Abstract
Although there is significant histological variability, embryonal tumors are grouped together because they are, at least partially, composed of immature neuroepithelial cells resembling the cells that make up the most primitive or embryonal stages of the CNS: the germinal matrix stem cell population. They are tumors mainly, but not exclusively, occurring in children and adolescents (0–14 years) and together comprise 15–20% of all CNS tumors in this age group. Embryonal tumors are characterized by an aggressive behavior with a high frequency of local recurrence, spread through the CSF, and even extraneural metastasis (CNS WHO grade 4). In the 2021 WHO classification, embryonal tumors are classified according to a combination of histopathological and molecular features into two general categories: (1) medulloblastoma, with four molecularly defined groups and four histologically defined groups, and (2) other embryonal tumors, which include atypical teratoid/rhabdoid tumor (AT/RT), embryonal tumor with multilayered rosettes (ETMR), FOXR2-activated CNS neuroblastoma, and CNS tumor with BCOR internal tandem duplication. In addition, cribriform neuroepithelial tumor has been introduced as a provisional entity within this category, whereas the broad designation CNS embryonal tumor is included for embryonal tumors that defy a more specific diagnosis, e.g., that are NOS (diagnostic information necessary to assign a specific diagnosis is not available) or NEC (adequate testing does not reveal signature molecular aberrations). In this chapter, the clinicopathological features and differential diagnosis of these entities are reviewed.
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Medulloblastoma
Czapiewski P, Gorczynski A, Radecka K, et al. Expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma. Pathol Res Pract. 2016;212:965–71.
DeSouza RM, Jones BRT, Stephen P, et al. Pediatric medulloblastoma—update on molecular classification driving targeted therapies. Front Oncol. 2014;4:176.
Ellison DW, Dalton J, Kocak M, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 2011;121:381–96.
Hovestadt V, Ayrault O, Swartling FJ, et al. Medulloblastomics revisited: biological and clinical insights from thousands of patients. Nat Rev Cancer. 2020;20:42–56.
Khanna V, Achey RL, Ostrom QT, et al. Incidence and survival trends for medulloblastomas in the United States from 2001 to 2013. J Neuro-Oncol. 2017;135:433–41.
Kumar R, Liu APY, Northcott PA. Medulloblastoma genomics in the modern molecular era. Brain Pathol. 2020;30:679–90.
Lacruz CR, Catalina-Fernández I, Bardales RH, et al. Intraoperative consultation on pediatric central nervous system tumors by squash cytology. Cancer Cytopathol. 2015;123:331–46.
Lacruz CR, Sáenz de Santamaría J, Bardales RH. Medulloblastoma. In: Central nervous system intraoperative cytopathology. 2nd ed. Switzerland AG: Springer Nature; 2018. p. 186–92.
Liu Y, Xiao B, Li S, et al. Risk factors for survival in patients with medulloblastoma: a systematic review and meta-analysis. Front Oncol. 2022;12:827054.
Louis DN, Perry A, Burger P, et al. International society of neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol. 2014;24:429–35.
Massimino M, Antonelli M, Gandola L, et al. Histological variants of medulloblastoma are the most powerful clinical prognostic indicators. Pediatr Blood Cancer. 2013;60:210–6.
Massimino M, Biassoni V, Gandola L, Garrè ML, et al. Childhood medulloblastoma. Cri Rev. Oncol Hematol. 2016;105:35–51.
Merchant TE, Pollack IF, Loeffler JS. Brain tumors across the age spectrum: biology, therapy, and late effects. Semin Radiat Oncol. 2010;20:58–66.
Northcott PA, Buchhalter I, Morrissy AS, et al. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017;547:311–7.
Northcott PA, Shih DJ, Remke M, et al. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol. 2012;123:615–26.
Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro-Oncology. 2019;21(Suppl 5):v1–v100.
Robinson GW, Orr BA, Wu G, et al. Vismodegib exerts targeted efficacy against recurrent sonic hedgehog-subgroup medulloblastoma: results from phase II pediatric brain tumor consortium studies PBTC-025B and PBTC-032. J Clin Oncol. 2015;33:2646–54.
Schwalbe EC, Lindsey JC, Nakjang S, et al. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. Lancet Oncol. 2017;18(7):958–71.
Schwalbe EC, Williamson D, Lindsey JC, et al. DNA methylation profiling of medulloblastoma allows robust subclassification and improved outcome prediction using formalin-fixed biopsies. Acta Neuropathol. 2013;125:359–71.
Waszak SM, Northcott PA, Buchhalter I, et al. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018;19:785–98.
Atypical Teratoid/Rhabdoid Tumor
Biegel JA, Zhou JY, Rorke LB, et al. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999;59:74–9.
Burger PC, Yu IT, Tihan T, et al. Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric oncology group study. Am J Surg Pathol. 1998;22:1083–92.
Fossey M, Li H, Afzal S, et al. Atypical teratoid rhabdoid tumor in the first year of life: the Canadian ATRT registry experience and review of the literature. J Neuro-Oncol. 2017;132:155–62.
Frühwald MC, Biegel JA, Bourdeaut F, et al. Atypical teratoid/rhabdoid tumors—current concepts, advances in biology, and potential future therapies. Neuro-Oncology. 2016;18:764–78.
Geller JI, Roth JJ, Biegel JA. Biology and treatment of rhabdoid tumor. Crit Rev. Oncog. 2015;20:199–216.
Hasselblatt M, Nagel I, Oyen F, et al. SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited germline alterations and poor prognosis. Acta Neuropathol. 2014;128:453–6.
Johann PD, Erkek S, Zapatka M, et al. Atypical teratoid/rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes. Cancer Cell. 2016;29:379–93.
Lacruz CR, Sáenz de Santamaría J, Bardales RH. Atypical teratoid/rhabdoid tumor. In: Central nervous system intraoperative cytopathology. 2nd ed. Switzerland AG: Springer Nature; 2018. p. 199–205.
Lee J, Kim D, Han JW, et al. Atypical teratoid/rhabdoid tumors in children treated with multimodal therapies: the necessity of upfront radiotherapy after surgery. Pediatr Blood Cancer. 2017;64:12.
Ostrom QT, Chen Y, de Blank MP, et al. The descriptive epidemiology of atypical teratoid/rhabdoid tumors in the United States, 2001–2010. Neuro-Oncology. 2014;16:1392–9.
Sévenet N, Sheridan E, Amram D, et al. Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet. 1999;65:1342–8.
Sredni ST, Tomita T. Rhabdoid tumor predisposition syndrome. Pediatr Dev Pathol. 2015;18:49–58.
Torchia J, Picard D, Lafay-Cousin L, et al. Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis. Lancet Oncol. 2015;16:569–82.
Embryonal Tumor with Multilayered Rosettes
de Kock L, Priest JR, Foulkes WD, et al. An update on the central nervous system manifestations of DICER1 syndrome. Acta Neuropathol. 2020;139:689–701.
Horwitz M, Dufour C, Leblond P, et al. Embryonal tumors with multilayered rosettes in children: the SFCE experience. Childs Nerv Syst. 2016;32:299–305.
Kleinman CL, Gerges N, Papillon-Cavanagh S, et al. Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nat Genet. 2014;46:39–44.
Korshunov A, Sturm D, Ryzhova M, et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. Acta Neuropathol. 2014;128:279–89.
Korshunov A, Ryzhova M, Jones DT, et al. LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR). Acta Neuropathol. 2012;124:875–81.
Lacruz CR, Sáenz de Santamaría J, Bardales RH. CNS embryonal tumors replacing PNET. In: Central nervous system intraoperative cytopathology. 2nd ed. Switzerland AG: Springer Nature; 2018. p. 189–99.
Lambo S, von Hoff K, Korshunov A, et al. ETMR: a tumor entity in its infancy. Acta Neuropathol. 2020;140:249–66.
Raghuram N, Khan S, Mumal I, et al. Embryonal tumors with multi-layered rosettes: a disease of dysregulated miRNAs. J Neuro-Oncol. 2020;150:63–73.
Spence T, Sin-Chan P, Picard D, et al. CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity. Acta Neuropathol. 2014;128:291–303.
CNS Neuroblastoma, FOXR2-Activated
Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555:469–74.
Holsten T, Lubieniecki F, Spohn M, et al. Detailed clinical and histopathological description of 8 cases of molecularly defined CNS neuroblastomas. J Neuropathol Exp Neurol. 2021;80:52–9.
Hwang EI, Kool M, Burger PC, et al. Extensive molecular and clinical heterogeneity in patients with histologically diagnosed CNS-PNET treated as a single entity: a report from the children’s oncology group randomized ACNS0332 trial. J Clin Oncol. 2018;36:JCO2017764720.
Lacruz CR, Sáenz de Santamaría J, Bardales RH. CNS embryonal tumors replacing PNET. In: Central nervous system intraoperative cytopathology. 2nd ed. Switzerland AG: Springer Nature; 2018. p. 189–99.
Łastowska M, Trubicka J, Sobocińska A, et al. Molecular identification of CNS NB-FOXR2, CNS EFT-CIC, CNS HGNET-MN1 and CNS HGNET-BCOR pediatric brain tumors using tumor-specific signature genes. Acta Neuropathol Commun. 2020;8:105.
Poh B, Koso H, Momota H, et al. Foxr2 promotes formation of CNS-embryonal tumors in a Trp53-deficient background. Neuro-Oncology. 2019;21:993–1004.
Sturm D, Orr BA, Toprak UH, et al. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell. 2016;164:1060–72.
CNS Tumor with BCOR Internal Tandem Duplication
Appay R, Macagno N, Padovani L, et al. HGNET-BCOR tumors of the cerebellum: clinicopathologic and molecular characterization of 3 cases. Am J Surg Pathol. 2017;41:1254–60.
Ferris SP, Velazquez Vega J, Aboian M, et al. High-grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication-a comprehensive clinical, radiographic, pathologic, and genomic analysis. Brain Pathol. 2020;30:46–62.
Łastowska M, Trubicka J, Sobocińska A, et al. Molecular identification of CNS NB-FOXR2, CNS EFT-CIC, CNS HGNET-MN1 and CNS HGNET-BCOR pediatric brain tumors using tumor-specific signature genes. Acta Neuropathol Commun. 2020;8:105.
Sturm D, Orr BA, Toprak UH, Hovestadt V, et al. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell. 2016;164:1060–72.
Yoshida Y, Nobusawa S, Nakata S, et al. CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication: a comparison with its counterparts in the kidney and soft tissue. Brain Pathol. 2018;28:710–20.
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Lacruz, C.R., Leonardo, E. (2023). Embryonal Tumors. In: Lacruz, C.R. (eds) Central Nervous System Tumors . Springer, Cham. https://doi.org/10.1007/978-3-031-51078-6_9
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DOI: https://doi.org/10.1007/978-3-031-51078-6_9
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