Abstract：
Giant cell tumor (GCT) of the bone is a locally aggressive primary bone tumor, that can rarely metastasize. Arising mostly in epiphysis of the long bones in young adults, the tumor is composed of mononuclear cells that are admixed with osteoclastic giant cells(OLGCs), which express RANK ligand and RANK respectively. Denosumab a monoclonal antibody against RANK ligand has been shown to reduce the tumor by causing bone lysis by inhibiting RANKL. Histological changes in 11 patients of GCT who were treated with denosumab are presented here.
Clinical records and slides of 11 patients of GCT who had been administered neoadjuvant denosumab were included in the study. Evaluation of pre and post therapy GCT specimens was performed by two pathologists (RK and VM). There were 4 males and 7 females. Their mean age was 30 years. All the patients received 120 mg denosumab subcutaneously every week with additional 120 mg on days 8 and 15 of therapy. The histological slides were reviewed and following points noted: 1) degree of ossification,2) fibrosis,3) loss of osteoclastic giant cells,4) proliferation of mononuclear cells,5) atypia,6) Permeation of osteoid by malignant cells.
Out of 11 cases, 2 cases did not show any significant histological improvement. 7 cases showed reduction in giant cells, increased fibrosis, enhanced mononuclear cell proliferation and ossification consistent with a pathological response. Atypia and osteoid permeation were noted in 2 cases which showed transformation to osteosarcoma.
Denosumab treated giant cell tumor show dramatic histological changes. The post therapy lesions may bear no resemblance to pretherapy lesion. There may be complete resolution or may be confused with benign or malignant lesions Rarely they may show sarcomatous transformation. It is imperative that the pathologist is aware of these changes to prevent diagnostic pitfalls as it poses therapeutic and prognostic implications.
Clinical records and slides of 11 patients of GCT who had been administered neoadjuvant denosumab were included in the study. Evaluation of pre and post therapy GCT specimens was performed by two pathologists (RK and VM). There were 4 males and 7 females. Their mean age was 30 years. All the patients received 120 mg denosumab subcutaneously every week with additional 120 mg on days 8 and 15 of therapy. The histological slides were reviewed and following points noted: 1) degree of ossification,2) fibrosis,3) loss of osteoclastic giant cells,4) proliferation of mononuclear cells,5) atypia,6) Permeation of osteoid by malignant cells.
Out of 11 cases, 2 cases did not show any significant histological improvement. 7 cases showed reduction in giant cells, increased fibrosis, enhanced mononuclear cell proliferation and ossification consistent with a pathological response. Atypia and osteoid permeation were noted in 2 cases which showed transformation to osteosarcoma.
Denosumab treated giant cell tumor show dramatic histological changes. The post therapy lesions may bear no resemblance to pretherapy lesion. There may be complete resolution or may be confused with benign or malignant lesions Rarely they may show sarcomatous transformation. It is imperative that the pathologist is aware of these changes to prevent diagnostic pitfalls as it poses therapeutic and prognostic implications.
摘要：
■骨巨细胞瘤（GCT）是一种局部侵袭性原发性骨肿瘤，很少会转移。主要出现在年轻的成年人长骨的骨phy，肿瘤由与破骨细胞（OLGC）混合的单核细胞组成，其分别表达RANK配体和RANK。Denosumab是一种针对RANK配体的单克隆抗体，已被证明可以通过抑制RANKL引起骨溶解来减少肿瘤。本文介绍了11例接受denosumab治疗的GCT患者的组织学变化。
■本研究纳入了11例接受新辅助治疗的GCT患者的临床记录和切片。治疗前和治疗后GCT标本的评估由两名病理学家(RK和VM)进行。有4名男性和7名女性。他们的平均年龄是30岁。所有患者每周皮下接受120mg地诺塞马，在治疗的第8天和第15天额外接受120mg。回顾了组织学切片，并指出以下几点：1）骨化程度，2）纤维化，3）破骨细胞巨细胞丢失，4）单核细胞增殖，5)非典型性，6)恶性细胞对类骨质的渗透。
■在11例病例中，2例没有显示任何显著的组织学改善。7例巨细胞减少，纤维化增加，增强单核细胞增殖和骨化与病理反应一致。在2例表现为骨肉瘤的转化中发现了异型和类骨渗透。
■Denosumab治疗的巨细胞瘤显示出戏剧性的组织学变化。治疗后病变可能与治疗前病变没有相似之处。可能有完全缓解或可能与良性或恶性病变混淆。病理学家必须意识到这些变化以防止诊断陷阱，因为它具有治疗和预后意义。
■本研究纳入了11例接受新辅助治疗的GCT患者的临床记录和切片。治疗前和治疗后GCT标本的评估由两名病理学家(RK和VM)进行。有4名男性和7名女性。他们的平均年龄是30岁。所有患者每周皮下接受120mg地诺塞马，在治疗的第8天和第15天额外接受120mg。回顾了组织学切片，并指出以下几点：1）骨化程度，2）纤维化，3）破骨细胞巨细胞丢失，4）单核细胞增殖，5)非典型性，6)恶性细胞对类骨质的渗透。
■在11例病例中，2例没有显示任何显著的组织学改善。7例巨细胞减少，纤维化增加，增强单核细胞增殖和骨化与病理反应一致。在2例表现为骨肉瘤的转化中发现了异型和类骨渗透。
■Denosumab治疗的巨细胞瘤显示出戏剧性的组织学变化。治疗后病变可能与治疗前病变没有相似之处。可能有完全缓解或可能与良性或恶性病变混淆。病理学家必须意识到这些变化以防止诊断陷阱，因为它具有治疗和预后意义。
