ResumoObjetivo: Relatar a ocorrência de pancitopenia transitória, decorrente de infecção pelo parvovírus B19, em um paciente portador de anemia hemolítica hereditária e comentar a importância do diagnóstico desta infecção.Métodos: Relato de caso clínico acompanhado pelos autores, diagnosticado sorologicamente e pelo método da reação em cadeia da polimerase (PCR), e revisão da literatura.Resultados: Menino de 12 anos, portador de esferocitose hereditária, apresentando quadro infeccioso inespecífico seguido de pancitopenia grave, transitória, com diagnóstico de infecção por parvovírus B19.Conclusões: O diagnóstico da infecção por parvovírus B19 é de particular importância em hematologia, principalmente quando estão presentes algumas condições mórbidas, entre elas as anemias hemolíticas hereditárias, sendo o método de PCR útil por permitir rapidez e boa sensibilidade no diagnóstico específico desta patolog i a .J. pediatr. (Rio J.). 2000; 76(4): 323-326: pancitopenia, crise aplástica, anemias hemolíticas, esferocitose hereditária, parvovírus B19. AbstractObjective: To describe the occurrence of transient pancytopenia induced by parvovirus B19 infection in a patient with hereditary hemolytic anemia and to discuss the importance of the diagnosis of this pathology.Methods: Case report of a child whose diagnosis was made by polymerase chain reaction (PCR) and serology, and review of the literature.Clinical report: A twelve year-old male patient with hereditary spherocytosis, presenting non-specific symptoms of an infectious syndrome followed by severe and transient pancytopenia, whose diagnosis was a parvovirus B19 infection.Conclusion: The diagnosis of parvovirus infection has a particular importance in hematology, especially on some morbid conditions, among them the hereditary hemolytic anemias. PCR is useful because of its rapidness and sensitivity on the specific diagnosis of this disease. J. pediatr. (Rio J.). 2000; 76(4): 323-326: pancytopenia, aplastic crisis, hemolytic anemias, hereditary spherocytosis, parvovirus B19

Medulloblastoma (MB) treatment is continuously evolving. Better treatment approaches, focused on particular molecular pathways involved in MB development and progression support new treatment strategies. This article explores the antiproliferative, proapoptotic and radiosensitizing effects of Methoxyamine (MX), a base excision repair (BER) inhibitor that has shown anticancer potential by sensitizing tumor cells to ionizing radiation and chemotherapy. The DAOY (a desmoplastic cerebellar-derived MB) and ONS-76 (classical MB) cell lines were treated with MX at different concentrations, either alone or combined with various chemotherapeutic compounds: cisplatin (CDDP), temozolomide (TMZ) and thiotepa (THIO). Additionally, cell lines were exposed to MX and treated at different ionizing radiation fractions. Measurement of cell growth by XTT assay, clonogenic assay and detection of apoptotic cell death through caspase activity was obtained. Exposure to MX significantly decreased cell proliferation (p<0.05) while increasing cell apoptosis (p<0.05). Growth reduction was concentration-dependent for both DAOY and ONS-76 cells lines. Conversely, MX failed to enhance the cytotoxicity of CDDP, TMZ, and THIO. Moreover, MX treatment radiosensitized both cell lines, with ONS-76 cells being more prone to radiation effects at higher doses of exposure. These data support the role of MX as a direct cytotoxic compound for pediatric MB cells by inhibiting the BER pathway. Nevertheless, an antagonism, rather than a synergic or additive effect of MX with different concentrations of CDDP, TMZ and THIO was observed. Likewise, the radiosensitizing effect on MB cell lines seems to depend on radiation doses and MB subtype. This information may be relevant for clinical study designs employing BER inhibitors for MB.

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INTRODUCTION: High grade gliomas (HGG) represent approximately 10% of all pediatric central nervous system (CNS) tumors. Despite a variety of therapies, outcomes remain dismal. In contrast to adults with HGG, there is no apparent standard of care (SOC) for the treatment of children with HGG after surgery. We undertook an internet-based survey to better understand what the perceived SOC is for children. 3 years with newly diagnosed HGG. METHODS: An 8 question internet-based survey was e-mailed to 120 physicians who treat children with CNS tumors. Demographic data, including medical specialty, experience and institutional affiliations were collected. Respondents were asked what they consider as SOC for children with newly diagnosed HGG after a maximal surgical resection. RESULTS: The entire survey was completed by 62.5% (75/120) of respondents. 83% (62/75) identified themselves as pediatric oncologists/neuro-oncologists. The remaining were pediatric neurosurgeons, radiation oncologists and neurologists. 65% had .10 years' experience and approximately 84% worked in a large academic or cancer center. More than 70% answered that their affiliated institution sees more than 5 pediatric HGG patients each year. The most commonly answered SOC was to treat patients on any available Phase I or II clinical trial (26.7%). In the absence of a clinical trial, physicians most commonly answered that they personally would treat a newly diagnosed patient with focal radiation plus temozolomide followed by maintenance temozolomide (30.7%).

Objective: To report the experience with OK-432 therapy for lymphangioma in children.Methods: Retrospective study of 19 children with lymphangioma treated with OK-432 in Ribeirão Preto, state of São Paulo, Brazil, between 1999 and 2003.Results: All patients presented response to OK-432, 12 had total shrinkage and seven had partial shrinkage varying from 50 to 80%. Patients had fever after injections of OK-432 for 2 to 10 days, no damage to the overlying skin was observed.Conclusion: OK-432 is safe, effective and can be used as primary choice of treatment of patients with lymphangiomas because of the excellent response. In these cases surgery should not be necessary. In patients with partial regression new injections of OK-432 must be used to shrink the lesion. Thereby safely surgery could be made.

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Pathogenic germline variants in DICER1, a gene encoding an RNase key in microRNA-mediated silencing, cause DICER1 syndrome. This genetic disorder predisposes to the development of a wide array of mainly childhood-onset conditions including genitourinary tumors such as cystic nephroma (CN), anaplastic sarcoma of the kidney, Wilms’ tumor (WT), Sertoli-Leydig cell tumor (SLCT), and cervical embryonal rhabdomyosarcoma (ERMS). As the spectrum of clinical manifestations is not yet fully defined, we sought to explore the involvement of DICER1 mutations in pediatric genitourinary lesions not previously well studied. A series of 31 formalin-fixed, paraffin-embedded tumor samples including 15 paratesticular ERMS (ptERMS), one unclassifiable ovarian sex cord-stromal tumor, one fallopian tube ERMS (ftERMS), six cystic partially differentiated nephroblastomas (CPDN), two cystic WT, two CN, and four rare renal lesions were collected. Median age at diagnosis was 4 years. Tumor DNA was screened for DICER1 variants using Sanger sequencing or a Fluidigm array. Sanger sequencing on tumor DNA was used to validate the variants, and on normal DNA, to determine the germline status. Seven samples harbored biallelic DICER1 mutations and in 6/7 cases, the loss-of-function variant was confirmed to be of germline origin. The paratesticular tumors were initially diagnosed as ERMS, but pathology review reclassified one as an ectomesenchymoma and another as an undifferentiated low-grade myxoid sarcoma. No DICER1 mutation was identified in any of the ptERMS, but the myxoid sarcoma had DICER1 mutations. Interestingly, the patient with the paratesticular myxoid sarcoma also developed a CN. We identified DICER1 mutations in a tumor originally classified as an ovarian WT. Subsequent pathologic evaluation of the lesion led to its reclassification as a retiform SLCT with rhabdomyosarcomatous elements. A typical hotspot and a potential splicing mutation were detected in the ftERMS. Also, two atypical cystic kidney lesions harbored DICER1 mutations: one composed of blastema-type cells expressing nuclear WT1 diagnosed as a CPDN and another unusual multicystic renal lesion considered to be a CN that had moved into a proliferative phase but lacked blastema and anaplastic foci. The patient with the latter renal lesion had previously developed a unilateral CN with a distinct hotspot mutation. As expected, the two classical CN had DICER1 mutations. Based on these results, patients diagnosed with rare genitourinary tumors (except for ptERMS), may have DICER1 syndrome, especially if these individuals have a personal or family history of DICER1-associated lesions. In these cases, surveillance for DICER1-related conditions is advised given that the risk of tumor development is highest in early childhood. In summary, specialist pathology review and DICER1 testing in this setting will lead to improved diagnosis with potential implications for clinical care. Citation Format: Maria V. Apellaniz-Ruiz, Catherine Goudie, Noelle Cullinan, Elvis T. Valera, Krisztina Z. Hanley, Luiz G. Tone, Paula Marrano, Ronald Grant, W. Glenn McCluggage, Gordan M. Vujanic, Paul S. Thorner, William D. Foulkes. Novel childhood genitourinary manifestations of DICER1 syndrome [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A01.