Compared to medulloblastoma (MB), atypical teratoid rhabdoid tumor (AT/RT) is characterized by a lower incidence, younger age at onset, and a poorer prognosis. Preoperative clinical and neuroimaging differentiation between these tumors remains challenging. This study aimed to evaluate the diagnostic utility of conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in distinguishing AT/RT from MB in children. We retrospectively included 32 patients with AT/RT and 82 patients with MB confirmed by surgery and pathology in our hospital between 2010 and 2023. We analyzed the clinical data, preoperative MRI characteristics, and apparent diffusion coefficient (ADC) values of these patients to evaluate their diagnostic value. The overall survival time of AT/RT patients was significantly shorter than that of MB patients (P < 0.001), with a higher mortality rate (81.4% vs. 35.5%,P = 0.007). Significant differences were found between AT/RT and MB in T2WI signal, off-midline growth, supratentorial ventriculomegaly, cystic degeneration, hemorrhage, peritumoral edema, tumor boundary clarity, and metastasis/dissemination (P < 0.05). No significant differences were observed in gender, age, lesion size, T1WI signal, or enhancement pattern (P > 0.05). The mean ADC value differed significantly between the two groups (P < 0.001), with an optimal cut-off value of 0.622 × 10⁻3 mm2/s. MRI features, including more cystic degeneration, hemorrhage, supratentorial ventriculomegaly, and peritumoral edema, combined with a lower ADC value may provide reliable information to differentiate AT/RT from MB in children.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors during infancy and associated with a dismal prognosis. The majority of patients suffer from tumor progression or recurrence, but underlying mechanisms remain unknown. To better understand such mechanisms, we performed single-nucleus RNA sequencing (snRNAseq) of eight paired primary tumors and recurrences. Tumor cells and cells of the tumor microenvironment (TME) were analyzed separately. Potentially therapy-resistant tumor cells were identified through the comparison of global gene expression profiles between primary and recurrent tumor cell populations using CIBERSORT. Histopathology, in vitro experiments, bulk RNA sequencing, and survival analysis were performed for validation. Paired primary and recurrent AT/RT showed significant differences in their gene expression profiles. Potentially therapy-resistant AT/RT-MYC tumor cells revealed changes in the extracellular matrix (ECM) as well as altered developmental processes and immune signaling pathways. Respective gene signatures were correlated with inferior survival in AT/RT-MYC patients. Tumor cells of relapsed AT/RT-MYC underwent partial epithelial-mesenchymal transition (pEMT), a feature that was confirmed by immunohistochemistry (IHC) and by analyzing AT/RT cells after standard therapy in vitro. Together, we identified potential mechanisms of tumor relapse and therapy resistance in AT/RT, which could be employed to improve therapy in future.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly malignant pediatric brain tumor with dismal prognosis. We aimed to characterize dynamic survival patterns using conditional survival (CS) and annual hazard rate (AHR) analyses, identify key prognostic factors through machine learning (ML)-based feature selection, and develop an interpretable CS-nomogram for individualized prognostication. Data of AT/RT patients diagnosed between 2000 and 2022 were obtained from the SEER database. CS and AHR analyses were performed to assess temporal survival dynamics. Four complementary algorithms-LASSO regression, Boruta algorithm, stepwise regression, and best subset regression-were used for feature selection. The final CS-nomogram was validated using ROC curves, calibration plots, and decision curve analysis (DCA). Model interpretability was evaluated with Shapley additive explanations (SHAP), and a web-based calculator was created for clinical application. A total of 382 patients were analyzed. The 5-year survival probability at diagnosis was 34.11%,but increased to 95.14% among those surviving beyond 4years, while AHR declined from 44.76% in the first year to < 5% after 5 years. Tumor extension, radiotherapy, and chemotherapy were consistently identified as key predictors. The CS-nomogram showed excellent discrimination (1-, 3-, and 5-year AUCs: 0.860, 0.796, and 0.762 in training; 0.857, 0.764, and 0.744 in validation), and SHAP analysis confirmed radiotherapy, chemotherapy, and tumor extension as major contributors. CS analysis revealed a marked improvement in long-term survival among AT/RT survivors. The ML-based CS-nomogram provides a robust, interpretable, and clinically applicable tool for dynamic, individualized prognostication and personalized follow-up planning in this rare malignancy.

Revisiting Preoperative Diagnostic Clues for Adult Primary Sellar Atypical Teratoid/Rhabdoid Tumor: A Rare Entity Mimicking Pituitary Adenoma.

A rare case of atypical teratoid rhabdoid tumor with extracranial extension in a child

Objectives: Germline variants in cancer predisposition genes have been increasingly recognized in pediatric cancers. However, their spectrum in East Asian children with central nervous system (CNS) tumors remains insufficiently defined. This study investigated the prevalence and clinical significance of pathogenic or likely pathogenic (P/LP) germline mutations in Korean children, adolescents, and young adults (AYAs) with CNS tumors. Methods: We performed targeted next-generation sequencing of 358 cancer-associated genes using peripheral blood DNA from 108 patients. Germline variants were classified according to ACMG/AMP guidelines and curated using ClinVar and relevant literature. Results: Among 108 patients, 17 (15.7%) carried P/LP germline variants. The median age at diagnosis was 7.7 years (range, 1.0–24.0), and 64.7% were male. P/LP variants were most frequent in other CNS tumors (4/11, 36.4%), including 2 glioneuronal tumors, 1 schwannoma, 1 atypical teratoid rhabdoid tumor (ATRT), and gliomas (9/32, 28.1%), followed by medulloblastomas (3/31, 9.7%). In gliomas, P/LP variants in MLH1, NF1, MUTYH, PALB2, PMS2, FANCM, and TP53 were observed, while medulloblastomas carried alterations in SUFU, BRIP1, and FANCI. SMARCB1 variant was found in ATRT. Among 25 patients with intracranial germ cell tumors, only a single case carried a P/LP germline variant, identified in FANCI. Conclusion: Germline P/LP mutations were identified in 15.7% of Korean children and AYAs with CNS tumors, most commonly in gliomas and other CNS tumors. Our findings highlight the molecular heterogeneity of germline predisposition in CNS tumors and emphasize the importance of germline testing for risk assessment and surveillance.

Claudin-6 has emerged as a promising immunotherapeutic target, yet protein-level data in atypical teratoid/rhabdoid tumors (AT/RTs) have been inconsistent. We analyzed 36 well-characterized AT/RT samples and found membranous claudin-6 protein expression in 58% of cases, with striking enrichment in the molecular subgroup AT/RT-TYR (100%) and significantly higher staining scores compared with AT/RT-SHH and AT/RT-MYC. Correspondingly, AT/RT-TYR showed lower CLDN6 promoter methylation. Pilot spatial transcriptomic experiments in AT/RT-TYR confirmed heterogeneous CLDN6 transcription, and co-expression analyses linked CLDN6 to epithelial-mesenchymal transition-related genes. These findings clarify subgroup-specific expression patterns and support claudin-6 as a biologically and therapeutically relevant target in AT/RT-TYR.

Background/Objectives: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and aggressive pediatric embryonal tumor of the central nervous system with marked histological and immunophenotypic heterogeneity, which can make diagnosis difficult in some cases. This study aimed to summarize the clinicopathological and molecular features of pediatric AT/RT and to evaluate an HE–IHC dual-path deep learning model as an auxiliary diagnostic approach. Methods: Clinical, histopathological, immunophenotypic, ultrastructural, and fluorescence in situ hybridization (FISH) data were retrospectively collected from 18 children with AT/RT treated at Beijing Children’s Hospital between February 2010 and April 2021. A total of 361 pathological images were used to train and test a ResNet50-based dual-path classification model with transfer learning and feature fusion. An additional independent test set of 175 histological and immunohistochemical images from six newly collected patients was used for supplementary validation. Results: The mean age at diagnosis was 2 years and 3 months. All cases showed loss of INI1 expression, positivity for CK and EMA, and a high Ki-67 index. FISH analysis identified SMARCB1 deletion in 7 of 15 tested cases. In the original image-based test set, the dual-path model achieved an accuracy of 90.91%, compared with 81.82% for the model without transfer learning, 86.36% for the single-path immunohistochemistry model, and 50.00% for the single-path histological model. In the additional independent test set, the trained model correctly classified all 175 images. Conclusions: Pediatric AT/RT shows diverse clinicopathological features and complex SMARCB1 alteration patterns. The HE–IHC dual-path model showed encouraging preliminary performance for auxiliary pathological assessment; however, larger multicenter cohorts with molecular subgroup annotation are needed for further validation before routine clinical application.

Quantification of the Kiel 67 (Ki-67) labeling index (LI) is critical for assessing proliferation and prognosis in tumors but manual scoring remains a common practice. We present an automated framework for Ki-67 scoring in whole slide images (WSIs) developed for research settings using an Apache Groovy code script for QuPath and complemented by a Python postprocessing script that provides cell density maps and summary tables. Tissue segmentation is performed by pixel classifiers and cell segmentation is conducted using StarDist, a deep learning model, followed by adaptive thresholding to classify Ki-67 positive and negative nuclei. The pipeline was applied to a cohort of 632 pediatric brain tumor cases with 734 Ki-67 WSIs from the Children's Brain Tumor Network. Medulloblastomas showed the highest Ki-67 LI (median: 19.84), followed by atypical teratoid rhabdoid tumors (median: 19.36), brainstem glioma-diffuse intrinsic pontine gliomas (median: 11.50), high-grade gliomas (grades 3, 4) (median: 9.50), and ependymomas (median: 5.88). Lower indices were found in meningiomas (median: 1.84) and the lowest were seen in low-grade gliomas (grades 1, 2) (median: 0.85), dysembryoplastic neuroepithelial tumors (median: 0.63), and gangliogliomas (median: 0.50). The results demonstrate a significant correlation (P < .05) in Ki-67 LI across most of the tumor families/types aligning with neuro-oncology and neuropathology consensus.

Extensive molecular analyses by many groups have revealed a heterogenous landscape of embryonal brain tumors, but patient-derived tumor organoid (TO) model development has remained limited. Here, we describe the establishment of TO and TO xenografts (TOX) from patient-derived orthotopic xenografts (PDOXs) of medulloblastoma, embryonal tumor with multilayer rosettes, and atypical teratoid rhabdoid tumors. DNA methylation, bulk- and single-cell RNA sequencing, and whole-genome sequencing demonstrated that TOs and TOXs faithfully recapitulate the epigenetic, transcriptomic, and genetic landscape of PDOXs, as well as replicate the intratumor cellular heterogeneity of PDOXs that are often lost in established cell lines. We show that TOs and PDOXs have similar drug responses. The development of embryonal brain TOs will facilitate in vitro functional assays, including high-throughput drug or CRISPR screens, without the need for fresh tumors from tumor-bearing mice. This will accelerate the identification and validation of vulnerabilities and therapeutic strategies for preclinical testing toward clinical trials.

Drug-resistant epilepsy (DRE) following treatment for atypical teratoid rhabdoid tumor (ATRT) is rare. The authors report a case in which hemispherotomy was performed to palliate new-onset DRE after ATRT therapy. A 6-year-old boy with a large left thalamic ATRT underwent subtotal resection, chemotherapy, and radiation therapy. His neurological baseline remained stable, with right hemiparesis, right hemifield neglect, and apraxia of speech. Two years after tumor recurrence and treatment, he developed frequent tonic seizures of left hemispheric origin. Despite trials of multiple antiseizure medications, the seizures persisted. Evaluation revealed left hemispheric seizure onset and hypometabolism. Given his existing deficits and unilateral disease, the potential benefits of hemispherotomy were determined to outweigh the risks. The patient underwent a left peri-insular hemispherotomy and has remained seizure free off medication without worsened neurological function. In carefully selected patients with aggressive tumor, unilateral seizure onset and preexisting deficits, hemispherotomy can be a well-tolerated and effective treatment for DRE, even in nontraditional contexts such as ATRT. This case highlights the importance of weighing surgical risks against functional baseline when considering epilepsy surgery in pediatric tumor cases. https://thejns.org/doi/10.3171/CASE24728.

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal central nervous system malignancy occurring predominately in infants and toddlers. Spinal AT/RT (spAT/RT) cases are even more limited, and as a result, little is known regarding prognostic factors and optimal treatment regimens. Molecularly, AT/RT is divided into three groups: AT/RT-SHH, AT/RT-TYR and AT/RT-MYC. spAT/RT is predominantly of the MYC subtype. Additionally, a third of patients with AT/RT have a germline Rhabdoid Tumor Predisposition Syndrome (RTPS) that increases the likelihood of developing additional rhabdoid tumors, including renal rhabdoid tumors. Due to the rarity of these tumors, there is a lack of consensus on treatment strategies to be employed. This review paper details the published literature on spAT/RT, with particular emphasis on the recent advances in understanding the biology of these aggressive tumors and currently available therapeutic options, and highlights the challenges associated with the management of this extremely rare condition.

Abstract BACKGROUND: Glypican-3 (GPC3) is uniquely expressed and has been associated with the development of several pediatric solid embryonal tumors, making it a prime target for GPC3 CAR-T cell killing. TGF-β, a cytokine associated with immunosuppression, has also been shown to be highly expressed in the microenvironment of these tumors, potentially hindering CAR-T cell antitumor activity. In this study, we examined the therapeutic efficacy of AZD5851, an autologous CAR-T product that expresses a CAR specific for GPC3 and a dominant negative (dn)TGFβRII as an armoring strategy. METHODOLOGY: To assess the drug’s in vivo efficacy, 5 established patient-derived orthotopic xenograft (PDOX) models of pediatric medulloblastoma (ICb-2123MB, -1299MB, -S1129MB), atypical teratoid rhabdoid tumor (IC-L1115ATRT) and a high grade glioma (IC-2664HGG), with confirmed expression of GPC3 and TGF-β through immunohistochemical staining, were treated with untransduced T cells [dosed at 12x106 cells/mouse, intravenously (IV) once] or GPC3 CAR-T cells (dosed at 5x106 cells/mouse, IV once). 20 eight-week-old SCID mice per model received intra-cerebral (IC) or intra-cerebellar (ICb) tumor cell implantation and were divided into 2 treatment groups (n=10 per group): Untransduced T cells and GPC3 CAR-T cells. Animal survival times were analyzed using Gehan-Breslow-Wilcoxon analysis. RESULTS: GPC3 CAR-T cell treatment was well tolerated in mice with no loss of body weight or other toxicities. GPC3 CAR-T cell treatment significantly improved the median survival time in 2/5 models, including ICb-2123MB from 90.5 days in the untransduced T cell group to 162.5 days (P=0.02) and IC-L1115ATRT from 136 days to 174 days (P=0.02). CONCLUSION: Our data identifies single agent antitumor activity for GPC3 CAR-T cells for PDOX models of pediatric medulloblastoma and atypical teratoid rhabdoid tumor. The results support further clinical translational efforts involving the use of AZD5851 alone or in combination with other therapies for the treatment of these tumors. Citation Format: Milagros Suarez, Aalaa Abdallah, Xin Zhai, Zilu Huang, Yuchen Du, Nitin Wadhwani, Alicia Lenzen, Jee Young Kwon, Steven B. Neuhauser, Timothy Stearns, Jeffrey H. Chuang, Emily L. Jocoy, Carol J. Bult, Beverly Teicher, Malcolm A. Smith, Xiao Nan Li. AZD5851, a TGF-β-resistant GPC3 CAR-T cell product, prolongs animal survival times in patient derived orthotopic xenograft models of medulloblastoma and atypical teratoid rhabdoid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1528.

Management of Pediatric Brain Tumors with the Aid of PET/MR Imaging.

CLO26-126: Survival Trends and Prevalence Disparities in Atypical Teratoid Rhabdoid Tumor: A Population Based Univariate vs Multivariate Retrospective Study.

Atypical teratoid rhabdoid tumor (ATRT) is a malignant brain tumor of children that has an overall survival of less than 40 percent even with aggressive therapy. We identified upregulation of the mitogen activated protein (MAP) kinase pathway in ATRT. The novel, brain-penetrant MEK inhibitor mirdametinib inhibited the growth of ATRT cell lines in culture at nanomolar concentrations. Mirdametinib suppressed proliferation as measured by BrdU incorporation and induced apoptosis as measured by cPARP and Annexin V staining. Monotherapy with mirdametinib extended the life of mice bearing orthotopic xenografts. Combination therapy with the brain-penetrant cyclin dependent kinase 4/6 inhibitor abemaciclib further suppressed growth and BrdU incorporation in ATRT cell lines representing all molecular subgroups. Mirdametinib and abemaciclib combined to extend survival of mice bearing orthotopic ATRT xenografts. In conclusion, mirdametinib has single agent activity against ATRT and combines with abemaciclib to decrease proliferation and extend survival in orthotopic xenograft models of ATRT.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal neoplasm of the central nervous system, primarily diagnosed in children under three years of age, with spinal presentations accounting for fewer than 2% of patients. This report describes an unusual primary thoracolumbar spinal AT/RT in a 7-year-old girl who presented with severe, rapidly progressive pain impairing mobility. Magnetic resonance imaging revealed a large intradural extramedullary mass extending from T11 to L3 with marked compression of the conus medullaris and cauda equina. Surgical resection was performed, and histopathological evaluation confirmed rhabdoid morphology with characteristic immunophenotypic features, including loss of nuclear SMARCB1 (INI1) expression and elevated proliferative index, consistent with AT/RT. This case report highlights the diagnostic complexity due to overlapping features with other pediatric spinal tumors, necessitating comprehensive histological, immunohistochemical, and molecular analyses for accurate classification. Discussion integrates the patient tumor profile within the framework of WHO 2021 molecular subgroups, underscoring the clinical heterogeneity and poor prognosis associated with spinal AT/RT, particularly the aggressive AT/RT-MYC subtype. Despite maximal surgical and multimodal therapy, outcomes remain dismal, emphasizing the urgent need for collaborative research exploring targeted molecular and immunotherapeutic strategies. This case report expands limited literature, offering valuable insights for early recognition and management of spinal AT/RT in older pediatric patients.

Pediatric brain tumor survivors remain at high risk of recurrence, yet current surveillance strategies relying on neuroimaging and cerebrospinal fluid (CSF) cytology have limited sensitivity for early or minimal disease. Tumor-specific peptides (TSPs) derived from individual tumors represent a promising class of highly specific biomarkers for longitudinal disease monitoring through CSF-based proteomic analysis. In this study, tumor tissue and serial CSF samples from six pediatric brain tumor patients (five medulloblastomas and one atypical teratoid/rhabdoid tumor (ATRT)) were analyzed using an integrated proteogenomic workflow combining discovery and targeted mass spectrometry. TSPs were identified from resected tumor tissue and matched against shotgun CSF proteomic datasets to nominate candidate biomarkers. High-confidence peptides were synthesized as isotopically labeled standards and quantified longitudinally using targeted multiple reaction monitoring. Two TSP biomarkers derived from individualized pediatric brain tumors (one medulloblastoma and one ATRT) demonstrated robust detection in serial CSF samples and exhibited temporal concordance with radiographic disease course, declining with treatment response and increasing during disease progression. These findings establish the feasibility of detecting and longitudinally quantifying TSPs in CSF and support further investigation of individualized proteomic biomarkers for treatment response monitoring and disease surveillance in pediatric brain tumors.

Pediatric central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children. Development of more effective therapies for pediatric CNS tumors has been slow, underscoring an urgent need for novel and innovative approaches. This review summarizes current pediatric clinical trials of oncolytic viruses for pediatric brain tumors including high-grade glioma (HGG), diffuse midline glioma (DMG), medulloblastoma (MDB), atypical teratoid rhabdoid tumors (ATRT), and other high-grade tumors, while highlighting limitations of early-phase data, exploratory biomarkers, imaging challenges, pseudoprogression, and future directions. Key platforms include HSV-based agents (HSV1716, G207, and M032); adenoviral vectors (DNX2401, Ad-TD-nsIL12, and ICOVIR-5); MV-NIS (measles virus); PVS-RIPO (poliovirus); and Reolysin (reovirus). We review trial status, innovations in viral engineering and delivery, combinatorial strategies and translational challenges to establish oncolytic virotherapy as part of the future standard care for pediatric brain tumors. Oncolytic virotherapy or immunovirotherapy offers a promising strategy to selectively kill tumor cells and generate antitumor immune response while minimizing toxicity to healthy cells compared to conventional treatments. Although still emerging in pediatric neuro-oncology, preclinical studies and early-phase clinical trials show encouraging safety and efficacy signals. Not applicable.

Atypical teratoid rhabdoid tumor (AT/RT) of the brain is a highly malignant (CNS WHO grade 4) embryonal neoplasm. Majority of AT/RTs occur in the posterior fossa although supratentorial examples may also be observed. Pathologically, the tumor typically consists of cells with rhabdoid morphology that are immunoreactive for synaptophysin, EMA, and variably for GFAP. Diagnosis is typically confirmed by observing loss of INI-1 or BRG-1 expression from the nucleus of the tumor cells. Little is known regarding the embryogenesis of AT/RT. We therefore present here a case of supratentorial AT/RT in a 3-year-old male who presented with fatigue, irritability, left facial drop, left sided weakness of arm and leg, headaches, and vomiting. Neuroimaging revealed a large tumor involving the basal ganglia and foramen of Monro. Neuropathologic examination of the resected tumor revealed morphologic, immunohistochemical, and molecular evidence of an AT/RT (Group 1, SHH subtype). The tumor cells additionally exhibited immunoreactivity for TTF-1 (also known as NKX2.1), which has been reported to be expressed in GABAergic precursor cells in the medial ganglionic eminence. This example may provide at least a small insight into embryonic origins of supratentorial AT/RT.