5-Fluoruracil blocked giant cell tumor progression by suppressing osteoclastogenesis through NF-kappaB signals and blocking angiogenesis

Giant cell tumor of bone (GCTB) is a bone destroying tumor comprised of spindle-like stromal cells and monocytes of myeloid lineage that are differentiated into osteoclast-like multinucleated giant cells. Nuclear factor-Kappa B (NF-κB) has been identified to be essential for GCT progression. Herein, we found that 5-Fluorouracil (5-FU), a widely used chemotherapeutics, is a promising anticancer agent for GCT both targeting spindle-like stromal cells and osteoclast giant cells through NF-κB pathway. In this study, in vitro 5-FU not only directly blocked both stromal cell- and RANKL-induced osteoclastogenesis through NF-κB pathway, but also indirectly inhibited osteoclast formation and angiogenesis by suppressing the expression of osteoclast-activating factors including IL-1β, MCP-1 and tumor angiogenesis factor VEGF in stromal cells. In vivo, we found that 5-FU blocked GCT progression through NF-κB pathway by utilizing our chick embryo chorioallantoic membrane (CAM) model. Taken together, our results suggest that 5-FU can inhibit GCT development by suppressing osteoclast formation through NF-κB pathway and blocking angiogenesis, and may serve as a novel agent in the treatment of GCT.     

PTHrP increases RANKL expression by stromal cells from giant cell tumor of bone

Giant cell tumor of bone (GCT) presents with numerous osteoclast-like multinucleated giant cells that are principally responsible for the extensive bone resorption by the tumor. Although the precise etiology of GCT remains uncertain, the accumulation of giant cells is partially due to the high expression of the receptor activator of nuclear factor-κB ligand (RANKL) from the neoplastic stromal cells. Here, we have investigated whether parathyroid hormone-related protein (PTHrP) plays a role in the pathogenesis of GCT. Immunohistochemistry results revealed PTHrP expression in the stromal cells of the tumor, and that its receptor, the parathyroid hormone type 1 receptor (PTH1R), is expressed by both the stromal cells and giant cells. PCR and Western blot analyses confirmed the expression of PTHrP and PTH1R by isolated stromal cells from five patients presenting with GCT. Treatment of GCT stromal cells with varying concentrations of PTHrP (1-34) significantly increased both RANKL gene expression and the number of multinucleated cells formed from RAW 264.7 cells in co-culture experiments, whereas inhibition of PTHrP with a neutralizing antibody decreased RANKL gene expression. These results suggest that PTHrP is expressed within GCT by the stromal cells and can contribute to the abundant RANKL expression and giant cell formation within the tumor.     

Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in giant cell tumors of bone

Osteolysis is a common complication of tumors that arise in, or metastasize to, bone. The recent discovery of key regulators of osteoclast formation and activity, including receptor activator of nuclear factor of kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG), may facilitate new treatment regimes for certain tumors associated with excessive bone loss. We recently showed that the stromal cells of osteolytic giant cell tumors (GCT) of bone express high levels of mRNA encoding RANKL, relative to mRNA for the RANKL antagonist, OPG, compared with the expression patterns of other lytic and nonlytic bone tumors. In this study, we found that expression of RANKL and OPG mRNA continued by the stromal element of these tumors in a constitutive manner for at least 9 days in the absence of giant cells. Immunostaining of unfractionated GCT cultured in vitro revealed punctate cytoplasmic/membranous staining for RANKL and both cytoplasmic and extracellular matrix staining for OPG in stromal cells. Giant cells (osteoclasts) were negative for RANKL staining, but stained brightly for cytoplasmic OPG protein. We also investigated the functional relevance of these molecules for GCT osteolysis by adding recombinant OPG and RANKL to cultured GCT cells. We found that OPG treatment potently and dose-dependently inhibited resorption of bone slices by GCT, and could also inhibit the formation of multinucleated osteoclasts from precursors within the GCT. These effects of OPG were reversed by stoichiometric concentrations of exogenous RANKL. These data indicate that both the processes of osteoclast formation and activation in GCT are promoted by RANKL. Therefore, GCT represent a paradigm for the direct stimulation of osteoclast formation and activity by tumor stromal cells, in contrast to the mechanisms described for osteolytic breast tumors and multiple myeloma. The demonstration of these relationships is important in developing approaches to limit tumor-induced osteolysis.     

Bisphosphonates Induce Apoptosis of Stromal Tumor Cells in Giant Cell Tumor of Bone

Giant cell tumour of bone (GCT) is an aggressive primary neoplasm that results in the production of osteolytic lesions. Stromal cells, which form the main neoplastic component of this tumor, regulate the formation of osleoclast-like giant cells that are ultimately responsible for bone destruction. Bisphosphonates prevent bone resorption by inhibiting osteoclast activity and promoting osteoclast apoptosis, and they have been known to induce apoptosis of primary neoplastic cells such as those in breast and prostate cancers. We hypothesized that in bisphosphonates may induce apoptosis not only in osteoclast-like giant cells but also in neoplastic stromal cells of GCT both in vitro and in vivo. Twelve patients with GCT were treated with weekly injections of pamidronate for a period of 6 weeks prior to surgery. GCT specimens were collected at the time of biopsy and during definitive surgery. TUNEL assay was used to evaluate apoptotic DNA fragmentation in cells. In addition, twelve GCT primary cultures from these patients were treated with zoledronate, pamidronate, or alendronate for 48 hours at different doses (3, 30, or 150 M) and subjected to apoptosis assay by flow cytometry following fluorescent Annexin-V labeling. The results showed that pamidronate significantly induced apoptosis in both osteoclast-like giant cells and stromal tumor cells, in vivo. All three bisphosphonates caused substantial apoptosis of stromal tumor cells in cultures. Zoledronate was the most potent reagent, resulting in an average cell death of 27.41% at 150 M, followed by pamidronate (22.23%) and alendronate (15.3%). Our observations suggest that these drugs may be considered as potential adjuvants in the treatment of GCT.Both authors (Y.Y. Cheng and L. Huang) contributed equally to this work.     

Expression of osteoclast differentiation signals by stromal elements of giant cell tumors.

The mechanisms by which primary tumors of the bone cause bone destruction have not been elucidated. Unlike most other lytic bone tumors, osteoclastomas, otherwise known as giant cell tumors (GCT), contain osteoclast-like cells within the tumor stroma. A new member of the TNF-ligand superfamily member, osteoclast differentiation factor (ODF/OPGL/RANKL/TRANCE), was recently identified. ODF was shown to directly stimulate osteoclastogenesis, in the presence of M-CSF. In this study, the expression of ODF was examined in a number of tumor samples associated with bone lysis in vivo. In addition, we investigated expression of the ODF receptor on osteoclast precursors, RANK, as well as the ODF inhibitor osteoprotegerin (OPG), and another TNF-ligand superfamily member, TRAIL, previously shown to abrogate the inhibitory effects of OPG. We report here the novel finding that GCT stromal cells contain abundant ODF mRNA, whereas the giant cell population exclusively expresses RANK mRNA. These results are consistent with the osteoclast-mediated bone destruction by these tumors. We also report the expression of OPG and TRAIL mRNA in GCT samples. A comparison with other lytic and nonlytic tumors of bone showed that GCT express more ODF and TRAIL mRNA relative to OPG mRNA. In addition, GCT were found to express a number of cytokines previously reported to play central roles in osteoclastogenesis, namely, IL-1, -6, -11, -17, as well as TNF-alpha. Importantly, GCT were also found to express high levels of M-CSF mRNA, a cytokine shown to be an essential cofactor of ODF, and a survival factor for mature and developing osteoclasts. Furthermore, expression of these molecules by stromal cells isolated from GCT continued in vitro. Thus GCT constitutively express all of the signals that are currently understood to be necessary for the differentiation of osteoclasts from precursor cells.     

Modern Interpretation of Giant Cell Tumor of Bone: Predominantly Osteoclastogenic Stromal Tumor

Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists. The modern interpretation of GCT is predominantly osteoclastogenic stromal cell tumors of mesenchymal origin. A diverse array of inflammatory cytokines and chemokines disrupts osteoblastic differentiation and promotes the formation of excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)-6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This model represents a self-sufficient osteoclastogenic paracrine loop in a localized area. Consistent with this paradigm, a recombinant RANK-Fc protein and bisphosphonates are currently being tried for GCT treatment in addition to surgical excision and conventional topical adjuvant therapies.     

Giant cell tumour of the first metatarsal: a case report

The classical giant cell tumour (GCT) is a solitary lesion characterised by benign-appearing osteoclast-like giant cells and stromal cells that originate within the epiphysis of adults. Long tubular bones (75–90%) are frequent sites of involvement and make up 5% of all primary bone tumours. The foot is a rare site for GCT; less than 50 cases of GCT in foot bones have been reported in the literature. It is easy to misdiagnose a lytic lesion in the foot for commoner disorders. We report a case of GCT of the first metatarsal and highlight the importance of early and proper diagnosis.     

Histogenetic Characterization of Giant Cell Tumor of Bone

The unpredictable behavior of giant cell tumor (GCT) parallels its controversial histogenesis. Multinucleated giant cells, stromal cells, and CD68⁺ monocytes/macrophages are the three elements that interact in GCT. We compared the ability of stromal cells and normal mesenchymal stromal cells to differentiate into osteoblasts. Stromal cells and mesenchymal cells had similar proliferation rates and lifespans. Although stromal cells expressed early osteogenic markers, they were unable to differentiate into osteoblasts but they did express intracellular adhesion molecule-1, a marker of bone-lining cells. They were unable to form clones in a semisolid medium and unable to promote osteoclast differentiation, although they exerted a strong chemotactic effect on osteoclast precursors. Stromal cells may be either immature proliferating osteogenic elements or specialized osteoblast-like cells that fail to show neoplastic features but can induce the differentiation of osteoclast precursors. They might be secondarily induced to proliferate by a paracrine effect induced by monocyte-macrophages and/or giant cells. The increased number of giant cells in GCT may be secondary to an autocrine circuit mediated by the receptor activator of nuclear factor kB. One or more of the authors (NB) has received funding from the Italian Association for Cancer Research. Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.     

Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone

In giant cell tumour of bone (GCT), mononuclear stromal cells, which represent the neoplastic component of this lesion, regulate the formation of multinucleated osteoclast-like giant cells which are the characteristic hallmark of this tumour. However, the origin of stromal tumour cells has not yet been clearly defined. In this study, we evaluated several osteoblast markers including collagen type I, bone sialoprotein (BSP), osteonectin and osteocalcin in GCT using immunohistochemical techniques. Amongst the 13 GCT specimens and 7 GCT stromal cell (GCTSC) cultures studied, majority of the GCTSC synthesized type I collagen, BSP and osteonectin proteins but did not produce the differentiated osteoblast marker, osteocalcin. We further examined the regulation of several important osteogenic genes such as Cbfa-1, osterix and osteocalcin, and regulation of ALP activity in GCTSC in culture by bone morphogenetic protein 2 (BMP-2). Real-time PCR analysis indicated that Cbfa-1, osterix and osteocalcin mRNA were present in primary cultures of GCTSC. The addition of BMP-2 upregulated Cbfa-1 and osterix gene expression within 12 h and the enhancement was still observed at 24 h. ALP activity was minimal in untreated GCTSC in cultures. The number of ALP-positive GCTSC was significantly increased following treatment with BMP-2 or combinations with beta-glycerophosphate and ascorbic acid. In contrast, BMP enhancement of osterix mRNA level and ALP activity was also seen in SaOS2 osteoblast-like cells, but not in the primary culture of normal human skin fibroblasts. In summary, our data suggest that GCT stromal tumour cells may have an osteoblastic lineage and retain the ability to differentiate into osteoblasts.     

The relationship between cell kinetics and histological features of giant cell tumor of the bone

This study was undertaken to clarify the relationship between the proliferative activity and histological findings of the giant cell tumor (GCT) of bone by means of an epi-illumination cytofluorometer (NIKON SPM-RF1-D). Fresh tissues of GCT were surgically obtained from two cases. In both cases, small pieces of tumor tissues were obtained from several different regions based on the macroscopic characteristics of the cut surface, and processed for single cell preparation using enzymatic method. These isolated cells were smeared and stained with acridine orange, and then analyzed cytofluorometrically to determine simultaneously DNA and RNA contents of the individual cells. The results showed that the proliferative activity of tumor cells was much higher in the regions composed of both many histiocytic stromal cells having polygonal or ovoid shape and many multinucleated giant cells, than either in the regions composed of fibrocytic stromal cells accompanying abundant collagen fibers or in the regions composed of foamy cells.     

Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: a case-control study

BACKGROUND: Giant cell tumor (GCT) of bone is a benign but locally aggressive tumor that is characterized by the presence of mononuclear stromal cells and multinucleated giant cells. Although topical adjuvants have been used in the past, local recurrence following intralesional excision of GCT of bone continues to remain a problem. The use of bisphosphonates as an anti-osteoclastic agent in the management of osteolytic bone metastases is well accepted. Furthermore in vitro studies have shown that bisphosphonates also induce apoptosis in GCT stromal cells. Therefore our clinical study aims to investigate whether the administration of bisphosphonate as an adjuvant can further decrease local recurrence following the surgical treatment of GCT of bone. METHOD: A retrospective case-control study was performed between 1988 and 2004. Forty-four patients with histological diagnosed appendicular GCT were included. Intralesional curettage or wide excision of the lesions was followed with cementation or biological reconstruction. Additional intravenous and oral bisphosphonates were given peri-operatively to 24 patients who were treated between 1998 and 2004. The average follow-up of the control group was 115 months while that of the treatment group was 48 months. RESULTS: In the bisphosphonate treated group, 1 of 24 patients (4.2%) developed local recurrence. In the control group, 6 of 20 patients (30%) developed local recurrence. The difference in the recurrence rate was statistically significant between the bisphosphonate treatment group and the control group (Log Rank test p=0.056). The effect of reduction of local recurrence was significant in patients with stage III diseases. Patients treated with bisphosphonate did not report any untoward effects. CONCLUSION: Clinical use of bisphosphonates as an adjuvant therapy for giant cell tumor of bone demonstrated a lower local recurrence rate. The clinical response seems to be more promising in stage III diseases.     

An unusual tumor of rib diaphysis—report of a giant cell tumor and a brief review of literature

Giant Cell Tumor of bone (GCT) is a benign but aggressive tumor, which forms about 4?C5% of primary bone tumors and 1?C2% of all chest wall tumors. It arises in the epiphysis of bones. The epiphysis of a rib is in its head and tubercle posteriorly and hence a GCT arising in a rib??s anterior aspect, its diaphysis, is rare. In this unusual position, it can be mistaken for other more common diaphyseal pathologies. Radiological images are often diagnostic. A needle biopsy is best avoided and a wide excision biopsy is the treatment of choice. Microscopically, multinucleated giant cells are seen amidst stromal cells. Giant cells like these are also seen in other diseases like the brown tumor of primary hyperparathyroidism. Giant cell lesions are never caused by secondary hyperparathyroidism. We present a case of a diaphyseal GCT of rib in a patient with secondary hyperparathyroidism who was successfully treated.     

骨巨细胞瘤治疗进展

骨巨细胞瘤是一种局部具有侵袭性、溶骨活性的良性骨肿瘤,传统治疗手段为囊内刮除植骨,但有很高的局部复发率,通过辅助手段对瘤腔进行处理,有效降低了局部复发;对于不同部位骨巨细胞瘤应依据病变部位、大小、侵犯范围、复发率的高低可选择不同的手术方法,包括假体置换、广泛切除、En bloc切除等;对于特殊部位预计手术风险大、不能完整切除患者可行动脉栓塞,有利于病情得到控制或手术;双磷酸盐、地诺单抗的应用给骨巨细胞瘤的治疗带来新的希望,可有效降低肿瘤复发,目前主要应用于复发、难治、特殊部位、转移性骨巨细胞瘤的治疗。化疗主要应用于转移、恶性骨巨细胞瘤的治疗,放疗对于复发或难以手术切除部位骨巨细胞瘤可控制肿瘤进展,但有恶变可能。双磷酸盐、地诺单抗缺乏长期随访,远期疗效尚不明确,骨巨细胞瘤治疗领域新方法、新药的研发为其带来了更多希望。     

Transcriptomic and proteomic analyses in bone tumor cells: Deciphering parathyroid hormone-related protein regulation of the cell cycle and apoptosis

Giant cell tumor of bone (GCT) is an aggressive skeletal tumor characterized by local bone destruction, high recurrence rates, and metastatic potential. Previous works in our laboratory, including functional assays, have shown that neutralization of parathyroid hormone-related protein (PTHrP) in the cell environment inhibits cell proliferation and induces cell death in GCT stromal cells, indicating a role for PTHrP in cell propagation and survival. The objective of this study was to investigate the global gene and protein expression patterns of GCT cells in order to identify the underlying pathways and mechanisms of neoplastic proliferation provided by PTHrP in the bone microenvironment. Primary stromal cell cultures from 10 patients with GCT were used in this study. Cells were exposed to optimized concentrations of either PTHrP peptide or anti-PTHrP neutralizing antiserum and were analyzed with both cDNA microarray and proteomic microarray assays in triplicate. Hierarchical clustering and principal component analyses confirmed that counteraction of PTHrP in GCT stromal cells results in a clear-cut gene expression pattern distinct from all other treatment groups and the control cell line human fetal osteoblast (hFOB). Multiple bioinformatics tools were used to analyze changes in gene/protein expression and identify important gene ontologies and pathways common to this anti-PTHrP–induced regulatory gene network. PTHrP neutralization interferes with multiple cell survival and apoptosis signaling pathways by triggering both death receptors and cell cycle–mediated apoptosis, particularly via the caspase pathway, TRAIL pathway, JAK-STAT signaling pathway, and cyclin E/CDK2-associated G1/S cell cycle progression. These findings indicate that PTHrP neutralization exhibits anticancer potential by regulating cell-cycle progression and apoptosis in bone tumor cells, with the corollary being that PTHrP is a pro-neoplastic factor that can be targeted in the treatment of bone tumors. © 2012 American Society for Bone and Mineral Research.     

The pathogenesis and etiology of giant cell tumor of bone from a viewpoint of bone resorptive factors]

The pathogenesis and etiology of giant cell tumor of bone was studied by analysing the bone resorptive factors in the conditioned culture medium. In the primary culture characteristic multinucleated giant cells and mononuclear cells were coexisted. The values of interleukin 1 (IL-1) and prostaglandin E2 (PGE2) in the conditioned medium obtained from the primary culture were high. In the primary culture, an immunohistochemical technique revealed the presence of IL-1 both in mononuclear cells and in giant cells. When the medium obtained from the primary culture was tested for proteolytic activity by zymography with SDS/polyacrylamide containing gelatin, multiple gelatinolytic activities were observed. In subcultures, multinucleated giant cells were not persisted and only stromal cells were visible. In subcultures, the values of IL-1 and PGE2 were much lower. Proteolytic activities were similarly weak. However, the exposure of the passaged stromal cells to the medium containing IL-1 stimulated the stromal cells to produce PGE2 and proteolytic enzymes. Immunofluorescent localization technique revealed the expression of the proteolytic enzymes in the stromal cells. These findings demonstrated that coexistence of multinucleated giant cells with mononuclear cells should be needed for the tumor to express the original phenotype. In the presence of multi-nucleated cells, mononuclear cells seem to be stimulated to produce PGE2 and proteolytic enzymes, which accelerate the bone resorption. These factors are considered to act synergetically in the resorption of bones.     

Cellular biological study of giant cell tumor of bone: a 10-year summary

This article is a summary of the main research accomplishments on giant cell tumor of bone (GCT) carried out in this laboratory in the past ten years. The stromal cells (STC) in GCT have long been regarded as a single neoplastic element. By means of immunological method they are segregated into EA rosette-forming cells (RFC) and non-rosette-forming cells (NRFC). It is herein demonstrated that RFC are macrophages of the defensive mechanism, while NRFC bear the hallmarks of neoplastic cells. The views concerning the nature of the multinucleated giant cells (MGC) so far remains controversial. One of the authors, on the basis of the survival time in thin vitro culture, classifies them into short survival MGC (S-MGC) and long survival MGC (L-MGC). Immunological and cytochemical evidences indicate that S-MGC are similar to osteoblasts and foreign-body giant cells and express macrophage antigen. Moreover, macrophages in GCT can actually form MGC. L-MGC, however, present characteristics of neoplastic cells which are known to be able to form tumor giant cells. Thus the concept of GCT has been renovated. Evaluation of the aggressiveness of GCT is important and challenging, as the Jaffe grading system is no longer widely considered valid. In our laboratory this problem has been approached by cytomorphometry, nuclear DNA-cytometry and multifactor analysis techniques. Parameters which are conducive to predicting the prognosis of GCT are found, which would render help to clinical diagnosis and research of this semimalignant tumor.     

Bisphosphonates may reduce recurrence in giant cell tumor by inducing apoptosis

Giant cell tumor of bone is an aggressive tumor characterized by extensive bone destruction and high recurrence rates. This tumor consists of stromal cells and hematopoietic cells that interact in an autocrine manner to produce tumoral osteoclastogenesis and bone resorption. This autocrine regulation may be disrupted by novel therapeutic agents. Nonspecific local adjuvant therapies such as phenol or liquid nitrogen have been used in the treatment of giant cell tumor, but specific adjuvant therapies have not been described. The bisphosphonates pamidronate and Zoledronate can induce apoptosis in giant cell tumor culture in a dose-dependent manner. We established giant cell tumor cultures from patients with extensive destruction of bone. One of the four cultures formed osteoclastlike giant cells in vitro after more than six passages without exogenous receptor activator of NF-kappaB ligand or macrophage colony stimulating factor. Annexin V staining, presence of active cleaved form of caspase-3, and disappearance of poly (ADP-ribose) polymerase on Western blotting indicated activation of apoptosis by bisphosphonates in giant cell tumor. These results indicate that topical or systemic use of pamidronate or zoledronate can be a novel adjuvant therapy for giant cell tumor by targeting osteoclastlike giant cells, mononuclear giant cell precursor cells, and the autocrine loop of tumor osteoclastogenesis.     

Giant cell tumor and the skeletally immature patient

Conventional wisdom suggests that giant cell tumor (GCT) does not occur in the skeletally immature individual; however, we believe that GCTs of bone, though rare, do occur in children. We are reporting the occurrence of GCT of bone in three patients who were skeletally immature at the time of their initial presentation. In our review of the reports since 1954 that document this condition, we were also able to find a total of 318 patients, of whom 130 were skeletally immature at the time of their tumor presentation. From the data compiled, we found a 7.5% incidence of GCT of bone in skeletally immature individuals at a mean age of 10.5 years. Based on our review and the experience with our three patients, we believe the diagnosis of GCT of bone should be considered in the differential diagnosis of a destructive lesion of bone in skeletally immature individuals. Giant cell tumor in the skeletally immature is being reported here to better define its incidence and increase awareness of its occurrence. Management options will also be discussed.     

良性骨巨细胞瘤周边生物学行为及SMAa微血管标记的意义

目的：检测良性骨巨细胞瘤（Giant Cell Tumor of Bone,GCT)周边组织病理学改变及瘤组织对微血管的侵袭。方法：收集1995－1998年我科切除的8例良性GCT瘤段,对其病灶周边进行组织病理学及血管平滑肌肌动蛋白a(Smooth Muscular actin,SMAa)免疫组织化学研究。结果：组织学良性GCT可具有侵蚀皮质骨、松质骨及周围软组织的能力,边界处有大量新生微血管密度形成,肿瘤中多核巨细胞可侵袭微静脉,肿瘤细胞可由此进入血管。结论：良性GCT仍具有局部侵袭和潜在转移的能力。     

自体腓骨移植治疗桡骨远端骨巨细胞瘤

目的：探讨白体近端腓骨移植重建在桡骨远端骨巨细胞瘤临床治疗中的应用及效果。方法：对4例桡骨远端骨巨细胞瘤复发（Campanacci Ⅲ级）患者在行桡骨远端瘤段切除的同时,行自体近端腓骨移植重建手术。结果：所有患者随访27～50个月,疼痛症状消失,骨愈合时间5～9个月,平均愈合时间为6．5个月,无移植骨吸收和骨折,腕关节功能握持力为对侧手的55％（40～80％）,背伸活动度可达对侧50％（10～80％）,掌屈达40％（15～70％）,无神经血管损伤症状,恢复正常工作劳动。所有患者均未出现骨巨细胞瘤的复发及肺转移。结论：桡骨远端骨巨细胞瘤经广泛切除后,用自体近端腓骨移植进行保肢治疗,可较好地保留腕关节功能,是一种有效的治疗方法。