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Neuropathologie der Medulloblastome und anderer embryonaler Tumoren des ZNS

Präzisierung der Diagnostik durch Integration genetischer Marker

Neuropathology of medulloblastomas and other CNS embryonal tumors

Precision diagnostics through the integration of genetic markers

  • Schwerpunkt: Neuropathologie
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Zusammenfassung

Die überarbeitete WHO-Klassifikation von Tumoren des zentralen Nervensystems 2016 hat das Konzept der integrierten Diagnose eingeführt. Die Definition von Medulloblastomentitäten erfordert nun eine Kombination der traditionellen histologischen Informationen mit zusätzlichen molekularen/genetischen Merkmalen. Zur Definition der histopathologischen Komponente der Medulloblastomdiagnose sollten die Tumoren einer der 4 Entitäten klassisches, desmoplastisches/noduläres (DNMB), extensiv noduläres (MBEN) oder großzelliges/anaplastisches (LC/A) Medulloblastom zugeordnet werden. Die genetisch definierte Komponente ist eine der 4 Entitäten „WNT-aktiviert“, „SHH-aktiviert und TP53-Wildtyp“, „SHH-aktiviert und TP53-mutiert“ oder „Non-WNT-/Non-SHH-Medulloblastom“. Es stehen robuste und validierte Methoden zur Verfügung, um eine präzise Diagnose dieser Medulloblastomentitäten gemäß der aktualisierten WHO-Klassifikation und differenzialdiagnostische Abgrenzung zu anderen Tumorentitäten zu ermöglichen. Eine Analyse von immunhistochemischen Markern wie ß‑Catenin, Yap1, p75-NGFR, Otx2 und p53 in Kombination mit gezielter Sequenzierung und Beurteilung der chromosomalen Kopienzahl (wie FISH-Analyse der MYC-Gene) ermöglicht eine präzise Stratifizierung von Patienten zur risikoadaptierten Therapie. In die Gruppe der anderen embryonalen Tumoren des zentralen Nervensystems fallen die embryonalen Tumoren mit mehrlagigen Rosetten (ETMR), die zum großen Teil eine Amplifikation des microRNA-Clusters C19MC tragen, und die (Ganglio‑)Neuroblastome des ZNS (Zentralnervensystem). Auch diese seltenen Tumoren können durch charakteristische genetische und immunphänotypische Merkmale sicher identifiziert werden.

Abstract

The revised WHO classification of tumors of the central nervous system (CNS) in 2016 introduced the concept of the “integrated diagnosis.” The definition of medulloblastoma entities now requires a combination of traditional histological information with additional molecular/genetic features. To define the histopathological component of the medulloblastoma diagnosis, tumors have to be assigned to one of the four histological entities: classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma. The genetically defined component is one of the four entities: “WNT activated”, “SHH activated and TP53 wildtype”, “SHH activated and TP53 mutant”, or “non-WNT/non-SHH medulloblastoma.” Robust and validated methods are available that allow a precise diagnosis of these medulloblastoma entities according to the updated WHO classification and for differential diagnostic purposes. An immunohistochemical analysis of protein markers including ß‑Catenin, Yap1, p75-NGFR, Otx2 and p53, in combination with targeted sequencing and chromosomal copy number assessment (such as FISH analysis for MYC genes), allows a precise stratification of patients for risk-adapted treatment. The group of other embryonic tumors of the central nervous system includes embryonic tumors with multilayered rosettes (ETMR), which frequently carry an amplification of the micro-RNA cluster C19MC and the (ganglio-)neuroblastomas of the CNS. These rare tumors can also be identified by characteristic genetic and immunophenotypic features.

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  1. Institut für Neuropathologie, DGNN Hirntumor-Referenzzentrum, DZNE Deutsches Zentrum für Neurodegenerative Erkrankungen, Universität Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland

    T. Pietsch

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Pietsch, T. Neuropathologie der Medulloblastome und anderer embryonaler Tumoren des ZNS. Pathologe 40, 140–147 (2019). https://doi.org/10.1007/s00292-019-0580-9

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