Virchows Archiv

, Volume 475, Issue 5, pp 625–636 | Cite as

IDH1 immunohistochemistry reactivity and mosaic IDH1 or IDH2 somatic mutations in pediatric sporadic enchondroma and enchondromatosis

  • Essia Saiji
  • Fabienne Gumy Pause
  • Pierre Lascombes
  • Christelle Cerato Biderbost
  • Nathalie Lin Marq
  • Margaret Berczy
  • Laura Merlini
  • Anne-Laure RougemontEmail author
Original Article


Mosaic somatic mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) genes have been identified in most enchondromas by targeted mutation analysis. Next-generation sequencing (NGS), that may detect even low-level mosaic mutation rates, has not previously been applied to enchondromas. Immunohistochemistry using the H09 clone is routinely used as a surrogate for the common R132H IDH1 mutation in gliomas. We compared immunohistochemistry and NGS results in a series of 13 enchondromas from 8 pediatric patients. NGS identified a heterozygous IDH mutation in all enchondromas, showing identical mutation status in patients with multiple tumors assessed, thereby confirming somatic mosaicism. A majority of the tumors harbored an IDH1 mutation (p.R132H in 3 tumors; p.R132C in 4 tumors from 2 patients; p.R132L and p.R132G in one tumor each). A p.R172S IDH2 mutation was identified in 4 enchondromas, but not in the ependymoma from one patient with Ollier disease, who further displayed a heterozygous STK11 missense mutation. IDH mutation rates varied between 14% (indicative of mutations in 28% of the cells and of intratumoral mosaicism) and 45% (tumor content was close to 100%). Cytoplasmic H09 reactivity was observed as expected in tumors with an IDH1 p.R132H mutation; cross-reactivity was seen with the p.R132L variant. This first NGS study of pediatric enchondromas confirms that IDH mutations may occur in a mosaic fashion. STK11 gene mutations may provide insights in the development of multiple cartilaginous tumors in enchondromatosis, this tumor suppressor gene having been shown in animal models to regulate both chondrocyte maturation and growth plate organization during development.


IDH mutation Immunohistochemistry Next-generation sequencing NGS Ollier FFPE Children 



The authors thank Mrs. P. Bordignon for the immunohistochemistry techniques and Dr. L. Ho and Dr. S. Clement-Leboube for the OncoScan analysis.

Authors’ contributions

• Have substantially contributed to the conception or design of the work (Anne-Laure Rougemont and Essia Saiji) or the acquisition, analysis, or interpretation of data for the work (Essia Saiji, Fabienne Gumy Pause, Pierre Lascombes, Christelle Cerato Biderbost, Nathalie Lin Marq, Margaret Berczy, Laura Merlini, and Anne-Laure Rougemont).

• Have drafted the work (Anne-Laure Rougemont and Essia Saiji) or revised it critically for important intellectual content (Fabienne Gumy Pause, Pierre Lascombes, Christelle Cerato Biderbost, Margaret Berczy, Nathalie Lin Marq, and Laura Merlini).

• Gave final approval of the version to be published (Essia Saiji, Fabienne Gumy Pause, Pierre Lascombes, Christelle Cerato Biderbost, Nathalie Lin Marq, Margaret Berczy, Laura Merlini, and Anne-Laure Rougemont).

• Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved (Essia Saiji, Fabienne Gumy Pause, Pierre Lascombes, Christelle Cerato Biderbost, Nathalie Lin Marq, Margaret Berczy, Laura Merlini, and Anne-Laure Rougemont).

Compliance with ethical standards

The authors/coauthors declare that the study has complied with the ethical standards. This study was approved by the Commission Cantonale d’Ethique de la Recherche (CCER Review Board, approval number GE 14-229).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Essia Saiji
    • 1
  • Fabienne Gumy Pause
    • 2
  • Pierre Lascombes
    • 3
  • Christelle Cerato Biderbost
    • 1
  • Nathalie Lin Marq
    • 1
  • Margaret Berczy
    • 1
  • Laura Merlini
    • 4
  • Anne-Laure Rougemont
    • 1
    Email author
  1. 1.Division of Clinical Pathology, Molecular Pathology UnitGeneva University HospitalsGenevaSwitzerland
  2. 2.Department of Pediatrics, Onco-hematology UnitGeneva University HospitalsGeneva 14Switzerland
  3. 3.Pediatric Orthopedic DivisionGeneva University HospitalsGeneva 14Switzerland
  4. 4.Pediatric Radiology UnitGeneva University HospitalsGeneva 14Switzerland

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