RESUMEN
PURPOSE: The National Cancer Institute-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions. METHODS: COG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data. RESULTS: Of 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described. CONCLUSIONS: These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy.
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Servicios de Salud del Niño , Ensayos Clínicos Fase III como Asunto , Investigación sobre la Eficacia Comparativa , Oncología Médica/tendencias , Registro Médico Coordinado , Sistemas de Registros Médicos Computarizados/tendencias , Neoplasias , Adolescente , Niño , Servicios de Salud del Niño/economía , Servicios de Salud del Niño/normas , Servicios de Salud del Niño/estadística & datos numéricos , Preescolar , Ensayos Clínicos Fase III como Asunto/economía , Ensayos Clínicos Fase III como Asunto/normas , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Conducta Cooperativa , Costos y Análisis de Costo , Femenino , Hospitales Pediátricos , Humanos , Lactante , Masculino , Oncología Médica/economía , Oncología Médica/organización & administración , Oncología Médica/normas , Oncología Médica/estadística & datos numéricos , Sistemas de Registros Médicos Computarizados/economía , Sistemas de Registros Médicos Computarizados/normas , Sistemas de Registros Médicos Computarizados/estadística & datos numéricos , National Cancer Institute (U.S.) , Neoplasias/economía , Neoplasias/mortalidad , Neoplasias/terapia , Objetivos Organizacionales , Evaluación de Procesos y Resultados en Atención de Salud , Estados Unidos , Adulto JovenRESUMEN
The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.
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Factor Estimulante de Colonias de Granulocitos/farmacología , Leucemia Mieloide Aguda/genética , Sistema de Señalización de MAP Quinasas , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT5/genética , Transcriptoma , Proteínas Supresoras de Tumor/genética , Adolescente , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Niño , Preescolar , Criopreservación , Medios de Cultivo Condicionados/farmacología , Resistencia a Antineoplásicos , Femenino , Perfilación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Interleucina-13/farmacología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Análisis Multivariante , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Recurrencia , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT5/metabolismo , Análisis de Secuencia de ARN , Activación Transcripcional , Microambiente Tumoral , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia Arriba , Adulto JovenRESUMEN
The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions (AU)
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Regulación Neoplásica de la Expresión Génica , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/metabolismo , Insuficiencia del TratamientoRESUMEN
PURPOSE: Bone marrow transplantation (BMT) for Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) results in a 55% to 64% disease-free survival (DFS) rate in 20% to 30% of cases with a matched-sibling donor (MSD). Studies that include primarily adults with CML, using unrelated-donor (URD) BMT, have expanded this option to those without an MSD. We review and compare the efficacy of URD and MSD BMT in children with Ph1 CML. PATIENTS AND METHODS: Eleven children with URD BMTs were reviewed and compared with 11 children with MSD BMTs for Ph1 CML. Among the URD BMT recipients, there were three with fully matched marrows and 10 with advanced CML. The median time from diagnosis to transplant was 2.6 years. Among the MSD BMT recipients, 11 had fully matched marrows and five had advanced CML. The median time from diagnosis to BMT was 0.7 years. All received non-T-depleted marrows after cyclophosphamide and fractionated total-body irradiation. RESULTS: Both groups had similar engraftment times. Late graft failure occurred in two URD patients. Graft-versus-host disease (GVHD), > or = grade II, was similar in both groups (77% for URD BMT, 45% for MSD BMT), although more severe acute disease and more persistent chronic disease was seen in the URD group. The Kaplan-Meier estimate of DFS was 45% +/- 15% (SE) and 78% +/- 14% (SE) in the URD and MSD groups, respectively, at 3 years. All had Karnofsky scores of more than 70%, except one URD patient debilitated from GVHD. CONCLUSION: CML is eventually fatal to all patients without BMT. The high survival rate seen among children who receive a URD BMT, despite several adverse factors, opens this important therapeutic option to those without an MSD.
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Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Donantes de Tejidos , Adolescente , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/genética , Humanos , Masculino , Calidad de Vida , Análisis de SupervivenciaRESUMEN
PURPOSE: Past reports indicate that alpha hemolytic streptococcal (AHS) organisms are a common cause of infection among acute myeloid leukemia (AML) patients. This study was intended to ascertain the population incidence and rate (infections per 100 patient-days of treatment) of AHS and to identify associated risk factors. PATIENTS AND METHODS: Patients (n = 874 with 151,350 days of risk) enrolled on the Children's Cancer Group (CCG) protocol for newly diagnosed AML, CCG-2891, which randomly assigned intensity of induction and intensification, were prospectively evaluated for infectious complications. RESULTS: AHS occurred in 21% of patients, was primarily blood borne (86%), made up 21% of bacteremic infections, and had a recurrent incidence of 31% during subsequent therapy. AHS was more often life-threatening (59%) than other infections (41%) (P = .001). AHS rates increased with age less than 10 years (odds ratio [OR], 2.0; P = .007), intensively timed induction (OR, 1.8 to 1.9; P = .02), and high-dose cytarabine intensification (OR, 3.7; P<.0001). Among all courses, the greatest incidence (19%) and rate (0.41) were associated with the use of high-dose cytarabine. Gastrointestinal toxicity correlated significantly with AHS bacteremia (P<.01). Infection with AHS resulted in increased hospital days (P =.0001). Only among bone marrow transplant patients were overall survival (OR, 2.8; P = .0001) and disease-free survival (OR, 2.1; P = .008) decreased after AHS bacteremia. CONCLUSION: This study, the first to prospectively examine AHS incidence among uniformly treated patients in multiple institutions, established that as the intensity of AML therapy has increased, so has the rate of AHS. Young children, those with previous AHS bacteremias, and those receiving high-dose cytarabine are at particularly high risk of AHS bacteremia.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Infecciones Estreptocócicas/epidemiología , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Femenino , Hemólisis , Humanos , Incidencia , Lactante , Recién Nacido , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/microbiología , Masculino , Estudios Prospectivos , Factores de Riesgo , Infecciones Estreptocócicas/etiologíaRESUMEN
Bone marrow transplantation (BMT) has been established as a life-saving procedure in hematologic malignancies and bone marrow failure syndromes, and it may be valuable in other types of neoplastic disease. DNA polymorphisms are used to monitor engraftment after transplantation from a related or unrelated donor. DNA polymorphisms are not useful after autologous BMT or if the donor is an identical twin. The most valuable polymorphism for this purpose is caused by variation in certain repeated sequences that are known as variable number of tandem repeats (VNTR). The VNTRs are valuable because they each have several alleles increasing the probability of finding one that is useful in a given case. This method can be used to sensitively detect small amounts of residual recipient hematopoiesis. To accomplish this the laboratory must first find a polymorphic allele that is unique in the recipient. Detection of the unique allele in peripheral blood or bone marrow after BMT is tantamount to finding recipient hematopoiesis. The presence of both donor and recipient hematopoiesis can result in a state of stable mixed chimerism and not necessarily presage a relapse after BMT for leukemia; however, the presence of residual recipient cells in some cases may indicate an increased probability of relapse, particularly in chronic myelogenous leukemia.
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Trasplante de Médula Ósea , ADN/análisis , Polimorfismo Genético , Quimera , Femenino , Humanos , Leucemia/terapia , Masculino , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
The number of patients receiving a BMT is currently being used as a factor in the accreditation process in determining whether a center can provide a high-quality BMT. Such criteria particularly impact pediatric BMT centers as most of them perform a relatively small number of BMTs. To determine whether patient volume is a valid marker of pediatric BMT center's capabilities, the Pediatric Blood and Marrow Transplant Consortium (PBMTC) evaluated data from its registry to define the relationship between a pediatric transplant center's patient volume and day +100 mortality. The analyses evaluated 2575 transplants from 60 centers reporting to the PBMTC between the years 2002 and 2004. The volume-outcome relationship was evaluated while adjusting for 46 independent data categories divided between nine variables that were known- or suspected-mortality risk factors. We found no association between transplant center volume and day +100 mortality in several analyses. A calculated intraclass correlation coefficient also indicated that differences in individual transplant center volume contributed to only 1% of the variance in day +100 mortality within the PBMTC. The results of this study suggest that factors other than transplant center volume contribute to variation in day +100 mortality among pediatric patients.
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Acreditación , Trasplante de Médula Ósea/mortalidad , Hospitales Pediátricos , Sistema de Registros , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Tumors of the solid viscera are one of the most common types of pediatric malignancies. Due to the intra-abdominal location of many of these neoplasms, laparotomy and/or bowel resection are often necessary, predisposing patients to postoperative intestinal obstruction. Additionally, chemotherapy and radiation therapy may lead to acute and chronic bowel injury, also potentially predisposing these patients to postoperative bowel obstruction. We reviewed our data over an eleven-year period to identify the incidence of obstruction as well as factors associated with its development. METHODS: A retrospective data analysis of all patients diagnosed with intra-abdominal Wilms' tumor, rhabdomyosarcoma, neuroblastoma, and Hodgkin's and non-Hodgkin's lymphoma in a single institution from 1997 to 2007 was conducted. Data collected included demographic factors, operations, incidence of small bowel obstruction (SBO) and the use of adjuvant or neoadjuvant chemoradiation therapy. Patients who developed SBO were compared to those who did not develop obstruction. Data comparisons were analyzed statistically using Fisher's exact test, 2-tailed Student's t-Test, or chi-square proportional analysis with significance reported for p<0.05. RESULTS: A total of 291 patients were identified during the study period. Mean age at diagnosis was 8.1+/-5.8 years. Males accounted for 57% of all patients. Tumor distribution was as follows: Wilms' tumor: 56 (19%); non-Hodgkin's lymphoma: 71 (24%); Hodgkin's lymphoma: 64 (22%); rhabdomyosarcoma: 32 (11%); and neuroblastoma: 68 (24%). There were a total of 12 bowel obstructions in 11 patients (3.7%). Mean follow-up for all patients was 3.6+/-2.7 years. Children with bowel obstruction were more likely to be male (4.5:1, p=0.061) and younger (4.2 years versus 8.1 years; p=0.087). Wilms' tumor accounted for 45% of patients with bowel obstruction, but made up only 19% of the study population. The incidence of bowel obstruction in patients with Wilms' tumor was 8.9% compared to an overall incidence of 3.8% (p=0.043). CONCLUSION: Bowel obstruction is relatively uncommon after intra-abdominal malignancies in children. Wilms' tumor, rhabdomyosarcoma and Burkitt's lymphoma appear to be associated with the highest risk of bowel obstruction.
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Neoplasias Abdominales/cirugía , Obstrucción Intestinal/etiología , Laparotomía/efectos adversos , Neoplasias Abdominales/tratamiento farmacológico , Neoplasias Abdominales/radioterapia , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
Recent whole-genome sequencing efforts led to the identification of IDH1(R132) mutations in acute myeloid leukemia (AML) patients. We studied the prevalence and clinical implications of IDH1 genomic alterations in pediatric and adult AML. Diagnostic DNA from 531 AML patients treated on Children's Oncology Group trial COG-AAML03P1 (N=257), and Southwest Oncology Group trials SWOG-9031, SWOG-9333 and SWOG-9500 (N=274), were tested for IDH1 mutations. Codon R132 mutations were absent in the pediatric cohort, but were found in 12 of 274 adult patients (4.4%, 95% CI 2.3-7.5). IDH1(R132) mutations occurred most commonly in patients with normal karyotype, and those with FLT3/ITD and NPMc mutations. Patients with IDH1(R132) mutations trended toward higher median diagnostic white blood cell counts (59.2 x 10(9) vs 29.1 x 10(9) per liter, P=0.19) than those without mutations, but the two groups did not differ significantly in age, bone marrow blast percentage, overall survival or relapse-free survival. Eleven patients (2.1%) harbored a novel V71I sequence alteration, which was found to be a germ-line polymorphism. IDH1 mutations were not detected in pediatric AML, and are uncommon in adult AML.
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Biomarcadores de Tumor/genética , Codón/genética , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/genética , Mutación/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Cariotipificación , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Nucleofosmina , Prevalencia , Pronóstico , Secuencias Repetidas en Tándem/genética , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
Intelligence and academic achievement testing of long-term survivors of childhood cancer reveal a high incidence of memory deficits, visual-spatial skill impairment, and attention deficit disorders. While the results of various studies must be interpreted carefully, the data available identify CNS irradiation and the toxic synergism of CNS irradiation and intrathecal chemotherapy as primary etiologic factors in the neuropsychologic sequelae of curative therapy. Early education intervention is mandatory to identify survivors of childhood cancer who require assistance in overcoming intellectual disabilities.
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Neoplasias Encefálicas/psicología , Trastornos del Conocimiento/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Neoplasias Encefálicas/terapia , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/efectos de la radiación , Niño , Discapacidades del Desarrollo/etiología , Educación Especial , Estudios de Seguimiento , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
The widespread presence of fingernail polish remover in the home makes the product a common source of ingestion, as evidenced by recent poison center data. Its principal component, acetone, is present in relatively high concentration. The syndrome of acetone intoxication presents as generalized central nervous system/respiratory depression, hyperglycemia, and ketosis. Despite its ubiquitous presence and high potential for severe intoxication, no reports are found describing the toxicity and supportive care following its ingestion by children. The authors present a 30-month-old patient with severe acetone intoxication secondary to fingernail polish remover ingestion. Also noted is the need to include acetone ingestion in the differential diagnosis of apparent diabetic ketoacidosis.
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Acetona/envenenamiento , Preescolar , Humanos , MasculinoRESUMEN
Nitrous oxide (N2O) has been shown to be an effective analgesic in adult medical outpatients, yet no prospective studies of its use in the pediatric medical outpatient exist. Thirty-four children requiring laceration repair were randomly assigned to one of two treatment groups: 30% N2O/70% O2 or a placebo, 100% O2. Pain behavior, using the observer-scored Children's Hospital of Eastern Ontario Pain Scale, was assessed by double-blind techniques, before and during the laceration repair. Less pain behavior was seen in children less than 8 years old who received the N2O mixture than in those receiving the placebo. In patients 8 or more years old who received N2O, there was a significant improvement in the second evaluation as compared with those receiving only O2 during the procedure (P less than .05). There also was a smaller increase in pain behavior, from the first to the second evaluation, in those receiving N2O (P less than .05). No side effects were encountered. The authors conclude that continuous N2O inhalation is an effective and painless analgesic in children for outpatient procedures. More effective analgesia will likely occur with 40% to 50% N2O, although these concentrations remain to be studied in pediatric outpatients.
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Analgesia/métodos , Servicio de Urgencia en Hospital , Óxido Nitroso , Adolescente , Niño , Preescolar , Humanos , Dimensión del Dolor , Pediatría , Estudios ProspectivosRESUMEN
PURPOSE: alpha-Hemolytic streptococcal (AHS) sepsis is increasing in oncology patients receiving myelosuppressive chemotherapy. In response to a high rate of AHS sepsis in this population at our institution, an oral care protocol was instituted, including vancomycin 0.5% in flavored methylcellulose (vanc paste) applied orally t.i.d. at the oncologists' discretion. PATIENTS AND METHODS: A retrospective cohort study of 239 neutropenic episodes among 42 children receiving myelosuppressive chemotherapy between 1988 and 1991 compared the incidence of septicemia based on the prophylactic use of vanc paste. RESULTS: A total of 236 consecutive neutropenic episodes were evaluable, 121 with vanc paste and 115 without. AHS sepsis occurred in one child using vanc paste and in six children not using vanc paste (p = 0.06). Excluding staph-only positive blood cultures, which would not be reduced with a topical oral antibiotic drug, there were 6 and 13 positive blood cultures in the vanc-paste and nonvanc-paste patients, respectively (p = 0.09). There was no increase in incidence of gram-negative bacteremia among vanc-paste recipients. Vancomycin resistance was not encountered. CONCLUSION: This analysis suggests that vanc paste effectively reduces AHS sepsis, does not increase gram-negative bacteremia, and is not associated with vancomycin resistance. A multicentered, placebo-controlled, double-blind study is currently planned.
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Enfermedades de la Boca/prevención & control , Sepsis/prevención & control , Infecciones Estreptocócicas/prevención & control , Vancomicina/administración & dosificación , Adolescente , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/microbiología , Enfermedades de la Boca/epidemiología , Enfermedades de la Boca/microbiología , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Neoplasias/microbiología , Neutropenia/epidemiología , Neutropenia/microbiología , Pomadas , Higiene Bucal , Estudios Retrospectivos , Sepsis/epidemiología , Sepsis/microbiología , Infecciones Estreptocócicas/epidemiología , StreptococcusRESUMEN
Clinical data from 10 episodes of disseminated infection with Fusarium among eight recipients of bone marrow transplants and from 31 cases reported previously in the literature were analyzed in an effort to characterize the natural history of this rare infection and its response to therapy. The characteristic signs of fusarial infection--disseminated skin nodules, fungemia, and multiple-organ involvement--are results of its propensity for early spread. From a review of the literature and our own experience, it appears that recovery of phagocytic mechanisms (the primary immunologic defenses against Fusarium) in the form of rising neutrophil counts is mandatory for clinical resolution. Even after a graft begins to function adequately, Fusarium may not be completely eradicated, as evidenced by the high incidence of recurrence among patients with subsequent neutropenic episodes. Fusarium is highly resistant to conventional antifungal drugs in vitro, but its progression may be slowed by intensive antifungal therapy until the recovery of adequate neutrophil levels.
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Trasplante de Médula Ósea , Fusarium/aislamiento & purificación , Micosis/etiología , Neutropenia/complicaciones , Adolescente , Adulto , Niño , Preescolar , Femenino , Fusarium/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Terapia de Inmunosupresión , Masculino , Micosis/tratamiento farmacológico , Micosis/inmunología , Estudios RetrospectivosRESUMEN
Primary epithelial neoplasms of the salivary gland in children are uncommon but are well recognized and occur principally in the major salivary glands. The purpose of this report is to document our experience with an adenocarcinoma of the buccal submucosa (one of several sites of minor salivary gland tissue) that metastasized to multiple bones as the initial sites of distant disease after a local recurrence. The clinical history, imaging studies, and microscopic sections including immunoperoxidase studies were evaluated from the primary tumor, local recurrence, and a metastatic lesion from the femur. The histopathologic features and immunohistochemical phenotype of the adenocarcinoma in the buccal submucosa supported its salivary gland origin. This case of adenocarcinoma of the intraoral buccal tissues independent of the parotid gland in a 12-year-old female is an unusual clinical presentation of a salivary gland neoplasm in childhood, and its ability to metastasize to distant skeletal sites is also remarkable in terms of a primary salivary gland carcinoma regardless of age at diagnosis.
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Adenocarcinoma/patología , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales Menores/patología , Niño , Femenino , Humanos , Técnicas para Inmunoenzimas , Coloración y EtiquetadoRESUMEN
At initial diagnosis, an 11-year-old girl with glioblastoma multiforme (GBM) presented with diffuse osteoblastic metastases. Primary brain tumors rarely metastasize outside of the central nervous system (CNS) without prior neurosurgery. Extracranial spread at diagnosis has been previously documented in just two adults. Extracranial metastasis of a childhood glioma without prior neurosurgery at any time during the course of the disease is exceedingly rare. Spread to bone by gliomas is also infrequent, and when they occur, bony metastases are usually isolated to one or two sites in any given patient. The widespread osseous metastases in our patient have been reported in three prior cases of high-grade gliomas. This child's GBM likely reflects a highly aggressive variant with the potential to spread outside the CNS and with a predilection for bone. Oncologists should be aware that GBM may present in this fashion during childhood.