RESUMEN
Ewing sarcoma is the third most common sarcoma in children and young adults. Its characteristic chromosomal rearrangement results in a chimerical EWSR1-ETS transcription factor. Secondary genetic alterations are very common. Membranous expression of CD99 is seen in almost all tumors. We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6. The latter has not been described previously in pediatric neoplasms. Molecular pathways in tumorigenesis and genetic complexity in cancer are discussed.
Asunto(s)
Neoplasias Óseas/genética , Eliminación de Gen , Factores de Transcripción de Tipo Kruppel/genética , Proteínas Proto-Oncogénicas/genética , Sarcoma de Ewing/genética , Antígeno 12E7 , Antígenos CD/genética , Moléculas de Adhesión Celular/genética , Niño , Humanos , Hibridación Fluorescente in Situ , Factor 6 Similar a Kruppel , MasculinoRESUMEN
The ossifying renal tumor of infancy is a rare neoplasm diagnosed in the first 2 years of life, predominantly in boys. The neoplasm is primarily characterized by the presence of a large ossifying component. Its most common mode of presentation is hematuria, and it has a uniformly benign behavior. The karyotypic makeup of the process has not been reported. Thus, a study was undertaken and it allowed demonstration of clonal trisomy 4, which was confirmed by the fluorescent in-situ hybridization-probing of two additional archival formalin-fixed, paraffin-imbedded similar tumors. On the basis of the findings in these three cases, it seems that clonal trisomy 4 may be considered as a characteristic of the tumor, which makes it distinct from any other infantile renal tumor.
Asunto(s)
Cromosomas Humanos Par 4 , Neoplasias Renales/patología , Osificación Heterotópica/patología , Trisomía/patología , Humanos , Lactante , Neoplasias Renales/genética , Masculino , Osificación Heterotópica/genética , Trisomía/genéticaRESUMEN
Anthracycline, used in oncological chemotherapy, has one well-known side effect: cardiotoxicity. Another is abnormal intestinal motility such as constipation and ileus, the pathogenesis of which, to our knowledge, has not been morphologically investigated. We conducted a study in search of morphological evidence that might shed some light on the pathogenesis of the motility dysfunction. Autopsies performed between 2002 and 2007 were reviewed to select cases of children who had received anthracycline therapy for various neoplasms. The seven patients found had leukemias, lymphomas, or renal solid tumors. They all suffered from constipation or intestinal dysmotility, and no case of anthracyclin-treated neoplasia without the side effect was found in the files. Tissue samples from the heart, gastrointestinal tract, uterus, urinary bladder, and skeletal muscles were examined by light and electron microscopy. As described by others, the myocardium of all anthracycline-treated patients showed loss of myofilaments, fibrosis, mitochondrial proliferation, and pools of accumulated Z-band material. In the gastrointestinal tract and other smooth muscle-endowed organs such as muscular blood vessels, bladder and uterus, the muscularis displayed hyalinization and disorganization, including loss of myofilaments and moderate-severe fibrosis. This study illustrates changes in the smooth muscle, and that of the gastrointestinal tracts and their vessels in particular, in patients treated with anthracycline, who had experienced motility dysfunction associated with their chemotherapy, suggesting that, in addition to the heart, anthracycline may also damage smooth muscle fibers and thus be instrumental in the pathogenesis of the side effects.
Asunto(s)
Antraciclinas/efectos adversos , Motilidad Gastrointestinal/efectos de los fármacos , Ileus/inducido químicamente , Músculo Liso/efectos de los fármacos , Músculo Liso/ultraestructura , Adolescente , Autopsia , Niño , Preescolar , Estreñimiento/inducido químicamente , Estreñimiento/patología , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/ultraestructura , Corazón/efectos de los fármacos , Humanos , Ileus/patología , Microscopía Electrónica de Transmisión , Músculo Liso/irrigación sanguínea , Neoplasias/tratamiento farmacológico , Adulto JovenRESUMEN
Rhabdomyosarcoma is the most common pediatric soft tissue malignancy. Two major subtypes, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma, constitute 20 and 60% of all cases, respectively. Approximately 80% of alveolar rhabdomyosarcoma carry two signature chromosomal translocations, t(2;13)(q35;q14) resulting in PAX3-FOXO1 fusion, and t(1;13)(p36;q14) resulting in PAX7-FOXO1 fusion. Whether the remaining cases are truly negative for gene fusion has been questioned. We are reporting the case of a 9-month-old girl with a metastatic neck mass diagnosed histologically as solid variant alveolar rhabdomyosarcoma. Chromosome analysis showed a t(8;13;9)(p11.2;q14;9q32) three-way translocation as the sole clonal aberration. Fluorescent in situ hybridization (FISH) demonstrated a rearrangement at the FOXO1 locus and an amplification of its centromeric region. Single-nucleotide polymorphism-based microarray analysis illustrated a co-amplification of the FOXO1 gene at 13q14 and the FGFR1 gene at 8p12p11.2, suggesting formation and amplification of a chimerical FOXO1-FGFR1 gene. This is the first report to identify a novel fusion partner FGFR1 for the known anchor gene FOXO1 in alveolar rhabdomyosarcoma.
Asunto(s)
Factores de Transcripción Forkhead/genética , Amplificación de Genes , Fusión Génica , Neoplasias de Cabeza y Cuello/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Rabdomiosarcoma Alveolar/genética , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Análisis Citogenético , Femenino , Proteína Forkhead Box O1 , Neoplasias de Cabeza y Cuello/patología , Humanos , Hibridación Fluorescente in Situ , Lactante , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Rabdomiosarcoma Alveolar/secundario , Translocación GenéticaRESUMEN
We describe the rare finding of a 33-month-old child neonatally diagnosed with Down syndrome, who presented with pre-B acute lymphoblastic leukemia (ALL) with a pretreatment bone marrow karyotype in which a low hypodiploid cell line (38 chromosomes) was identified in 17/19 cells studied. The abnormal cell line retained the extra constitutional chromosome 21. Hypodiploidy (loss of one or more chromosomes) is seen in approximately 5% of all childhood pre-B ALL cases and in approximately 2.2% cases of individuals with a constitutional trisomy 21. Low hypodiploidy, associated with a high risk of relapse, is rare in pediatric ALL cases in the general population, and, to our knowledge, is previously unreported in patients with trisomy 21.
Asunto(s)
Linfoma de Burkitt/genética , Diploidia , Síndrome de Down/genética , Linfoma de Burkitt/complicaciones , Preescolar , Síndrome de Down/complicaciones , Femenino , Humanos , Cariotipificación , MasculinoRESUMEN
Gliomatosis confined to the cerebellum is most unusual. We report such a case in a 20-month-old male who presented with unsteadiness. Magnetic resonance imaging revealed a diffuse area of abnormal signal intensity within both cerebellar hemispheres, which did not enhance after contrast administration. The patient underwent a biopsy, which revealed a diffuse glioma infiltrating the cerebellum. Overall, the tumor cells had oligodendroglioma-like features and exhibited only focal vimentin immunoreactivity. They were negative for glial fibrillary acidic protein, synaptophysin, ßIII-tubulin, and neurofilament protein. Immunofluorescence, performed on primary biopsy explants maintained in cell culture without exposure to growth factors or differentiation-promoting agents, revealed widespread nestin immunoreactivity and immunolabeling of occasional cells with antibodies to platelet-derived growth factor-α and O1/O4, markers of oligodendrocyte precursor-cells and immature oligodendrocytes, respectively. Fluorescent in situ hybridization performed on explants, touch preparations, and paraffin sections failed to reveal loss of heterozygosity for either 1p36 or 19q13. The patient was treated with temozolomide and remains stable, albeit with residual quiescent tumor, more than 3 years after surgery. This report calls attention to an unusual presentation of gliomatosis confined to the cerebellum of a toddler and addresses salient aspects of clinical and radiological differential diagnosis, as well as therapeutic challenges encountered.
Asunto(s)
Neoplasias Cerebelosas , Cerebelo/patología , Neoplasias Neuroepiteliales , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/cirugía , Preescolar , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Humanos , Proteínas de Filamentos Intermediarios/metabolismo , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Neoplasias Neuroepiteliales/diagnóstico , Neoplasias Neuroepiteliales/tratamiento farmacológico , Neoplasias Neuroepiteliales/cirugía , Proteínas del Tejido Nervioso/metabolismo , Nestina , Neurocirugia , Oligodendroglía/metabolismo , Oligodendroglía/patología , Oligodendroglioma/metabolismo , Oligodendroglioma/patología , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Temozolomida , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patología , Vimentina/metabolismoRESUMEN
We describe the rare finding of a T-cell acute lymphoblastic leukemia (T-ALL) and a pretreatment bone marrow karyotype mosaic for four distinct cell lines in a 4-year-old boy. G-banding analysis of metaphase cells identified a hyperdiploid cell line (52 chromosomes) trisomic for chromosomes 6, 9, 11, 13, 19, and 22. Fluorescence in situ hybridization (FISH) analysis demonstrated that these hyperdiploid cells were missing all three copies of the CDKN2A locus (alias p16/Ink4) at 9p21. FISH analysis of interphase nuclei identified two abnormal cell lines: the majority of cells with homozygous deletions of the CDKN2A locus and some with a heterozygous deletion. In addition, a normal signal pattern was identified in a few cells. This case represents a rare case of hyperdiploidy in T-ALL, and characterizes the clonal evolution of the 9p21 deletion leading to the abnormal karyotype.
Asunto(s)
Eliminación de Gen , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Trisomía/genética , Aneuploidia , Preescolar , Mapeo Cromosómico , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , MasculinoRESUMEN
We report the presence of divergent populations of cells in a hypothalamic/chiasmatic pilomyxoid astrocytoma of an 11-month-old male, exhibiting differential immunohistochemical localizations for glial fibrillary acidic protein (GFAP) and synaptophysin. The tumor cells were negative for Neu-N and neurofilament protein. Ultrastructurally, the tumor comprised 2 cell types, one with features attributable to a neuronal phenotype alongside cells exhibiting an overt astroglial phenotype. This composite organization was confirmed by confocal microscopy, which revealed 2 distinct, albeit tightly interwoven, populations of GFAP and synaptophysin-labeled tumor cells. Our results indicate that a subset of the so-called pilomyxoid astrocytomas of the hypothalamic/chiasmatic region may represent phenotypically mixed glioneuronal neoplasms distinct from the pilocytic astrocytomas.
Asunto(s)
Astrocitoma/patología , Neoplasias Encefálicas/patología , Ganglioglioma/patología , Hipotálamo/patología , Astrocitos/ultraestructura , Astrocitoma/química , Neoplasias Encefálicas/química , Ganglioglioma/química , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Técnicas para Inmunoenzimas , Lactante , Imagen por Resonancia Magnética , Masculino , Microscopía Confocal , Microscopía Electrónica de Transmisión , Neuronas/ultraestructura , Fenotipo , Sinaptofisina/análisisRESUMEN
This report describes the youngest patient to develop a malignant peripheral nerve sheath tumor arising from a ganglioneuroma (MPNST ex Ganglioneuroma). The patient, a 6-year-old boy, was never irradiated and had no history or stigmata of neurofibromatosis. The report also includes a review of the previously published related cases, and an analysis of the immunohistochemistry and electron microscopy data available to date on the subject.