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Ewing-Sarkome und Ewing-artige Sarkome

Neue Aspekte

Ewing sarcomas and Ewing-like sarcomas

New aspects

  • Schwerpunkt: Knorpel, Knochen, Chorda – Molekulare Pathologie
  • Published:
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Zusammenfassung

Sarkome der Ewing-Familie sind aggressive Tumoren, die im Knochen und Weichgewebe zumeist bei Kindern und jungen Erwachsenen auftreten. Pathognomonisch für klassische Ewing-Sarkome sind Fusionen zwischen einem Gen der RNA-bindenden TET-Familie (EWSR1 oder FUS) mit einem Gen der ETS-Transkriptionsfaktor-Familie (FLI1, ERG, ETV1, ETV4 oder FEV). In den letzten Jahren wurden neben klassischen Ewing-Tumoren rundzellige Sarkome identifiziert, die bei teilweise überlappender Morphologie und immunhistochemischem Profil aus praktischen und therapeutischen Erwägungen als „Ewing-Sarkom-artig“ eingestuft wurden. Zu diesen Tumoren gehören sowohl die sehr seltenen Sarkome mit Fusion von EWSR1 mit non-ETS-Genen (NFATC2, POU5F1, SMARCA5, PATZ, ZSG, SP3) als auch rundzellige Sarkome mit neu charakterisierten molekularen Veränderungen wie einer CIC-DUX4-Fusion oder BCOR-Alterationen mit jeweils distinkten Genexpressionssignaturen und unterschiedlicher Klinik. Im Gegensatz zu klassischen Ewing-Sarkomen ist das morphologische Spektrum dieser neuen Tumorentitäten sehr viel breiter und umfasst neben rundzelligen auch spindelzellige und myxoide Tumorareale. Das immunhistochemische Profil mit inkonsistenter CD99-Expression erschwert zusätzlich die diagnostische Einordnung und führt zu einer beträchtlichen Erweiterung des in der Routinediagnostik anzuwendenden immunhistochemischen Panels, der molekularen Aufarbeitung und damit zu einer Änderung des diagnostischen Algorithmus. Das zukünftige Therapiemanagement dieser neu definierten rundzelligen Sarkome sowie die Charakterisierung möglicher neuer, bisher nicht bekannter genetischer Aberrationen zur weiteren molekularen Subklassifikation sind Gegenstand intensiver Forschungsanstrengungen.

Abstract

Sarcomas of the Ewing family of tumors are aggressive neoplasms occurring in bone and soft tissue of mostly children and young adults. Classical Ewing sarcomas are pathognomonically characterized by fusions between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family (FLI1, ERG, ETV1, ETV4 or FEV). Less frequent cases designated as Ewing-like sarcomas show different genetic rearrangements between EWSR1 and non-ETS genes (NFATC2, POU5F1, SMARCA5, PATZ, ZSG, SP3). Moreover, new molecular alterations biologically unrelated to Ewing sarcomas have recently been described in the category of undifferentiated round cell sarcomas including CIC-DUX4 fusions or BCOR alterations, each carrying unique gene expression signatures. In contrast to classical Ewing sarcomas, the morphologic spectrum of these tumor entities is much broader and includes round cell areas as well as spindled and myxoid components. The immunohistochemical profile with inconsistent CD99 positivity makes diagnosis more difficult and requires the use of a broad spectrum of antibodies and elaborate molecular work-up. Further studies for future therapeutic decision making in these newly described round cell sarcomas as well as for molecular subclassification of undifferentiated round cell sarcomas are ongoing.

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Danksagung

Wir danken Herrn Thomas Engleitner für die Erstellung der Grafik in Abb. 1.

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  1. Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland

    K. Specht

  2. Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Münster, Deutschland

    W. Hartmann

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Specht, K., Hartmann, W. Ewing-Sarkome und Ewing-artige Sarkome. Pathologe 39, 154–163 (2018). https://doi.org/10.1007/s00292-018-0421-2

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