[Juvenile multiple xanthogranuloma in a patient with Langerhans cell histiocytosis]. / Xantogranuloma juvenil múltiple en una paciente con histiocitosis de células de Langerhans.

We present the case of a 10-week-old girl who had erythematous papules with a yellowish hue from birth with diagnosis of Langerhans cell histiocytosis, that was accompanied by a lytic lesion in the skull and hepatic involvement. After several months of treatment with prednisone and vinblastine with skin and systemic improvement, several rounded erythematous papules with a yellowish hue appeared in the right cheek. The biopsy showed a histiocytic infiltrate with positivity for CD68 and negative staining for S100 and CD1a, with a final diagnosis of juvenile xanthogranuloma. This association has been previously described in the literature in few cases. Although several hypotheses have been suggested, the causal relationship between both entities has still not been demonstrated.

Xantogranuloma juvenil múltiple en una paciente con histiocitosis de células de Langerhans / Juvenile multiple xanthogranuloma in a patient with Langerhans cell histiocytosis

Presentamos el caso de una niña de 10 semanas de edad que presentaba lesiones papulosas eritemato-amarillentas desde el nacimiento con diagnóstico de histiocitosis de células de Langerhans, que se acompañaba de lesiones líticas en cráneo y afectación hepática. Tras varios meses de tratamiento con prednisona y vinblastina, con mejoría cutánea y sistémica, aparecieron varias lesiones papulosas eritemato-amarillentas redondeadas en mejilla derecha; la biopsia mostró un infiltrado histiocitario con positividad para CD68 y tinción negativa para S100 y CD1a, con diagnóstico final de xantogranuloma juvenil. Dicha asociación ha sido previamente descrita en la literatura en pocos casos; aunque se han insinuado varias hipótesis, la relación causal entre ambas entidades aún no ha sido demostrada

We present the case of a 10-week-old girl who had erythematous papules with a yellowish hue from birth with diagnosis of Langerhans cell histiocytosis, that was accompanied by a lytic lesion in the skull and hepatic involvement. After several months of treatment with prednisone and vinblastine with skin and systemic improvement, several rounded erythematous papules with a yellowish hue appeared in the in right cheek. The biopsy showed a histiocytic infiltrate with positivity for CD68 and negative staining for S100 and CD1a, with a final diagnosis of juvenile xanthogranuloma. This association has been previously described in the literature in few cases. Although several hypotheses have been suggested, the causal relationship between both entities has still not been demonstrated

Pediatric giant cell glioblastoma: a case report and review of the literature.

INTRODUCTION: Giant cell glioblastoma is a subtype of glioblastoma multiforme (GM) whose most characteristic histology is the presence of plentiful multinucleated giant cells. These tumours are very rare and account for only 5% of GM. They do not have specific localization, although normally they are supratentorial and affect mostly the temporal lobe. They may occur at any age, but mostly they occur in younger people than GM. They are infrequent in childhood, but they have longer survival in paediatric age. CASE REPORT: We present an 11-year-old girl that was operated but whose tumour recurred in a month after apparent total removal. DISCUSSION: We review in the literature the clinical, histological, immuno-histochemical and genetic characteristics, as well the prognosis of this tumour.

[Acute leukemia in patients with Down syndrome]. / Leucemia aguda en pacientes con síndrome de Down.

BACKGROUND: Children with Down syndrome (DS) have a higher risk of acute leukemia than the remaining pediatric population. A favorable outcome of acute myeloid leukemia (AML) has recently been described in these patients whereas the prognosis of acute lymphoblastic leukemias (ALL) is similar to that in other children. The main cause of morbidity and mortality in children with Down syndrome are complications related to chemotherapy, leading to numerous modifications in treatment protocols. OBJECTIVES: To characterize acute leukemias in children with Down syndrome in our center and determine their clinical outcome. METHODS AND RESULTS: Between 1990 and 2002, 214 children were diagnosed with acute leukemia at the Niño Jesus Hospital (40 with AML and 174 with ALL). Of these, eight children (3.8 %) had Down syndrome. AML (2/40) represented 5 % of myeloid leukemias and ALL (6/174) represented 3.4 % of lymphoblastic leukemias. The most frequent complication was hematologic toxicity due to chemotherapy, causing a high incidence of infections: pneumonia (5/8) and bacteriemia (5/8). In all patients, these complications led to treatment interruption or dose reduction. Two children died from treatment-related toxicity. Of these, one with AML developed fulminant sepsis due to Candida infection and the other, diagnosed with high risk ALL, died from multiorgan failure after high doses of methotrexate and ARA-C. CONCLUSIONS: Patients with Down syndrome diagnosed with acute leukemia show a higher incidence of treatment-related complications, which affects their prognosis. Consequently, individualized treatment of these children in qualified units is essential.

Leucemia aguda en pacientes con síndrome de Down / Acute leukemia in patients with down syndrome

Antecedentes: Los niños con síndrome de Down tienen mayor riesgo de leucemia aguda que el resto de la población infantil. Recientemente se ha descrito una evolución favorable de las leucemias mieloides agudas (LMA) en estos niños, mientras que las leucemias linfoblásticas agudas (LLA) tienen un pronóstico similar al del resto. Las complicaciones atribuidas a la quimioterapia son la principal causa de morbi-mortalidad, lo que ocasiona modificaciones de los protocolos de tratamiento. Objetivos: Caracterizar las leucemias agudas en niños con síndrome de Down en nuestro centro y la evolución clínica de éstos. Métodos y resultados: Entre 1990 y 2002 se han diagnosticado 214 leucemia aguda en el Hospital Niño Jesús (40 LMA y 174 LLA). De ellos, 8 casos (3,8 por ciento) eran pacientes con síndrome de Down. Las LMA 2/40 representaron el 5 por ciento del total mientras que las LLA un 6/174 el 3,4 por ciento. La toxicidad hematológica por el tratamiento fue la complicación más habitual, condicionando una elevada frecuencia de procesos infecciosos: neumonías (5/8) y bacteriemias (5/8). Además, las complicaciones obligaron a interrumpir y/o reducir las dosis del tratamiento en todos los pacientes. Dos niñas fallecieron como consecuencia de la toxicidad del tratamiento. Una diagnosticada de LMA desarrolló una sepsis fulminante por Candida, y la otra, diagnosticada de LLA de alto riesgo, falleció por fallo multiorgánico tras recibir altas dosis de metotrexato y arabinósido de citocina (Ara-c).Conclusiones Los pacientes con síndrome de Down diagnosticados de leucemia aguda presentan una mayor incidencia de complicaciones relacionadas con el tratamiento lo que condiciona de gran modo su pronóstico. Por ello, es importante un tratamiento individualizado de estos niños en unidades cualificadas (AU)

Topotecan asociado a ciclofosfamida como tratamiento de tumores sólidos pediátricos avanzados / Topotecan associated to cyclophosphamide as treatment of advanced pediatric solid tumors

Se presenta un estudio retrospectivo de la utilización de topotecan y ciclofosfamida como terapia de rescate en niños con tumores solidos refractarios ó recidivados que habían recibido previamente terapia intensiva, incluyendo en dos de ellos megaterapia con rescate hematopoyetico. Se incluyeron 19 pacientes (seis sarcomas de partes blandas, cuatro neuroblastomas, tres sarcomas de Ewing, tres tumores neuroectodermicos primitivos, dos retinoblastomas bilaterales y un meduloblastoma. La dosis total por ciclo fue de 1.250 mg de ciclofosfamida y 3,75 mg de topotecan. Los ciclos se repitieron cada 28 días. Se administraron un total de 79 ciclos. Se observaron 3 remisiones completas (dos rabdomiosarcomas y un sarcoma sinivial) y 6 remisiones parciales (dos neuroblastomas, un meduloblastoma, un retinoblastoma y un tumor desmoplasico) lo que significa un 47 por ciento de casos con respuesta objetiva al tratamiento. La principal toxicidad observada fue la mielosupresion (tras el 20 por ciento de los ciclos) (AU)

Topotecán en el tratamiento de niños con tumores sólidos refractarios o recidivantes / Topotecan for pediatric patients with resistant and recurrent solid tumors

Antecedentes: Topotecán es un quimioterápico alcaloide derivado de la planta Camptotheca acuminata (originaria de China) con capacidad de inhibir la enzima topoisomerasa I y de reciente uso en el tratamiento del cáncer pediátrico. Objetivos: Evaluar nuestra experiencia preliminar con el topotecán en el tratamiento de segunda línea de tumores sólidos refractarios en la edad pediátrica.Pacientes y métodos Estudio retrospectivo de 10 pacientes con tumores sólidos refractarios o recidivantes a la primera línea de tratamiento que reciben topotecán en monoterapia o en asociación con otros agentes quimioterápicos. Resultados: Se incluyeron 10 pacientes con tumores sólidos refractarios o recidivantes al tratamiento convencional (dos neuroblastomas, tres rabdomiosarcomas, dos tumores neuroectodérmicos primitivos (PNET)/Ewing, un astrocitoma anaplásico, un tumor desmoplásico y un sarcoma sinovial). Obtuvieron respuesta favorable 5 pacientes (dos remisiones completas, dos remisiones parciales y un estabilización de la enfermedad). En 5 pacientes no se consiguió ninguna respuesta. Todos los pacientes presentaron toxicidad hematológica de grado III-IV. Conclusiones: En nuestra experiencia, topotecán sería beneficioso en determinados tumores sólidos refractarios o recidivantes, sobre todo neuroblastomas y sarcomas de partes blandas, con una aceptable tolerancia a la toxicidad hematopoyética con el uso de factores estimulantes de colonias granulocíticas. Los pacientes en remisión completa de su enfermedad tras topotecán podrían beneficiarse de una intensificación de quimioterapia con rescate autólogo de progenitores hematopoyéticos (AU)

[Topotecan for pediatric patients with resistant and recurrent solid tumors]. / Topotecán en el tratamiento de niños con tumores sólidos refractarios o recidivantes.

BACKGROUND: Topotecan is a cytotoxic drug isolated from the Camptotheca acuminata tree (from China). It is able to block the enzyme DNA topoisomerase I and has recently been used in the treatment of pediatric cancer. OBJECTIVES: To evaluate our preliminary experience with topotecan in the second line treatment of refractory solid tumors in the pediatric age group. PATIENTS AND MEHTODS: We performed a retrospective study of 10 patients with various recurrent solid tumors resistant to first line treatment who were treated with topotecan alone or in association with other chemotherapeutic agents. RESULTS: Ten patients with recurrent solid tumors or tumors that were refractory to conventional treatment (two neuroblastomas, three rhabdomyosarcoma, two PNET/Ewing's sarcoma, one anaplastic astrocytoma, one soft tissue sarcoma and one synovial sarcoma) were included. Five patients showed favorable responses (two had complete responses, two had partial responses and one had stable disease). Five patients showed no response. All patients showed grade II-IV hematological toxicity. CONCLUSIONS: In our experience, topotecan is beneficial in some refractory or recurrent solid tumors, especially neuroblastomas and soft tissue sarcomas. Myelosuppression was tolerable with the use of granulocyte colony-stimulating factors. Patients with a complete response to topotecan could benefit from high-dose chemotherapy and autologous stem cell rescue therapy.

Identification of ins(8;21) with AML1/ETO fusion in acute myelogenous leukemia M2 by molecular cytogenetics.

A high percentage of cases of acute myelogenous leukemia (AML) of the M2 subtype show a rearrangement between the AML1 and ETO genes. The detection of the AML1/ETO fusion has clinical relevance because patients with this subtype have a good prognosis. We present the results of conventional and molecular cytogenetic studies in a patient with acute myelogenous leukemia French-American-British M2 classification, who had a complex karyotype involving chromosomes 8 and 21. Dual-color fluorescence in situ hybridization (FISH) using the AML1/ETO probe demonstrated a recombination of both genes on an add(8) chromosome. The use of other FISH probes (CEP8, c-myc and TEL21) and spectral karyotyping indicated that AML1/ETO fusion occurred as a consequence of a previously undescribed ins(8;21)(q22;q22.1q22.3).

Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The TEL/AML1 fusion is the most common genetic abnormality found in childhood acute lymphoblastic leukemias (ALL). Although it is very difficult to identify by conventional cytogenetic techniques it can be readily detected using fluorescence in situ hybridization (FISH). We carried out cytogenetic and FISH studies on 42 children with ALL in order to know the frequency of this translocation in our population, the incidence of TEL and/or AML1 gene alterations, and their correlation with clinical evolution and prognosis. In addition, we performed reverse transcription polymerase chain reaction (RT-PCR) in some cases, confirming the feasibility of FISH techniques in the detection of this translocation. DESIGN AND METHODS: Bone marrow samples were obtained from 42 childhood ALL patients. The copy number of AML1 and TEL genes were studied using fluorescent in situ hybridization with a dual color DNA probe specific for the AML1 and TEL genes. RESULTS: We found a frequency of TEL/AML1 fusion of 17% in our sample. Double TEL/AML1 fusion, lack of TEL signal and extra AML1 signals were frequent additional FISH abnormalities. Duplication of a chromosomal complement, deletion of chromosome 12p arm, and polysomies of chromosome 21 are plausible explanations for these additional FISH findings. However, a relatively high proportion of our cases (9.5%) presented specific amplification of AML1. A statistically significant difference in prognosis was found between patients with and without these additional AML1 or TEL FISH alterations (p<0.02), which could be related to the presence of specific karyotypes. INTERPRETATIONS AND CONCLUSIONS: The frequency of TEL/AML1 fusion is similar to that found in other populations (17%). We found that FISH analysis of AML and TEL is related to the evolution of the disease. The absence of alterations in these genes revealed by FISH could be indicative of bad prognosis, while the presence of alterations is related to a good evolution. Our results suggest that interphase FISH analysis to search for alterations in AML and TEL genes could be extremely useful for complementing cytogenetic studies and for providing additional information about the possible outcome of the disease in patients with ALL.

Results of the cooperative protocol (N-III-95) for metastatic relapses and refractory neuroblastoma.

BACKGROUND: Prognosis of relapsed and refractory neuroblastoma is uniformly fatal; new therapeutic approaches are needed. PROCEDURE: Relapsed and refractory neuroblastoma patients were treated with continuous infusion chemotherapy combined with MIBG. RESULTS: Over 4 years, 35 heavily pretreated patients were registered, 29 with bone or/and bone marrow metastases. Grade 3 or 4 hematologic toxicity was frequent, without toxic deaths. Sixteen patients responded. The probability of 5-year overall survival was 0.19. CONCLUSIONS: This approach is feasible and toxicity manageable; it rescued some patients and prolonged their survival. It merits assay in newly diagnosed high-risk neuroblastoma patients.

Cleavage of the ALL1 gene in acute lymphoid leukemia before treatment disappears in relapse.

BACKGROUND AND OBJECTIVE: ALL1 gene rearrangements are frequently found in secondary acute leukemias (ALs). A site-specific cleavage of the ALL1 gene in a consensus sequence for topoisomerase II recognition has been considered to be the initial step leading to ALL1 rearrangement and subsequent therapy-related AL. The aim of the present study was to evaluate this cleavage in our patients, to analyze whether it is a laboratory-produced artefact and to check whether it persists or causes a real ALL1 gene rearrangement at relapse. DESIGN AND METHODS: We studied ALL1 rearrangement in 74 cases of AL before treatment by Southern blot avoiding room temperature exposure or delay in processing the samples which could produce ALL1 cleavage. DNA was available for two cases with ALL1 cleavage; it was analyzed by three different Southern blots in one and two in the other. One case with ALL1 cleavage was also studied in relapse. RESULTS: The presence of the cleavage of the ALL1 DNA was found in 3 of 74 (4%) patients. Two of these three patients had the ALL1 cleavage in three and two different analyses. One case was positive for ALL1 cleavage at diagnosis, but negative for both ALL1 cleavage and ALL1 rearrangement at relapse. INTERPRETATION AND CONCLUSIONS: The fact that a constant pattern was obtained from the same patients in different DNA preparations, supports the notion that ALL1 cleavage is not a laboratory artefact. The absence of the cleavage in a sample from a relapsed patient suggests that the subclone with the ALL1 cleavage, in this case, did not play a clear role in the pathogenesis of disease recurrence.

[Usefulness of molecular screening in childhood lymphoblastic leukemias]. / Utilidad de un screening molecular en las leucemias linfoblásticas pediátricas.

PURPOSE: To demonstrate that a molecular screening by reverse transcriptase polymerase chain reaction (RT-PCR) of TEL/AML1, E2A/PBX1 and BCR/ABL genes in pediatric acute lymphoblastic leukaemia is a rapid method that allows one to exceed the percentage of adult patients with the BCR/ABL rearrangement. PATIENTS AND METHODS: 12 Spanish children with acute lymphoblastic leukaemia were studied, 11 of them newly diagnosed and 1 relapsed. The patients were between 18 months and 10 years old. Bone marrow aspiration was collected between april and december 1996, RNA was isolated and cDNA was subjected to PCR amplification for TEL/AML1, E2A/PBX1 and BCR/ABL genes. Normal ABL and E2A genes were studied as amplification controls. RESULTS: One of these hybrid genes was found in 33.3% of patients studied. TEL/AML1 in two cases (16.6%), E2A/PBX1 in one case (8.3%) and BCR/ABL in another one (8.3%). CONCLUSIONS: On the basis of these data it would be useful to achieve a molecular screening of TEL/AML1, E2A/PBX1 and BCR/ABL genes in pediatric acute lymphoblastic leukaemia for allowing a molecular classification in a great percentage of patients that exceed the BCR/ABL positivity in adults.

[Non-Hodgkin's lymphoma associated with human immunodeficiency virus infection in children]. / Linfoma no Hodgkin asociado a infección por el virus de la inmunodeficiencia humana en niños.

A 3-year-old boy with infection by the human immunodeficiency virus (HIV) developed stage IV Burkitt's lymphoma. Complete remission was achieved with the BFM-86 protocol. One month after finishing treatment, and still in complete remission, fever appeared and seropositivity to HIV was found. The child was diagnosed of AIDS (P2-E1) and died 10 days later. Although the association of HIV infection and Burkitt's lymphoma is well known in adults, it is extremely rare in children. The routine HIV screening is suggested for children with non-Hodgkin's lymphoma.