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Knorpeltumoren: Morphologie, Genetik und Basisaspekte der Targettherapie

Cartilage tumors: morphology, genetics, and current aspects of target therapy

  • Schwerpunkt: Tumoren des Knochens und der Gelenke
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Zusammenfassung

Knorpeltumoren sind eine heterogene Gruppe von mesenchymalen Tumoren, deren gemeinsames Charakteristikum die Bildung von chondroblastisch differenzierter Grundsubstanz durch die Tumorzellen ist. Die Grundzüge ihrer histologischen Klassifikation wurden bereits in den 1940er-Jahren entwickelt mit Ergänzungen durch weitere Entitäten in den darauffolgenden Jahrzehnten. Grundlegend neue Erkenntnisse wurden dann erst wieder in den vergangenen 10–15 Jahren durch die molekulargenetische Untersuchung gewonnen. So sind die Osteochondrome durch Alterationen im EXT1- und EXT2-Gen charakterisiert. Besonders wichtig ist die Beschreibung von Mutationen der Isocitratdehydrogenase 1 und 2 (IDH1 und 2) in den Chondromen und Chondrosarkomen. Das mesenchymale Chondrosarkom ist durch eine Fusion der Gene HEY1-NCOA2 charakterisiert. Die für die einzelnen Tumorentitäten charakteristischen, molekulargenetischen Alterationen sind zunächst eine wesentliche Ergänzung für die Differenzialdiagnose radiologisch und histologisch schwieriger Fälle. Sie stellen aber darüber hinaus auch die Grundlage zur Etablierung von molekularen Targettherapien für die malignen chondrogenen Tumoren dar. Dies gilt insbesondere für das konventionelle Chondrosarkom, bei dem sich alle Ansätze zu einer Chemo- und Strahlentherapie als wirkungslos erwiesen haben. Allerdings steht hier der Einsatz von Targettherapien noch in den Anfängen.

Abstract

Cartilage tumors are a heterogeneous group of mesenchymal tumors whose common characteristic is the formation of a chondroblastic differentiated groundsubstance by the tumor cells. The basic features of their histological classification were already developed in the 1940s and supplemented by further entities in the following decades. Only in the past 10–15 years have fundamental new insights been gained through molecular genetic analysis. So, osteochondromas are characterized by alterations in the EXT1 and EXT2 genes. The description of mutations of isocitrate dehydrogenase 1 and 2 (IDH 1 and 2) in chondromas and chondrosarcomas is particularly important. The mesenchymal chondrosarcoma is characterized by a fusion of the HEY1-NCOA2 genes. The molecular genetic alterations characteristic for the individual tumor entities are first of all an essential supplement for the differential diagnosis of radiologically and histologically difficult cases. They also provide the basis for the establishment of molecular target therapies for malignant chondrogenic tumors. This applies in particular to conventional chondrosarcoma, for which all approaches to chemo- and radiotherapy have proven to be ineffective. However, the use of target therapies is still in its beginnings.

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  1. Institut für Pathologie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Straße 44, 39120, Magdeburg, Deutschland

    Albert Roessner, Victor Schoeder & Johannes Haybaeck

  2. Universitätsklinik für Orthopädie und Traumatologie, Medizinische Universität Graz, Graz, Österreich

    Maria Smolle

  3. Institut für Pathologie, Neuropathologie und Molekularpathologie, Medizinische Universität Innsbruck, Innsbruck, Österreich

    Johannes Haybaeck

  4. Diagnostik und Forschungszentrum für Molekulare BioMedizin, Institut für Pathologie, Medizinische Universität Graz, Graz, Österreich

    Johannes Haybaeck

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  1. Albert Roessner
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Roessner, A., Smolle, M., Schoeder, V. et al. Knorpeltumoren: Morphologie, Genetik und Basisaspekte der Targettherapie. Pathologe 41, 143–152 (2020). https://doi.org/10.1007/s00292-020-00752-5

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