Neonatal leukaemia.

Neonatal leukaemia is defined as occurring within the first 28 days of life and most, if not all, cases are congenital. With the exception of Down syndrome-associated transient abnormal myelopoiesis, which is not considered here, neonatal leukaemias are rare. In two-thirds of patients the disease manifests as an acute myeloid leukaemia, frequently with monocytic/monoblastic characteristics. Most other cases are acute lymphoblastic leukaemia, particularly B lineage, but some are mixed phenotype or blastic plasmacytoid dendritic cell neoplasms. The most frequently observed cytogenetic/molecular abnormality is t(4;11)(q21.3;q23.3)/KMT2A-AFF1 followed by t(1;22)(p13.3;q13.1)/RBM15-MKL1 and t(8;16)(p11.2;p13.3)/KAT6A-CREBBP. Common clinical features include prominent hepatosplenomegaly and a high incidence of skin involvement, sometimes in the absence of bone marrow disease. A distinctive feature is the occurrence of spontaneous remission in some cases, particularly in association with t(8;16). In this review, we summarise current knowledge of the clinical, cytogenetic and molecular features of neonatal leukaemia and discuss clinical management of these cases.

Valoración radiológica de los tumores congénitos / Radiological evaluation of congenital tumors

Los tumores congénitos son aquellos tumores diagnosticados durante el embarazo y los tres primeros meses de vida. Constituyen un grupo heterogéneo de neoplasias con unas características biológicas y epidemiológicas especiales que los diferencian del resto de los tumores pediátricos y de la edad adulta. Su detección prenatal ha aumentado en las dos últimas décadas debido a la generalización del cribado ecográfico prenatal. El desarrollo de las técnicas de imagen, especialmente la resonancia magnética (RM) fetal, ha permitido mejorar el diagnóstico, el seguimiento y el manejo clínico y terapéutico perinatal de estos tumores. Presentamos una revisión basada en imágenes de los tumores congénitos más frecuentes, describiendo los tipos histológicos, localizaciones y sus características en las distintas técnicas de imagen empleadas (AU)

In this article, we consider tumors that are diagnosed during pregnancy or in the first three months of life. This is a heterogeneous group of neoplasms with special biological and epidemiological characteristics that differentiate them from tumors arising in children or adults. In the last two decades, the prenatal detection of congenital tumors has increased due to the generalized use of prenatal sonographic screening. Advances in imaging techniques, especially in fetal magnetic resonance imaging, have enabled improvements in the diagnosis, follow-up, clinical management, and perinatal treatment of these tumors. This image-based review of the most common congenital tumors describes their histologic types, locations, and characteristics on the different imaging techniques used (AU)

Leucemia congénita / Congenital leukemia

La leucemia congénita constituye una entidad rara que se diagnostica entre el momento del nacimiento y los primeros 30 días de vida. Menos del 1 por ciento de las leucemias de la infancia se diagnostican en el neonato. Se caracteriza por la presencia en un recién nacido, de hepatomegalia, esplenomegalia y lesiones hemorrágicas o infiltrativas en piel. El hemograma completo, el examen de la lámina de la sangre periférica, el aspirado de médula ósea, junto con el inmunofenotipaje y los estudios de biología molecular confirmarán el diagnóstico. El trastorno mieloproliferativo transitorio y las infecciones congénitas constituyen los principales diagnósticos diferenciales. El pronóstico de la enfermedad es sombrío. El tratamiento está basado en regímenes de poliquimioterapia intensiva y el trasplante de progenitores hematopoyéticos constituye una opción terapéutica en un grupo de pacientes

Congenital leukemia is a rare but well documented disease which can be diagnosed on the first 30 days of life. The diagnosis requires a high index of clinical suspicion in a newborn with hepatosplenomegaly and hemorragic or infiltratives cutaneous lesions (red, brown or purple papules or nodules) along with further investigations such as complete blood count, peripheral blood smear, bone marrow aspirate and immunopfenotypic profile. A true congenital leukemia has to be distinguished from other conditions such as a transient mieloproliferative disorder described in Down´s syndrome and congenital infections. The prognosis of neonatal leukemia is dismal. Treatment includes intensive multi-agent chemotherapy and supportive care, being the hematopoietic stem cell transplantation an additional treatment option in a group of patients

Leucemia congénita / Congenital leukemia

La leucemia congénita constituye una entidad rara que se diagnostica entre el momento del nacimiento y los primeros 30 días de vida. Menos del 1 por ciento de las leucemias de la infancia se diagnostican en el neonato. Se caracteriza por la presencia en un recién nacido, de hepatomegalia, esplenomegalia y lesiones hemorrágicas o infiltrativas en piel. El hemograma completo, el examen de la lámina de la sangre periférica, el aspirado de médula ósea, junto con el inmunofenotipaje y los estudios de biología molecular confirmarán el diagnóstico. El trastorno mieloproliferativo transitorio y las infecciones congénitas constituyen los principales diagnósticos diferenciales. El pronóstico de la enfermedad es sombrío. El tratamiento está basado en regímenes de poliquimioterapia intensiva y el trasplante de progenitores hematopoyéticos constituye una opción terapéutica en un grupo de pacientes(AU)

Congenital leukemia is a rare but well documented disease which can be diagnosed on the first 30 days of life. The diagnosis requires a high index of clinical suspicion in a newborn with hepatosplenomegaly and hemorragic or infiltratives cutaneous lesions (red, brown or purple papules or nodules) along with further investigations such as complete blood count, peripheral blood smear, bone marrow aspirate and immunopfenotypic profile. A true congenital leukemia has to be distinguished from other conditions such as a transient mieloproliferative disorder described in Down´s syndrome and congenital infections. The prognosis of neonatal leukemia is dismal. Treatment includes intensive multi-agent chemotherapy and supportive care, being the hematopoietic stem cell transplantation an additional treatment option in a group of patients(AU)

Clinicopathological features of transient myeloproliferative syndrome and congenital leukaemia.

OBJECTIVE: The objectives of the study were to determine the spectrum of the clinical and pathological findings, the management and prognosis of patients of transient myeloproliferative syndrome (TMS) and congenital leukaemia. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The study was conducted over a period of 8 years, from January 2000 to December 2007, at the Children's Hospital and the Institute of Child Health, Lahore. METHODOLOGY: Suspected patients presenting with fever, pallor, bruises and hepatosplenomegaly and diagnosed as either transient myeloproliferative disorder or congenital leukaemia were studied. The complete blood count, reticulocyte count, leukocyte alkaline phosphatase score, liver function tests, karyotyping studies and bone marrow aspiration biopsy were performed in all of those patients. Management and out come was noted. Results were described as frequency percentages. RESULTS: Out of 10,000 patients presenting during this period, 24 patients were diagnosed as either of transient myeloproliferative syndrome or congenital leukaemia. Fifteen of these were diagnosed as patients of TMS and 9 as patients of congenital leukaemia. Down syndrome (DS) was diagnosed in 75% of these patients. TMS patients were put on supportive treatment and recovered spontaneously. One DS patient with congenital leukaemia went into spontaneous remission and 2 of DS patients with congenital leukaemia responded to chemotherapy while rest of them either died or lost to follow-up. CONCLUSION: TMS and congenital leukaemia were not very uncommon in the studied population. Majority had Down syndrome. It is important to differentiate their clinical and pathological presentations for proper management. TMS may resolve with supportive treatment while congenital leukaemia is a fatal condition requiring chemotherapy.

A case of fetal leukemia with intracranial hemorrhage and early-onset jaundice. Fetal leukemia with intracranial hemorrhage and jaundice.

We report a case of a neonate who was diagnosed as having congenital leukemia after presenting with an intracranial hemorrhage. The chief symptom was early-onset jaundice due to the hemorrhage. The intracranial hemorrhage and post-hemorrhage hydrocephalus advanced. In addition, the leukemia worsened leading to death at 14 days old. The possibility of leukemia, although rare, should be considered as a cause of intracranial hemorrhage in term babies.

Anomalías hematológicas asociadas al síndrome de Down: síndrome mieloproliferativo transitorio neonatal y leucemia mieloblástica congénita / Hematological abnormalities associated with Down syndrome: transient myeloproliferative disorder and congenital acute myeloblastic leukemia

La asociación entre síndrome de Down y anomalías hematológicas es bien conocida. En el periodo neonatal son frecuentes las alteraciones inespecíficas (neutrofilia, trombocitopenia y policitemia), pero la entidad más importante clínicamente es el síndrome mieloproliferativo transitorio (SMPT), casi exclusivo de recién nacidos con fenotipo Down. Se presentan dos casos de recién nacidos con este fenotipo con hiperleucocitosis, en uno de ellos asociada además a colestasis y lisis tumoral (AU)

It is known that Down syndrome is frequently associated with hematological abnormalities. In newborn infants, it is not unusual to find nonspecific features (neutrophilia, thrombocytopenia, polycythemia),but the entity of the greatest clinical importance is transient myeloproliferative disorder (TMD), which is observed almost exclusively in neonates with Down syndrome. Two newborns with Down syndrome are presented. They were studied forhyperleukocytosis, in one case, associated with cholestasis and tumor lysis síndrome (AU)

Fetal leukemia with umbilical artery embolism and circulatory failure.

BACKGROUND: This is a case report of fetal leukemia associated with hydramnios. CASE: When the hydramnios was treated with amnioreduction, near-term bradycardia was recorded ultrasonographically, resulting in immediate cesarean delivery. At birth, neonatal leukemia was diagnosed and there was no evidence of chromosomal abnormalities. The infant died of pulmonary hemorrhage. Autopsy showed umbilical venous embolization with tumor cells, and there was arterial invasion of the vessel wall by tumor. CONCLUSION: Fetal leukemia is extremely rare, and its prenatal diagnosis is difficult. In cases of hepatomegaly, fetal leukemia should be considered in the differential diagnosis.

Congenital leukemia cutis with subsequent development of leukemia.

We describe a newborn infant who was born with a purpuric rash and subcutaneous nodules. Skin biopsies demonstrated acute myeloid leukemia. Cytogenetic studies revealed an 11q23 rearrangement. Initial bone marrow and cerebrospinal fluid examination did not demonstrate medullary or meningeal disease. Chemotherapy was initiated on the basis of the abnormal cytogenetic findings in the skin biopsy. Intensive chemotherapy was, given but the infant's leukemia progressed. The patient died of refractory leukemia and secondary fungal disease. This case report supports the observation that leukemia cutis with an 11q23 rearrangement should be treated aggressively.

[Transient neonatal myeloproliferative disorder in the absence of Down syndrome]. / Síndrome mieloproliferativo transitorio neonatal en ausencia de síndrome de Down.

Transient neonatal leukemia or transient neonatal myeloproliferative disorder is commonly associated with Down syndrome. It usually resolves spontaneously in 4-5 months. However, 25 % of patients will subsequently develop acute megakaryoblastic leukemia or myelodysplastic syndrome. It has seldom been described without constitutional anomalies and is even less frequent in twins. We present three phenotypically normal patients with this disorder. One of them was diagnosed because he presented blueberry muffin syndrome. Diagnosis was guided by pathological examination of the skin lesions. The other two patients were monochorionic triplets. Their bichorionic sister presented no hematological disorders. Constitutional chromosomal abnormalities were ruled out in all three patients. They received support treatment only without chemotherapy. The clinical course was favorable with disappearance of marrow and peripheral blastosis in 4-5 months. Follow-up of 18 and 19 months has not revealed any hematological disorders. Caution must be exercised before initiating chemotherapy in these patients. We discuss the differential diagnosis with congenital leukemia and the prognostic and therapeutic implications that this entails.

Demographic study of leukaemia presenting within the first 3 months of life in the Northern Health Region of England.

AIMS: To determine the incidence and outcome of congenital leukaemia. METHODS: Retrospective population based study of putative leukaemia arising during the first 3 months of life over an 18 year period within the Northern Health Region of England. RESULTS: Nine infants with putative leukaemia were identified. Five had acute leukaemia and four had transient myeloproliferative disorder (TMD). Trisomy 21, either as Down's syndrome or perhaps restricted to proliferating marrow cells, was present in all four infants with TMD. The incidence of congenital acute leukaemia was 8.6/10(6) live births/year, but would be less than half this value if only patients presenting within 4 weeks of birth were counted. Remission was induced in three of the five patients with acute leukaemia. One patient, who presented at birth, remains well five years after diagnosis. All four patients with TMD survive. CONCLUSIONS: Congenital leukaemia is very rare but is not inevitably fatal. Finding trisomy 21 in spontaneously dividing blood or bone marrow cells of an infant with putative acute leukaemia, particularly within 3 months of birth, should encourage a cautious clinical approach and suggests that the diagnosis might be TMD.

[Recent progress of molecular diagnosis in pediatric malignancies].

Recent progress of molecular and cytogenetic techniques has led to remarkable advances in molecular diagnosis of pediatric malignancies, including malignant bone and soft tissue sarcoma (MSTS). Fusion genes, such as EWS-FLI1 and PAX3-FKHR, were cloned at the chromosome breakpoints of t(11;22) and t(2;13) in Ewing's sarcoma and rhabdomyosarcoma, respectively. Minimal residual disease can be detected by reverse transcriptase-polymerase chain reaction using these translocations. These fusion genes contribute to differential diagnosis of pediatric small round cell tumor, which was difficult to diagnose morphologically. Some of these fusion genes, including SYT-SSX in synovial sarcoma and EWS-FLI1 in Ewing sarcoma, have been reported to be associated with prognosis. Recently, genome-wide searches using microarray and single nucleotide polymorphisms have been performed in pediatric malignancies. These advances have led to the increased importance of molecular diagnosis as well as morphological diagnosis. We review here the recent progress of molecular diagnosis in pediatric malignancies.