Diffuse infiltrating tumour with the molecular profile of an atypical teratoid rhabdoid tumour (AT/RT SHH-1B) in an adult patient.

We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.

Survival Benefit from Multimodal Treatment for Patients with Atypical Teratoid Rhabdoid Tumor in a Surveillance, Epidemiology, and End Results Database Analysis.

INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is among the most aggressive central nervous system malignancies. Although rare, this tumor typically afflicts young children and results in mortality within months. Here, we aim to determine key clinical features and treatment options that impact the survival of patients with ATRT. METHODS: From the year 2000 to 2019, 363 patients with ATRT were identified from the Surveillance, Epidemiology, and End Results database. Univariate analysis was used to identify variables that had a significant impact on the primary endpoint of overall survival (OS). Multivariable analysis was then used to identify independent predictors of survival. RESULTS: The median OS of the entire cohort was 13 months. Univariate analysis identified ages between 1 and 3 years, ages between 4 and 17 years, years of diagnosis between 2010 and 2019, and the receipt of treatment to have a significant impact on survival. In multivariable analysis, ages between 1 and 3 years and receipt of treatment were the only significant independent predictors of survival. The median OS was significantly greater in patients who received surgical treatment, chemotherapy, or radiation when compared to those who did not receive any treatment. In general, the receipt of any combination of therapies improved the median OS significantly. The receipt of triple therapy had the greatest impact on survival. DISCUSSION: This study highlights the survival benefit of a multimodal approach in the treatment of ATRT. The use of triple therapy, including surgery, radiation, and chemotherapy, was found to have the greatest survival benefit for patients. Overall, these findings may guide future care for patients with ATRT.

Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.

PURPOSE: Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse. METHODS: Two pediatric patients with CNS embryonal tumors with EWSR1-PLAGL1 rearrangements treated at Arkansas Children's Hospital with histopathologic and molecular data are described. RESULTS: These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data. At relapse both patient's disease was reclassified as atypical teratoid rhabdoid tumor (ATRT) based on loss of INI-1, presence of SMARCB1 alterations, and methylation profiling results. CONCLUSION: CNS embryonal tumors with EWSR1-PLAGL1 rearrangements acquire or include a population of cells with SMARCB1 alterations that are the component that predominate at relapse, suggesting treatment aimed at this disease component at diagnosis should be considered.

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.

Horseshoe kidney with teratoid type of Wilms tumor: a rare case report.

BACKGROUND: Horseshoe kidney is the most common renal fusion anomaly, and Wilms tumor is the most frequent renal malignancy in children. The occurrence of Wilms tumor in association with horseshoe kidney is a scarce anomaly. However, the arising of a teratoid type, which is a rare variant of Wilms tumor in a horseshoe kidney, is exceptionally unique. CASE PRESENTATION: This report presents a 5-year-old male admitted with horseshoe kidney involved by a large heterogeneous calcified mass that was diagnose on biopsy as Wilms tumor blastemal dominant. According to the local and regional extension and metastatic tumor in the lungs, the patient underwent neoadjuvant chemotherapy and then surgery. Post-operative pathologic findings confirmed the diagnosis of teratoid Wilms tumor. CONCLUSIONS: The occurrence of renal anomalies associated with a malignancy might be more frequent in the clinical environment. There are numerous differential diagnoses for renal tumors and masses, but the possibility of exceptional anomalies should not be denied, and clinicians should be prepared for these occasions. Although studies propose that chemotherapy has a trivial effect on teratoid Wilms tumors, it is essential to evaluate the tumor for any possibility of regression in non-teratoid regions before proceeding to upfront tumoral resection.

Direct Administration of Chemotherapy and Other Agents into the Fourth Ventricle to Treat Recurrent Malignant Brain Tumors in Children.

Direct administration of chemotherapy and other agents into the fourth ventricle of the brain is a novel approach to treating recurrent malignant posterior fossa brain tumors in children. Candidates for this treatment approach include patients with recurrent medulloblastoma, ependymoma, atypical teratoid/rhabdoid tumor, and potentially other neoplasms that originate in the fourth ventricle or elsewhere in the posterior fossa. In this chapter, the authors first explain the rationale for considering fourth ventricular drug infusions in patients with recurrent malignant posterior fossa tumors. We then summarize the results of translational experiments conducted in piglets and non-human primates that demonstrated safety and favorable pharmacokinetics. These translational experiments led to several pilot human clinical trials, and the results of these trials are reviewed. Finally, currently open clinical trials testing infusion of various agents into the fourth ventricle are discussed, and thoughts about potential future directions are shared.

Multifocal atypical teratoid/rhabdoid tumour in an infant-a rare case report.

BACKGROUND: Atypical teratoid/rhabdoid tumours (AT/RT) are uncommon but aggressive, malignant tumours in the paediatric age group. Presentation of concomitant supratentorial and infratentorial lesions in an infant is extremely rare. We discuss an infant diagnosed with such lesions. Systematic PubMed search was conducted using keywords 'atypical teratoid /rhabdoid tumor', 'paediatric' and 'multifocal'. Reports were included for patients younger than 18 years with two or more lesions. The search yielded additional five cases and were tabulated. Age, sex, location, treatment given and survival/outcome were noted. CASE REPORT: A 10-month-old child presented with complaints of drowsiness and intractable vomiting. Imaging showed multifocal supra- and infratentorial lesions with obstructive hydrocephalus. The child underwent ventriculoperitoneal shunt followed by surgical removal of the posterior fossa lesion. Histopathological features were consistent with AT/RT. CONCLUSIONS: Multifocal AT/RT are very rare. The impact of multifocality in the outcome is not known as very few reports are available. Newer targeted therapies may offer insight in improving outcomes in the future.

Cerebrospinal fluid cytology in a case of epithelioid glioblastoma.

Epithelioid glioblastoma (eGB) is a rare GB subtype exhibiting characteristic morphology and genetic alterations. The efficacy of BRAF and MEK-1/2 inhibitors is demonstrated in eGB treatment, and therefore, considering eGB is important to enhance patient care and prognosis.

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. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). MAIN RESULTS AND THE ROLE OF CHANCE: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). LIMITATIONS, REASONS FOR CAUTION: RTs are very rare malignancies and our results are based on a small number of children with RT_ART. WIDER IMPLICATIONS OF THE FINDINGS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. STUDY FUNDING/COMPETING INTEREST(S): M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Radiotherapy for Atypical Teratoid/Rhabdoid Tumor (ATRT) on the Pediatric Proton/Photon Consortium Registry (PPCR).

PURPOSE: Atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system (CNS) are rare tumors with a poor prognosis and variable use of either focal or craniospinal (CSI) radiotherapy (RT). Outcomes on the prospective Pediatric Proton/Photon Consortium Registry (PPCR) were evaluated according to RT delivered. METHODS: Pediatric patients receiving RT were prospectively enrolled on PPCR to collect initial patient, disease, and treatment factors as well as provide follow-up for patient outcomes. All ATRT patients with evaluable data were included. Kaplan-Meier analyses with log-rank p-values and cox proportional hazards regression were performed. RESULTS: The PPCR ATRT cohort includes 68 evaluable ATRT patients (median age 2.6 years, range 0.71-15.40) from 2012 to 2021. Median follow-up was 40.8 months (range 3.4-107.7). Treatment included surgery (65% initial gross total resection or GTR), chemotherapy (60% with myeloablative therapy including stem cell rescue) and RT. For patients with M0 stage (n = 60), 50 (83%) had focal RT and 10 (17%) had CSI. Among patients with M + stage (n = 8), 3 had focal RT and 5 had CSI. Four-year overall survival (OS, n = 68) was 56% with no differences observed between M0 and M + stage patients (p = 0.848). Local Control (LC) at 4 years did not show a difference for lower primary dose (50-53.9 Gy) compared to ≥ 54 Gy (73.3% vs 74.7%, p = 0.83). For patients with M0 disease, four-year OS for focal RT was 54.6% and for CSI was 60% (Hazard Ratio 1.04, p = 0.95. Four-year event free survival (EFS) among M0 patients for focal RT was 45.6% and for CSI was 60% (Hazard Ratio 0.71, p = 0.519). For all patients, the 4-year OS comparing focal RT with CSI was 54.4% vs 60% respectively (p = 0.944), and the 4-year EFS for focal RT or CSI was 42.8% vs 51.4% respectively (p = 0.610). CONCLUSION: The PPCR ATRT cohort found no differences in outcomes according to receipt of either higher primary dose or larger RT field (CSI). However, most patients were M0 and received focal RT. A lower primary dose (50.4 Gy), regardless of patient age, is appealing for further study as part of multi-modality therapy.

Focal versus craniospinal radiation for disseminated atypical teratoid/rhabdoid tumor following favorable response to systemic therapy.

PURPOSE: Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI). METHODS: After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double-reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre-radiation chemotherapy (N = 57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded. RESULTS: The 2- and 4-year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow-up of 2 years (range 0.3-13.5). The median age was 2 years (range 0.2-19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p = .0007), pre-radiation chemotherapy response (p < .001), and high-dose chemotherapy with stem cell recuse (HDSCT, p = .002) correlated with survival. On multivariate analysis, pre-radiation chemotherapy response (p = .02) and GTR (p = .012) retained survival significance as compared to a trend for HDSCT (p = .072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400 cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p = .089) over CSI. CONCLUSION: Chemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.

Prognostic factors of pediatric pineal region tumors at a single institution.

PURPOSE: This study aimed to identify factors of a worse prognosis among different histological types of pineal region tumors in pediatric patients treat at a single institution in a 30-year period. MATERIAL AND METHODS: Pediatric patients (151; < 18 years of age) treated between 1991 and 2020 were analyzed. Kaplan-Meyer survival curves were created, and the log-rank test was used to compare the main prognostic factors in the different histological types. RESULTS: Germinoma was found in 33.1%, with an overall 60-month survival rate of 88%; the female sex was the only factor of a worse prognosis. Non-germinomatous germ cell tumors were found in 27.1%, with an overall 60-month survival rate of 67.2%; metastasis upon diagnosis, residual tumor, and the absence of radiotherapy were associated with a worse diagnosis. Pineoblastoma was found in 22.5%, with an overall 60-month survival rate of 40.7%; the male sex was the only factor of a worse prognosis; a tendency toward a worse outcome was found in patients < 3 years of age and those with metastasis upon diagnosis. Glioma was identified in 12.5%, with an overall 60-month survival rate of 72.6%; high-grade gliomas were associated with a worse prognosis. Atypical teratoid rhabdoid tumors was found in 3.3%, and all patients died within a 19-month period. CONCLUSION: Pineal region tumors are characterized by the heterogeneity of histological types, which exert an influence on the outcome. Knowledge of the prognostic factors for each histological types is of extreme importance to the determination of guided multidisciplinary treatment.

Spinal atypical teratoid rhabdoid tumor-narrative review and report of a rare case managed with multimodality approach.

BACKGROUND: Spinal atypical teratoid rhabdoid tumor (AT/RT) is an extremely rare tumor and represents less than 2% of all AT/RTs. METHODS: Available medical literature on spinal AT/RT in English was retrieved from PubMed and comprehensively reviewed. Clinical presentation, diagnosis, management, prognosis, and outcome in patients with spinal AT/RT have been elucidated by citing a case of extradural AT/RT of the cervicodorsal spine. RESULTS: The age at presentation is usually less than 3 years. The most common site is the cervicodorsal spine. The most frequent tumor location is intradural extramedullary. A contrast-enhanced magnetic resonance imaging (MRI) of the entire neuraxis is the imaging modality of choice. The incidence of leptomeningeal dissemination is high (15-30%). Histopathological examination shows an admixture of primitive neuroectodermal, mesenchymal, and epithelial elements along with rhabdoid cells. Loss of SMARCB1/INI1 is considered pathognomonic of AT/RT. Maximal safe resection of tumor is the initial management of choice. Thereafter focal radiotherapy for localized tumor or craniospinal irradiation for leptomeningeal dissemination should be considered. Post-operative intensive polychemotherapy including intrathecal and high-dose chemotherapy (with autologous stem cell rescue) is usually considered to optimize survival. Typically, the time to recurrence and overall survival are less than 6 and 12 months, respectively. However, with judicious multimodality management long-term survivors are increasingly being recognized. The illustrative patient was a 18-month-old girl diagnosed with extradural AT/RT of the cervicodorsal spine (C3-D1), who was managed with maximal safe resection of tumor, multiagent chemotherapy (ICE-ifosfamide, carboplatin, etoposide) and focal RT to the tumor bed-50.4 Gy/28 fractions/5.5 weeks. At the last follow-up visit, 30 months after surgery, she had complete clinicoradiological response. CONCLUSION: Multimodal treatment comprising maximal safe resection of tumor, multiagent chemotherapy (ICE), and focal RT can lead to successful outcome in patients with localized spinal AT/RT, under the age of 3 years.

Embryonal Tumors of the Central Nervous System with Multilayered Rosettes and Atypical Teratoid/Rhabdoid Tumors.

The 2016 WHO classification of tumors of the central nervous system affected importantly the group of CNS embryonal tumors. Molecular analysis on methylome, genome, and transcriptome levels allowed better classification, identification of specific molecular hallmarks of the different subtypes of CNS embryonal tumors, and their more precise diagnosis. Routine application of appropriate molecular testing and standardized reporting are of pivotal importance for adequate prognosis and treatment, but also for epidemiology studies and search for efficient targeted therapies. As a result of this approach, the term primitive neuroectodermal tumor-PNET was removed and a new clinic-pathological entity was introduced-Embryonal tumor with multilayered rosettes (ETMR). The group of CNS embryonal tumors include also medulloblastoma, medulloepithelioma, CNS neuroblastoma, CNS ganglioneuroblastoma, atypical teratoid/rhabdoid tumor (ATRT) and their subtypes. This chapter will focus mainly on ETMR and ATRT. Embryonal tumors with multilayered rosettes and the atypical teratoid/rhabdoid tumors are undifferentiated or poorly differentiated tumors of the nervous system that originate from primitive brain cells, develop exclusively in childhood or adolescence, and are characterized by a high degree of malignancy, aggressive evolution and a tendency to metastasize to the cerebrospinal fluid. Their clinical presentation is similar to other malignant, intracranial, neoplastic lesions and depends mainly on the localization of the tumor, the rise of the intracranial pressure, and eventually the obstruction of the cerebrospinal fluid pathways. The MRI image characteristics of these tumors are largely overlappingintra-axial, hypercellular, heterogeneous tumors, frequently with intratumoral necrosis and/or hemorrhages. Treatment options for ETMR and ATRT are very restricted. Surgery can seldom achieve radical excision. The rarity of the disease hampers the establishment of a chemotherapy protocol and the usual age of the patients limits severely the application of radiotherapy as a therapeutic option. Consequently, the prognosis of these undifferentiated, malignant, aggressive tumors remains dismal with a 5-year survival between 0 and 30%.

Brain and Spinal Cord Tumors of Embryonic Origin.

Embryonal tumors (ETs) of the central nervous system (CNS) comprise a large heterogeneous group of highly malignant tumors that predominantly affect children and adolescents. Currently, the neoplasms classified as ET are the medulloblastoma (MB), embryonal tumors with multilayered rosettes (ETMR), medulloepithelioma (ME), CNS neuroblastoma (NB), CNS ganglioneuroblastoma (GNB), atypical teratoid/rhabdoid tumors (AT/RT), and CNS embryonal tumors with rhabdoid features. All these tumors are classified as malignant-grade IV neoplasms, and the prognosis of patients with these neoplasms is very poor. Currently, except for the histological classification of MB, the recently utilized WHO classification accepts a novel molecular classification of MBs into four distinct molecular subgroups: wingless/integrated (WNT)-activated, sonic hedgehog (Shh), and the numerical Group3 and Group 4. The combination of both histological and genetic classifications has substantial prognostic significance, and patients are categorized as low risk with over 90% survival, the standard risk with 75-90% survival, high risk with 50-75% survival, and very high risk with survival rate lower than 50%. Children under three years are predominantly affected by AT/RT and represent about 20% of all CNS tumors in this age group. AT/RT is typically located in the posterior fossa (mainly in cerebellopontine angle) in 50-60% of the cases. The pathogenesis of this neoplasm is strongly associated with loss of function of the SMARCB1 (INI1, hSNF5) gene located at the 22q11.23 chromosome, or very rarely with alterations in (SMARCA4) BRG1 gene. The cells of this neoplasm resemble those of other neuronal tumors, and hence, immunochemistry markers have been utilized, such as smooth muscle actin, epithelial membrane antigen, vimentin, and lately antibodies for INI1. ETMRs are characterized by the presence of ependymoblastic rosettes formed by undifferentiated neuroepithelial cells and neuropil. The tumorigenesis of ETMRs is strongly related to the amplification of the pluripotency factor Chr19q13.41 miRNA cluster (C19MC) present in around 90% of the cases. Additionally, the expression of LIN28A is a highly sensitive and specific marker of ETMR diagnosis, as it is overexpressed in almost all cases of ETMR and is related to poor patient outcomes. The treatment of patients with ETs includes a combination of surgical resection, radiotherapy (focal or craniospinal), and chemotherapeutic agents. Currently, there is a trend to reduce the dose of craniospinal irradiation in the treatment of low-risk MBs. Novel targeted therapies are expected in the treatment of patients with MBs due to the identification of the main driver genes. Survival rates vary between ET types and their subtypes, with ganglioneuroblastoma having over 95% 5-year survival rate, while ATRT is probably linked with the worst prognosis with a 30% 5-year survival rate.

Paediatric atypical teratoid/rhabdoid tumour of the pineal region mimicking a meningioma: a case report and literature review.

PURPOSE: Atypical teratoid/rhabdoid tumour (AT/RT) is a highly malignant central nervous system tumour of early childhood. According to the latest WHO classification, the diagnosis of AT/RTs needs to be confirmed by the absence of SMARCB1 (INI1) or SMARCA4 (BRG1) protein expression. AT/RT in the pineal region is infrequent and most have not been proven genetically. Here, we report a case of AT/RT in the pineal region, preoperatively misdiagnosed as a meningioma. Immunohistochemistry revealed the absence of INI1 protein expression. METHOD: A 29-month-old boy was admitted to the hospital after 14 days of emotional apathy and a 2-day vomiting history. AT/RT was not considered during the initial diagnosis because this tumour is rare in this region and is often accompanied by cystic degeneration and necrosis on imaging. Subsequently, the patient underwent surgery and the tumour was completely excised. RESULT: The pathological diagnosis was AT/RT. After discharge, the patient continued chemotherapy in other hospitals but died five months after surgery because of disease progression. CONCLUSION: To our knowledge, this is the fifth case of paediatric pineal AT/RT confirmed genetically. Although in children AT/RT in the pineal gland is rare, a differential diagnosis of AT/RT should be considered when new pineal masses appear in children. For this highly malignant disease with poor prognosis, it is very important to detect and recognize the disease as soon as possible, and to adopt surgery plus multiple treatment management.

Atypical teratoid rhabdoid tumour in the third ventricle of a young adult - a rare presentation.

INTRODUCTION: Atypical teratoid/rhabdoid tumours (AT/RT) are malignant CNS tumours predominantly seen in infants and children. Adult AT/RTs have a predilection for mid-line structures, such as the pineal and pituitary glands. We report a case of AT/RT in a young adult, with its origin from the third ventricle. This is the first documented case of adult AT/RT in the third ventricle. CASE PRESENTATION: A 20-year-old male presented with acute onset headache and vomiting. MRI showed a lesion involving the optic chiasm, hypointense on T1, and heterogeneously hyperintense on T2, with stippled post-contrast enhancement. He underwent a right peri-coronal parasagittal craniotomy, transforaminal and sub choroidal approach with gross total tumour resection. Histopathological report was ATRT, WHO grade 4, with loss of SMARCB1 (INI1) protein. He later underwent a ventriculo-peritoneal shunt placement for postoperative hydrocephalus and was later given adjuvant chemoradiotherapy. No recurrence was noted on follow up MRI. CONCLUSION: AT/RTs are not limited to the paediatric age group, and their incidence among adults is being increasingly reported. Occurrence of AT/RT in the third ventricle of a young adult male has never been reported in the past. It merits consideration as a differential diagnosis of any midline lesion with malignant appearance in adults.

Novel Strategy Involving High-Dose Chemotherapy with Stem Cell Rescue Followed by Intrathecal Topotecan Maintenance Therapy without Whole-Brain Irradiation for Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.

Spatial molecular profiling of a central nervous system low-grade diffusely infiltrative tumour with INI1 deficiency featuring a high-grade atypical teratoid/rhabdoid tumour component.

We performed spatial epigenetic and transcriptomic analyses of a highly unusual low-grade diffusely infiltrative tumour with INI1 deficiency (CNS LGDIT-INI1), which harboured a high-grade component corresponding to an atypical teratoid/rhabdoid tumour (AT/RT). Methylation profiles of both low-grade and high-grade components yielded high similarity with AT/RTs of the MYC subgroup, whereas RNA expression analyses revealed increased translational activity and MYC pathway activation in the high-grade component. Close follow-up of patients harbouring CNS LGDIT-INI1 is warranted.

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.