Lowered Cisplatin Dose and No Bleomycin in the Treatment of Pediatric Germ Cell Tumors: Results of the GCT-99 Protocol From the Brazilian Germ Cell Pediatric Oncology Cooperative Group.

Purpose: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors.

Patients And Methods: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site.

Hemophagocytic Lymphohistiocytosis After Initiation of Chemotherapy for Bilateral Adrenal Neuroblastoma.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome characterized by overactivation of the immune system. Although secondary HLH has been frequently associated with malignancies, this entity is rarely triggered by solid tumors, such as neuroblastomas. Herein, we describe a 14-month-old girl with a late diagnosis of bilateral adrenal neuroblastoma who developed HLH 6 days after the initiation of chemotherapy.

Correlation between FLT3-ITD status and clinical, cellular and molecular profiles in promyelocytic acute leukemias.

Internal tandem duplications (ITD) of FLT3 gene occur in about a third of acute promyelocytic leukemias (APL). We investigated the patterns of blood count, surface antigen, expression, chromosome aberrations, PML-RARa isoform, gene expression profile (GEP) and survival in 34 APL patients according to FLT3-ITD status. 97% had a t(15;17) and all of them carried PML-RARa gene fusion, 8 (23.

Cytomorphometric and cytomorphologic analysis of oral mucosa in children with sickle cell anemia.

Background: Sickle cell anemia (SCA) is an autosomal recessive genetic disorder, characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs, consequence of vaso occlusive phenomenon and vasculopathy. Several forms of the chronic anemia, consequence of hemolysis, can be associated with oral epithelial cells changes. Exfoliative cytology can be used to detect real changes in the oral mucosa in SCA.

Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors.

Purpose: The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers.

Patients And Methods: Free newborn screening was offered at all hospitals in the state of Paraná.

Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI.

Background: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes.

SNP array profiling of childhood adrenocortical tumors reveals distinct pathways of tumorigenesis and highlights candidate driver genes.

Context: Childhood adrenocortical tumors (ACT) are rare malignancies, except in southern Brazil, where a higher incidence rate is associated to a high frequency of the founder R337H TP53 mutation. To date, copy number alterations in these tumors have only been analyzed by low-resolution comparative genomic hybridization.

Objective: We analyzed an international series of 25 childhood ACT using high-resolution single nucleotide polymorphism arrays to: 1) detect focal copy number alterations highlighting candidate driver genes; and 2) compare genetic alterations between Brazilian patients carrying the R337H TP53 mutation and non-Brazilian patients.

Molecular epidemiology of adrenocortical tumors in southern Brazil.

The high frequency of TP53 R337H carriers in southern Brazil is responsible for the highest known incidence of childhood adrenocortical tumor (ACT). Our aims were to examine other contributing mutations, age-related risk factors, epidemiological differences in ACT and to shed light on a method for increasing the survival rate of children. The fetal zone of the adrenal cortex is believed to be one of the tissues most susceptible to adenoma or carcinoma formation due to loss of p53 function.

Placental alkaline phosphatase in pediatric adrenocortical cancer.

The germline R337H mutation in the TP53 gene is considered to be responsible for the increased incidence of adrenocortical tumors (ACTs) in children from Brazil. High level production of hormones in ACTs (>95%) cause virilization alone (60%), Cushing syndrome (<5%), the mixed type (30%), or other rarer manifestations. ACT probably develops owing to events occurring during the final stages of intrauterine life based on the very common early onset of signs and symptoms shortly after birth.

High frequency of loss of heterozygosity at 11p15 and IGF2 overexpression are not related to clinical outcome in childhood adrenocortical tumors positive for the R337H TP53 mutation.

A germline TP53 R337H mutation is present in childhood adrenocortical tumors (ACT) from southern Brazil. Other genetic alterations are also frequently found in these tumors. This study was designed to assess whether alterations of the 11p15 region exist in childhood ACT, accounting for IGF2 overexpression in these tumors, and how they are related to clinical outcome.

[Prevalence of hemoglobin S in the State of Paraná, Brazil, based on neonatal screening].

The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped.

Specific immunoassays for placental alkaline phosphatase as a tumor marker.

Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57-71) of hPLAP (ICA-PEP assay); the working range was 0.

Gene expression profiling of childhood adrenocortical tumors.

Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor.

SF-1 overexpression in childhood adrenocortical tumours.

The steroidogenic factor 1 (SF-1) gene encodes a transcription factor playing a pivotal role in the regulation of adrenogenital development. We have recently shown that SF-1 is amplified in childhood adrenocortical tumours (ACT). This study was aimed to assess if an increase in SF-1 gene copy number was associated with increased protein levels and to study the correlation between SF-1 expression and ACT clinical parameters.

Neuroblastoma in southern Brazil: an 11-year study.

The authors report on the incidence and clinical characteristics of neuroblastoma in southern Brazil. The aims of the study were to evaluate the age at diagnosis, tumor stage, MYCN status, and tumor histopathology, and to relate these factors to survival. All patients with neuroblastoma, 15 years old or younger (n = 125), admitted to the three major pediatric oncology hospitals in the state of Parana over a period of 11 years (between January 1990 and December 2000), were included in the analysis.

[Treatment of childhood adrenocortical tumor].

Adrenocortical tumors (ACT) in children are uncommon. However, the incidence of these tumors in Paraná is 15 times higher than that worldwide. A germline mutation, R337H TP53, present in more than 95% of our patients, is probably the reason for the higher incidence in our state.

Mortality rate of adrenocortical tumors in children under 15 years of age in Curitiba, Brazil.

Background: Several reports refer to an increased frequency of adrenal cortex tumors (ACT) among children in Southern Brazil, yet all data have been derived from hospital-based registries. An inherited germline mutation in the p53 gene (TP53 R337H) is detected in virtually all children with ACT in this region and accounts for the excess cases observed.

Procedure: We reviewed all death certificates that mentioned ACT or adrenal neuroblastoma (NB) and which were reported to the Paraná State Department of Health between 1998 and 2003, for individuals younger than 15 years who resided in the Curitiba metropolitan region.

[Histoplasmoma as isolated central nervous system lesion in an immunocompetent patient].

The cerebral lesions are uncommon in patients with histoplasmosis, occurring more frequently in the disseminated form of the disease. Rarely, the disease may present as a histoplasmoma, simulating a neoplastic lesion. The histoplasmoma as the only manifestation of this infection in immunocompetent patients is even rarer.

[Thyroid cancer in childhood and adolescence--report of 15 cases].

Thyroid tumors are rare in childhood and adolescence. A retrospective analysis was done of fifteen patients (8 female) with thyroid carcinoma attended in the Pediatric Endocrinology Unit of the HC-UFPR, from February 1988 to March 2003. The most frequent initial complaint was an anterior cervical nodule.

Amplification of the steroidogenic factor 1 gene in childhood adrenocortical tumors.

Southern Brazil has one of the highest incidences of childhood adrenocortical tumors (ACTs), occurring 10-15 times more frequently than worldwide estimates. The reasons for this increase remain elusive. In an attempt to further characterize the genetic changes in childhood ACTs, we recently detected a consistent gain of 9q (or a portion of it) in eight of nine cases of pediatric ACTs and amplification of 9q34 in the majority of these cases using comparative genomic hybridization.