Methylation and copy number profiling: emerging tools to differentiate osteoblastoma from malignant mimics?

Modern Pathology, vol. 35, pp. 1204–1211

Abstract

Rearrangements of the transcription factors FOS and FOSB have recently been identified as the genetic driver event underlying osteoid osteoma and osteoblastoma. Nuclear overexpression of FOS and FOSB have since then emerged as a reliable surrogate marker despite limitations in specificity and sensitivity. Indeed, osteosarcoma can infrequently show nuclear FOS expression and a small fraction of osteoblastomas seem to arise independent of FOS/FOSB rearrangements. Acid decalcification and tissue preservation are additional factors that can negatively influence immunohistochemical testing and make diagnostic decision-making challenging in individual cases. Particularly aggressive appearing osteoblastomas, also referred to as epithelioid osteoblastomas, and osteoblastoma-like osteosarcoma can be difficult to distinguish, underlining the need for additional markers to support the diagnosis. Methylation and copy number profiling, a technique well established for the classification of brain tumors, might fill this gap. Here, we set out to comprehensively characterize a series of 77 osteoblastomas by immunohistochemistry, fluorescence in-situ hybridization as well as copy number and methylation profiling and compared our findings to histologic mimics. Our results show that osteoblastomas are uniformly characterized by flat copy number profiles that can add certainty in reaching the correct diagnosis. The methylation cluster formed by osteoblastomas, however, so far lacks specificity and can be misleading in individual cases.

Authors 9

1. Baptiste Ameline

   University of Basel · University Hospital of Basel

   Affiliation as printed

   Bone Tumor Reference Center at the Institute for Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland

2. Michaela Nathrath

   TUM Klinikum · Klinikum Kassel · Technical University of Munich

   Affiliation as printed

   Department of Pediatrics and Children's Cancer Research Center, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany

   Pediatric Hematology and Oncology, Klinikum Kassel, Kassel, Germany

3. Karolin H. Nord

   Lund University

   Affiliation as printed

   Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden

4. Felix Haglund

   Karolinska University Hospital · Karolinska Institutet

   Affiliation as printed

   Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Solna, Stockholm, Sweden

   Department of Oncology-Pathology, Karolinska Institutet, Solna, Stockholm, Sweden

5. Judith V.M.G. Bovée Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

6. Andreas Heinrich Krieg

   University of Basel · University Children’s Hospital Basel

   Affiliation as printed

   Bone and Soft tissue Sarcoma Center, University of Basel, University Children's Hospital Basel (UKBB), Basel, Switzerland

7. Sylvia Höller

   University of Basel · University of Zurich · University Hospital of Basel · Stadtspital Zürich

   Affiliation as printed

   Bone Tumor Reference Center at the Institute for Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland

   Stadtspital Zürich, Institute of Clinical Pathology, University of Zürich, Zürich, Switzerland

8. Jürgen Hench

   University of Basel · University Hospital of Basel

   Affiliation as printed

   Institute for Medical Genetics and Pathology, Division of Neuropathology, University Hospital Basel, Basel, Switzerland

9. Daniel Baumhoer corresponding

   University of Basel · University Hospital of Basel

   Affiliation as printed

   Bone Tumor Reference Center at the Institute for Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland. Daniel.Baumhoer@usb.ch

   Bone Tumor Reference Center at the Institute for Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland