A cycling, progenitor-like cell population at the base of atypical teratoid rhabdoid tumor subtype differentiation trajectories.

Background: Atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive pediatric central nervous system tumors defined by the inactivation of the SMARCB1 gene. Despite the identification of three distinct molecular subtypes, each defined by unique clinical and molecular characteristics, no subtype-specific therapeutic strategies are currently available. This highlights an urgent need to deepen our understanding of the cellular heterogeneity and developmental origins of ATRTs.

Malignant Rhabdoid Tumors of Cranial Nerves-A Clinically Distinct Group With Characteristic Neuroradiological, Histopathological, and Molecular Features.

Background: Malignant rhabdoid tumors occasionally develop along cranial nerves, but clinical, histopathological, and molecular features have not been examined in larger series.

Procedure: We retrospectively interrogated data from the European Rhabdoid Registry, EU-RHAB, to identify malignant rhabdoid tumors affecting cranial nerves. We retrieved clinical information and reviewed magnetic resonance imaging (MRI) data.

Mutational Spectrum in Intracranial CNS-Neoplasias-A Review and a Report from the CNS-InterREST GPOH Study Center.

DICER1 tumor predisposition syndrome is a genetic condition that increases the risk of developing certain cancer types. While thyroid tumors are the main tumors caused by this condition in adult oncology, children and adolescents with germline mutations may suffer from a broader spectrum of tumors, including Sertoli-Leydig cell tumors, pleuropulmonary blastomas, embryonal rhabdomyosarcomas, and pineoblastomas. Although these diseases-many of which are hallmark tumors of DICER1 syndrome and rarely occur sporadically-have been known for several years, the more recent identification of mutations in embryonal tumors with multilayered rosettes (ETMR) and DICER1-associated intra- and extracranial sarcomas has expanded the spectrum of tumor types potentially linked to DICER1 syndrome.

Clinical and Molecular Risk Factors in Extracranial Malignant Rhabdoid Tumors: Toward an Integrated Model of High-Risk Tumors.

Purpose: Extracranial malignant rhabdoid tumors (eMRT) are a challenging entity. Despite the use of multimodal treatment approaches, therapy failure occurs in 55% to 67% of these. Molecular markers for identification of patients at increased risk for relapse or refractory (R/R) disease are not available.

Human-Level Differentiation of Medulloblastoma from Pilocytic Astrocytoma: A Real-World Multicenter Pilot Study.

Medulloblastoma and pilocytic astrocytoma are the two most common pediatric brain tumors with overlapping imaging features. In this proof-of-concept study, we investigated using a deep learning classifier trained on a multicenter data set to differentiate these tumor types. We developed a patch-based 3D-DenseNet classifier, utilizing automated tumor segmentation.

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

Background: Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers.

Methods: To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets.

Rhabdoid tumors in patients conceived following ART: is there an association?

Study Question: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART?

Summary Answer: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT.

What Is Known Already: Anecdotal evidence suggests an association of ART with RT.

Study Design, Size, Duration: This was a multi-institutional retrospective survey.

Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4).

Outcome for Pediatric Adreno-Cortical Tumors Is Best Predicted by the COG Stage and Five-Item Microscopic Score-Report from the German MET Studies.

Background: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management. Patients: Data from the ACT patients (<18 years) were analyzed.

DNA methylation-based classification of sinonasal tumors.

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles.

Renal Medullary Carcinomas Harbor a Distinct Methylation Phenotype and Display Aberrant Methylation of Genes Related to Early Nephrogenesis.

Renal medullary carcinomas (RMC) are rare aggressive tumors of the kidneys, characterized by a loss of SMARCB1. Characteristically, these tumors arise in patients with sickle cell trait or other hemoglobinopathies. Recent characterization efforts have unraveled oncogenic pathways that drive tumorigenesis.

Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor in infants that is characterized by loss of nuclear expression of SMARCB1 or SMARCA4 proteins. Recent studies show that AT/RTs comprise three molecular subgroups, namely AT/RT-TYR, AT/RT-MYC and AT/RT-SHH. The subgroups show distinct expression patterns of genes involved in ciliogenesis, however, little is known about the functional roles of primary cilia in the biology of AT/RT.

Infants and Newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB Registry: A Unique and Challenging Population.

Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment.

ATRT-SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance.

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT-TYR, ATRT-MYC and ATRT-SHH. ATRT-SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT-SHH might also have biological and clinical importance.

SMARCB1-deficient and SMARCA4-deficient Malignant Brain Tumors With Complex Copy Number Alterations and TP53 Mutations May Represent the First Clinical Manifestation of Li-Fraumeni Syndrome.

Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant central nervous system tumor predominantly affecting infants. Mutations of SMARCB1 or (rarely) SMARCA4 causing loss of nuclear SMARCB1 or SMARCA4 protein expression are characteristic features, but further recurrent genetic alterations are lacking. Most AT/RTs occur de novo, but secondary AT/RTs arising from other central nervous system tumors have been reported.

Single-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors.

Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we establish and characterize different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets.

Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors.

Extracranial malignant rhabdoid tumors (extracranial MRT) are rare, highly aggressive malignancies affecting mainly infants and children younger than 3 years. Common anatomic sites comprise the kidneys (RTK - rhabdoid tumor of kidney) and other soft tissues (eMRT - extracranial, extrarenal malignant rhabdoid tumor). The genetic origin of these diseases is linked to biallelic pathogenic variants in the genes , or rarely , encoding subunits of the SWI/SNF chromatin-remodeling complex.

Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant: A clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC.

Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant, is a histopathological distinct low-grade lesion encountered in older children and young adults that shows epigenetic similarity with ATRT-MYC and has the potential for malignant progression.

Clinical response to nivolumab in an INI1-deficient pediatric chordoma correlates with immunogenic recognition of brachyury.

Poorly differentiated chordoma (PDC) is a recently recognized subtype of chordoma characterized by expression of the embryonic transcription factor, brachyury, and loss of INI1. PDC primarily affects children and is associated with a poor prognosis and limited treatment options. Here we describe the molecular and immune tumour microenvironment profiles of two paediatric PDCs produced using whole-genome, transcriptome and whole-genome bisulfite sequencing (WGBS) and multiplex immunohistochemistry.

Cui Bono? Identifying Patient Groups That May Benefit From Granulocyte Transfusions in Pediatric Hematology and Oncology.

Introduction: Granulocyte transfusions have long been used to bridge the time to neutrophil recovery in patients with neutropenia and severe infection. Recent randomized controlled trials did not prove a beneficial effect of granulocyte transfusions, but were likely underpowered and suffered from very heterogeneous study populations.

Methods: We retrospectively reviewed data of all patients treated with granulocyte transfusions at our pediatric center from 2004 to 2019.

Treatment and outcome of intracranial ependymoma after first relapse in the 2nd AIEOP protocol.

Background: More than 40% of patients with intracranial ependymoma need a salvage treatment within 5 years after diagnosis, and no standard treatment is available as yet. We report the outcome after first relapse of 64 patients treated within the 2nd AIEOP protocol.

Methods: We considered relapse sites and treatments, that is, various combinations of complete/incomplete surgery, if followed by standard or hypofractionated radiotherapy (RT) ± chemotherapy (CT).

Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors.

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells.