PD-1 and LAG-3 expression in EBV-associated pediatric Hodgkin lymphoma has influence on survival.

In pediatric Hodgkin lymphoma (HL), the inability of the cytotoxic microenvironment induced by EBV presence to eliminate tumor cells could reflect the fact that the virus might be able to induce the expression of exhaustion markers to evade an immune response. Therefore, the expression of exhaustion markers in pediatric EBV-associated HL was evaluated. A balance between cytotoxic GrB and Th1 Tbet markers with regulatory Foxp3 was proved in EBV+ cases. In addition, exclusively in EBV-associated cHL, a correlation between PD-1 and LAG-3 expression was observed. Furthermore, those cases also displayed a trend to worse survival when they expressed LAG-3 and inferior event-free survival when both PD-1 and LAG-3 molecules were present. Therefore, even though a cytotoxic and inflammatory environment was supposed to be triggered by EBV presence in pediatric cHL, it seems that the virus may also induce the synergic effect of inhibitory molecules LAG-3 and PD-1 in this series. These observations may reflect the fact that the permissive and exhausted immune microenvironment succeeds to induce lymphomagenesis.

Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Type 1 Insulin-Like Growth Factor Receptor Nuclear Localization in High-Grade Glioma Cells Enhances Motility, Metabolism, and In Vivo Tumorigenesis.

Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less common in children than in adults, though they are similar in their aggressive clinical behavior. In adults, glioblastoma is the most lethal tumor of the central nervous system. Insulin-like growth factor 1 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that, in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors, worst clinical outcome, and increased risk of death. Herein we explore the role of IGF1R intracellular localization by comparing two glioblastoma cell lines that differ only in their IGF1R capacity to translocate to the nucleus. In vitro, IGF1R nuclear localization enhances glioblastoma cell motility and metabolism without affecting their proliferation. In vivo, IGF1R has the capacity to translocate to the nucleus and allows not only a higher proliferation rate and the earlier development of tumors but also renders the cells sensitive to OSI906 therapy. With this work, we provide evidence supporting the implications of the presence of IGF1R in the nucleus of glioma cells and a potential therapeutic opportunity for patients harboring gliomas with IGF1R nuclear localization.

Molecular alterations in the integrated diagnosis of pediatric glial and glioneuronal tumors: A single center experience.

OBJECTIVES: Tumors of the central nervous system (CNS) are the most common pediatric solid tumors, where low grade (LGG) and high grade gliomas (HGG) represent up to 55% of CNS tumors. Current molecular classification of these tumors results in a more accurate diagnosis and risk stratification, which ultimately enables individualized treatment strategies. Identifying known alterations is a suitable approach, particularly in developing countries, where NGS approaches are not easily accessible. We sought to assess molecular alterations in BRAF and histone 3 genes. STUDY DESIGN: FISH, IHC and Sanger sequencing were performed in a series of 102 pediatric glial and glioneuronal tumors. We also correlated these results with clinical and histological findings to evaluate their usefulness as diagnostic and/or prognostic tools. RESULTS: We found that the KIAA1549-BRAF gene fusion was a relevant diagnostic tool for pilocytic astrocytoma, but not related to progression free survival (PFS) and overall survival (OS). BRAFV600E mutation was associated with a decreased OS in LGG, and with decreased PFS and OS among pilocytic astrocytomas. All HGG of the midline were H3K27M mutants, while H3G34R mutant cases were located in brain hemispheres. HGG harboring the H3K27M variant were associated with a decreased PFS and OS. CONCLUSIONS: Assessing druggable molecular markers with prognostic value is particularly important in those cases where complete resection or further radiation therapy is not possible. These potential diagnostic/prognostic markers may be suitable as further screening tests to reduce the requirement on NGS, which is not available in all laboratories. Furthermore, these results broaden data on BRAF and Histone 3 alterations in children from geographic regions, other than USA and Europe.

Accuracy of central neuro-imaging review of DIPG compared with histopathology in the International DIPG Registry.

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. METHODS: Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, <50% pontine involvement, focally exophytic morphology, sharply defined margins, and/or marked diffusion restriction throughout. RESULTS: Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. CONCLUSIONS: The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

Characteristics of patients ≥10 years of age with diffuse intrinsic pontine glioma: a report from the International DIPG/DMG Registry.

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG) generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR). METHODS: Patients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included. The primary outcome was overall survival (OS) categorized as long-term survivors (LTS) (≥24 months) or short-term survivors (STS) (<24 months). RESULTS: Among 1010 patients, 208 (21%) were ≥10 years of age at diagnosis; 152 were eligible with a median age of 12 years (range 10-26.8). Median OS was 13 (2-82) months. The 1-, 3-, and 5-year OS was 59.2%, 5.3%, and 3.3%, respectively. The 18/152 (11.8%) LTS were more likely to be older (P < .01) and present with longer symptom duration (P < .01). Biopsy and/or autopsy were performed in 50 (33%) patients; 77%, 61%, 33%, and 6% of patients tested had H3K27M (H3F3A or HIST1H3B), TP53, ATRX, and ACVR1 mutations/genome alterations, respectively. Two of 18 patients with IDH1 testing were IDH1-mutant and 1 was a LTS. The presence or absence of H3 alterations did not affect survival. CONCLUSION: Patients ≥10 years old with DIPG have a median survival of 13 months. LTS present with longer symptom duration and are likely to be older at presentation compared to STS. ATRX mutation rates were higher in this population than the general DIPG population.

Childhood liver tumors in Argentina: Incidence trend and survival by treatment center. A report from the national pediatric cancer registry, ROHA network 2000-2015.

BACKGROUND: Information on the epidemiology of pediatric liver tumors in Latin America is limited. PURPOSE: To describe the incidence of liver tumors in a pediatric registry in Argentina according to geographic region, national trends over 16 years, and survival related to stage, age, sex, and care center. METHODS: Newly diagnosed liver tumors cases are registered in the Argentine Pediatric Oncology Hospital Registry (ROHA) with an estimated coverage of 91% of national cases. Age-standardized incidence rate per millon (ASR) was calculated based on the National Vital Statistics Reports. Five-year overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare subgroup survival. RESULTS: Two hundred seven cases of hepatoblastoma (HB) and 73 of hepatocellular carcinoma (HCC) were identified. ASR of liver tumors was 1.8/million (95% confidence Interval [CI], 1.6-2.0) per year. ASR was 1.4 (1.2-1.6) for HB and 0.4 (0.3-0.5) for HCC. For HB, the highest incidence was found in the northwest region including the Altiplano. OS was 60.4% (53.4-66.8) for HB and 36.1% (25.2-47.2) for HCC. Five-year survival rate of children with metastatic HB treated at liver transplant hospitals (LTH) was 54.2% (30.3-73.0) compared to 13.3% (2.2-34.6) for those seen at other hospitals (OH) (P = .02), while for HCC this rate was 46.3% (30.7-60.6) at LTH compared to 17.5% (3.1-41.9) at OH (P = .01). CONCLUSIONS: The incidence rate of pediatric liver tumors was stable over the 16-year study period. Patients may benefit if at treatment initiation they are evaluated jointly with LTH specialists to define treatment strategies.

Changes in EBV Association Pattern in Pediatric Classic Hodgkin Lymphoma From a Single Institution in Argentina.

In classic Hodgkin lymphoma (cHL), Epstein Barr virus (EBV) association varies worldwide. Aims: Our aim was to analyze EBV association with pediatric cHL for the last 28 years. Methods: EBV presence was evaluated by EBERs in situ hybridization and LMP1 immunohistochemistry. Results: Until 2008, we found in pediatric cHL a similar percentage of EBV presence to those observed in adult cHL from developed populations. Nevertheless, in the last 8 years, an unexpected difference in cHL EBV association was proven, along with a slight bias of EBV association with the nodular sclerosis (NS) subtype. Concerning histological subtype distribution, even though MC still prevailed in the whole series, those cases diagnosed as NS showed a sustained rise from 1989 until today. Conclusion: Variations of EBV association of cHL related to geography, age, ethnicity, and histological type have been largely described when compared with different world regions, but interestingly, this single-center revised series brought to light the dynamic process behind the evolution of this relationship over time.

Overexpression of survivin in pediatric Hodgkin lymphoma tumor cells: Characterization of protein expression and splice-variants transcription profile.

Survivin is abundantly expressed during fetal development but absent in most differentiated adult tissues; an exception being components of the immune system, such as B and T lymphocytes. Beyond acting as a master regulator of the cell cycle, survivin acts as an inhibitor of apoptosis and is overexpressed in almost all carcinoma types; however, its expression in lymphomas is lesser-explored. Survivin's role in carcinogenesis was subjected to its sub-cellular localization and splice transcripts expression, namely wild-type survivin, survivin-∆Ex3 and survivin-2B. To assess survivin's expression and sub-cellular localization in Epstein Barr virus positive and negative biopsies from treatment naïve pediatric patients with Hodgkin lymphoma (HL), samples were stained for survivin protein by immunofluorescence. The proportion of survivin+ cells was calculated, survivin sub-cellular localization assessed and its fluorescence intensity quantified. Transcription profile of survivin mRNA variants was studied by RT-qPCR. Survivin was overexpressed in the nucleus of tumor cells, and also in a greater proportion of tumor cells, in comparison with the non-tumoral infiltrating cells. Although a higher expression of survivin was observed in advanced clinical stages, no correlation was found between the expression level of survivin and a proliferation marker, or event-free survival. Instead, survivin was related to apoptosis inhibition in tumor cells. Additionally, survivin's transcriptional variants displayed similar expression levels. Present results suggest that although survivin is overexpressed in Hodgkin's tumor cells, it may not play a central role in the progression of classic HL, or act as a suitable progression biomarker, as suggested for most carcinomas.

Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome.

Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.

Guías de Vacunación en Huéspedes Especiales / Guidelines for the Vaccination of Special Hosts

Los niños con alteración de su sistema inmunológico son más vulnerables ante las infecciones que el resto de la población. Una de las formas de protegerlos de infecciones graves es a través de la vacunación, deben ser correctamente evaluados al planear los esquemas a fin de establecer los riesgos vs. los beneficios que implican inmunizarlos. El rol del médico pediatra y del médico especialista trabajando en equipo es fundamental, para que puedan beneficiarse con vacunas y esquemas especiales que requieran por su patología de base. Una protección óptima de estos pacientes incluye además la adecuada inmunización de los convivientes y del equipo médico tratante. La inmunización de los huéspedes especiales es una situación clínica compleja que requiere un análisis exhaustivo personalizado en cada caso, debido a las diferentes características de estos pacientes con enfermedades crónicas y/o inmunosuprimidos, los diversos grupos y muchos tipos de terapias inmunosupresoras que se están desarrollando y utilizando en un número cada vez mayor. Es fundamental el trabajo en equipo del médico especialista y el pediatra de cabecera para lograr el mejor control de las enfermedades inmunoprevenibles en estos pacientes de tan alta complejidad

Children with weakened immune systems are more vulnerable to infections than the rest of the population. One of the ways to protect them against serious infections is vaccination; they must be correctly evaluated when planning schedules in order to define the risks versus the benefits involved by their immunization. The role of pediatricians and medical specialists working as a team is fundamental, so that patients can benefit from vaccines and special schedules that they may require due to their underlying pathologies. Optimal protection of these patients also includes the adequate immunization of household members and their treating medical teams. The immunization of special hosts is a complex clinical situation that requires an exhaustive personalized case-by-case analysis, due to the different characteristics of these patients who have chronic diseases and / or are immunosuppressed, the various groups and many types of immunosuppressive therapies that are being developed and increasingly used. The teamwork of specialists and family pediatricians is essential to achieve the best control of immuno-preventable diseases in these highly complex patients

High-risk human papilloma virus infection, tumor pathophenotypes, and BRCA1/2 and TP53 status in juvenile breast cancer.

Juvenile breast cancer is rare and poorly known. We studied a series of five breast cancer patients diagnosed within 25 years of age that included two adolescents, 12- and 15-years-old, and 3 young women, 21-, 21-, and 25-years-old, respectively. All cases were scanned for germline mutations along the entire BRCA1/2 coding sequences and TP53 exons 4-10, using protein truncation test, denaturing high performance liquid chromatography and direct sequencing. Paraffin-embedded primary tumors (available for 4/5 cases), and a distant metastasis (from the 15-years-old) were characterized for histological and molecular tumor subtype, human papilloma virus (HPV) types 16/18 E6 sequences and tumor-associated mutations in TP53 exons 5-8. A BRCA2 germline mutation (p.Ile2490Thr), previously reported in breast cancer and, as compound heterozygote, in Fanconi anemia, was identified in the 21-year-old patient diagnosed after pregnancy, negative for cancer family history. The tumor was not available for study. Only germline polymorphisms in BRCA1/2 and/or TP53 were detected in the other cases. The tumors of the 15- and 12-years-old were, respectively, classified as glycogen-rich carcinoma with triple negative subtype and as secretory carcinoma with basal subtype. The tumors of the 25-year-old and of the other 21-year-old were, respectively, diagnosed as infiltrating ductal carcinoma with luminal A subtype and as lobular carcinoma with luminal B subtype. No somatic TP53 mutations were found, but tumor-associated HPV 16 E6 sequences were retrieved from the 12- and 25-year-old, while both HPV 16 and HPV 18 E6 sequences were found in the tumor of the 15-year-old and in its associated metastasis. Blood from the 15- and 25-year-old, diagnosed with high-stage disease, resulted positive for HPV 16 E6. All the HPV-positive cases were homozygous for arginine at TP53 codon 72, a genotype associated with HPV-related cancer risk, and the tumors showed p16(INK4A) immunostaining, a marker of HPV-associated cancers. Notably menarche at 11 years was reported for the two adolescents, while the 25-year-old was diagnosed after pregnancy and breast-feeding. Our data suggest that high-risk HPV infection is involved in a subset of histopathologically heterogeneous juvenile breast carcinomas associated with menarche or pregnancy and breast-feeding. Furthermore we implicate BRCA2 in a juvenile breast carcinoma diagnosed at 21 years of age, 4 years after an early full-term pregnancy, in absence of cancer family history.

Germline TP53 mutations and single nucleotide polymorphisms in children / Mutaciones y polimorfismos de un único nucleótido del gen TP53 en línea germinal en niños

Mutations in the gene TP53, which codifies the tumor suppressor protein p53, are found in about 50% of tumors. These mutations can occur not only at somatic level, but also in germline. Pediatric cancer patients, mostly with additional family history of malignancy, should be considered as potential TP53 germline mutation carriers. Germline TP53 mutations and polymorphisms have been widely studied to determine their relation with different tumors' pathogenesis. Our aim was to analyze the occurrence frequency of germline TP53 mutations and polymorphisms and to relate these to tumor development in a pediatric series. Peripheral blood mononuclear cell samples from 26 children with solid tumors [PST] and 21 pediatric healthy donors [HD] were analyzed for germline mutations and polymorphisms in TP53 gene spanning from exon 5 to 8 including introns 5 and 7. These PCR amplified fragments were sequenced to determine variations. A heterozygous mutation at codon 245 was found in 1/26 PST and 0/21 HD. Comparative polymorphisms distribution, at position 14181 and 14201(intron 7), between HD and PST revealed a trend of association (p= 0.07) with cancer risk. HD group disclosed a similar polymorphism distribution as published data for Caucasian and Central/South American populations. This is the first study about TP53 variant frequency and distribution in healthy individuals and cancer patients in Argentina.

El gen que codifica para la proteína supresora de tumor p53 (TP53) se encuentra mutado en aproximadamente el 50% de los tumores. Estas mutaciones pueden presentarse como somáticas o en línea germinal. Los niños con tumores, sobre todo aquellos con historia familiar de enfermedad oncológica, deben considerarse potenciales portadores de mutaciones en línea germinal. Las mutaciones de TP53 y los polimorfismos son estudiados para determinar su relación con la patogénesis de diferentes tumores. El objetivo del trabajo fue analizar la frecuencia de mutaciones y polimorfismos en línea germinal de TP53 y relacionarlos con el desarrollo de tumor en un grupo de pacientes pediátricos. Se analizaron muestras de sangre periférica de 26 pacientes con tumores sólidos [PST] y 21 niños donantes sanos [HD] para determinar la presencia de mutaciones y polimorfismos de TP53 en línea germinal. Se analizó por PCR seguida de secuenciación, la región que comprende a los exones 5 a 8 (incluyendo intrones 5 y 7). En 1/26 PST se encontró una mutación heterocigótica en el codón 245. La distribución de los polimorfismos, en la posición 14181 y 14201 (intrón 7), entre HD y PST mostró una tendencia de asociación (p = 0.07) con el riesgo para desarrollar cáncer. La frecuencia de distribución de dichos polimorfismos en HD fue similar a la publicada para poblaciones caucásicas y de América Central/del Sur. Este estudio aporta información original sobre la frecuencia de distribución de las variantes TP53 en individuos sanos y con tumores en la Argentina.

Diffuse hyperplastic perilobar nephroblastomatosis.

Nephroblastomatosis is a rare preneoplastic lesion defined as the presence of diffuse or multifocal nephrogenic rests. They are divided into 4 categories: perilobar, intralobar, combined, and universal. The aim of this report is to describe a case of diffuse hyperplastic perilobar nephroblastomatosis. A 1-year-old boy presented with an abdominal mass on the left side. Computed tomography scan showed a homogeneous, isointense enlarged left kidney. A fine needle aspiration cytology was reported as Wilms tumor. After chemotherapy, the left kidney was excised. Nephrectomy specimen presented a thick cortical rim of hyperplastic nephrogenic tissue, well delineated from preserved renal parenchyma without pseudocapsule. Nephroblastomatosis is a rare condition affecting renal parenchyma. Diagnosis is based on imaging studies, such as ultrasound, computed tomography scan, and magnetic resonance imaging. Fine needle aspiration cytology is of limited value. Therapeutic management is controversial. Chemotherapy is used preoperatively, and surgical excision may be an alternative for refractory cases.

No Influence of bcl-2, p53, and p21waf1 protein expression on the outcome of pediatric Hodgkin lymphomas.

In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them are Hodgkin lymphoma. Previous studies of lymphoma series have reported the expression of apoptotic and cell cycle proteins. Our aim was to study these markers in our pediatric patients and correlate them with their outcome. Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21, and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases. We failed to find any statistically significant correlation between oncogene expression and patient's survival. It seems that p53 plays an important role in lymphomagenesis in our studied population, because it is overexpressed in 81% of Hodgkin lymphoma cases and in more than 50% of cases, it might be able to activate its cellular effectors. Bcl-2 staining observed in 44% of our cases could represent a failure in bcl-2 down-regulation that leads to a rescue event in defective germinal center B-cells, that allows them to develop into Reed-Sternberg and Hodgkin cells.

Colorectal carcinoma in children, adolescents, and young adults.

The authors conducted a retrospective evaluation of patients younger than 30 years with colorectal carcinoma in Argentina. Patients were divided into group 1 (patients treated at pediatric institutions from 0 to 20 years of age, n = 14) and group 2 (patients from 21 to 30, n = 7, treated at adult centers). Group 1 had significantly more advanced disease and a poorer prognosis. Six patients (2/14 in group 1 and 4/7 in group 2) survive disease-free. Thirteen patients died of progressive disease, 1 died of a non-tumor-related cause, and 1 is still on treatment. Patients younger than 20 years have a poorer prognosis, probably because of advanced disease on presentation.