Embryonal Tumor With Abundant Neuropil And True Rosettes Research Articles

ATRT-19. RARE EMBRYONAL TUMORS INCLUDING EMBRYONAL TUMOR MULTILAYER ROSETTE, OUTCOME AND PATTERN OF TREATMENT FAILURE: MD ANDERSON CANCER CENTER EXPERIENCE

Abstract Rare embryonal tumors (excluding medulloblastoma and ATRT) are aggressive pediatric cancers that include embryonal tumor with multilayer rosettes (ETMR), embryonal tumor with abundant neuropil and true rosettes (ETANTR), and embryonal tumors not otherwise specified (ET-NOS). The presence of driver events like C19MC amplification, DICER1 mutations and other microRNA-related aberrations are vital in diagnostic classification of these tumors. The prognosis of these tumors is dismal despite intensive multimodal treatments with the 5-year overall survival being less than 30%. We retrospectively reviewed 12 patients with rare embryonal tumors who were treated at MD Anderson Cancer Center from 2010 to 2022. Of the 12 patients identified, the mean age at diagnosis was 3.6 years (range: 1-12 years) with no sex differences. Histologically, they were classified into ETMR (4/12), ETANTR (3/12) and ET-NOS (5/12) with C19MC found positive in 2/4 ETMR cases. All patients presented with large infiltrative tumors to the supratentorial (6/12), brainstem (4/12), and spinal (2/12) regions. The majority of patients (10/12) were treated by gross/subtotal resection. Treatment at diagnosis included surgery alone (3/12), surgery with chemotherapy (4/12), surgery with chemotherapy plus radiation (4/12),and chemotherapy plus radiation without surgery (1/12). Five patients reported with de-novo metastasis and 10/12 patients had disease progression at 4.1 months of median follow-up (range: 1.2-10.6 months). Six patients had local recurrence and three patients had local with distant disease at progression. Eight patients are still alive, with 5/8 of them surviving more than 5 years. In conclusion, these rare embryonal tumors are hard to diagnose and treat effectively. Even with successful surgery and intense chemotherapy, almost all of them progress/relapse but combined treatments seem to be effective in a subset of patients. Collaborative multi-institutional efforts are required to define standard treatment approaches and future patient stratification.

Fatal outcome of intracranial embryonal tumor with multiple rosettes: Case report and review of the literature

There are three known histological variant within the family of embryonal tumor with multiple rosettes. This family included embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). Here we report a case and performed a comprehensive overview in terms of clinical, pathological, molecular and management outcomes of this rare entity of paediatric brain tumor. Clinically these variants found to have similar characteristics like age (<4 year) associated with highly aggressive nature with reported survival period of 2-3 years. In immunohistochemistry (IHC), most commonly applied markers were synaptophysin, neurofilament protein, Neu-N and glial fibrillary acidic protein (GFAP). Recent data on molecular subgroups of PNETs have led to new insights on diagnosis and treatment of these tumors. Subsequently, LIN28A immunoexpression was identified as a highly specific marker for ETMR. As these tumor having poor prognosis because of aggressiveness in nature, treated as high risk brain tumors. Here we want to report a highly aggressiveness nature of disease, a 6 year old child presented with fever, headache and vomiting. Radiological diagnosis suggestive of left parieto-occipital lesion in brain underwent two time surgery and IHC suggestive of embryonal tumors with multilayered rosettes -WHO grade-IV. He had not responded to treatment and died with overall survival of 2 months.

Clinicopathological characteristics and outcomes in embryonal tumor with multilayered rosettes: A decade long experience from a tertiary care centre in North India

BackgroundEmbryonal tumor with multilayered rosettes (ETMR) are a heterogenous group clinically, pathologically and topographically. Due to limited cases, data regarding its molecular genetics, pathology and prognostic factors is evolving. We retrospectively analysed our cohort of ETMR over last decade in order to study their clinicopathological characteristics and outcome. MethodsOur cohort consisted of patients diagnosed with Embryonal tumor with abundant neuropil and true rosettes (ETANTR)/Ependymoblastoma (EBL)/ Medulloepithelioma (MEPL) over the past decade. Clinical details, including outcome and imaging data was retrieved. Histological analysis including immunohistochemical work-up was performed. ResultsCohort included 15 patients with age range between 1 and 28 years and M:F ratio of 1.5:1. Supratentorial location predominated in comparison to tumors arising in posterior fossa. ETANTR and EBL patterns were equally distributed (40% each), followed by one case each of mixed pattern (EBL + ETANTR), MEPL and embryonal tumor, unclassified. All tumors readily expressed LIN 28A and INI-1 was retained. Recurrence with evidence of glial and rhabdoid differentiation was noted in a single patient 9 months following resection. Follow-up period ranged from 1 to 31 months, with overall median survival of 6.4 months. Eight patients were planned for adjuvant treatment following surgery, of which only four could complete it. All patients, except for one, succumbed to the disease. ConclusionsETMR have a heterogenous morphology and gathers ETANTR, EBL, MEPL within its spectrum. Following treatment, the recurrent tumor may feature glial/rhabdoid differentiation. LIN28A is expressed in all cases, however should be interpreted in context of histology. Prognosis of ETMR remains dismal despite multimodal therapy.

Embryonal tumors with multilayered rosettes: A tertiary care centre experience

BackgroundEmbryonal tumors with multilayered rosettes (ETMR) is an extremely rare and highly aggressive tumor. It includes three distinct entities i.e, embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL) and medulloepithelioma (MEPL). Here, we present our institutional experience of seven ETMR cases treated over a period of five years. Materials and methodsPatients’ records from 2015 to 2019 were reviewed manually and electronically to retrieve the data. Clinicopathological and outcome details of ETMR cases were entered in a predesigned proforma. ResultsA total of seven cases of ETMR were registered from 2015 to 2019 with a median age at presentation of four years (range 3–7 years). All patients underwent surgery. However, only three patients completed the planned adjuvant treatment, comprising of focal radiotherapy (RT) alone, craniospinal irradiation (CSI) alone and CSI followed by six cycles of chemotherapy in one patient each respectively. Two patients commenced CSI but deteriorated during RT and thereafter needed best supportive care. Two patients could not be started on any adjuvant treatment. Unfortunately, six patients succumbed to their disease within one year of their diagnosis. Only one patient who received both CSI and adjuvant chemotherapy is alive at 15 months of diagnosis. ConclusionETMR is a rare and aggressive entity. Majority of the patients die within one year of the diagnosis despite multimodality treatment.

A case of Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR): a distinct genetic locus with an excellent outcome (P3.6-010)

A case of Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR): a distinct genetic locus with an excellent outcome (P3.6-010)

Radiation for ETMR: Literature review and case series of patients treated with proton therapy

Background and purposeEmbryonal tumors with multilayered rosettes (ETMRs) are aggressive tumors that typically occur in young children. Radiation is often deferred or delayed for these patients due to late effects; proton therapy may mitigate some of these concerns. This study reviews the role of radiation in ETMR and describes initial results with proton therapy. Materials and methodsRecords of patients with embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma (MEP), and ependymoblastoma (EPL) treated with proton therapy at our institution were retrospectively reviewed. A literature review of cases of CNS ETANTR, MEP, and EPL published since 1990 was also conducted. ResultsSeven patients were treated with proton therapy. Their median age at diagnosis was 33 months (range 10–57 months) and their median age at radiation start was 42 months (range 17–58 months). Their median overall survival (OS) was 16 months (range 8–64 months), with three patients surviving 36 months or longer. Five patients had disease progression prior to starting radiation; all 5 of these patients failed in the tumor bed. A search of the literature identified 204 cases of ETMR with a median OS of 10 months (range 0.03–161 months). Median OS of 18 long-term survivors (≥36 months) in the literature was 77 months (range 37–184 months). Of these 18 long-term survivors, 17 (94%) received radiotherapy as part of their initial treatment; 14 of them were treated with craniospinal irradiation. ConclusionsOutcomes of patients with ETMR treated with proton therapy are encouraging compared to historical results. Further study of this rare tumor is warranted to better define the role of radiotherapy.

Embryonal tumors with multilayered rosettes in children: the SFCE experience.

The purpose of this study was to retrospectively study embryonal tumors with multilayered rosettes (ETMR), a rare new entity that gathers ETAN-TR (embryonal tumor with abundant neuropil and true rosettes), ependymoblastomas, and medulloepitheliomas, in order to improve their descriptions and try to better define therapeutic modalities. Patients with ETMR, ETAN-TR, ependymoblastoma, and medulloepithelioma treated in SFCE centres (Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'adolescent) since 2000 were collected. Data were retrieved from clinical charts. Thirty-eight patients were included in the analysis. Seventeen had an ETAN-TR, 13 had a medulloepithelioma, and 8 had an ETMR. No ependymoblastoma was included. The median age at diagnosis was 31 months (range, 2.8-141 months). The predominant tumor location was supratentorial (66%); 18.4% patients had metastatic lesion. LIN28A expression was positive in 11/11 patients. Amplification of the locus 19q13.42 was positive in 10/12 patients. Thirty patients were treated according to the primitive neuroectodermal tumors of high risk (PNET-HR) protocol. The median time of follow-up was 0.9 years (range 0.1 to 15.3 years). The 1-year event-free survival (EFS) and overall survival (OS) were, respectively, 36% CI 95% (23-55) and 45% CI 95% (31-64). On multivariate analysis, complete surgical resection, radiotherapy, and high-dose chemotherapy were associated with a better overall survival with a relative risk of, respectively, 7.9 CI 95% (2.6-23.5) p < 0.0002, 41.8 CI 95% (9.4-186) p < 0.0001, and 3.5 CI 95% (1.3-9.5) p = 0.012. Prognosis of ETMR remains dismal despite multimodal therapy. LIN28A immunostaining and 19q13.42 amplification should be systematically done to secure the diagnosis. Complete surgical resection, radiotherapy, and high-dose chemotherapy are associated with better outcome.

Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR).

The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57 months). Survival data are available for 48 children (including our case): the median overall survival is 13.0 months, though 6 (9%) of the children have had a relative long survival (>30 months). The aggressive combined treatment, involving primary surgical tumor removal, adjuvant polychemotherapy, including high-dose chemotherapy with stem cell transplantation, radiotherapy and radiochemotherapy, might play an important role in the longer survival. We have performed a literature review and we present here a multimodal-treated case of a 2- year-old girl with a long survival, who was reoperated when recurrence occurred. The residual tumor demonstrated a good response to temozolomide radiochemotherapy (craniospinal axis + boost) and followed by maintenance temozolomide. The described complex aggressive treatment option might be considered for future cases of this tumor entity.

Embryonal tumor with multilayered rosettes of the fourth ventricle: case report.

Embryonal tumor with multilayered rosettes (ETMR) is a recently described pathological entity. These primitive central nervous system tumors harbor amplification of the 19q13.42 locus and resultant overexpression of the LIN28A protein. Although the WHO currently recognizes 3 distinct histopathological entities-embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma-recent studies indicate that these tumors have a common molecular profile and clinical course and that they are now classified as a single entity. Here the authors present a case of ETMR located in the fourth ventricle in a 12-month-old boy. The histopathology featured areas of neuropil-like stroma and highly cellular foci with characteristic multilayered rosettes. The authors discuss the clinical, radiological, and histopathological findings in this case and compare them with data in previously published cases in the literature. A review of studies assessing the molecular mechanisms underlying these tumors is also presented.

Abstract 3093: Unravelling the biology of aggressive and therapy-resistant embryonal tumors with multilayered rosettes (ETMR)

Abstract Embryonal tumor with multilayered rosettes (ETMR) is a highly aggressive embryonal CNS tumor, which predominantly affects children under the age of three to four years and is associated with a highly aggressive disease course with reported overall survival times ranging from 5-30 months. As these tumors have often been misdiagnosed as medulloblastoma or CNS-PNETs it was thought that ETMR is a very rare tumor. However, now molecular tools are available to detect ETMR and distinguish them from other brain tumors it has become clear that it is one of the most common brain tumors among infants. Amplification of a miRNA cluster at 19q13.42 and high expression of LIN28A have been identified as molecular hallmarks of ETMR, affecting 95-100% of samples tested and are considered unifying molecular diagnostic markers to detect them and distinguish from other brain tumors. Three histological variants of ETMR are known. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). A comprehensive clinical, pathological, and molecular analysis of 97 cases of these fatal brain neoplasms identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. In particular, DNA methylation (Illumina 450k arrays) and gene expression data (Affymetrix 133plus2.0 arrays) showed that the three histological variants of ETMR are biologically indistinguishable but together highly distinct from other pediatric brain tumors. In order to better understand the biology of these highly aggressive pediatric CNS malignancies, we performed whole genome DNA sequencing of 15 tumor-normal pairs including 3 recurrences, complemented by (mi)RNA sequencing of tumor RNA. Mutations detected included mutations in TP53, CTNNB1, and mutations affecting the miRNA processing pathway. Chromothripsis was detected in several cases and in all cases affecting chromosome 19q. Finally, as DNA sequencing identified only very few somatic mutations per tumor, we next studied the epigenome of these tumors by performing whole genome bisulfite sequencing. Integrating these high throughput genomic analyses may now lead to alternative treatment strategies for these highly aggressive and therapy-resistant tumors. Citation Format: Marcel Kool, Natalie Jäger, Dominik Sturm, David T.W. Jones, Volker Hoverstadt, Ivo Buchhalter, Pascal Johann, Christin Schmidt, Marina Ryzhova, Paul A. Northcott, Pablo Landgraf, Marc Remke, Michael D. Taylor, Martin Hasselblatt, Ulrich Schüller, Annie Huang, Marie-Laure Yaspo, Andreas von Deimling, Roland Eils, Peter Lichter, Andrey Korshunov, Stefan M. Pfister. Unravelling the biology of aggressive and therapy-resistant embryonal tumors with multilayered rosettes (ETMR). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3093. doi:10.1158/1538-7445.AM2014-3093

CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.

Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-014-1291-1) contains supplementary material, which is available to authorized users.

Embryonal tumor with multilayered rosettes: Diagnostic tools update and review of the literature

Embryonal tumor with multilayered rosettes (ETMR), including embryonal tumor with abundant neuropil and true rosettes (ETANTR), and ependymoblastoma (EBL) constitute a distinct entity of the primitive neuroectodermal tumor (PNET) family. The presence of a focal amplification at chromosome region 19q13.42 associated with an up-regulation of the oncogenic miRNA cluster C19MC suggests that they may represent a histological spectrum of a single biological entity. Their histopathological spectrum is wide, including medulloepithelioma, their location may be supra- or infra-tentorial, their prognosis is poor. Recent data on molecular subgroups of PNETs have led to new insights on diagnosis and treatment of these tumors. Subsequently, LIN28A immunoexpression was identified as a highly specific marker for ETMR. In this study, we report 4 cases diagnosed initially as ETANTR with CGH-array data, including 19q13.42 gain with absence of other amplicons, particularly of the MYC gene family, and inconstant gain of whole chromosome 2. Immunohistochemical positive expression of LIN28A and absence of Olig2 expression were observed. We summarize the literature on ETMR, pointing out on the nosological evolution of this entity and the findings on genetic hallmarks of this particular tumor. Our results emphasize the usefulness of immunohistochemistry as a highly sensitive and fast diagnostic tool for ETMR and for genetic data, especially for 19q13.42 locus. Biological features may offer new therapeutic options for these embryonal tumors that do not usually respond to conventional treatments of PNETs.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity

Three histological variants are known within the family of embryonal rosette-forming neuroepithelial brain tumors. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). In this study, we performed a comprehensive clinical, pathological, and molecular analysis of 97 cases of these rare brain neoplasms, including genome-wide DNA methylation and copy number profiling of 41 tumors. We identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. As such, future WHO classification schemes should consider lumping these variants into a single diagnostic category, such as embryonal tumor with multilayered rosettes (ETMR). We recommend combined LIN28A immunohistochemistry and FISH analysis of the 19q13.42 locus for molecular diagnosis of this tumor category. Recognition of this distinct pediatric brain tumor entity based on the fact that the three histological variants are molecularly and clinically uniform will help to distinguish ETMR from other embryonal CNS tumors and to better understand the biology of these highly aggressive and therapy-resistant pediatric CNS malignancies, possibly leading to alternate treatment strategies.

The Role of CD133+ Cells in a Recurrent Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR)

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently described embryonal neoplasm of the central nervous system, consisting of a well-circumscribed embryonal tumor of infancy with mixed features of ependymoblastoma (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma (neuroblastic rosettes) in the presence of neuropil-like islands. We present the case of a young child with a very aggressive tumor that rapidly recurred after gross total resection, chemotherapy and radiation. Prominent vascular sclerosis and circumscribed tumor led to the diagnosis of malignant astroblastoma; however, rapid recurrence and progression of this large tumor after gross total resection prompted review of the original pathology. ETANTR is histologically distinct with focal glial fibrillary acid protein (GFAP) and synaptophysin expression in the presence of neuronal and ependymoblastic rosettes with focal neuropil islands. These architectural features, combined with unique chromosome 19q13.42 amplification, confirmed the diagnosis. In this report, we describe tumor stem cell (TSC) marker CD133, CD15 and nestin alterations in ETANTR before and after chemotherapy. We found that TSC marker CD133 was richly expressed after chemotherapy in recurrent ETANTR, while CD15 is depleted compared with that expressed in the original tumor, suggesting that CD133+ cells likely survived initial treatment, further contributing to formation of the recurrent tumor.

Embryonal Tumor With Abundant Neuropil And True Rosettes With Melanotic (Retinal) Differentiation

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare variant of central nervous system primitive neuroectodermal tumor occurring exclusively in the pediatric population. We report a unique case of a 6-month male child presenting with a large intraventricular lesion. Histological examination revealed a tumor composed of primitive neuroectodermal cells in dense aggregates, interspersed by hypocellular areas containing small round cells widely dispersed in neuropil-like material. Few ependymal and occasional ependymoblastic rosettes were appreciated. Focal melanotic neuroepithelium recapitulating retinal differentiation was also seen. Documentation of such cases may expand the neuroectodermal differentiation spectrum of ETANTR.

Embryonal tumor with abundant neuropil and true rosettes: an autopsy case-based update and review of the literature

IntroductionEmbryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare subtype of primitive neuroectodermal tumors first reported in 2000. It is rare among the group of embryonal central nervous system tumors with approximately 50 reported cases. ETANTR has been suggested to be a separate entity among this group of tumors.Case reportHerein, we present only the second autopsy case of ETANTR, which occurred in a 17-month-old boy, and was located in the brainstem. The tumor was inoperable, and despite chemotherapy, the child died 3 months after initial hospitalization. A brain only autopsy was performed.DiscussionNeuropathological and neuroimaging examinations suggest ETANTR grew by expansion rather than invasion distorting anatomical structures of the posterior fossa. We suggest that the characteristic histopathological picture of the tumor is the result of multifocal and dispersed germinative activity surrounded by mature neuropil-like areas.ConclusionETANTR is a pediatric tumor occurring in children under 4 with a significantly poor prognosis with more cases and research required to characterize this rare embryonal tumor.

Analysis of Chromosome 19q13.42 Amplification in Embryonal Brain Tumors with Ependymoblastic Multilayered Rosettes

Recently, it was reported that ependymoblastoma and embryonal tumor with abundant neuropil and true rosettes (ETANTR) show 19q13.42 amplification at a high frequency, suggesting that these tumors may constitute a single entity. As ependymoblastic rosettes are the most prominent features in both subtypes, embryonal tumor with multilayered rosettes (ETMR) was proposed, for which 19q13.42 amplification represents a specific molecular hallmark. However, ependymoblastic rosettes are not specific to ependymoblastoma and ETANTR, and are also found in a few other embryonal tumors as well as immature teratomas, and knowledge on 19q13.42 amplification in these tumors is limited. In this study, we performed fluorescence in situ hybridazation (FISH) analysis and differential polymerase chain reaction (PCR), and detected 19q13.42 amplification in three out of four ETANTR, one ependymoblastoma and one medulloepithelioma with ETANTR components, whereas none of the two atypical teratoid/rhabdoid tumors (AT/RT) with ependymoblastic rosettes nor two immature teratomas with developing neuroectodermal structures showed such amplification, suggesting that medulloepitheliomas would possibly be included in ETMR, and ependymoblastic rosettes in AT/RT do not signify that these tumors constitute ETMR. Also, we found C19MC rather than miR-371-373 was amplified in one ETANTR, suggesting that C19MC miRNA cluster seems to be more closely linked to the pathogenesis of ETMR.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with loss of morphological but retained genetic key features during progression

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently recognized, rare embryonal CNS tumor, which predominantly occurs in young children and is associated with a highly aggressive disease course [1–3, 5–8, 13, 14, 18, 19, 23]. The histopathological diagnosis of ETANTR is based on the presence of primitive neuroectodermal tumor cells forming distinct multilayered ‘ependymoblastic’ rosettes and characteristic neuropil islands. Recently, genome-wide analyses have revealed a novel amplification at 19q13.42 [16, 19], which is meanwhile considered the genetic hallmark of ETANTR [13, 16]. The characteristic clinical, morphological, and genetic features support the concept of a distinct CNS PNET variant and suggest its introduction to the WHO classification of Tumors of the Central Nervous System [17]. As the amplification at 19q13.42 has also been found in the vast majority of ependymoblastomas analyzed to date [13, 16], the common genetic background suggests the fusion of these two tumor types to a single entity. Herein, we report for the first time the evolution of morphological features and genetic aberrations during the disease course in a patient with ETANTR. A 33-monthold girl presented with a 6-month history of episodic headaches, increased head circumference and mild gait disturbance. Magnetic resonance (MR) imaging showed a 9.6 9 8.6 9 11.7 cm left parieto-occipital, space-occupying, partly cystic lesion displaying T1-weighted hypoto isointense signals (Fig. 1a) with cerebrospinal fluid-intense cysts on FLAIR sequence (Fig. 1b), and marked choline/ creatine increase as a sign of cell proliferation on single voxel spectroscopy (Fig. 1c). Near-total surgical resection was performed. Histopathology revealed a primitive neuroectodermal tumor with highly cellular areas. Furthermore, hypocellular neuropil islands and multilayered rosettes were

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with a focal amplification at chromosome 19q13.42 locus: Further evidence of two new instances in China

Recently, the term "embryonal tumor with multilayered rosettes" (ETMR), including embryonal tumor with abundant neuropil and true rosettes (ETANTR) and ependymoblastoma (EBL) as a distinct tumor entity, has become an important topic of discussion for neuropathologists since the discovery of a unique genomic alteration in 2009. Here, we contribute two new East Asian instances of ETANTR in a 29-month-old boy who underwent subtotal resection of a large tumor in the bilateral parieto-occipital lobes and a 4-year-old boy who underwent subtotal resection of the right midpontine neoplasm. Both tumors showed a typical histopathological pattern of hypercellular clusters of undifferentiated small cells and ependymoblastic rosettes admixed with paucicellular neuropil-like zones indicative for ETANTR. Rare Homer-Wright neuroblastic rosettes and papillary pseudorosettes, as well as enlarged lumina with mucinous material, were also observed. Immunohistological studies revealed that tumor cells in hypercellular and paucicellular zones were diffusely positive for microtubule-associated protein 2; ependymoblastic rosette cells stained with epithelial membrane antigen at the luminal membrane and exhibiting strong immunoreactivity with p53 protein. β-Catenin and Nestin were frequently detected in the hypercellular zones as well as in the ependymoblastic rosettes. Fluorescence in situ hypribization analysis revealed that both cases contained a unique focal amplification at the 19q13.42 chromosome locus and chromosome 2 polysomy. A new WHO classification of tumors of the CNS should be considered for these neoplasms with unique focal amplification at the 19q13.42 chromosome locus, based on the clinicopathological and molecular features of ETANTR that are distinct and reproducibly recognizable.

Embryonal tumor with abundant neuropil and true rosettes: a report of three cases of a rare tumor, with an unusual case showing rhabdomyoblastic and melanocytic differentiation

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is an increasingly recognized entity that belongs to the family of embryonal tumors of the CNS. The authors present three cases of this rare tumor that were encountered at King Hussein Cancer Center, Amman, Jordan. Discussion of the clinicopathological findings is presented along with a recent literature review. Sixteen-, 57- and 30-month-old children presented with tumors located in the pineal gland, the right fronto- parieto-temporal region and the cerebellum, respectively. The findings of hypocellular neuropil as well as the characteristic ependymoblastic rosettes were seen. In addition the third case showed an abnormal combination of patterns including melanocytic and rhabdomyoblastic differentiation. The tumors stained positively for synaptophysin in the neuropil and small cell component, while the ependymoblastic rosettes stained for vimentin only. Epithelial membrane antigen and CD99 were negative in all components. One of the cases showed tetraploidy of chromosome 2. All cases exhibited an aggressive course. This is a rare and recently recognized tumor with dismal outcome, and reporting of additional new cases should help in gaining more knowledge about it.