| Autor: |
Hasenfratz M; Institute of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Mellert K; Institute of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Marienfeld R; Institute of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany., von Baer A; Department of Trauma and Orthopaedic Surgery, University of Ulm, Ulm, Germany., Schultheiss M; Department of Trauma and Orthopaedic Surgery, University of Ulm, Ulm, Germany., Roitman PD; Pathology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina., Aponte-Tinao LA; Institute of Orthopaedics ''Carlos E. Ottolenghi'', Italian Hospital of Buenos Aires, Buenos Aires, Argentina., Lehner B; Department of Orthopaedics and Trauma, University of Heidelberg, Heidelberg, Germany., Möller P; Institute of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany., Mechtersheimer G; Institute of Pathology, University of Heidelberg, Heidelberg, Germany., Barth TFE; Institute of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany. thomas.barth@uniklinik-ulm.de. |
| Abstrakt: |
Giant cell tumor of bone (GCTB) is a locally aggressive lesion of intermediate malignancy. Malignant transformation of GCTB is a rare event. In 2013, the humanized monoclonal antibody against receptor activator of nuclear factor-κb-Ligand (RANKL) denosumab was approved for treatment of advanced GCTB. Since then, several reports have questioned the role of denosumab during occasional malignant transformation of GCTB. We report on three patients with H3F3A-mutated GCTBs, treated with denosumab. The tissue samples were analysed by histomorphology, immunohistochemistry, and in two instances by next generation panel sequencing of samples before and after treatment. One patient had a mutation of ARID2 in the recurrence of the GCTB under treatment with denosumab. One patient developed a pleomorphic sarcoma and one an osteoblastic osteosarcoma during treatment. Sequencing revealed a persisting H3F3A mutation in the osteosarcoma while the pleomorphic sarcoma lost the H3F3A mutation; however, a FGFR1 mutation, both in the recurrence and in the pleomorphic sarcoma persisted. In addition, the pleomorphic sarcoma showed an AKT2 and a NRAS mutation. These data are inconclusive concerning the role denosumab plays in the event of malignant progression/transformation of GCTB and point to diverging pathways of tumor progression of GCTB associated with this treatment. |
