Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab

Abstract Background Advancements in diagnostic and therapeutic modalities for giant cell tumors of bone (GCTB) have introduced molecular and radiological tools that refine clinical decision-making. H3.3 G34W immunohistochemical staining has become a routine diagnostic marker, while H3F3A mutational...

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Main Authors: Jasminka Igrec, Lisa Jernej, Maria Anna Smolle, Jakob Steiner, Susanne Scheipl, Birgit Lohberger, Andreas Leithner, Iva Brcic
Format: Article
Language:English
Published: SpringerOpen 2025-05-01
Series:Journal of Orthopaedics and Traumatology
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Online Access:https://doi.org/10.1186/s10195-025-00841-2
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author Jasminka Igrec
Lisa Jernej
Maria Anna Smolle
Jakob Steiner
Susanne Scheipl
Birgit Lohberger
Andreas Leithner
Iva Brcic
author_facet Jasminka Igrec
Lisa Jernej
Maria Anna Smolle
Jakob Steiner
Susanne Scheipl
Birgit Lohberger
Andreas Leithner
Iva Brcic
author_sort Jasminka Igrec
collection DOAJ
description Abstract Background Advancements in diagnostic and therapeutic modalities for giant cell tumors of bone (GCTB) have introduced molecular and radiological tools that refine clinical decision-making. H3.3 G34W immunohistochemical staining has become a routine diagnostic marker, while H3F3A mutational analysis enhances prognostic insights. Treatment primarily involves surgical methods such as curettage or en bloc resection, with denosumab serving as an adjunct in high-risk or inoperable cases. Methods We retrospectively analyzed 55 patients with GCTB, focusing on clinicopathologic and radiological findings. Tumors were evaluated using the Campanacci grading system. Immunohistochemical analysis with H3.3 G34W antibody and next-generation sequencing (NGS) were performed to detect H3F3A mutations. A subgroup of nine patients treated with denosumab was further analyzed for clinical outcomes and histological changes. Results The cohort had a mean age of 37.7 years, with tumors most commonly affecting the knee joint (55%). All tested tumors demonstrated positive H3.3 G34W staining, with eight exhibiting H3F3A G34W mutations. Recurrence rates were 32% following curettage and 18% after en bloc resection. Denosumab treatment, administered for an average of 14.6 months, facilitated tumor downsizing and new bone formation without major side effects. Histologically, treated tumors showed a depletion of giant cells and increased bone matrix deposition. Conclusions Surgery remains the cornerstone of GCTB treatment, with curettage or resection tailored to tumor characteristics. Denosumab offers a valuable adjunct in high-risk cases, enhancing surgical feasibility and promoting joint preservation. The Campanacci grading system continues to be a crucial tool for prognostication and treatment planning, particularly when complemented by molecular and radiological diagnostics. Future research should focus on integrating advanced imaging and artificial intelligence for personalized GCTB management. Level of evidence: Level 4
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spelling doaj-art-bde6a82bcb624d8d8762ddf5e83ca5772025-08-20T02:55:27ZengSpringerOpenJournal of Orthopaedics and Traumatology1590-99992025-05-0126111210.1186/s10195-025-00841-2Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumabJasminka Igrec0Lisa Jernej1Maria Anna Smolle2Jakob Steiner3Susanne Scheipl4Birgit Lohberger5Andreas Leithner6Iva Brcic7Division of General Radiology, Department of Radiology, Medical University of GrazDepartment of Orthopaedics and Trauma, Medical University of GrazDepartment of Orthopaedics and Trauma, Medical University of GrazDivision of General Radiology, Department of Radiology, Medical University of GrazDepartment of Orthopaedics and Trauma, Medical University of GrazDepartment of Orthopaedics and Trauma, Medical University of GrazDepartment of Orthopaedics and Trauma, Medical University of GrazD&R Institute of Pathology, Medical University of GrazAbstract Background Advancements in diagnostic and therapeutic modalities for giant cell tumors of bone (GCTB) have introduced molecular and radiological tools that refine clinical decision-making. H3.3 G34W immunohistochemical staining has become a routine diagnostic marker, while H3F3A mutational analysis enhances prognostic insights. Treatment primarily involves surgical methods such as curettage or en bloc resection, with denosumab serving as an adjunct in high-risk or inoperable cases. Methods We retrospectively analyzed 55 patients with GCTB, focusing on clinicopathologic and radiological findings. Tumors were evaluated using the Campanacci grading system. Immunohistochemical analysis with H3.3 G34W antibody and next-generation sequencing (NGS) were performed to detect H3F3A mutations. A subgroup of nine patients treated with denosumab was further analyzed for clinical outcomes and histological changes. Results The cohort had a mean age of 37.7 years, with tumors most commonly affecting the knee joint (55%). All tested tumors demonstrated positive H3.3 G34W staining, with eight exhibiting H3F3A G34W mutations. Recurrence rates were 32% following curettage and 18% after en bloc resection. Denosumab treatment, administered for an average of 14.6 months, facilitated tumor downsizing and new bone formation without major side effects. Histologically, treated tumors showed a depletion of giant cells and increased bone matrix deposition. Conclusions Surgery remains the cornerstone of GCTB treatment, with curettage or resection tailored to tumor characteristics. Denosumab offers a valuable adjunct in high-risk cases, enhancing surgical feasibility and promoting joint preservation. The Campanacci grading system continues to be a crucial tool for prognostication and treatment planning, particularly when complemented by molecular and radiological diagnostics. Future research should focus on integrating advanced imaging and artificial intelligence for personalized GCTB management. Level of evidence: Level 4https://doi.org/10.1186/s10195-025-00841-2Giant cell tumor of boneDenosumabH3.3H3F3ARadiological imaging
spellingShingle Jasminka Igrec
Lisa Jernej
Maria Anna Smolle
Jakob Steiner
Susanne Scheipl
Birgit Lohberger
Andreas Leithner
Iva Brcic
Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab
Journal of Orthopaedics and Traumatology
Giant cell tumor of bone
Denosumab
H3.3
H3F3A
Radiological imaging
title Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab
title_full Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab
title_fullStr Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab
title_full_unstemmed Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab
title_short Surgical and radiological outcomes of giant cell tumor of the bone: prognostic value of Campanacci grading and selective use of denosumab
title_sort surgical and radiological outcomes of giant cell tumor of the bone prognostic value of campanacci grading and selective use of denosumab
topic Giant cell tumor of bone
Denosumab
H3.3
H3F3A
Radiological imaging
url https://doi.org/10.1186/s10195-025-00841-2
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