RESUMEN
ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.
Asunto(s)
Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/análisis , Trastornos Histiocíticos Malignos/tratamiento farmacológico , Trastornos Histiocíticos Malignos/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Adulto , Quinasa de Linfoma Anaplásico/genética , Niño , Preescolar , Femenino , Trastornos Histiocíticos Malignos/complicaciones , Trastornos Histiocíticos Malignos/genética , Humanos , Lactante , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/patología , Proteínas de Fusión Oncogénica/análisis , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial. CASE PRESENTATION: A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far. CONCLUSION: Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases.
Asunto(s)
Lipoblastoma , Niño , Preescolar , Diagnóstico Diferencial , Humanos , Lactante , Lipoblastoma/diagnóstico , Lipoblastoma/cirugía , Recurrencia Local de Neoplasia , Pronóstico , Factores de TranscripciónRESUMEN
Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism. Here, we report on the postmortem identification of a de novo heterozygous mutation in the COL2A1 gene (c.1529G>A, p.Gly510Asp) in a fetus who presented with generalized hydrops fetalis and severe micromelia during prenatal sonographic examinations. Initially, a reciprocal translocation t(4;17)(q31;p13) was detected in this fetus by chorionic villus sampling. Subsequent chromosomal analysis of maternal and paternal blood showed that the patient's mother was carrier of the same reciprocal translocation. SNP array analysis of the fetus did not provide evidence for chromosomal imbalances or CNVs that could be associated with the fetal phenotype. The coexistence of a cytogenetic (reciprocal translocation) and a molecular genetic (COL2A1 mutation) abnormality in the fetus carries important implications for genetic counseling.
Asunto(s)
Anomalías Múltiples/genética , Acondroplasia/genética , Colágeno Tipo II/genética , Anomalías Musculoesqueléticas/genética , Aborto Inducido , Femenino , Asesoramiento Genético , Humanos , Hidropesía Fetal , Mutación , Embarazo , Diagnóstico Prenatal , Translocación Genética/genéticaRESUMEN
While neonatal skin physiology has been thoroughly examined using non-invasive techniques in recent years, only few systematic studies and review articles addressing the histopathology of neonatal skin have been published thus far. In most cases, histopathological findings of dermatoses in neonatal skin do not significantly differ from those seen in adult skin. Nevertheless, a comprehensive knowledge of embryonic and fetal skin development as well as the microanatomical structure of neonatal skin can contribute to a better understanding of various dermatoses of infancy. In the first part of this review article, we present the histopathological features of such skin diseases, which, though generally rare, almost exclusively appear during the first weeks of life due to distinctive structural and functional features of neonatal skin. The second part is dedicated to classic dermatoses of infancy and their histopathological features.
Asunto(s)
Dermatología/tendencias , Dermoscopía/tendencias , Patología/tendencias , Pediatría/tendencias , Enfermedades de la Piel/diagnóstico , Niño , Femenino , Alemania , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Rhabdomyosarcoma is the most frequent malignant intraorbital tumour in paediatric patients. Differentiation of tumour recurrence or metastases from post-therapeutic signal alteration can be challenging, using standard MR imaging techniques. Diffusion-weighted MRI (DWI) is increasingly considered a helpful supplementary imaging tool for differentiation of orbital masses. CASE PRESENTATION: We report on a 15-year-old female adolescent of Caucasian ethnicity who developed isolated bilateral thickening of extraocular eye muscles about two years after successful multimodal treatment of orbital alveolar rhabdomyosarcoma. Intramuscular restricted diffusion was the first diagnostic indicator suggestive of metastatic disease to the eye muscles. DWI subsequently showed signal changes consistent with tumour progression, complete remission under chemoradiotherapy and tumour recurrence. CONCLUSIONS: Restricted diffusivity is a strong early indicator of malignancy in orbital tumours. DWI can be the key to correct diagnosis in unusual tumour manifestations and can provide additional diagnostic information beyond standard MRI and PET/CT. Diffusion-weighted MRI is useful for monitoring therapy response and for detecting tumour recurrence.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias de los Músculos/diagnóstico , Neoplasias de los Músculos/secundario , Músculos Oculomotores , Rabdomiosarcoma/diagnóstico , Rabdomiosarcoma/secundario , Adolescente , Femenino , Humanos , Neoplasias Orbitales/patologíaAsunto(s)
Hemangioendotelioma , Inmunosupresores , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Sirolimus , Hemangioendotelioma/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Síndrome de Kasabach-Merritt/tratamiento farmacológico , Sarcoma de Kaposi/tratamiento farmacológico , Sirolimus/uso terapéuticoRESUMEN
Lipoblastoma is a rare benign mesenchymal neoplasm that typically occurs in infancy but may also occur in older age groups and various locations. Thus, there are often numerous clinical differential diagnoses. Moreover, lipoblastomas can show a broad histologic spectrum, which can hamper the correct diagnosis, particularly in small biopsies. At the genomic level, lipoblastomas are characterized by chromosomal fusions involving the PLAG1 gene. We investigated 11 lipoblastoma samples from 10 pediatric patients (age range five months to 12 years), including one patient with local recurrence, in view of their histopathological features, and performed targeted RNA sequencing. We found a broad histological spectrum with some tumors with prominent myxoid changes, but also tumors composed mainly of mature adipocytic cells, and classified the cases according to the literature as classic (mixed), maturing, or myxoid subtype. By targeted RNA sequencing analysis, we identified characteristic PLAG1 rearrangements in 70% of the investigated cases. Moreover, these analyses revealed three novel gene fusions, two affecting the PLAG1 gene and one involving HMGA2. Besides, we performed PLAG1 immunohistochemistry and identified positive cells, typically immature adipocytic cells and spindle cells, at various numbers in all cases. However, in the maturing areas, only very sparsely positive cells were found, limiting the value of the PLAG1 immunohistochemistry as an adjunct in the diagnosis of lipoblastoma, particularly for the maturing subtype and small biopsies. The presented case series confirms the broad morphological spectrum of lipoblastoma described in the literature and underlines the value of modern molecular diagnostic approaches as a supportive diagnostic tool in challenging cases and for gaining further insights into the molecular basis of this rare mesenchymal tumor.
Asunto(s)
Proteínas de Unión al ADN/genética , Proteína HMGA2/genética , Lipoblastoma/genética , Lipoblastoma/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Fusión de Oncogenes/genéticaRESUMEN
In vitro models represent a critical tool in cancer research to study tumor biology and to evaluate new treatment options. Unfortunately, there are no effective preclinical models available that represent Wilms tumor (WT) - the most common pediatric renal tumor. Especially the high-risk blastemal WT subtype is not represented by the few primary cell lines established until now. Here, we describe a new 3D approach for in vitro cultivation of blastemal WT cells, where primary cultures grown in suspension as spheroids could be propagated long-term. Besides blastemal cultures, we could generate spheroids representing epithelial and stromal WT. Spheroid cultures were analyzed by immunohistochemistry in comparison to corresponding tumor sections and were further characterized by RNA sequencing. Histological appearance of spheroids resembled the original tumor and they expressed marker genes characteristic of early renal development and blastemal WT elements. The cultures were amenable to genetic manipulation and they formed xenograft tumors, which resemble the primary human tumor. This collection of WT spheroids that carry different genetic drivers forms a long-sought tool for drug testing and in vitro modeling.
Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/patología , Esferoides Celulares/patología , Tumor de Wilms/patología , Animales , Biomarcadores de Tumor/metabolismo , Técnicas de Cultivo de Célula , Preescolar , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Técnicas In Vitro , Lactante , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Ratones Endogámicos NOD , Ratones SCID , Cultivo Primario de Células , Factores de Riesgo , Esferoides Celulares/metabolismo , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND Neonatal acute leukemia is a rare condition. Little is known about its incidence and outcomes, and treatment options have not been standardized. CASE REPORT A 3-day old, apparently healthy male newborn was referred to the pediatric intensive care unit with multiple violaceous macules and a few papules on his face and upper trunk. After initial spontaneous regression, the lesions reappeared. Skin biopsy and bone marrow aspirate revealed a diagnosis of acute lymphoblastic leukemia (ALL). ALL induction therapy was initiated on day 24, resulting in morphological remission at the end of induction therapy. ALL chemotherapy was guided by sequential PCR-based monitoring of minimal residual disease (MRD). The patient received a transplant from an unrelated HLA high-resolution matched (10/10 loci) permissive donor. He was followed-up after transplant conducted by sequential PCR-based measurements of MRD in bone marrow. CONCLUSIONS Neonatal leukemia often presents as congenital skin lesions known as blueberry muffin rash. ALL induction therapy was started at the end of the neonatal period. Treatment was well-tolerated and effective. Early donor search and PCR-MRD guided treatment surveillance can help to achieve and maintain molecular remission.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción , Lactante , Recién Nacido , Masculino , Neoplasia Residual , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Embarazo , Inducción de Remisión , Trasplante Homólogo , Donante no EmparentadoRESUMEN
Bone marrow biopsies (BMB) are the conventional staging method for assessing marrow involvement by lymphoma. Morphological criteria provide basic data determining their dignity, but concerning microfocal infiltrates, these criteria are rather inaccurate. Here, by examination of immunoglobulin H (IgH) receptor rearrangement and comparison of medullar and nodular lymphoma sites, diagnostic reliability was improved. Employing non-nested IgH rearrangement analysis with FR3A and JHa consensus primers, B-cell clonality was assessed on glutardialdehyde fixed, decalcified BMB with and without lymphoma infiltration and on the corresponding lymph node specimens. Malignancy was confirmed when polymerase chain reaction (PCR) generated no more than two peaks and was observed in 60% of the medullar B-cell lymphoma. Comparison of lymph node tissues and BMB revealed an identical pattern in 50% of the probes. In 25% of the cases a single clonal peak derived from the lymph node tissues was also observed in the BMB but was surrounded by additional peaks. Here, direct comparison of the data permitted determination of lymphoma in the BMB. Therefore, IgH FR3 PCR analysis is a suitable tool to examine small lymphoid infiltrates in BMB, and direct comparison with corresponding nodal lymphoma can further facilitate estimation of their dignity.
Asunto(s)
Médula Ósea/inmunología , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Ganglios Linfáticos/inmunología , Linfoma de Células B , Linfocitos B/citología , Linfocitos B/inmunología , Biopsia , Médula Ósea/patología , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Amplified MYCN oncogene defines a subgroup of neuroblastomas with poor outcome. However, a substantial number of MYCN single-copy neuroblastomas exhibits an aggressive phenotype similar to that of MYCN-amplified neuroblastomas even in the absence of high MYCN mRNA and/or protein levels. EXPERIMENTAL DESIGN: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN-amplified and single-copy high-risk neuroblastomas, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk neuroblastoma tumors (n = 49) using cDNA microarrays. Candidate gene expression was validated in a separate cohort of 117 patients using quantitative PCR, and protein expression was analyzed in neuroblastoma tumors by immunoblotting and immunohistochemistry. RESULTS: We identified a genetic signature characterized by a subset of MYCN/MYC and E2F targets, including Skp2, encoding the F-box protein of the SCF(Skp2) E3-ligase, to be highly expressed in high-risk neuroblastomas independent of amplified MYCN. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n = 117) using quantitative PCR. High Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54; 95% confidence interval, 1.56-8.00; P = 0.002). Skp2 protein expression was inversely correlated with expression of p27, the primary target of the SCF(Skp2) E3-ligase, in neuroblastoma tumors. CONCLUSION: Skp2 may have a key role in the progression of neuroblastomas and should make an attractive target for therapeutic approaches.
Asunto(s)
Genes myc , Neuroblastoma/genética , Proteínas Quinasas Asociadas a Fase-S/fisiología , Factor de Transcripción E2F1/genética , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/análisis , Riesgo , Proteínas Quinasas Asociadas a Fase-S/análisis , Proteínas Quinasas Asociadas a Fase-S/genéticaRESUMEN
The recent World Health Organization (WHO) classification of hematopoietic and lymphoid tissue tumors represents the first worldwide consensus classification of these malignancies. However, the applicability of this classification to a representative number of hepatic lymphomas in liver biopsy specimens has not yet been investigated. The frequency and infiltration pattern of a series of 205 liver biopsies with lymphoma manifestations was analyzed with the aid of immunohistochemical and molecular pathological analyses. Diffuse large B-cell lymphoma (DLBCL) was by far the most frequent entity, comprising 45% of the cases analyzed. Using a previously published immunohistochemical algorithm, 35% of 80 DLBCL were assigned to a germinal center B-cell-like (GCB) and 65% to a non-GCB group. Most B-cell lymphoma entities involving the liver revealed a characteristic infiltration pattern. Diagnostically challenging entities were T-cell-rich B-cell lymphomas, anaplastic large cell lymphomas and peripheral T-cell lymphomas, which frequently required additional molecular clonality assessment. Overall, the percentage of T-cell lymphomas in the liver (12%) was higher as compared to other extranodal sites except for the skin and the small intestine. This study provides relevant data on the distribution of hepatic lymphomas and demonstrates the applicability of the WHO classification proposing a diagnostic algorithm for liver biopsies.
Asunto(s)
Neoplasias Hepáticas/patología , Linfoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Estudios de Factibilidad , Femenino , Técnica del Anticuerpo Fluorescente Directa , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/química , Neoplasias Hepáticas/clasificación , Linfoma/química , Linfoma/clasificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Organización Mundial de la SaludRESUMEN
PURPOSE: Identification of molecular characteristics of spontaneously regressing stage IVS and progressing stage IV neuroblastoma to improve discrimination of patients with metastatic disease following favorable and unfavorable clinical courses. EXPERIMENTAL DESIGN: Serial analysis of gene expression profiles were generated from five stage IVS and three stage IV neuroblastoma. Differential expression of candidate genes was evaluated by real-time quantitative reverse transcription-PCR in 76 pretreatment tumor samples (stage IVS n=27 and stage IV n=49). Gene expression-based outcome prediction was determined by Prediction Analysis for Microarrays using 38 tumors as a training set and 38 tumors as a test set. RESULTS: Comparison of serial analysis of gene expression profiles from stage IV and IVS neuroblastoma revealed approximately 500 differentially expressed transcripts. Genes related to neuronal differentiation were observed more frequently in stage IVS tumors as determined by associating transcripts to Gene Ontology annotations. Forty-one candidate genes were evaluated by quantitative reverse transcription-PCR and 18 were confirmed to be differentially expressed (PAsunto(s)
Perfilación de la Expresión Génica
, Neuroblastoma/genética
, Preescolar
, Progresión de la Enfermedad
, Estudios de Seguimiento
, Humanos
, Lactante
, Estimación de Kaplan-Meier
, Estadificación de Neoplasias
, Neuroblastoma/diagnóstico
, Neuroblastoma/terapia
, Análisis de Secuencia por Matrices de Oligonucleótidos/métodos
, Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
, Tasa de Supervivencia
, Transcripción Genética/genética
RESUMEN
A 31-year-old woman with a history of infection with human papilloma virus was found to have an elevated human chorionic gonadotropin level (beta-HCG) of more than 9000 IU/L in January 2006. The patient reported an irregular menstrual cycle. Extensive clinical work-up including gynecologic examinations with laparoscopy, hysteroscopy, and curettage were performed but no pathologic explanation of this elevated beta-HCG could be found. In the initial computed tomography (CT) of the abdomen and the thorax, a tumor could not be detected. Based on a clinical decision, chemotherapy with methotrexate in a dose of 1 mg/kg body weight was started. Four months after beginning of the chemotherapy the beta-HCG level dropped to 3048 IU/L. At this time a first F-18 FDG PET was performed and the findings were negative. After completion of 7 cycles of chemotherapy the beta-HCG level rose again. In a second F-18 FDG PET in August 2006 focal, intense and pathologic F-18 FDG accumulation with a SUV max. of 5.4 was seen in the mediastinum in the region of the thymus. At this time the beta-HCG level was 7000 IU/L. In a subsequent CT of the chest a retrosternal mass of 4 x 1.7 cm was detected with contrast enhancement. Resection of the tumor and thymus gland demonstrated a choriocarcinoma in part adjacent to the thymus and in part in the thymus. Postoperative beta-HCG levels dropped to 105 IU/L.
Asunto(s)
Coriocarcinoma no Gestacional/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neoplasias del Mediastino/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Neoplasias del Timo/diagnóstico por imagen , Adulto , Femenino , Humanos , RadiofármacosRESUMEN
TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease.
RESUMEN
There is a well-known association between patient outcome and tumor ploidy in neuroblastoma. To date, however, most clinical trials have not used this parameter for therapy stratification. Using conventional cytogenetics and fluorescence in situ hybridization (FISH), we investigated 36 tumors in terms of ploidy and chromosome 1 copy number (polysomy). In addition, interphase FISH for polysomy was performed on a second cohort of 440 neuroblastomas, together with the status of 1p, MYCN, and 11q. The main goals were as follows: (1) to assess the reliability of FISH to determine ploidy; (2) to illustrate associations between somy 1 and clinical/biologic factors; and (3) to investigate the role of somy 1 for predicting outcome. The comparison between karyotyping and FISH in the smaller cohort revealed 86% consistency between ploidy and polysomy (31/36). According to FISH, trisomic tumors in the second cohort showed structural chromosomal aberrations less frequently compared to di-/tetrasomic tumors (15 vs. 60%, P < 0.001). The portion of trisomic neuroblastomas was higher in stages 1, 2, and 4S versus stages 3 and 4 (55 vs. 24%, P < 0.001) and in children 18 months or younger versus those older than 18 months (55 vs. 19%, P < 0.001). Prognosis was significantly better for trisomic tumors versus di-/tetrasomic in the whole cohort [event-free (EFS) and overall survival (OS), P < 0.001]. In the subgroup without abnormalities of other molecular markers, EFS of trisomic neuroblastomas was better (P = 0.048), but was most likely due to an unequal stage distribution. In further subgroups, in terms of age and stage, significance between the somy groups was not reached, neither for EFS nor OS. The multivariate analyses including age, stage, chromosomal markers, and somy 1 confirmed the lack of independent prognostic power for the copy number of chromosome 1. This study demonstrates the following: (1) FISH is a practical alternative to other more labor-intensive techniques for determining ploidy; (2) trisomic tumors correlate with younger age at diagnosis, localized stage, and the lack of structural alterations; and (3) polysomy is not an independent prognostic marker. The sharp decline of trisomic tumors after the age of 18 months supports the idea of different genetic tumor entities.