Inequalities in diagnosis and registration of pediatric very rare tumors: a European study on pleuropulmonary blastoma.

Very rare tumors (VRTs) account for up to 11% of childhood cancers. Dedicated national groups and registries only exist in some European countries. Pleuropulmonary blastoma (PPB) is a very rare intrathoracic pediatric tumor with a potentially severe prognosis. Due to its rarity, it sometimes goes unrecognized. We investigated PPB diagnostic capability and possible correlations between diagnostic performance and VRT-dedicated activities. The number of cases of PPB registered between 2000 and 2014 at pediatric oncology centers in Europe was compared with the number of expected cases. Data sources included VRT registries, population-based cancer registries, and hospital registries. Data were obtained for 25 countries, grouped into 4 geographical regions. The expected cases were 111, and the observed cases were 129. The observed-to-expected ratio was 1.86 for Northern Europe, 1.33 for Southern Europe, 1.22 for Central Europe, and 0.65 for Eastern Europe. More cases than expected were registered in all countries with an official VRT registry.Conclusion: The number of cases observed is consistent with expectations, but disparities exist across Europe. Difficulties in diagnosing PPB emerged in most Eastern countries. The incidence rate of PPB may be underestimated. The creation of VRT-dedicated groups and a European Registry for VRTs could help to reduce inequalities.What is Known:• Very rare pediatric tumors are often not recognized, despite representing almost 11% of childhood cancers .• Pleuropulmonary blastoma is a rare pediatric tumor with a poor prognosis.What is New:• The ability to diagnose and register pleuropulmonary blastoma varies in Europe.Registries dedicated to very rare pediatric tumors improve the diagnostic rates.• The incidence rate of pleuropulmonary blastoma may currently be underestimated.

[Paracentesis as abdominal decompression therapy in neuroblastoma MS with massive hepatomegaly]. / Paracentesis como tratamiento descompresivo abdominal en neuroblastoma MS con hepatomegalia masiva.

Neuroblastoma MS with massive hepatomegaly is a small percentage of cases of neuroblastoma. It is more common in infants less than 4-6 weeks of life, and involves, in contrast to the standard of the NB MS, poor prognosis given the complications that can have. In the case of abdominal compartment syndrome it is recommended a quick start of chemotherapy, associating or not radiation therapy, to try to reduce the size of the liver, and if necessary, decompressive laparotomy. We present the case of a patient with NB MS, massive hepatomegaly and threatening symptoms for life, in which the surgical attitude that got relieve intra-abdominal compression syndrome consisted just in an evacuating paracentesis.

El neuroblastoma MS (o 4S según la nomenclatura clásica) con hepatomegalia masiva supone un mínimo porcentaje de los casos de neuroblastoma. Es más frecuente en lactantes de menos de 4-6 semanas de vida, y conlleva, al contrario que la norma del NB MS, mal pronóstico dadas las complicaciones que puede tener. En caso de síndrome compartimental abdominal se aconseja inicio rápido de tratamiento quimioterápico, asociando o no radioterapia para intentar reducir el tamaño del hígado, y en caso de ser necesario, laparotomía descompresiva. Presentamos el caso de una paciente con NB MS, hepatomegalia masiva y síntomas amenazantes para la vida, en la que la actitud quirúrgica que consiguió aliviar el síndrome de compresión intraabdominal consistió únicamente en paracentesis evacuadora.

[Severe cerebellar mutism after posterior fossa tumor resection]. / Mutismo cerebeloso grave tras cirugía de un tumor de fosa posterior.

Cerebellar mutism is an infrequent but important complication after posterior fossa surgery in children. Dysarthria, irritability and ataxia are among the signs and symptoms of this disorder, which are usually mild and self-limiting. However, in severe cases, there can be impairment of higher-level cognitive functions, affecting the child's future personal and social relations. This disorder has been described in many other situations and consequently pediatricians should be familiar with its symptoms, physiopathology, diagnosis, degrees of severity, treatment, and prognosis, since a multidisciplinary approach is required. We present the case of a 5-year-old boy who underwent surgery for a low-grade ependymoma in the fourth ventricle; 48 hours after surgical resection, the boy developed irritability, cranial nerve involvement and stereotyped movements in the context of active hydrocephalus. His symptoms progressively improved 6 weeks after the intervention. We review the literature on cerebellar mutism and discuss the physiopathology of this disorder, which seems to confirm that the cerebellum not only acts as a simple coordinator of motor function, but also plays an important role in higher-level cognitive functions, such as language.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

[Neonatal neoplasms: a single-centre experience]. / Neoplasias neonatales: experiencia de un centro.

INTRODUCTION: Malignant tumors are uncommon in the neonatal period and benign tumors may have malignant potential. OBJECTIVES: To describe the neoplasms diagnosed and treated in newborns (

[Posterior urethral valves, unilateral vesicoureteral reflux and renal dysplasia (VURD syndrome). Long-term follow-up of kidney function]. / Válvulas de uretra posterior, reflujo vesicoureteral unilateral y displasia renal (síndrome VURD). Seguimiento de la función renal a largo plazo.

Posterior urethral valves, unilateral vesicoureteral reflux and renal dysplasia (VURD syndrome) is an infrequent entity in childhood that has provoked multiple controversies. The shortage of studies that evaluate the long-term outcome in these children prompted up to write the present article. Three patients that met strict criteria for a diagnosis of VURD syndrome were retrospectively reviewed, with special emphasis on several indicators of renal function in these patients at diagnosis and in adulthood. The three patients currently have normal renal function, unlike a large percentage of patients diagnosed with posterior urethral valves with vesicoureteral bilateral reflux. Although the sample is small, our results support the hypothesis of good long-term renal function in affected children.

[Assessment of the immigrant child]. / Valoración del niño inmigrante.

In the last twenty years Spain has turned into one of the principal countries recipients of foreign population. As consequence of this massive entry of people, our country is among the first ones of Europe for interannual increase of population. The concept of immigrant child is very wide and includes minors of very diverse characteristics, as the proceeding from international adoptions, the children coming from developing countries or those that come from other developed countries. The immigrant children do not represent health risk for the autochthonous population, on the contrary, they are in situation of defenselessness for their scanty vaccination coverages, their situation of marginality and the precarious sanitary systems of the countries of origin. At the moment of offering medical paediatric attention to foreign children, we must individualize our actions in conformity with the characteristics of each patient. It is not possible to simplify in one unique protocol the best studies to resolve a problem of health in an immigrant child. The attention of these children implies an overstrain for the pediatrician and the sanitary personnel that receives them, because it is necessary to conquer idiomatic, cultural and social barriers to optimize the level of health of these patients. The syndromic initial description can help to prioritize the studies in each case (according to the most probable diagnoses). The children who return to the native land of their parents meet in a special situation of risk, for not being prepared to resist the attack of pathogen that do not exist or are rare in Spain.

[The role of molecular genetics in childhood cancer]. / Papel de la genética molecular en el cáncer infantil.

In the last few years molecular genetic studies of childhood cancer have acquired great importance. Advances in these techniques have increased knowledge of the various genes involved in tumoral development. Genetic alterations can occur in three large groups of genes: oncogenes, tumor suppressor genes, and DNA repair genes. Cytogenetic analyses (karyotyping) are complemented by various molecular techniques, such as fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and spectral karyotyping (SKY). These are the most reliable techniques and improve the sensitivity of karyotyping. The present article reviews the most representative and best characterized genes involved in the molecular etiology of childhood cancer, both hematologic malignancies (leukemia and lymphoma) and solid tumors (brain tumors, neuroblastoma, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma, Ewing's sarcoma and retinoblastoma). Molecular techniques have enabled more precise diagnosis as well as identification of new prognostic factors and the development of more effective treatments. These techniques can also be useful in identifying minimal residual disease during and after treatment for leukemias, neuroblastomas and sarcomas, with the aim of predicting recurrence.

Paracentesis como tratamiento descompresivo abdominal en neuroblastoma MS con hepatomegalia masiva / No disponible

El neuroblastoma MS (o 4S según la nomenclatura clásica) con hepatomegalia masiva supone un mínimo porcentaje de los casos de neuroblastoma. Es más frecuente en lactantes de menos de 4-6 semanas de vida, y conlleva, al contrario que la norma del NB MS, mal pronóstico dadas las complicaciones que puede tener. En caso de síndrome compartimental abdominal se aconseja inicio rápido de tratamiento quimioterápico, asociando o no radioterapia para intentar reducir el tamaño del hígado, y en caso de ser necesario, laparotomía descompresiva. Presentamos el caso de una paciente con NB MS, hepatomegalia masiva y síntomas amenazantes para la vida, en la que la actitud quirúrgica que consiguió aliviar el síndrome de compresión intraabdominal consistió únicamente en paracentesis evacuadora

Neuroblastoma MS with massive hepatomegaly is a small percentage of cases of neuroblastoma. It is more common in infants less than 4-6 weeks of life, and involves, in contrast to the standard of the NB MS, poor prognosis given the complications that can have. In the case of abdominal compartment syndrome it is recommended a quick start of chemotherapy, associating or not radiation therapy, to try to reduce the size of the liver, and if necessary, decompressive laparotomy. We present the case of a patient with NB MS, massive hepatomegaly and threatening symptoms for life, in which the surgical attitude that got relieve intra-abdominal compression syndrome consisted just in an evacuating paracentesis

Exoftalmos unilateral de corta evolución. Una forma de debut de un neuroblastoma / Unilateral exophthalmos with short evolution. One way to debut a neuroblastoma

El neuroblastoma (NB) es el tumor extracraneal sólido más frecuente en la infancia. Representa el 7% de los cánceres pediátricos. Se origina de la cresta neural, y puede aparecer en cualquiera de los sitios anatómicos a lo largo de la cadena ganglionar simpática, así como en la glándula suprarrenal. El 90% ocurre en menores de 5 años. Presenta un amplio espectro de comportamiento clínico. Los estudios muestran metástasis orbitarias en el 10-20% de los casos. La proptosis y equimosis periorbitaria son consideradas dos de los signos clásicos del neuroblastoma en niños. Presentamos el caso de una paciente de 4 años de edad con un neuroblastoma metastásico que se manifestó como una proptosis de corta evolución al diagnóstico, sin otro tipo de sintomatología ni hallazgos en la exploración física. Tras las pruebas complementarias, se la diagnosticó de neuroblastoma estadio IV de la INSS (The International Neuroblastoma Staying System). No se localizó el tumor primario. Se realizó tratamiento con quimioterapia de inducción, terapia de acondicionamiento y trasplante autólogo de progenitores hematopoyéticos, entrando en remisión completa. Posteriormente inmunoterapia, manteniendo enfermedad residual negativa. Queremos destacar la importancia de un diagnóstico precoz en esta patología de cara a la supervivencia del paciente, y que siempre debe considerarse el diagnóstico de NB ante un exoftalmos en un paciente previamente sano. El tratamiento de los pacientes con neuroblastoma de alto riesgo es multimodal, habiendo mejorado el pronóstico el uso combinado de inmunoterapia, ácido 13 cis-retinoico y trasplante autólogo de médula ósea

Neuroblastoma (NB) is an extracranial solid brain tumor found most frequently during childhood. It represents 7% of the pediatric cancers. It originates in the neural crest and can appear in any part of the anatomy along the ganglionic sympathetic chain, as well as in the adrenal gland. 90% of cases occur en children under the age of 5. It presents a broad spectrum of behavior. Studies have shown orbital metastases in 10-20% of cases. Proptosis and ecchymosis periorbitary are considered two classic signs of neuroblastoma in children. We are presenting a case of a 4 year old female patient with metastatic neuroblastoma that manifested like a proptosis of short evolution to its diagnosis, without any other type of symtomatololgy or findings in the physical exploration. After complementary tests she was diagnosed with stage IV neuroblastoma in the INSS (The International Neuroblastoma Staying System). The primary tumor was not located. Complete remission was obtained using induction chemotherapy, conditioning therapy and autologous hematopoietic progenitors transplant. After immunotherapy negative residual disease was maintained. We would like to highlight the importance of early diagnosis in this pathology facing the patient’s survival and must always consider the NB diagnosis when an exophthalmos presents in a previously healthy patient. Treatment in patients with high risk neuroblastoma is multimodal, having improved the prognosis by using a combination of immunotherapy, 13-cis-retinoic acid and the autologous bone marrow transplant

Mastocitosis cutánea difusa. Presentación de 3 casos y revisión de su manejo terapéutico / Diffuse cutaneous mastocytosis. Presentation of 3 cases and therapeutic management review

No disponible

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

Introduction. SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. Materials and methods. Italian and Spanish metastatic INES patients’ data are reported. SPSS 20.0 was used for statistical analysis. Results. Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. Conclusions. The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data (AU)

No disponible

[Vertically transmitted bacteremias: to treat or not to treat?]. / Bacteriemias verticales: ¿tratar o no tratar?

OBJECTIVE: To analyze the incidence, etiology and management of infants born in 1977 with vertically transmitted bacteremia or suspected early neonatal sepsis. PATIENTS AND METHODS: The total number of newborn infants in this period was 2,365. We revised the clinical histories of the infants diagnosed with bacteremia and classified them into two groups: a) those with vertically transmitted bacteremias, according to the recommendations of the Castrillo Group, and b) those with suspected early onset neonatal sepsis in whom blood culture was positive and analytical data suggested bacterial infection but who showed no clinical symptoms of vertically transmitted sepsis. Birthweight, sex, gestational age, risk factors for neonatal infection, clinical signs and laboratory tests suggestive of bacterial infection and microbiological agents were analyzed. The clinical and analytical evolution of the treated and untreated newborn infants was studied. RESULTS: The newborn infants were diagnosed with vertically transmitted bacteremia (an incidence of 4.2x1,000 live newborn infants) and 17 were diagnosed with suspected early onset neonatal sepsis (7.8x1,000 live newborns). All the infants had risk factors for neonatal sepsis. The most common of them was prolonged membrane rupture (>- 18 hours) due to which sepsis screening was carried out (hemogram, C-reactive protein at 12 and 36-48 hours of life, and blood culture). In both groups the most commonly isolated microorganism was group B streptococcus, which was found in 30% of vertically transmitted bacteremias and in 41.2% of suspected early onset neonatal sepsis. All the newborn infants with suspected sepsis and two with vertically transmitted bacteremia were treated without incident. The remaining eight infants with untreated vertically transmitted bacteremia were followed-up clinically ana analytically for one year, and remained asymptomatic. CONCLUSIONS: The most common microorganism in vertically transmitted bacteremia and suspected early onset neonatal sepsis was group B streptococcus. None of the untreated infants developed late sepsis or meningitis. Our findings suggest that non-treatment of asymptomatic infants with vertically transmitted bacteremias is appropriate as long and close clinical surveillance is maintained.

[Cutaneous involvement as the form of presentation in B-cell lymphoblastic leukemia/lymphoma]. / Nódulo cutáneo como forma de presentación de una leucemia/linfoma linfoblástico de estirpe B.

Primary cutaneous involvement in B-cell lymphoblastic leukemia/lymphoma is rare in childhood. We present the case of an eleven and a half year old girl who, five months prior to being referred to our center, had undergone surgery to remove a small gluteal tumor diagnosed histopathologically as lymphoid proliferation suggestive of large cell lymphoma. On examination the presence of small nodes close to the scar where the tumor had previously been removed was observed. Hemogram revealed 2.7 x 9/l white blood cells with 0.5 x 9/l neutrophils; the remaining series and complementary investigations were normal. Bone marrow aspiration revealed 52 % blastic cells with immunophenotype and morphological characteristics of common (B-cell) acute lymphoblastic leukemia with L2 subtype in the French-American-British (FAB) classification. Ten months after finishing polychemotherapy, the patient is now in complete remission. We would like to highlight that a small slow-growing cutaneous node could be the presenting form of lymphoblastic lymphoma or acute lymphoblastic leukemia.

Valoración del niño inmigrante / Assessment of the immigrant child

En los últimos veinte años España se ha convertido en uno de los principales países receptores de población extranjera. Como consecuencia de esa entrada masiva de personas, nuestro país se encuentra entre los primeros de Europa en cuanto a incremento interanual de población. El concepto de niño inmigrante es muy amplio y engloba a menores de características muy diversas, como los procedentes de adopciones internacionales, los hijos de familias provenientes de países en vías de desarrollo o aquellos que vienen de otros países desarrollados. Los niños inmigrantes no representan un riesgo de salud para la población autóctona, muy al contrario, suelen estar en situación de desprotección por sus escasas coberturas vacunales, su situación de marginalidad y los precarios sistemas sanitarios de los países de los que proceden.A la hora de brindar atención médica pediátrica a niños extranjeros, debemos individualizar nuestras actuaciones conforme a las características de cada paciente. No se puede simplificar en un protocolo único los estudios a realizar ante un problema de salud en un niño inmigrante. La atención de estos niños implica un sobreesfuerzo para el pediatra y el personal sanitario que los recibe, pues hay que vencer barreras idiomáticas, culturales y sociales para conseguir optimizar el estado de salud de estos pacientes. La descripción sindrómica inicial puede ayudar a priorizar los estudios a realizar en cada caso (según los diagnósticos más probables).Los niños que regresan al país de origen de sus padres se ven en una especial situación de riesgo, por no estar preparados para defenderse de patógenos que no existen o son raros en España

In the last twenty years Spain has turned into one of the principal countries recipients of foreign population. As consequence of this massive entry of people, our country is among the first ones of Europe for interannual increase of population. ;;The concept of immigrant child is very wide and includes minors of very diverse characteristics, as the proceeding from international adoptions, the children coming from developing countries or those that come from other developed countries. ;;The immigrant children do not represent health risk for the autochthonous population, on the contrary, they are in situation of defenselessness for their scanty vaccination coverages, their situation of marginality and the precarious sanitary systems of the countries of origin. ;;At the moment of offering medical paediatric attention to foreign children, we must individualize our actions in conformity with the characteristics of each patient. It is not possible to simplify in one unique protocol the best studies to resolve a problem of health in an immigrant child. The attention of these children implies an overstrain for the pediatrician and the sanitary personnel that receives them, because it is necessary to conquer idiomatic, cultural and social barriers to optimize the level of health of these patients. ;;The syndromic initial description can help to prioritize the studies in each case (according to the most probable diagnoses). ;;The children who return to the native land of their parents meet in a special situation of risk, for not being prepared to resist the attack of pathogen that do not exist or are rare in Spain

Tumores vasculares en la infancia / Infantile vascular tumors

La utilización en el pasado de una terminología imprecisa para designar a los tumores vasculares infantiles ha contribuido durante años a diagnósticos incorrectos y, como consecuencia, a tratamientos inadecuados. En la infancia pueden presentarse diferentes tipos de tumores vasculares, como los hemangiomas infantiles, que son con diferencia los más frecuentes, y otros mucho más raros, como los hemangiomas congénitos (rápidamente involutivo y no involutivo), el hemangioendotelioma kaposiforme, el angioblastoma o angioma en penacho, o el granuloma piógeno. Su correcto conocimiento y diagnóstico, siempre en el contexto de un equipo multidisciplinario, es imprescindible para reducir errores diagnósticos, exámenes complementarios y pruebas invasivas innecesarias, y así, si fuera preciso, recibir el tratamiento más indicado y efectivo en cada caso. En el presente artículo revisamos la evolución histórica en cuanto a la nomenclatura y clasificación de las lesiones vasculares, las diferentes características clinicopatológicas de cada uno de los tumores vasculares, los exámenes complementarios indicados para llegar a un correcto diagnóstico, su diagnóstico diferencial y los distintos tipos de tratamiento que existen con sus indicaciones más reconocidas, en el momento actual, para los diferentes tumores vasculares y situaciones clínicas concretas (AU)

The use in the past of an imprecise terminology to designate vascular tumors has contributed to its incorrect diagnosis, and as a consequence, to inadequate treatment. In childhood, different types of vascular tumors may be present. Hemangiomas of infancy are by far the most frequent, and other less common types are congenital hemangiomas (rapidly involuting or RICH and non-involuting or NICH), kaposiform hemangioendothelioma, angioblastoma or tufted angioma and pyogenic granuloma. The correct knowledge and diagnosis, always in a multidisciplinary setting, is required to reduce incorrect diagnosis, unnecessary complementary examinations and invasive tests, and for the patient to receive the most effective and precise treatment in each case. This article reviews the historical evolution, nomenclature and classification of vascular lesions, the different clinical and pathological characteristics of each vascular tumor, the complementary examinations required correct diagnosis, the differential diagnosis, as well as highlighting the treatment options currently available for different vascular tumors and related clinical conditions (AU)

Estudio de la enfermedad mínima residual en el cáncer infantil / Study of minimal residual disease of childhood cancer

El estudio de la enfermedad mínima residual (EMR), en distintas neoplasias infantiles, ha ido adquiriendo en los últimos años una importancia trascendental en la detección y seguimiento de pacientes con mayor probabilidad de recaída y como consecuencia, un mal pronóstico a largo plazo. Existen diferentes técnicas de estudio para determinar y cuantificar la EMR, según el tipo de neoplasia: la citometría de flujo, la inmunocitología y técnicas moleculares como la hibridación in situ con fluorescencia (FISH) y la transcripción inversa acoplada a la reacción en cadena de la polimerasa (RTPCR). En este artículo se repasan las diferentes técnicas utilzadas en busca de EMR durante y/o tras finalizar el tratamiento en leucemias agudas infantiles, neuroblastomas, rabdomiosarcomas y tumores de la familia del sarcoma de Ewing, así como su utilidad como factor pronóstico (AU)