Catarata congênita e surdez neurossensorial foram diagnosticadas. Surgiu lesão hepática com posterior confirmação de hepatoblastoma, tratado com ressecção cirúrgica de 70% do volume hepático e quimioterapia neoadjuvante (ifosfamida, cisplatina e doxorubicina). CONCLUSÃO: Sabe-se que a doença de Hirschsprung pode estar associada a síndromes de predisposição ao câncer, da mesma forma que o hepatoblastoma já foi correlacionado a certas síndromes congênitas malformativas. No entanto, até o momento, a associação de hepatoblastoma com a doença de Hirschsprung não foi descrita. Relatamos o caso de um menino que nasceu com atresia ileal, doença de Hirschsprung, catarata congênita bilateral e com posterior diagnóstico de hepatoblastoma.

Hirschsprung disease and hepatoblastoma: case report of a rare association.

CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.

Tumor size and prognosis in patients with Wilms tumor / Tamanho tumoral e prognóstico em pacientes portadores de tumor de Wilms

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .

OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .

[Tumor size and prognosis in patients with Wilms tumor]. / Tamanho tumoral e prognóstico em pacientes portadores de tumor de Wilms.

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ >500 mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10 mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable.

Wilms tumor: experience of a hospital in southern Brazil.

BACKGROUND: Wilms tumor (WT) is the most common renal malignancy of childhood. The aim of this study was to verify the epidemiological profile and prognosis of a sample of patients from Brazil and compare them to similar data from other Latin American studies. METHOD: The sample consisted of consecutive patients diagnosed with WT in an oncohematology service of a referral hospital in Southern Brazil, between 1989 and 2009. Clinical, radiological, pathological and survival data were collected from the medical records. Analysis was done using Excel and SPSS version 18.0. The significance level was set at P < 0.05. RESULTS: The final sample consisted of 45 patients. The male/female ratio was 1.25:1. Mean age at diagnosis was 43.9 months and all patients were of European descent. Thirty-three patients (73.3%) had both signs/symptoms of abdominal mass and hypertension. Malformation was observed in nine patients (20%) and there was one case of Fanconi's anemia (2.2%). Three patients had bilateral disease (6.7%). The majority of patients had stage III and IV (62.2%). Patients with malformation had an earlier age at diagnosis (P = 0.018) and a higher prevalence of bilateral disease (P = 0.044). Overall survival was 75%. Age at diagnosis was the only significant independent predictor associated with death. CONCLUSION: Death is closely related to late diagnosis in WT. Oncologic services should also be concerned about morbidity caused by therapeutic options in cases of late diagnosis, and the consequences for quality of life.

Ossificacao endometrial: relato de caso / Endometrial ossification: case report

Os autores relatam o caso de uma paciente feminina, 37 anos, que durante a investigacao para infertilidade apresentou o diagnostico de ossificacao endometrial. A etiologia, patogenese e diagnosticos diferenciais de ossificacao endometrial sao...