Multicentric giant cell tumour of bone

Although giant cell tumour (GCT) is seen quite frequently, multicentric giant cell tumour (MCGCT) is a rare entity occurring in less than 1% of patients with GCT. The pathogenesis of MCGCT is debated; various mechanisms have been postulated, including contiguous spread, iatrogenic tumour cell seeding, benign metastasis, malignant transformation and de novo formation. A literature review revealed 101 cases of MCGCT reported worldwide, of which we could trace and review 83 cases. We noted that MCGCT, unlike the solitary GCT, more frequently involves the short bones of the hand and feet and is commoner in the meta-diaphyseal region of long bones. The present literature review noted a higher incidence in females and skeletally immature patients (21%). Individual lesions in a patient with MCGCT are radiologically and histologically indistinguishable from the solitary GCT. In our review we noted 42 recurrences in 157 lesions (26%), thus negating the commonly held point of view that MCGCT was clinically more aggressive. Four lung metastases and two histologically malignant lesions were found. The literature does not define the exact time period beyond which a lesion can be classified as metachronous; however a significant number of the subsequent lesions occur within 2-3 years of the index lesion. We recommend from our review, that with the present state of knowledge, special care should be taken in cases with primary meta-diaphyseal lesions, GCTs seen at atypical locations, and in females of younger age group, to ensure that multicentricity is picked up earlier.     

An unusual giant cell tumour of bone

Summary This is a report of an 18-year old girl with an unusual giant cell tumour. Although it is difficult to distinguish between a multifocal giant cell tumour of bone and a primary giant cell tumour with metastases in other bones, we believe that our case is either a multicentric or a multifocal giant cell tumour.

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Résumé Présentation d'une tumeur à cellules géantes de type inhabituel chez une jeune fille de 18 ans. Bien qu'il soit difficile de distinguer une tumeur à cellules géantes à foyers multiples d'une tumeur primitive accompagnée de métastases au niveau d'autres os, il semble bien que ce cas soit une tumeur à cellules géantes multifocale.

     

Local recurrences in giant cell tumour of bone

Summary. We studied the value of histopathological grading in determining the prognosis of giant cell tumour (osteoclastoma) and the rate of local and distant recurrences in a consecutive series of 31 patients. We found that grading had no prognostic value. Eighteen patients were treated by intralesional curettage and 13 by wide excision. Ten patients (56%), who were all treated by curettage, had local recurrences, but none of the tumours with wide excision recurred (p <0.05). Five (16%) had local recurrences as well as distant metastases, usually to the lungs. The recurrences developed later than an average of 12 years after primary treatment in 3 patients. Wide excision and life-long follow up should be considered in the management of these tumours. Résumé. Nous avons étudié l’interêt pronostic du classement anatomo-pathologique des tumeurs à cellules géantes (osteoclastomes) et le taux de récidives à long terme, locales et à distance, dans une série consécutive de 31 patients. Le classement anatomo-pathologique n’a eu aucun interêt pronostic. Dix-huit patients furent traités par curetage, alors que 13 patients furent traités par une excision large. Dix patients (56%), tous traités par curetage, récidivèrent localement, alors qu’aucune des tumeurs traitées par excisision large ne récidiva (p <0.05). Cinq patients (16%) récidivèrent localement et à distance, généralement au niveau pulmonaire. Chez 3 patients, la récidive se déclara en moyenne 12 ans après le traitement initial. L’excision large avec suivi à vie est nécessaire dans ces rares cas de tumeur osseuse. Accepted: 14 September 1995     

Radiosensitive giant cell tumour of the sphenoid bone

Giant cell tumours rarely occur in the cranial region. We encountered a radiosensitive giant cell tumour of the sphenoid in a 12-year-old girl. After a two-stage operation, the residual tumour regrew rapidly. The adjuvant radiotherapy subsequent to additional surgery has suppressed the growth of the residual tumour for 5 years.     

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.     

Serum acid phosphatase as a tumour marker in giant cell tumour of bone

The serum acid phosphatase value was examined in nine patients with giant cell tumour of bone. Five showed a high level of acid phosphatase, which fell to within normal limits after surgery. Although the remaining four patients showed a normal acid phosphatase level before surgery, the postoperative acid phosphatase level was lower than the preoperative level in each case. Therefore, it is strongly suggested that serum acid phosphatase is a useful tumour marker in diagnosing giant cell tumour of bone as well as in evaluating the efficacy of treatment. Received: 9 March 2000     

腺病毒介导VEGF基因在人骨髓基质干细胞中的表达

[目的] 体外培养人骨髓基质干细胞(hBMSc),将VEGF165基因腺病毒载体共转染hBMSc,观察其表达.[方法] 共转染实验分为3组:VEGF165和eGFP转染组、空腺病毒载体转染组和未转染组.取重组腺病毒Ad-VEGF165(MOI=20 pfu/cell)感染hBMSe.荧光显微镜下观察eGFP的表达,判断感染效率及细胞生长情况,RT-PCR检测,ELISA和Westernblot检测分别用于观察基因转染的表达.[结果] MOI=20 pfu的转染率已达80%以上,取此值为转染滴度.提取出的总RNA质量较好.以双链cDNA为模板扩增VEGF165基因,产物经1%琼脂糖凝胶电泳,均可见到549 bp(GAPDH)2条带.转染组可见VEGF165表达,空载体组和空白对照组未检测到VEGF165表达.ELISA结果显示基因转染组与转染空载体组和未转染组结果差异呈显著性(P<0.05).Western blot显示:转染组在50 KD处出现特征性条带,而空载体组和空白对照组未见条带.[结论] 外源性VEGF基因在人骨髓基质干细胞(hBMSc)内获得稳定表达,在本实验条件下培养的hBMSc具有典型成骨细胞的形态学特征和较强的生物学活性,向成骨细胞方向分化效率较高,细胞数量可以满足骨组织工程研究的要求.     

Multinucleated giant cells in cultured giant cell tumor of bone

Further observations on multinucleated giant cells (MGCs) in 12 giant cell tumors of bone (GCT) were made, by means of tissue culture, electron microscopy and immunohistochemistry. In continuous in vitro culture, two distinct types of MGCs were found and herein termed preliminarily short-lived MGCs and long-lived MGCs respectively. The former type had limited life span of about 2-3 weeks, whereas the latter type of MGCs maintained growth or continual formation. They had entirely different appearance and characteristics. This fact reflects two types of MGCs exist in GCT in vivo. Besides, the origin of MGCs were also investigated and discussed in considerable depth.     

The Goltz syndrome associated with giant cell tumour of bone

Summary The Goltz syndrome is a rare condition in which there are congenital anomalies in skin, teeth, eyes and bone. We report an unusual case of a 17 year old girl who had various anomalies associated with the syndrome. She sustained a pathological fracture of the left femur at the site of a giant cell tumour. Another lesion occurred in the right fibula, but resolved spontaneously.

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Résumé Le syndrome de Gotz est une affection rare qui comporte des anomalies congénitales de la peau, des dents, des yeux et du squelette. Nous présentons un cas inhabituel chez une jeune fille de 17 ans qui était porteuse de diverses anomalies associées à ce syndrome. Elle souffrait d'une fracture pathologique du fémur gauche au niveau d'une tumeur à cellules géantes. Une autre lésion atteignit le péroné droit, mais guérit spontanément.

     

人工半骨盆置换术结合自体骨移植1例

在半骨盆假体置换术后若发生假体松动,处理非常棘手。为了延缓半骨盆假体松动,我们曾在术中加用自体骨移植1例,随访至今,疗效满意。1　病例资料患者,女,24岁,因左髋臼部骨巨细胞瘤行刮除加骨胶填塞术,术后2年肿瘤复发(见图1),于1992年4月行人工半骨盆置换加全髋关节置换术。利用术中切下的股骨头、颈及大转子部骨质修剪成2ｃｍ×2ｃｍ×5ｃｍ的骨条块,列队移植于假体内侧,分别与耻骨及髂骨残端相连,用钛丝将其与假体捆扎固定。见图2。2　结果患者术后随访至今已8年(现32岁)。术后第2年Ｘ线检查发现移植的自体骨块融合,形成了具有生物活性的…     

Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone.

Giant cell tumor (GCT) of bone is a unique bone lesion that is characterized by an excessive number of multinucleated osteoclasts. GCT consists of neoplastic stromal cells, multinucleated osteoclasts and their precursors, thus serving as a naturally occurring human disease model for the study of osteoclastogenesis. It still remains unclear how stromal cells of GCT recruit osteoclast precursors. In the present study, we characterized the cellular components of GCT and confirmed the presence of CD14(+)-monocytes/CD68(+)-macrophages and CD34(+)-hematopoetic stem cells that express CXCR4, a specific receptor for SDF-1; SDF-1 gene expression and presence of SDF-1 protein were confirmed by real time RT-PCR, in situ hybridization, and immunohistochemistry in the GCT tissue and cultured cells. SDF-1 was present at 25-50 ng/ml in the conditioned media from the GCT cultures, which is in the range of physiological chemotactic concentration. Migration of osteoclast precursors was 2.5-fold higher in response to GCT conditioned media compared to the control media; and migration was inhibited by an average of 36% with anti-SDF-1 neutralizing antibody or competing recombinant SDF-1. These results suggest that SDF-1 is one of the significant chemoattractant factors involved in the recruitment of hematopoietic osteoclast precursor cells during tumor-induced osteoclastogenesis.     

Heterotransplantation of the cultured cell from a human giant cell tumour of bone

Summary We have transplanted cultured cells derived from a human giant cell tumour of bone (G-1 cell) into immunologically suppressed mice. The resulting growths were morphologically and cytokinetically analyzed. We have obtained information on the cytokinetic influences of anti-cancer agents on heterotransplanted tumours using the double labelling method.Tumour formation was noted in 56 out of 76 mice, i.e. 76%. In 3 mice which had been kept under observation the large tumours led to death.The heterotransplanted tumours of G-1 cells had morphologically malignant and non-epithelial characteristics. The cells appeared to have undergone malignant change during their long period of cultivation.Using the double labelling method, 5-FU was found to prolong the DNA synthetic time and decrease the cell birth rate of G-1 cells in vivo. Accordingly, 5-FU is the most effective anti-cancer agent to G-1 cells.In order to improve the prognosis in a malignant bone tumour the most effective anti-cancer agent should be determined by testing on a heterotransplanted tumour derived from the patient.

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Résumé Les auteurs ont greffé des cellules cultivées à partir d'une tumeur osseuse à cellules géantes humaine (cellule G-1) sur des souris ayant subi une suppression immunitaire. Les tumeurs résultantes ont été analysées sur le plan morphologique et cytocinétique. Grâce à la technique du double marquage, on a obtenu des informations concernant les influences cytocinétiques des agents anticancéreux sur les tumeurs hétérotransplantées.Des tumeurs se sont développées chez 56 souris sur 76, soit 76%. Chez trois animaux soumis à une observation prolongée, on a constaté que les volumineuses tumeurs qui se sont formées ont entraîné la mort.Les tumeurs hétérotransplantées des cellules G-1 étaient morphologiquement malignes et non épithéliales. Les cellules ont apparemment subi une transformation maligne pendant leur longue période de culture.A l'aide du double marquage on a trouvé que le 5-fluoro-uracile prolongeait le temps de synthèse de l'ADN tandis qu'il diminuait le taux de division des cellules G-1 in vitro. Le 5-fluoro-uracile est donc l'agent anticancéreux le plus efficace à l'égard des cellules G-1.Pour améliorer le pronostic d'une tumeur osseuse maligne, on devrait déterminer l'agent anticancéreux le plus efficace en le testant sur une tumeur hétérotransplantée dérivée du malade.

     

分离培养骨巨细胞瘤破骨样细胞的方法学研究

本文通过组织块贴壁法、机械分离法和酶消化法对骨巨细胞瘤的破骨样细胞进行分离、培养。通过比较,结果显示：酶消化法提纯程度最高,收获量较多;机械分离法居中,但操作简单,对原位杂交、免疫组织化学和骨吸收功能检测具有一定的应用价值;组织块培养法需要时间长,各细胞成分混杂,对研究各细胞成分之间的关系,有一定帮助     

An unusual presentation of a rare chest wall tumour: giant cell tumour of bone

Giant cell tumour of bone is an aggressive benign bone tumour. It rarely affects the ribs. It usually involves the posterior end of the ribs and literature regarding anterior end involvement is scanty. We report a case of giant cell tumour of the anterior end of the rib masquerading as a sub-mammary abscess in lactating women.     

Serum acid phosphatase can be a useful tumour marker for giant cell tumour of bone

Introduction

The purpose of this study was to elucidate the clinical significance of acid phosphatase in giant cell tumour of bone.

Patients and methods

Serum acid phosphatase levels were measured in 32 patients with this tumour both preoperatively and postoperatively.

Results

Serum acid phosphatase value before surgery was high in 15 patients, whereas it was within normal limits in 17 patients. The serum acid phosphatase values of all the 15 patients with high preoperative serum level fell within normal limits postoperatively. In the remaining 17 patients in whom preoperative serum acid phosphatase values were within normal limits, postoperative serum acid phosphatase levels were lower than that of preoperative ones in all the patients. In addition, there was a statistically significant positive correlation between the tumour volume and the preoperative serum acid phosphatase level.

Conclusion

It is concluded that serum acid phosphatase is a useful tumour marker for giant cell tumour of bone.     

Expression of neuronal markers in differentiated marrow stromal cells and CD133+ stem-like cells

Bone marrow stromal cells, which normally give rise to bone, cartilage, adipose tissue, and hematopoiesis-supporting cells, have been shown to differentiate in vitro and in vivo into neural-like cells. In this study, we examined the expression of neuronal and glial markers in human marrow stromal cells under culture conditions appropriate for neural stem cells, and compared the unsorted cell population to bone marrow CD133+ stem-like cells using immunofluorescence, Western blot, and functional patch-clamp analysis. Overall, the expression of the early neuronal marker beta3-tubulin was most pronounced in the presence of DMEM/F12 and neurotrophin 3 (NT3) or brain-derived neurotrophic factor (BDNF), when marrow stromal cells were cultured onto fibronectin. Electrophysiological examination, however, could not show fast sodium currents or functional neurotransmitter receptors in differentiated marrow stromal cells. CD133+ mesenchymal stem-like cells, but not CD34+/CD133- cells, generally showed a higher expression of neuronal markers than did unsorted marrow stromal cells, and differentiated CD133+ cells more resembled neuron-like cells.     

Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant

This study was designed to evaluate the feasibility and effectiveness of the use of anhydrous alcohol as an adjuvant treatment for giant cell tumours (GCTs) of long bone. Between October 1989 and January 2004, 42 GCT patients were treated and followed up for an average of 4.1 years (range 1-13 years). Mean patient age was 34 years (range 17-67 years). After curettage and additional burring, anhydrous alcohol was used as an adjuvant therapy in all patients before the bone defect was filled with bone graft or cement. Four patients (9.5%) experienced local recurrence. There were no alcohol-related complications. Recurrence-free probability was 87.6% at final follow-up (13 years) after index surgery by Kaplan-Meyer analysis. Our data suggest that anhydrous alcohol can be used as an effective safe adjuvant for the treatment of GCT of long bone.     

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.