La Unidad de Hematología y Oncología Pediátricas del Hospital Universitario Cruces (1992-2015) / Hematology and Pediatric Oncology unit of the Hospital Universitario Cruces (1999-2015)

Se realiza un breve recuerdo de cómo ha evolucionado la atención a los niños con procesos neoplásicos en el mayor hospital de la CAPV desde su origen hascael momento actual. Se describen los cambios que han tenido lugar en las actividades asistenciales, docentes e investigadoras condicionados por los medios disponibles y los avances que se han ido implantando con mejoras en el área física de hospitalización,en la atención en hospital de día y domiciliaria, en las consultas multidisciplinares de seguimienro de los supervivientes y de transición al adulto y en la investigación relacionada. Las actividades docentes de estudiantes de pregrado, la formación de residentes de Pediatría del centro y de rotantes externos de otras especialidades como la Hematologia, Oncología Radioterápica y Oncología Médica de los Servicios del propio hospital y de comunidades limítrofes sin dotación de Oncología Pediátrica. La dirección de tesis doctorales relativas a la especialidad, realización de cursos de doctorado de la UPV y Máster de Oncología, Neurociencias y Cuidados paliativos. La actividad investigadora clínico-traslacional y sus futuros objetivos para conrribuir al tratamienro inregral del cáncer infantil (AU)

A brief review is performed regarding how care to children with neoplastic processes has developed in the largest hospital of the Basque autonomous community from its origin to the present moment. The changes that have occurred in the care, teaching and investigator activities conditioned by the available resources and the advances that have been implemented with improvements in the physical area of hospitalization, in the attention in the day hospital and home care, in the multidisciplinary follow-up medical visits of the survivors and transition to adulthood and in related research are described. Teaching activities of pre-graduate students, training of pediatric residents of the site and external rotations in other specialties such as Hepatology, Radiation Oncology and Medical Oncology of the services of the hospital per se and of the neighboring communities without pediatric oncology resources. Direction of doctoral thesis regarding the specialty, performance of doctorate courses of UPV and Oncology, Neurosciences and Palliative Care Master. The investigator-clinical translational activity and its future objectives to contribution to the comprehensive treatment of childhood cancer (AU)

Nódulos subcutáneos como forma de presentación de síndrome linfoproliferativo maligno / Subcutaneous nodules as a sign of malignant lymphoproliferative syndrome

En su mayoría, las lesiones cutáneas de los procesos malignos aparecen de forma concomitante o posterior al diagnóstico del tumor primario. Se presenta el caso de una niña con tumefacción en la cara externa del pie derecho desde los 5 meses de vida, durante un ingreso hospitalario a los 7 meses por bronquiolitis con pancitopenia, el mielograma mostró hipoplasia mieloide y megacariocítica, con ecografía abdominal y del pie normales. Tras la administración de corticoterapia por su cuadro respiratorio y soporte transfusional, al alta se objetivó desaparición de la lesión del pie. Dos meses más tarde presentó reaparición de la tumefacción junto con nódulos subcutáneos diseminados. Confirmada la infiltración maligna en la biopsia cutánea, la estadificación demostró infiltración blástica del 6% en mielograma y afectación ganglionar abdominal en ecografía y tomografía computarizada. El inmunofenotipo F confirmó el diagnóstico de linfoma linfoblástico pre-B muy inmaduro. Se administró quimioterapia según protocolo EURO-LB-02 para estadio IV. En remisión completa al finalizar la fase de inducción; la paciente presentó recaída leucémica refractaria a los 13 meses del diagnóstico. Comentario: Ante una lesión cutánea de evolución tórpida se debe realizar una toma de biopsia para descartar malignidad. El diagnóstico diferencial de las lesiones cutáneas malignas en los niños (especialmente en lactantes) incluye fundamentalmente infiltración secundaria a leucemia o linfoma, metástasis de neuroblastoma o rabdomiosarcoma y, con menor frecuencia, otros procesos primarios. En esta paciente con presentación cutánea aislada, el curso de su proceso linfoproliferativo maligno pudo modificarse mediante la corticoterapia recibida previa al diagnóstico definitivo (AU)

Skin involvement in children with malignant processes usually appears at the same time or after the diagnosis of the primary tumour. We present the case of a girl with cutaneous involvement prior to the diagnosis of a malignant lymphoproliferative process. A previously healthy 5-month old girl who presented with an inflammatory subcutaneous lesion on the right foot. During hospital admission due to bronchiolitis at 7 months with associated pancytopenia while the myelogram showed myeloid and megakaryocytic hypoplasia, the abdominal and foot ultrasound were normal. After completing corticoid therapy for her respiratory process and transfusional support, the foot lesion had disappeared at discharge. Two months later she had a local recurrence with associated scattered subcutaneous nodules. The skin biopsy confirmed malignant infiltration; the myelogram showed 6% blast infiltration, and both abdominal ultrasound and CT scan demonstrated lymph node involvement. Immunophenotype confirmed the diagnosis of Precursor B Cell Lymphoblastic Leukemia-Lymphoma. Although complete remission was achieved at the end of the induction chemotherapy according EuroLB-02 protocol for stage IV, the patient presented a refractory leukaemia relapse thirteen months after diagnosis. Commentary: Malignancy should be suspected in the presence of a skin lesion with torpid evolution and biopsy should be considered. Differential diagnosis of malignant skin lesions in children, especially in infants, must include mainly secondary involvement of leukaemia, lymphoma, metastases of neuroblastoma or rhabdomyosarcoma and less frequently other primary processes. In our patient with an isolated cutaneous presentation, the progression of her malignant lymphoproliferative process could be modified by the corticotherapy given before the definitive diagnosis (AU)

[Subcutaneous nodules as a sign of malignant lymphoproliferative syndrome]. / Nódulos subcutáneos como forma de presentación de síndrome linfoproliferativo maligno.

UNLABELLED: Skin involvement in children with malignant processes usually appears at the same time or after the diagnosis of the primary tumour. We present the case of a girl with cutaneous involvement prior to the diagnosis of a malignant lymphoproliferative process. A previously healthy 5-month old girl who presented with an inflammatory subcutaneous lesion on the right foot. During hospital admission due to bronchiolitis at 7 months with associated pancytopenia while the myelogram showed myeloid and megakaryocytic hypoplasia, the abdominal and foot ultrasound were normal. After completing corticoid therapy for her respiratory process and transfusional support, the foot lesion had disappeared at discharge. Two months later she had a local recurrence with associated scattered subcutaneous nodules. The skin biopsy confirmed malignant infiltration; the myelogram showed 6% blast infiltration, and both abdominal ultrasound and CT scan demonstrated lymph node involvement. Immunophenotype confirmed the diagnosis of Precursor B Cell Lymphoblastic Leukemia-Lymphoma. Although complete remission was achieved at the end of the induction chemotherapy according Euro-LB-02 protocol for stage IV, the patient presented a refractory leukaemia relapse thirteen months after diagnosis. COMMENTARY: Malignancy should be suspected in the presence of a skin lesion with torpid evolution and biopsy should be considered. Differential diagnosis of malignant skin lesions in children, especially in infants, must include mainly secondary involvement of leukaemia, lymphoma, metastases of neuroblastoma or rhabdomyosarcoma and less frequently other primary processes. In our patient with an isolated cutaneous presentation, the progression of her malignant lymphoproliferative process could be modified by the corticotherapy given before the definitive diagnosis.

Reasons for the new Spanish Society of Paediatric Haematology and Oncology (SEHOP)

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[Pediatric neuro-oncology]. / Neurooncología pediátrica.

INTRODUCTION: Pediatric neuro-oncology is getting more important for various reasons, brain tumours are the most frequent solid tumours in children below fifteen year of age, besides due to the recent advances in neuro-image techniques that make possible an early diagnosis and the fact that the children are usually treated in pediatric oncology units, with protocols that are internationally based allow a better survival with a better degree of evidence. DEVELOPMENT: Actually the brain tumours should be classified according to their biological, genetic and molecular risk factors and their treatment should consider also the familial predisposition for developing a brain tumour, and the molecular markers expressed by the tumour. The objective of this work is to review the special characteristics of the brain tumours in the pediatric population and the differences with the brain tumours in adults, also to give the incidence and survival data of brain tumours in pediatric population from Spain based in the data from the National Registry of Pediatric Tumours. Also the clinical signs and symptoms of presentation that should alert for diagnosis in children, and how to make a diagnostic strategy based on the clinical manifestations, the image modalities for diagnosis, and the treatment strategy to be used based in multinational protocols, and stratified by histological, biological and genetic markers of risk are emphasized. Finally we describe the characteristics of the three more common histological subtypes because their prevalence in pediatric population; gliomas, medulloblastomas/primitive neuroectodermal tumours and ependymomas. CONCLUSION: Improving prognosis of brain tumors in childhood has to be achieved by early despistage throughout image and biological techniques, following multicentric protocols in specialized units and stratified treatments regarding the biological risk in order to diminish morbility and sequels.

Neurooncología pediátrica / Pediatric neuro-oncology

Introducción. La neurooncología pediátrica cada vez cobramayor entidad por varias razones; los tumores cerebrales constituyenel mayor número de tumores sólidos en la edad pediátrica,además, gracias a las técnicas de neuroimagen, se realiza un diagnósticocada vez más precoz que contribuye a mejorar la supervivenciade los niños. Éstos, a su vez, se tratan en unidades de oncologíapediátrica con protocolos multicéntricos y multinacionalespara lograr mayor grado de evidencia científica en los resultados.Desarrollo. Los tumores deben clasificarse por características deriesgo biológico, genético y molecular y los tratamientos debencontemplar los factores predisponentes genéticos en familias deriesgo y los marcadores moleculares expresados por el tumor. Losobjetivos de este trabajo son: actualizar las características especialesde los tumores cerebrales infantiles y sus diferencias con los deladulto, aportar los datos de incidencia y supervivencia de los tumorescerebrales en la edad pediátrica en España a partir de las estadísticasdel Registro Nacional de Tumores Infantiles, señalar lossignos y síntomas de alarma de presentación de tumores cerebralesinfantiles, analizar las causas del retraso diagnóstico enfatizandocómo hacer un buen cribado diagnóstico y apuntar una estrategiade tratamiento con base en la clínica, el diagnóstico por la imageny las pruebas histológicas, moleculares y genéticas. Finalmente, sedetallan las especiales características de los tres tipos histopatológicosde mayor prevalencia en la población pediátrica, gliomas,meduloblastoma/tumores neuroectodérmicos primitivos, y ependimomas.Conclusiones. La mejora del pronóstico de los tumores cerebralesen la infancia pasa por el diagnóstico precoz a través detécnicas de imagen y de biología, el seguimiento de protocolos multicéntricosen unidades especializadas y la estratificación de lostratamientos atendiendo al riesgo biológico para disminuir la morbilidady las secuelas

Introduction. Pediatric neuro-oncology is getting more important for various reasons, brain tumours are the mostfrequent solid tumours in children below fifteen year of age, besides due to the recent advances in neuro-image techniques thatmake possible an early diagnosis and the fact that the children are usually treated in pediatric oncology units, with protocolsthat are internationally based allow a better survival with a better degree of evidence. Development. Actually the brain tumoursshould be classified according to their biological, genetic and molecular risk factors and their treatment should consider alsothe familial predisposition for developing a brain tumour, and the molecular markers expressed by the tumour. The objective ofthis work is to review the special characteristics of the brain tumours in the pediatric population and the differences with thebrain tumours in adults, also to give the incidence and survival data of brain tumours in pediatric population from Spain basedin the data from the National Registry of Pediatric Tumours. Also the clinical signs and symptoms of presentation that shouldalert for diagnosis in children, and how to make a diagnostic strategy based on the clinical manifestations, the image modalitiesfor diagnosis, and the treatment strategy to be used based in multinational protocols, and stratified by histological, biologicaland genetic markers of risk are emphasized. Finally we describe the characteristics of the three more common histologicalsubtypes because their prevalence in pediatric population; gliomas, medulloblastomas/primitive neuroectodermal tumoursand ependymomas. Conclusion. Improving prognosis of brain tumors in childhood has to be achieved by early despistagethroughout image and biological techniques, following multicentric protocols in specialized units and stratified treatmentsregarding the biological risk in order to diminish morbility and sequels

[Difficulties in the diagnosis of familial hemophagocytic lymphohistiocytosis]. / Dificultades en el diagnóstico de la linfohistiocitosis hemofagocítica familiar.

Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and non-malignant activation of histiocytes and T lymphocytes in the reticuloendothelial system. Diagnostic guidelines include fever, splenomegaly, cytopenia, hypertriglyceridemia and/or hypofibrinogenemia with hemophagocytosis in the bone marrow, spleen or lymph nodes. In many patients diagnosis is difficult due to the lack of diagnostic criteria, hemophagocytosis, variability of clinical presentation, spontaneous improvement and the absence of a specific marker of the disease. When there is strong clinical suspicion of FHL, chemotherapy and immunosuppressor treatment should be started early to achieve complete cure and should be followed by hematopoietic stem cell transplantation. We present the case of a 2-month-old girl who presented fever, anemia and thrombocytopenia, enlarged liver and spleen, hyperferritinemia, hypertriglyceridemia, and hypertransaminasemia without the finding of hemophagocytosis in bone marrow. Two of the girl's relatives had died of fulminant hepatic failure of unknown etiology. The patient improved spontaneously but presented reactivation of the disease 3 weeks later and died after splenic biopsy.

Dificultades en el diagnóstico de la linfohistiocitosis hemofagocítica familiar / Difficulties in the diagnosis of familial hemophagocytic lymphohistiocytosis

La linfohistiocitosis hemofagocítica familiar es una enfermedad caracterizada por proliferación y activación no maligna de histiocitos y linfocitos T en el sistema reticuloendotelial. Los criterios para su diagnóstico incluyen fiebre, esplenomegalia, citopenias, hipertrigliceridemia o hipofibrinogenemia e histología con hemofagocitosis en medula ósea, bazo o ganglios linfáticos. El diagnóstico es difícil en muchos casos debido a la ausencia de algún criterio e incluso de hemofagocitosis, heterogeneidad clínica, posibilidad de regresión espontánea, frecuente antecedente infeccioso, así como la falta de un marcador específico de la enfermedad. Ante una fuerte sospecha diagnóstica, el tratamiento inmunosupresor y quimioterapia debe iniciarse precozmente para alcanzar la curación definitiva con posterior trasplante de progenitores hematopoyéticos. Se presenta el caso de una niña de 2 meses, con 2 familiares fallecidos por fallo hepático fulminante de etiología desconocida que presentó fiebre, anemia, plaquetopenia, hepatosplenomegalia, hiperferritinemia, hipertrigliceridemia y alteración hepática sin hemofagocitosis clara en medula ósea, regresó espontáneamente pero sufrió reactivación a las 3 semanas y falleció tras biopsia esplénica (AU)

[Hereditary spherocytosis in neonates. Review of our caseload]. / Esferocitosis hereditaria neonatal: revisión casuística.

AIM: Review of hereditary spherocytosis diagnosed in infants younger than two months and their follow up. PATIENTS AND METHODS: Retrospective study of 18 infants younger than two months diagnosed from 1973 to 1995. RESULTS: Diagnosis was established in the first week of life in 50% of the patients. Hereditary pattern was autosomic dominant in 94% of the cases. Anaemia was observed in all the patients and hyperbilirubinemia in only 44%, although the latter was the clinical presentation in patients diagnosed at younger age. Exchange transfusion was performed in 3 children (1 with the severe form and 2 with the typical form of the disease). During the first 6 months of age, 55% of infants presented hemolytic crises that required transfusion in 91% of them. Both periodicity of crises and transfusions decreased to 38 and 44% respectively after the first year. Splenectomy was performed in the 3 children with severe forms and in 6 with typical forms (mean age 8 years and 3 months). No cholecystectomy was required so far. CONCLUSIONS: The authors believe that neonatal spherocytosis does not implicate worse prognosis at follow up. Blood support is higher during the first year of life. Elective splenectomy depends on age and transfusional requirements.

Esferocitosis hereditaria neonatal: revisión casuística / Hereditary spherocytosis in neonates. Review of our casuistics

OBJETIVO: Revisión de los niños diagnosticados de esferocitosis hereditaria (EH) antes de los 2 meses de edad y su evolución. PACIENTES Y MÉTODOS: Estudio retrospectivo de 18 pacientes diagnosticados en los primeros 2 meses de vida entre 1973 y 1995.RESULTADOS: La mitad de los pacientes fueron diagnosticados en la primera semana de vida. Se encontró el patrón de herencia autosómica dominante en el 94 por ciento. Se objetivó anemia en el 100 por ciento de los pacientes e ictericia en el 44 por ciento, aunque esta última fue la presentación clínica más frecuente en las formas precoces. Al diagnóstico, 8 pacientes precisaron transfusión de hematíes. De los 3 que precisaron exanguinotransfusión únicamente uno evolucionó a la forma grave de la enfermedad. Se objetivaron un mayor número de crisis hemolíticas (55,5 por ciento) y de necesidades transfusionales (91 por ciento) durante los primeros 6 meses de vida, con disminución a partir del primer año (38 y 44 por ciento, respectivamente). Mientras que en los 3 pacientes con formas graves y en 6 con formas típicas se practicó la esplenectomía a una edad media de 8 años y 3 meses, ninguno de los pacientes ha precisado colecistectomía hasta la fecha. CONCLUSIÓN: No se encuentra una relación clara entre el inicio precoz de la EH y la evolución a formas graves. Las necesidades transfusionales son mayores durante el primer año de vida, con un comportamiento más benigno a partir del mismo. La indicación de esplenectomía viene condicionada por los requerimientos transfusionales y la edad del niño (AU)

[Ovarian tumors in childhood: apropos of a review of cases]. / Tumores ováricos en la infancia: a propósito de una revisión casuística.

OBJECTIVE: Our objective was to evaluate the incidence and behavior of ovarian tumors in our population. PATIENTS AND METHODS: Between 1984 and 1994, all clinical charts with the diagnosis of ovarian tumors were reviewed retrospectively. Of 158 tumors in females below 14 years of age, 7 were located in the ovary (4.4%). Clinical presentation, diagnostic methods, histology, treatment and survival were evaluated. RESULTS: The mean age of the patients was 11.3 years (range: 7 months-13.5 years). One child was asymptomatic, 4 complained of abdominal pain, 3 with vomiting and 3 with urinary symptoms. Palpable abdominal masses were found in all, with abdominal distension in 2, ascytes, general malaise and precocious puberty each in one case. Alpha-fetoprotein was elevated in 3 cases and CA 125 in 1. Image studies revealed pleural effusion in one X-ray abdominal mass in 6 abdominal X-rays, which was confirmed by echography in all girls. Histology revealed benign teratoma (3), endodermal sinus tumor (1), malignant teratoma (1), granulosa cell tumor (1) and mixed teratoma and dysgerminoma (1). Treatment consisted in surgical resection (7), total in 5 cases (stage I) and subtotal in 2 (one malignant teratoma and one TSE, stages III). Chemotherapy was added initially in 2 stage III tumors and after relapse in 3. Radiotherapy was not given. Six girls survived. CONCLUSIONS: We comment on the low incidence of these tumors, which can be well diagnosed by using echography. Mixed histology may be misdiagnosed. Chemotherapy may rescue the worse prognostic cases.

[Neuroblastoma in children under than 1 year of age]. / Neuroblastoma en niños menores de 1 año.

OBJECTIVE: Our objective was to carry out a prospective multicenter study of neuroblastoma patients diagnosed between 0 and 12 months of age. PATIENTS AND METHODS: Diagnostic procedures included histology, catecholamine excretion, bone marrow cytology and MIBG-scan. Staging was evaluated according to the INSS classification. After 1992, Simada criteria were used and also N-myc amplification, DNA index and P-glycoprotein determinations in tumoral tissue. The surgical technique employed and complications derived from it were also evaluated. The patients were treated according to stage with multicenter Spanish protocols N-I-87 and N-II-92. Overall survival and event free survival were calculated by actuarial methods. RESULTS: Between October 1987 and June 1992, a total of 140 infants less than one year of age were registered and diagnosed of neuroblastoma, representing 40% of all neuroblastoma cases. Median age was 0.3 years and 73% were less than 6 months of age at diagnosis. The most frequent stage was 1 (35%) followed by 4-S (20%). The frequency of unfavorable prognostic factors was the following: LDH (21%), NSE (14%), ferritin (18%), Shimada (7%), DNA (35%), NMA (3%), TrakA (23%), P-glycoprotein (19%). Surgery was performed in 133 children: total resection was reported in 94 and > 90% in another 22 cases. Complications attributed to surgery occurred in 12% of the cases. Chemotherapy was given in 73 cases and radiotherapy in 7. The five year total survival is 91% and the event free survival 88%. Survival by stages: Stage 1 = 91%, stage 2A = 88%, stage 2B = 100%, stage 3 = 84%, stage 4 = 56% and stage 4-S = 100%. CONCLUSIONS: 1) The majority of neuroblastoma cases in infants less than one year old are diagnosed before six months of age. 2) For this age group stages 1 and 4-S are the most frequently observed. 3) Unfavorable biological factors are less frequent than for children over one year of age and are associated with disseminated disease (advanced stage). 4) The outcome is excellent, except for stage 4 patients. The cases in stage 1 and 2 may be treated by surgery alone. Chemotherapy may be of benefit for stage 3 patients.

[Nutritional study of children with oncologic diseases]. / Estudio nutricional en niños oncológicos.

From October 1989 to June 1990 we have evaluated at diagnosis and after six months of treatment the nutritional status of 21 oncologic patients younger than 14 years. At diagnosis, 14% of the children showed slight malnutrition on anthropometric evaluation, although there were biochemical data of protein malnutrition in 47% of the cases. Children with abnormal anthropometric measurements and those with a high risk of becoming malnourished (infants with advanced abdominal diseases) were given dietary supplements. In the follow-up evaluation, 90% of the patients showed normal somatic indexes and 76% showed recuperation in their protein values. The recovery of the nutritional status was most important in the group of patients with Acute Lymphoblastic Leukemia.