Li Yang1, Hongjuan Zhang1, Xiaohui Zhang2, Yongqiang Tang3, Zhigang Wu4, Yingmei Wang1, Hai Huang4, Xin Fu1, Jiayan Liu1, Pancras C W Hogendoorn5, Hong Cheng6. 1. State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, the Fourth Military Medical University, Xi'an, Shaanxi province, China. 2. Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. Department of Radiology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi province, China. 4. Department of Orthopaedics, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi province, China. 5. Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: p.c.w.hogendoorn@lumc.nl. 6. State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, the Fourth Military Medical University, Xi'an, Shaanxi province, China. Electronic address: chenghongfmmu85@yahoo.com.
Abstract
GCTB is an osteolytic, locally-aggressive, rarely-metastasizing tumour, characterized by abundance of osteoclast-like giant cells, induced by neoplastic mononuclear cells expressing high-levels of the receptor activator of nuclear factor Kappa-B ligand (RANKL), a mediator of osteoclast activation. Although the mainstay of treatment is complete tumour removal with preservation of bone, therapy with denosumab, an inhibitor of RANKL, has been introduced for selected cases. OBJECTIVES: Denosumab-treated GCTB (DT-GCTB) was reported to show a wide spectrum of histological changes such as depletion of osteoclast-like giant cells and intralesional bone deposition, which may lead to diagnostic difficulties. We investigated clinicopathologic and molecular features of DT-GCTB, matched with pre-therapy samples. PARTICIPANTS: 21 cases were included (13 females, 8 males), aged 15 to 64 (median, 30 years). RESULTS: DT-GCTB showed development of sclerotic neocortex and varying degrees of osteosclerosis radiographically. Marked depletion of giant cells, different degree of ossification, fibrosis, and proliferation of mononuclear cells was observed. Staining for H3.3G34W was positive in mononuclear cells in 19 cases (90.5%), while one negative case was positive for H3.3G34V. H3F3A G34W mutation was confirmed in 17 of 19 cases (89.5%), corresponding to nuclear staining with H3.3 G34W antibody. G34L mutation was detected in one G34W negative case, in which H3.3 G34V nuclear positive staining was observed, possibly due to cross-reaction. CONCLUSIONS: Post-therapy tumours still exhibit a similar mutation profile, while significantly differing from classic GCTB morphologically. Correlation with history of denosumab administration, awareness of features of DT-GCTB, IHC and molecular studies for histone H3 mutations are important in its assessment.
GCTB is an osteolytic, locally-aggressive, rarely-metastasizing tumour, characterized by abundance of osteoclast-like giant cells, induced by neoplastic mononuclear cells expressing high-levels of the receptor activator of nuclear factor Kappa-B ligand (RANKL), a mediator of osteoclast activation. Although the mainstay of treatment is complete tumour removal with preservation of bone, therapy with denosumab, an inhibitor of RANKL, has been introduced for selected cases. OBJECTIVES: Denosumab-treated GCTB (DT-GCTB) was reported to show a wide spectrum of histological changes such as depletion of osteoclast-like giant cells and intralesional bone deposition, which may lead to diagnostic difficulties. We investigated clinicopathologic and molecular features of DT-GCTB, matched with pre-therapy samples. PARTICIPANTS: 21 cases were included (13 females, 8 males), aged 15 to 64 (median, 30 years). RESULTS: DT-GCTB showed development of sclerotic neocortex and varying degrees of osteosclerosis radiographically. Marked depletion of giant cells, different degree of ossification, fibrosis, and proliferation of mononuclear cells was observed. Staining for H3.3G34W was positive in mononuclear cells in 19 cases (90.5%), while one negative case was positive for H3.3G34V. H3F3A G34W mutation was confirmed in 17 of 19 cases (89.5%), corresponding to nuclear staining with H3.3 G34W antibody. G34L mutation was detected in one G34W negative case, in which H3.3 G34V nuclear positive staining was observed, possibly due to cross-reaction. CONCLUSIONS: Post-therapy tumours still exhibit a similar mutation profile, while significantly differing from classic GCTB morphologically. Correlation with history of denosumab administration, awareness of features of DT-GCTB, IHC and molecular studies for histone H3 mutations are important in its assessment.
Authors: Sanne Venneker; Robin van Eenige; Alwine B Kruisselbrink; Ieva Palubeckaitė; Alice E Taliento; Inge H Briaire-de Bruijn; Pancras C W Hogendoorn; Michiel A J van de Sande; Hans Gelderblom; Hailiang Mei; Judith V M G Bovée; Karoly Szuhai Journal: Cancers (Basel) Date: 2022-09-27 Impact factor: 6.575