Adrenocortical tumors associated with the TP53 p. R337H germline mutation can be identified during child-care consultations / Tumores adrenocorticais associados à mutação germinativa TP53 p. R337H podem ser identificados durante as consultas de puericultura

Abstract Objective: To evaluate the clinical features associated with adrenocortical hormone overexpression and familial cancer profiling as potential markers for early detection of adrenocortical tumors in children from South and Southeast Brazil. Methods: The clinical manifestations and anthropometric measurements of 103 children diagnosed with adrenocortical tumors were analyzed. Results: Between 1982 and 2011, 69 girls and 34 boys diagnosed with adrenocortical tumors were followed-up for a median time of 9.0 years (0-34 years). Signs of androgen overproduction alone (n = 75) or associated with cortisol (n = 18) were present in 90.3%. TP53 p.R337H mutation was found in 90.5% of patients. Stages I, II, III, and IV were observed in 45.6%, 27.2%, 19.4%, and 7.8% of patients, respectively. At diagnosis, there were no significant differences in height (p = 0.92) and weight (p = 0.22) among children with adrenocortical tumors, but children with virilization alone had significantly higher height-for-age Z-scores (0.92 ± 1.4) than children with hypercortisolism alone or combined (−0.32 ± 1,8; p = 0.03). The five-year overall survival was 76.7% (SD ± 4.2). Patients with advanced-stage disease had a significantly worse prognosis than those with limited disease (p < 0.001). During follow-up, ten of 55 p.R337H carrier parents developed cancer, whereas none of the 55 non-carriers did. Conclusions: Signs of adrenocortical hormone overproduction appear early, even in cases with early-stage. These signs can be identified at the physical examination and anthropometric measurements. In southern Brazil, pediatric adrenocortical tumor is a sentinel cancer for detecting families with germline p.R337H mutation in TP53 gene.

Resumo Objetivo: Avaliar as manifestações clínicas da hiperexpressão de hormônios do córtex da adrenal e câncer familiar como marcadores para a detecção precoce de tumores adrenocorticais em crianças do Sul e Sudeste do Brasil. Pacientes e métodos: Foram analisadas as manifestações clínicas e antropométricas de 103 crianças diagnosticadas com tumores adrenocorticais. Resultados: Entre 1982 e 2011, 69 meninas e 34 meninos diagnosticados com tumores adrenocorticais foram acompanhados por um tempo mediano de nove anos (0-34). Ao diagnóstico, sinais de virilização isolada (n = 75) ou associada ao cortisol (n = 18) estavam presentes em 90,3% dos pacientes; a mutação do gene TP53 p.R337H foi identificada em 90,5% dos pacientes. Os pacientes foram classificados em estádio I (45,6%), II (27,2%), III (19,4%) e IV (7,8%). Ao diagnóstico, não houve diferença significativa para as medidas de altura (p = 0,92) e de peso (p = 0,22) entre as crianças com tumores adrenocorticais, mas crianças com virilização tiveram escore-Z mais elevado para a idade (0,92 ± 1,4) do que aquelas com hipercortisolismo isolado ou combinado (−0,32 ± 1,8; p = 0,03). A sobrevida global de cinco anos foi de 76,7% (DP ± 4,2). Pacientes com estádios avançados tiveram pior prognóstico (p < 0,001). Durante o seguimento, 10 dos 55 genitores portadores da p.R337H desenvolveram câncer, enquanto que nenhum caso ocorreu entre os 55 não portadores. Conclusões: Os sinais de hiperprodução de hormônios adrenocorticais aparecem precocemente no desenvolvimento do tumor e podem ser identificados pelo exame físico e pelas medidas antropométricas na consulta pediátrica de rotina. O tumor adrenocortical pediátrico é sentinela para a detecção de câncer em famílias que segregam a mutação germinativa p.R337H do gene TP53.

Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22)/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described.

Effect of malnutrition at the time of diagnosis on the survival of children treated for cancer in El Salvador and Northern Brazil

Purpose: To investigate the relationship between survival and malnutrition at the time of diagnosis among children treated for cancer in two developing countries. Patients and Methods: We studied 443 children treated for cancer between 1995 and 1998 at two centers in San Salvador, El Salvador, and Recife, Brazil. Median age at diagnosis was 4.9 years; 283 children had leukemia and 260 had solid tumors. Z scores were calculated for weight for age (WAZ), height for age (HAZ), and weight for height (WHZ) at diagnosis. Z scores < -2 indicated malnutrition. Patients were also stratified by low-risk disease (solid tumors: stage I, stage II, or localized; acute lymphocytic leukemia: WBC count < 25,000/uL, negative CNS, no mediastinal mass and age > 1 and < 10 years) and high-risk disease (all other patients, including those with acute or chronic myelocytic leukemia). Results: Z scores indicated malnutrition in 15.7 por cento (WHZ), 23.5 por cento (WAZ), and 22.8 por cento (HAZ) of patients. Z score was not significantly related to overall survival rates, to survival rates analyzed by type of malignancy or risk status, or to survival rates at the end of the first month of treatment. Conclusions: We found no relationship between nutritional status and survival in these patients. This implies that future protocols for use in developing countries can be designed to provide optimal treatment intensity despite the high incidence of malnutrition

Fatores prognósticos na leucemia linfoblástica aguda da criança / Prognostic factors in acute lymphocytic leukemia in child

A efetividade do tratamento modifica a importância da maioria dos fatores associados com o prognóstico. Entre as manifestaçöes clínicas e laboratoriais de rotina, apenas a idade e a contagem leucocitária permanecem independentemente correlacionadas ao resultado do tratamento. A imunofenotipagem é útil para a classificaçäo das LLA, mas, possivelmente, com exceçäo do antígeno CD10, tem muito pouca importância prognóstica no contexto de uma abordagem terapêutica efetiva. Alteraçöes cariotípicas continuam a ter importante valor preditivo. Hiperdiplodia (>50 cromossomos) está associada ao bom prognóstico, enquanto que a t (9;22) e t(4;11), ao insucesso terapêutico. Casos com imunofenótipo pré-B e t(1;19) têm mau prognóstico, se tratados com regimes terapêuticos baseados em antimetabólicos, e, portanto, o tratamento desse grupo de pacientes deve incluir outras classes de drogas. Finalmente, algumas alteraçöes cromossômicas, como a dic(9;12), podem estar associadas ao bom prognóstico. Com exceçäo do tratamento da leucemia de células B, protocolos terapêuticos especificamente direcionados a grupos segregados por análise imunofenotípica ou genotípica näo têm sido bem sucedidos. portanto, a seleçao da melhor opçäo terapêutica para um determinado paciente deverá ser orientada pela probabilidade do insucesso terapêutico. Para pacientes com alto risco de recidivas (i.e. com uma probabilidade>70 por cento) a utilizaçäo de protocolos experimentais é justificável, mesmo em face dos efeitos colaterais agudos e tardios decorrentes do tratamento. Para o grupo de crianças de baixo risco de recidiva (<20 por cento de probabilidade), terapia que evita as medicaçöes mais perigosas deve ser administrada.