A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup ATRTs.

BACKGROUND: Atypical Teratoid Rhabdoid Tumor (ATRT) is a rare, devastating, and largely incurable pediatric brain tumor. Although recent studies have uncovered three molecular subgroups of ATRTs with distinct disease patterns, and signaling features, the therapeutic profiles of ATRT subgroups remain incompletely elucidated. METHODS: We examined the effect of 465 kinase inhibitors on a panel of ATRT subgroup-specific cell lines. We then applied multi-omics analyses to investigate the underlying molecular mechanism of kinase inhibitor efficacy in ATRT subgroups. RESULTS: We observed that ATRT cell lines are broadly sensitive to inhibitors of the PI3K and MAPK signaling pathways, as well as CDKs, AURKA/B kinases, and PLK1. We identified two classes of multi-kinase inhibitors (MKIs) predominantly targeting receptors tyrosine kinase (RTKs) including PDGFR and EGFR/ERBB2 in MYC/TYR ATRT cells. The PDGFRB inhibitor, Dasatinib, synergistically affected MYC/TYR ATRT cell growth when combined with broad-acting PI3K and MAPK pathway inhibitors, including Rapamycin and Trametinib. We observed that MYC/TYR ATRT cells were also distinctly sensitive to various inhibitors of ERBB2 signaling. Transcriptional, H3K27Ac ChIPSeq, ATACSeq, and HiChIP analyses of primary MYC/TYR ATRTs revealed ERBB2 expression which correlated with differential methylation and activation of a distinct enhancer element by DNA looping. Significantly, we show the brain penetrant EGFR/ERBB2 inhibitor, Afatinib, specifically inhibited in vitro and in vivo growth of MYC/TYR ATRT cells. CONCLUSIONS: Taken together our studies suggest combined treatments with PDGFR and ERBB2-directed TKIs with inhibitors of the PI3K and MAPK pathways as an important new therapeutic strategy for the MYC/TYR subgroup of ATRTs.

SMARCB1 Gene Therapy Using a Novel Tumor-Targeted Nanomedicine Enhances Anti-Cancer Efficacy in a Mouse Model of Atypical Teratoid Rhabdoid Tumors.

Purpose: Atypical teratoid rhabdoid tumor (ATRT) is a deadly, fast-growing form of pediatric brain cancer with poor prognosis. Most ATRTs are associated with inactivation of SMARCB1, a subunit of the chromatin remodeling complex, which is involved in developmental processes. The recent identification of SMARCB1 as a tumor suppressor gene suggests that restoration of SMARCB1 could be an effective therapeutic approach. Methods: We tested SMARCB1 gene therapy in SMARCB1-deficient rhabdoid tumor cells using a novel tumor-targeted nanomedicine (termed scL-SMARCB1) to deliver wild-type SMARCB1. Our nanomedicine is a systemically administered immuno-lipid nanoparticle that can actively cross the blood-brain barrier via transferrin receptor-mediated transcytosis and selectively target tumor cells via transferrin receptor-mediated endocytosis. We studied the antitumor activity of the scL-SMARCB1 nanocomplex either as a single agent or in combination with traditional treatment modalities in preclinical models of SMARCB1-deficient ATRT. Results: Restoration of SMARCB1 expression by the scL-SMARCB1 nanocomplex blocked proliferation, and induced senescence and apoptosis in ATRT cells. Systemic administration of the scL-SMARCB1 nanocomplex demonstrated antitumor efficacy as monotherapy in mice bearing ATRT xenografts, where the expression of exogenous SMARCB1 modulates MYC-target genes. scL-SMARCB1 demonstrated even greater antitumor efficacy when combined with either cisplatin-based chemotherapy or radiation therapy, resulting in significantly improved survival of ATRT-bearing mice. Conclusion: Collectively, our data suggest that restoring SMARCB1 function via the scL-SMARCB1 nanocomplex may lead to therapeutic benefits in ATRT patients when combined with traditional chemoradiation therapies.

Synergistic Antitumor Activity of Talazoparib and Temozolomide in Malignant Rhabdoid Tumors.

Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1 gene (occasionally SMARCA4)-a pivotal component of the SWI/SNF chromatin remodeling complex-is homozygously deleted, although the precise etiology of these tumors remains unknown. While young patients with localized MRT generally show improved outcomes, especially those who are older and have early-stage disease, the overall prognosis remains poor despite optimal standard treatments. This highlights the urgent need for more effective treatment strategies. We investigated the antitumor activity of a PARP1 inhibitor (talazoparib, TLZ) combined with a DNA alkylating agent (temozolomide, TMZ) in MRT xenograft models. PARP1 is a widely targeted molecule in cancer treatment and, beyond its role in DNA repair, it participates in transcriptional regulation by recruiting chromatin remodeling complexes to modulate DNA accessibility for RNA polymerases. To widen the therapeutic window of the drug combination, we employed PEGylated TLZ (PEG~TLZ), which has been reported to reduce systemic toxicity through slow drug release. Remarkably, our findings indicate that five out of six MRT xenografts exhibited an objective response to PEG~TLZ+TMZ therapy. Significantly, the loss of SMARCB1 was found to confer a protective effect, correlating with higher expression levels of DNA damage and repair proteins in SMARCB1-deficient MRT cells. Additionally, we identified MGMT as a potential biomarker indicative of in vivo MRT response to PEG~TLZ+TMZ therapy. Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response.

Case report: A rare case of omental extrarenal rhabdoid tumor and review of the literature.

Extrarenal rhabdoid tumor of the greater omentum is extremely rare, with only sporadic reports and limited documentation of its ultrasonographic findings. Here, we report a case of an extrarenal rhabdoid tumor of the greater omentum in a 16-year-old girl and review the relevant literature. It was found that the disease mainly occurred in female children and adolescents, and mainly manifested as lower abdominal pain and a large abdominal cystic or solid hemorrhagic mass. The clinical characteristics include a high degree of malignancy and mortality. Ultrasound shows some malignant features, but it is not specific; thus, it is easy to be misdiagnosed in the clinic.

Malignant Extrarenal Rhabdoid tumor derived from the greater omentum: A case report and literature review.

BACKGROUND: Malignant extrarenal rhabdoid tumor (MERT) is a rare and highly metastatic tumor, which is more than 75% of patients dying within 6 months of initial diagnosis, and it often leads to misdiagnosis and delayed treatment. CASE: This paper reports a 16-year-old girl who presented with the chief complaint of acute abdominal pain. She underwent laparoscopic exploration and excisional biopsy, then pathological examination and immunohistochemistry revealed "extrarenal malignant rhabdomyoma." One month after operation, she died of intra-abdominal hemorrhage and multiple organ dysfunction. CONCLUSION: MERT were often misdiagnosed and had a poor prognosis. The surgery and chemotherapy are usually beneficial to prolong the survival time of patients with MERT.

Congenital Disseminated Malignant Rhabdoid Tumor Mimicking a Vascular Lesion.

A congenital disseminated malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive pediatric cancer marked by the presence of malignant rhabdoid cells in various organs, including the brain, kidneys, and soft tissues, at birth. It is often detected prenatally or shortly post-birth. The malignancy's aggressiveness results in a bleak prognosis, offering limited treatment options and low survival rates. Early diagnosis and comprehensive medical intervention are crucial, but managing this condition is complicated by its rarity. We herein presented a case of a 37 and 1/7 week gestation male infant with a rapidly growing arm soft tissue mass within two weeks, diagnosed as an MRT. Post-delivery examinations revealed multiple lesions in the lungs, kidney, liver, and adrenal glands. Notably, chemotherapy yielded a significant improvement in the arm lesion, contrasting with other lesions showing a limited response. This observation suggests potential tumor heterogeneity, emphasizing the necessity of diverse therapeutic regimens. Our case underscores the complexities of congenital disseminated MRT, prompting a reevaluation of treatment strategies for enhanced efficacy in managing this challenging pediatric cancer.

Rare Coexistence: Pilocytic Astrocytoma With Atypical Teratoid/Rhabdoid Tumor Features in an Infant.

This case report describes the presentation, diagnostic evaluation, and management challenges encountered in an eight-month-old female infant with fever, seizure, and a large cystic brain lesion initially diagnosed as pilocytic astrocytoma but later demonstrating atypical teratoid/rhabdoid tumor (AT/RT) features on histopathological examination-the infant presented with a fever and cold persisting for 10 days, followed by a seizure episode. Laboratory investigations revealed abnormalities, including anemia and leukocytosis. Imaging studies identified a large cystic lesion causing hydrocephalus. Despite initial treatment, the patient continued to experience seizures, prompting surgical intervention. Debulking surgery was performed, resulting in postoperative motor deficits. Subsequent imaging revealed persistent lesions, leading to further surgical intervention with shunt placement. Histopathological examination confirmed pilocytic astrocytoma with features suggestive of AT/RT. Despite counseling regarding poor prognosis and recommendations for chemotherapy, the parents declined further treatment, and the patient was discharged. This case underscores the diagnostic complexity and therapeutic dilemmas associated with rare histological overlaps in pediatric brain tumors, emphasizing the importance of multidisciplinary collaboration and tailored treatment strategies for optimal patient care.

Mediastinal malignant rhabdoid tumor in an infant: A rare case report.

Mediastinal malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive neoplasm, particularly uncommon in infants. We present the case of a previously healthy 7-month-old male infant with mediastinal MRT. The patient initially presented with left eyelid ptosis and was otherwise asymptomatic. Initial investigations, including brain MRI, yielded unremarkable results, and the infant was discharged with vitamin B supplements. However, he was readmitted a week later with prolonged fever, poor feeding, diarrhea, and respiratory distress. Despite an initial diagnosis of bronchiolitis/viral respiratory tract infection, the patient's condition rapidly deteriorated. Subsequent evaluation revealed mediastinal MRT as the underlying cause. This case underscores the diagnostic challenges associated with mediastinal MRT in infants and highlights the importance of considering rare neoplastic etiologies in atypical clinical presentations.

Atypical teratoid/rhabdoid tumor of the central nervous system: Clinicopathological features of two challenging cases.

INTRODUCTION: Atypical Teratoid/Rhabdoid Tumor (AT/RT) is a rare aggressive neoplasm that mainly affects the pediatric population with a peak incidence in the first two years of life and a slight male predominance, whereas presentation of this neoplasm in older ages is extremely rare. CASE PRESENTATION: Herein, we present two cases of AT/RT. In the first case, a 9-year-old female presented with diplopia, dizziness, headache, and morning vomiting. CT Scan of the head demonstrated a heterogeneous mass in the left frontal-parietal region with vasogenic edema and midline deviation. In the second case, a 57-year-old female presented with severe generalized headache, numbness, and tingling in the right hand. MRI revealed a lobulated cystic mass in the right occipitotemporal region, with surrounding edema compressing the left lateral ventricle and causing a midline shift to the left, and enlargement of the right lateral ventricle. In both case, histopathological and immunohistochemical examinations revealed the diagnosis of Atypical teratoid/Rhabdoid tumors. CLINICAL DISCUSSION: Microscopic examination demonstrated the proliferation of medium-sized to large cells with abundant eosinophilic cytoplasm, large vesicular eccentric nuclei, and conspicuous nucleoli with areas of necrosis and hemorrhage, thus confirming the diagnosis with adequate immunohistochemical staining. The first patient developed signs of recurrence and passed away six months later, whereas in the second case, the 57-year-old female received radiotherapy for 6 weeks before being put on chemotherapy. CONCLUSION: Despite the challenges facing the diagnosis of this aggressive neoplasm, we managed to present our cases with detailed histopathological and immunohistochemical examinations.

Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

Dynamic Survival Risk Prognostic Model and Genomic Landscape for Atypical Teratoid/Rhabdoid Tumors: A Population-Based, Real-World Study.

BACKGROUND: An atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive pediatric central nervous system neoplasm. However, a universal clinical consensus or reliable prognostic evaluation system for this malignancy is lacking. Our study aimed to develop a risk model based on comprehensive clinical data to assist in clinical decision-making. METHODS: We conducted a retrospective study by examining data from the Surveillance, Epidemiology, and End Results (SEER) repository, spanning 2000 to 2019. The external validation cohort was sourced from the Children's Hospital Affiliated to Chongqing Medical University, China. To discern independent factors affecting overall survival (OS) and cancer-specific survival (CSS), we applied Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) regression analyses. Based on these factors, we structured nomogram survival predictions and initiated a dynamic online risk-evaluation system. To contrast survival outcomes among diverse treatments, we used propensity score matching (PSM) methodology. Molecular data with the most common mutations in AT/RT were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. RESULTS: The annual incidence of AT/RT showed an increasing trend (APC, 2.86%; 95% CI:0.75-5.01). Our prognostic study included 316 SEER database participants and 27 external validation patients. The entire group had a median OS of 18 months (range 11.5 to 24 months) and median CSS of 21 months (range 11.7 to 29.2). Evaluations involving C-statistics, DCA, and ROC analysis underscored the distinctive capabilities of our prediction model. An analysis via PSM highlighted that individuals undergoing triple therapy (integrating surgery, radiotherapy, and chemotherapy) had discernibly enhanced OS and CSS. The most common mutations of AT/RT identified in the COSMIC database were SMARCB1, BRAF, SMARCA4, NF2, and NRAS. CONCLUSIONS: In this study, we devised a predictive model that effectively gauges the prognosis of AT/RT and briefly analyzed its genomic features, which might offer a valuable tool to address existing clinical challenges.

Super-Enhancer Dysregulation in Rhabdoid Tumor Cells Is Regulated by the SWI/SNF ATPase BRG1.

Mutations in the SWI/SNF chromatin remodeling complex occur in ~20% of cancers. In rhabdoid tumors defined by loss of the SWI/SNF subunit SMARCB1, dysregulation of enhancer-mediated gene expression is pivotal in driving oncogenesis. Enhancer dysregulation in this setting is tied to retention of the SWI/SNF ATPase BRG1-which becomes essential in the absence of SMARCB1-but precisely how BRG1 contributes to this process remains unknown. To characterize how BRG1 participates in chromatin remodeling and gene expression in SMARCB1-deficient cells, we performed a genome-wide characterization of the impact of BRG1 depletion in multiple rhabdoid tumor cell lines. We find that although BRG1-regulated open chromatin sites are distinct at the locus level, the biological characteristics of the loci are very similar, converging on a set of thematically related genes and pointing to the involvement of the AP-1 transcription factor. The open chromatin sites regulated by BRG1 colocalize with histone-marked enhancers and intriguingly include almost all super-enhancers, revealing that BRG1 plays a critical role in maintaining super-enhancer function in this setting. These studies can explain the essentiality of BRG1 to rhabdoid tumor cell identity and survival and implicate the involvement of AP-1 as a critical downstream effector of rhabdoid tumor cell transcriptional programs.

Feeder-free differentiation of human iPSCs into natural killer cells with cytotoxic potential against malignant brain rhabdoid tumor cells.

Natural killer (NK) cells are cytotoxic immune cells that can eliminate target cells without prior stimulation. Human induced pluripotent stem cells (iPSCs) provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers. In this in vitro study, a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells, and distinct maturational stages of iPSC-NK were characterized. Mature cells of CD56bright CD16bright phenotype showed upregulation of CD56, CD16, and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure, while exposure to aggressive atypical teratoid/rhabdoid tumor (ATRT) cell lines enhanced NKG2D and NKp46 expression. Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γ secretion in activated NK cells. CD56bright CD16bright iPSC-NK cells showed a ratio-dependent killing of ATRT cells, and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT. The iPSC-NK cells were also cytotoxic against other brain, kidney, and lung cancer cell lines. Further NK maturation yielded CD56-ve CD16bright cells, which lacked activation markers even after exposure to interleukins or ATRT cells - indicating diminished cytotoxicity. Generation and characterization of different NK phenotypes from iPSCs, coupled with their promising anti-tumor activity against ATRT in vitro, offer valuable insights into potential immunotherapeutic strategies for brain tumors.

ESTRO-SIOPE guideline: Clinical management of radiotherapy in atypical teratoid/rhabdoid tumors (AT/RTs).

BACKGROUND AND PURPOSE: Treatment of patients with atypical teratoid/rhabdoid (AT/RT) is challenging, especially when very young (below the age of three years). Radiotherapy (RT) is part of a complex trimodality therapy. The purpose of this guideline is to provide appropriate recommendations for RT in the clinical management of patients not enrolled in clinical trials. MATERIALS AND METHODS: Nine European experts were nominated to form a European Society for Radiotherapy and Oncology (ESTRO) guideline committee. A systematic literature search was conducted in PubMed/MEDLINE and Web of Science. They discussed and analyzed the evidence concerning the role of RT in the clinical management of AT/RT. RESULTS: Recommendations on diagnostic imaging, therapeutic principles, RT considerations regarding timing, dose, techniques, target volume definitions, dose constraints of radiation-sensitive organs at risk, concomitant chemotherapy, and follow-up were considered. Treating children with AT/RT within the framework of prospective trials or prospective registries is of utmost importance. CONCLUSION: The present guideline summarizes the evidence and clinical-based recommendations for RT in patients with AT/RT. Prospective clinical trials and international, large registries evaluating modern treatment approaches will contribute to a better understanding of the best treatment for these children in future.

False-Positive Asymmetrical Tongue Muscle 18F-FDG Uptake in Hypoglossal Nerve Paralysis Following Lymph Node Dissection in a Pediatric Patient with Malignant Rhabdoid Tumor of the Neck.

BACKGROUND: Although positron emission tomography combined with computed tomography (PET-CT) plays an important role in detecting various types of childhood malignancy, it has low positive predictive value, owing to the nonspecific uptake of 18F-fluorodeoxyglucose (FDG) by normal tissue in various benign conditions. CASE SUMMARY: A 5-year-old male patient with a malignant rhabdoid tumor originating in the left neck underwent primary tumor resection concurrently with ipsilateral lymph node dissection after receiving neoadjuvant chemotherapy consisting of cyclophosphamide, carboplatin, etoposide, vincristine, and doxorubicin. He later received the same adjuvant chemotherapy as well as proton therapy for the primary tumor. Sixteen months after completing the initial therapy, follow-up PET-CT revealed a novel area of glucose hypermetabolism in the right side of the tongue, which was suspected of being a recurrence. However, a physical examination and magnetic resonance imaging (MRI) demonstrated no evidence of tumor recurrence. The patient had a significant leftward deviation of the tongue, suggesting left hypoglossal nerve paralysis. Denervation of the ipsilateral intrinsic tongue muscles secondary to the treatment had caused atrophy in the ipsilateral muscles and compensatory hypertrophy in the contralateral muscles, which increased FDG uptake. Physicians should carefully confirm any diagnosis of a locally recurrent tumor because PET-CT often produces ambiguous findings.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.

Targeting cholesterol biosynthesis for AT/RT: comprehensive expression analysis and validation in newly established AT/RT cell line.

Atypical teratoid/rhabdoid (AT/RT) is a rare and highly malignant tumor of the central nervous system (CNS). It is most commonly found in children less than 5 years of age and is associated with inactivation of loss of function of SMARCB1/INI1. An experimental model for AT/RT is necessary to develop new and effective therapies. We established a patient-derived new cell line (MZ611ATRT), which showed loss of BAF-47. MZ611ATRT genetically features somatic heterozygous deletion of SMARCB1 and single nucleotide deletion of the residual allele, exon 5 ([c.541delC]), resulting in a stop codon at codon 954 by frameshift. We assessed the RNA-sequencing data of the other two AT/RT cell lines with forced expression of SMARCB1 available from public databases. We found SMARCB1 overexpression significantly down-regulates the expression of a group of enzymes related to cholesterol biosynthesis. Simvastatin was highly sensitive against MZ611ATRT cells and induced apoptosis (IC50 was 3.098 µM for MZ611ATRT, 41.88uM for U-87 MG, 23.34uM for IOMM-Lee, and 18.12uM for U-251 MG.). Pathways involved in cholesterol biosynthesis may be new targets for adjuvant therapy of AT/RT.

An adult with recurrent atypical teratoid rhabdoid tumor of the spine.

Atypical teratoid rhabdoid tumors (AT/RT) are rare and highly malignant CNS neoplasms primarily affecting children. Adult cases are extremely uncommon, with only approximately 92 reported. Spinal AT/RT in adults is particularly rare. Here, we present the case of a 50-year-old patient diagnosed with AT/RT of the spine. Initially, they were diagnosed and treated for a spinal ependymoma. However, after 10 years, a recurrence was detected through magnetic resonance imaging (MRI) and the tumor was reclassified as AT/RT. We discuss the significance of SMARCB1 gene mutations in diagnosing AT/RT and describe our unique treatment approach involving surgery, radiation and anti-PD1 therapy in this patient.

Atypical teratoid rhabdoid tumors (AT/RT) are rare and serious cancers that affect the brain and spine, and mostly occur in children. AT/RT are rare in adults, with only about 92 cases reported. Our article tells the story of a 50-year-old patient, who was diagnosed with a spinal tumor, initially classified as an ependymoma. Ten years later, the tumor recurred, and was found on routine surveillance imaging. After pathological examination of the recurrent tumor, it was diagnosed as AT/RT. The initial tissue was re-examined, and the original tumor was reclassified as an AT/RT. We explain why a gene called SMARCB1 is important for diagnosing AT/RT. Additionally, we share details about the treatments utilized: including surgery, radiation, and medicines that stimulate the immune system to kill cancer cells. This case highlights the challenges and treatments for this rare cancer in adults.

Recurrent spinal atypical teratoid/rhabdoid tumor with pulmonary metastasis.

BACKGROUND: Atypical teratoid/rhabdoid tumors (ATRT) are aggressive pediatric central nervous system malignancies that predominantly affect the brain and have poor survival outcomes. However, spinal ATRT is an uncommon subset of ATRT, and its clinical course and management are poorly understood. CASE: We describe a case of spinal ATRT in a previously healthy 5-year-old girl who initially presented with rapid-onset gait disturbance. Magnetic resonance imaging (MRI) revealed an extramedullary tumor at thoracic level 5 (T5) without bony destruction or metastasis. The patient partially recovered after surgical resection. One month was required for a definitive diagnosis, and the pathology confirmed ATRT characterized by the loss of INI-1 protein expression. Chemoradiotherapy with local irradiation and high-dose chemotherapy with autologous peripheral blood stem cell transplantation led to complete remission and functional recovery for 5 months. However, the condition exhibited progression in the cerebrospinal fluid (CSF) region, resulting in cerebellar, cerebral, and spinal tumor development. Eventually, the disease metastasized to the lungs and disseminated to the entire cerebrospinal cord and fluid. The patient died 15 months after the initial diagnosis. CONCLUSION: This case emphasizes the importance of considering ATRT as a potential diagnostic modality for pediatric spinal cord tumors, enabling prompt multidisciplinary intervention. The heterogeneous appearance of spinal ATRT may make distinguishing it from other spinal tumors difficult, resulting in delayed diagnosis and treatment. The treatment approach for ATRT remains challenging with no established standards. Local irradiation may be preferable to minimize neurodevelopmental effects, and initial craniospinal irradiation may potentially prevent recurrence. Our case emphasizes the likelihood of extracranial metastasis in ATRT, thereby highlighting the importance of a comprehensive assessment of both genetic and epigenetic profiles to identify any factors that may influence the clinical course of this disease. Prompt diagnosis and comprehensive therapeutic strategies are critical for improving outcomes in spinal ATRT patients.