Diagnostic tools in the differential diagnosis of giant cell-rich lesions of bone at biopsy
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Jan Rehkämper1, Konrad Steinestel1,2, Birte Jeiler1, Sandra Elges1, Elena Hekeler1, Sebastian Huss1, Jan Sperveslage1, Jendrik Hardes3, Arne Streitbürger3, Georg Gosheger3, Eva Wardelmann1, Daniel Baumhoer4, Marcel Trautmann1,* and Wolfgang Hartmann1,*
1Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany
2Institute of Pathology and Molecular Pathology, Bundeswehrkrankenhaus Ulm, Ulm, Germany
3Department of Orthopaedics and Tumor Orthopaedics, University Hospital Münster, Münster, Germany
4Bone Tumor Reference Centre, Institute of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
*These authors contributed equally to this work
Jan Rehkämper, email: [email protected]
Wolfgang Hartmann, email: [email protected]
Keywords: giant cell tumor of bone; chondroblastoma; aneurysmal bone cyst; H3F3A/B; diagnostic algorithm
Received: April 30, 2018 Accepted: June 19, 2018 Published: July 10, 2018
The diagnosis of giant cell-rich lesions of bone can be challenging if radiological findings are ambiguous and tissue of the biologically deciding component is underrepresented in biopsy specimens. The frequent association of giant cell tumor of bone (GCT) and chondroblastoma (CB) with (secondary) aneurysmal bone cysts (ABC) may further impede correct classification. The present study evaluates the potentials and limitations of mutation-specific histone H3.3 and DOG1 immunohistochemistry, Sanger-/next generation sequencing (NGS) and FISH analysis in the differential diagnosis of 23 GCT, 14 CB and 19 ABC. All morphologically typical GCT and CB harbored mutations in the H3F3A or H3F3B gene, respectively. These were, except for one uncommon G34L mutation in a GCT, reliably and specifically detected by mutation-specific H3.3 G34W or H3.3 K36M immunohistochemistry and DNA sequencing. In the diagnostic substantiation of CB, DOG1 staining was less sensitive compared to H3.3 K36M immunohistochemistry. 47% of ABC specifically showed translocations of the USP6 gene, while mutations in H3F3A/B were absent.
Based on the results of this study, we conclude that mutation-specific H3.3 immunohistochemistry (selectively complemented with NGS-based DNA sequencing) and USP6 FISH analysis enable a reliable diagnostic distinction of GCT, CB and ABC of morphologically and radiologically difficult cases.
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