骨巨细胞瘤组织周边生物学行为研究

目的 研究骨巨细胞瘤（GCT）肿瘤组织与其周边组织的关系,探讨手术后复发及良性GCT远隔转移的病理学基础.方法 收集1998 年至2005 年第四军医大学西京医院手术切除的12 例良性GCT瘤段标本,对GCT肿瘤组织及周边组织进行病理学研究.肿瘤部位：股骨远端6 例、胫骨近端3 例、胫骨远端1 例、腓骨小头1例、髌骨1 例.放射影像学Campanacci＇s 分级Ⅰ级2 例,位于腓骨小头和髌骨;Ⅱ级2 例;Ⅲ级8 例,2 例合并病理性骨折,3 例病灶突入软组织内形成软组织内肿物.6 例为复发的GCT.Enneking 外科分期：ⅠA 5 例、ⅠB 7例.光镜下观察GCT肿瘤与周围组织（包括皮质骨、松质骨、软骨、软组织、周边血管、瘤内血管）多个边界的关系.结果 与皮质骨交接处可见9 例肿瘤组织侵蚀皮质骨,以形成骨吸收陷窝的行为进行侵蚀;2 例肿瘤组织呈现为＂指状突起＂的生长行为,深入到周围正常骨组织内.与松质骨交接处5 例可见一层反应性硬化骨或编织骨存在,2 例病灶外正常松质骨内有跳跃病灶存在.与软骨交接处肿瘤组织边界较整齐,全部标本的关节软骨面完整.与软组织交接处7 例肿瘤组织突破骨性界限,4 例可见两层正常的纤维组织间夹有肿瘤组织;9 例肿瘤组织周围软组织内血管增多、扩张、血管壁增厚.与周边血管交接处1 例肿瘤组织周围完整的骨壳外扩张的血管内有肿瘤组织存在;与瘤内血管交接处微动脉较微静脉厚,微静脉壁薄,2 例可见血管平滑肌被多核巨细胞侵袭而变薄、不完整甚至血管壁破溃,多核巨细胞进入血管中.结论 GCT肿瘤组织的边缘生物学行为与术后复发、转移密切相关,其特征性表现为手术治疗方法 的选择提供了参考依据.     

骨巨细胞瘤细胞生物学研究进展

骨巨细胞瘤(GCT)血管生成、局部浸润、细胞生物学方面的研究,近年有了新的进展.研究表明促血管内皮生长因子不仅可促进肿瘤血管生成,还可直接调节肿瘤细胞增殖;对基质金属蛋白酶在肿瘤细胞局部侵袭中的作用提出了怀疑;增殖调节基因p21、p27及细胞周期素D1之间的相互作用调节了肿瘤细胞增殖和巨细胞形成等;GCT可能来自成骨细胞谱系.这些新认识对GCT治疗、预后判断提供了帮助.     

骨良性纤维组织细胞瘤的分类和特征

目的探讨骨良性纤维组织细胞瘤、非骨化性纤维瘤及干骺端纤维性缺损的特殊表现。方法分析22例相关病例的组织形态学、影像诊断学及临床表现等指标,分析生物学行为的不同特点。结果肿瘤组织的微血管数、瘤灶与周围正常组织之间的微细变化以及病灶侵犯程度在3种病变中具有明显的差异。结论区别3种病变的主要依据是:肿瘤组织的微血管数、瘤灶与周围正常组织之间的微细变化、病灶侵犯程度等组织病理学和影像诊断学指标。而病程、年龄及部位等临床指标往往相互交叉重叠,具有明显的不确定性。     

骨巨细胞瘤诊断与治疗现状

骨巨细胞瘤(GCT)是最常见的原发性骨肿瘤之一.早期研究表明,病灶简单刮除、植骨术后关节功能满意,但局部复发率很高.随着更为先进的影像技术和各种物理化学辅助措施如液氮冷冻、骨水泥等的应用,GCT复发率降低,预后改善.GCT瘤体整块切除适用于部分患者,使复发率更低,但需行复杂的重建手术.普遍认为,GCT病理学及影像学分期...     

桡骨远端骨巨细胞瘤的手术治疗

<正>骨巨细胞瘤(giantcelltumor,GCT)是一种局部侵袭性病变,具有不可预测的行为^[1]。虽然GCT最常见于股骨远端和胫骨近端,但桡骨远端GCT具有更多的侵袭性行为,在桡骨远端的复发率也更高^[2-6]。桡骨远端周围组织相对紧绷和有限,腕部掌侧和背侧的软组织常常被肿瘤渗透,桡骨远端与尺骨远端、腕骨以及各种肌腱和神经血管关系密切,这都使得桡骨远端GCT相对于其他部位更容易复发^[7]。     

恶性倾向肾巨大血管平滑肌脂肪瘤伴下腔静脉瘤栓1例报告并文献复习

目的：报告1例巨大肾血管平滑肌脂肪瘤合并腔静脉瘤栓病例。通过文献复习,探讨恶性倾向肾血管平滑肌脂肪瘤（renalangiomyolipoma,AML）的诊断与治疗。方法：报道和分析1例巨大AML伴下腔静脉瘤栓的病例资料,并通过查阅文献,分析和探讨具有恶性倾向的AML的临床表现、临床与病理学特性、诊断与鉴别诊断及外科治疗。结果：患者以双下肢肿胀就诊并行CT及MRI检查,提示AML伴肝后下腔静脉瘤栓（MayoIII）形成。行根治性肾切除和腔静脉瘤栓取出术,术后恢复良好。组织病理学证实为AML及静脉内肿瘤栓子。结论：散发的或结节性硬化症（tuberous sclerosis complex,TSC）相关的AML通常为间叶组织来源的良性肿瘤。罕见的,当瘤体侵犯肾静脉或下腔静脉并形成瘤栓时具有侵袭性。这种恶性潜能被认为是上皮样血管平滑肌脂肪瘤（EAMLs）的生物学特性,手术切除肿瘤并取出瘤栓是可能治疗这类AML的惟一有效方法。 我们的研究强调了严密的术前评估、精细的术中操作、审慎的组织病理学检查及密切的术后随访,以求获得更好的预后。     

腕关节置换术治疗桡骨远端骨巨细胞瘤术后感染1例

正骨巨细胞瘤(giant cell tumor of bone, GCT)是一种良性肿瘤,但易发生局部侵袭、有复发倾向,对骨质侵蚀破坏性大~([1,2])。GCT除好发于股骨远端和胫骨近端外,也常累及桡骨远端~([1,3])。GCT诊断主要依靠临床表现、影像学及病理学检查等。桡骨远端骨巨细胞瘤的治疗大多采用自体骨移植重建腕关节~([4]),随着人工假体材料及其设计的不断改进,使肿瘤性人工假     

膝关节周围骨巨细胞瘤手术治疗的相关预后因素

 骨巨细胞瘤 (giant cell tumor of bone, GCT) 作为良性和恶性之间的交界性肿瘤,外科手术是唯一的治疗措施。GCT手术后虽然发生远处转移的概率很小,但局部复发率却很高,文献报道局部复发率多在10%~30%,但在各种骨肿瘤分类中一直将GCT定义为“一种良性、侵袭性骨肿瘤”,因此,临床医生容易产生“良性肿瘤”所带来的假安全感,而轻视对手术治疗的研究和重视[1－2]。     

对成骨性肿瘤中微血管数量及形态的分析

目的 探索成骨性肿瘤组织中微血管的形态及数量与瘤细胞分化、增殖的关系。方法 采用免疫组织化学染色对成骨性肿瘤中CD34和IV型胶原蛋白阳性血管计数及形态进行分析。结果 骨肉瘤以血窦型及芽状细索型血管为主,CD34阳性血管数多于IV型胶原阳性血管数;良性病变以规则型血管为主,CD34阳性血管数少于IV型胶原阳性血管数。结论 良、恶性病变的血管形态结构及数量有本质差别。CD34高表达是新生血管形成活跃的表现,说明肿瘤组织的高增殖性;IV型胶原高表达是血管发育成熟和结构完整的标志,说明肿瘤及其血管增殖缓慢;对瘤组织中微血管和形态进行分析,对于了解肿瘤的生物学行为及临床治疗具有一定的指导意义。     

肺上皮样血管内皮瘤1例

上皮样血管内皮瘤(epithelioid hemangioendothelioma, EH)是一种起源于血管内皮细胞的罕见肿瘤,属于中低度恶性肿瘤,位于良性血管瘤与侵袭性的血管肉瘤之间[1].据统计,EH的发病率低于百万分之一[2].该肿瘤为多中心型起源,可发生于全身多个器官,以肝最多见,也可见肺、骨肌系统等[2].单...     

Giant cell tumors of soft tissue: a clinicopathologic study of 18 benign and malignant tumors

Primary giant cell tumors (GCTs) of soft tissue resembling osseous GCTs are uncommon but distinct entities. Malignant GCTs of soft tissue have been designated giant cell malignant fibrous histiocytomas; however, there is scant data regarding benign GCTs of soft tissue. Eleven benign and seven malignant GCTs of soft tissue were identified from the authors' consultation files and the surgical pathology files of the Vancouver General Hospital and Massachusetts General Hospital. The tumors occurred in adults (eight men, 10 women; age range, 25-89 years; mean age, 54 years) in the extremities (n = 14) and in the trunk, abdomen, and pelvis (n = 4). In each patient the skeleton was normal and there was no history of prior osseous GCT. Tumors ranged in size from 0.8 to 9.0 cm. Eleven occurred in the superficial soft tissue and seven occurred in deep soft tissue. Grossly they were circumscribed and frequently hemorrhagic. Cystic change was present in seven tumors. Nine tumors were partially surrounded by a shell of reactive bone. In all tumors, multinucleated osteoclast-like giant cells were distributed uniformly and evenly among mononuclear cells. The histologically benign GCTs of soft tissue were identical to typical osseous GCTs. The mononuclear cells in these tumors lacked nuclear atypia or pleomorphism, and the mitotic rate within this population was low (mean, three mitoses per 10 high-power fields [HPF]). In the malignant GCTs of soft tissue, the mononuclear cells exhibited anisocytosis, nuclear atypia, pleomorphism, and readily detectable mitoses including atypical forms (mean, 25 mitoses per 10 HPF). None of the benign or malignant tumors exhibited neoplastic bone production. The benign and malignant GCTs of soft tissue demonstrated a similar immunohistochemical staining profile to GCT of bone ( 12 tumors examined), exhibiting strong positive staining for CD68 within multinucleated osteoclastlike cells, and focal staining of mononuclear cells for CD68, Ham 56, and smooth muscle actin. All tumors were treated by surgical resection. Follow-up information is available for 15 patients (range, 0-108 months). No benign tumor has recurred or metastasized. Of the four patients with malignant tumors for whom follow-up information is available, one died of metastatic disease at 13 months and one developed a local recurrence at 84 months but is alive, apparently free of disease after additional excisional surgery. Primary GCTs of soft tissue are distinctive neoplasms that, like osseous GCTs, exhibit a wide clinicopathologic spectrum. These neoplasms should be distinguished from other giant cell-rich soft-tissue tumors with which they may be confused.     

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.     

骨肿瘤DNA流式细胞术定量分析

应用流式细胞术对６２例未经化疗或放疗的原发骨肿瘤的石蜡包埋标本细胞核ＤＮＡ进行了测定，其中３例为良性肿瘤或瘤样病变，３３例为骨巨细胞瘤，２６例为其他恶性骨肿瘤。结果表明，良性骨肿瘤与瘤样病变中未见异倍体，骨巨细胞瘤中ＤＮＡ异倍体的发生率也很低，而其他恶性骨肿瘤中异倍体的发生率非常之高，故异倍体可作为恶性骨肿瘤的一个较特异的标志。且单个骨肿瘤在活检与大体标本、原发与复发肿瘤上表现了稳定的倍性，而基于病理学基础上的骨肉瘤的分型与分级在ＤＮＡ含量上并无明显的区别。     

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.     

Giant cell tumor of bone: A basic science perspective

Comprehending the pathogenesis of giant cell tumor of bone (GCT) is of critical importance for developing novel targeted treatments for this locally-aggressive primary bone tumor. GCT is characterized by the presence of large multinucleated osteoclast-like giant cells distributed amongst mononuclear spindle-like stromal cells and other monocytes. The giant cells are principally responsible for the extensive bone resorption by the tumor. However, the spindle-like stromal cells chiefly direct the pathology of the tumor by recruiting monocytes and promoting their fusion into giant cells. The stromal cells also enhance the resorptive ability of the giant cells. This review encompasses many of the attributes of GCT, including the process of giant cell formation and the mechanisms of bone resorption. The significance of the receptor activator of nuclear factor-κB ligand (RANKL) in the development of GCT and the importance of proteases, including numerous matrix metalloproteinases, are highlighted. The mesenchymal lineage of the stromal cells and the origin of the hematopoietic monocytes are also discussed. Several aspects of GCT that require further understanding, including the etiology of the tumor, the mechanisms of metastases, and the development of an appropriate animal model, are also considered. By exploring the current status of GCT research, this review accentuates the significant progress made in understanding the biology of the tumor, and discusses important areas for future investigation.     

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.     

Surgical treatment of primary tumors of the sacrum

Twenty-two patients with primary tumors of the sacrum were surgically treated between 1983 and 1997. Seventeen male and 5 female patients were followed up for a mean of 53.6 months (range 12-203 months). The histopathologic diagnoses were giant cell tumor (GCT) in 7 patients, chordoma in 4 patients, aneurysmal bone tumor in 3 patients, chondrosarcoma in 2 patients, osteoblastoma in 2 patients, synovial sarcoma in 2 patients, Ewing's sarcoma in 1 patient, and simple bone cyst in 1 patient. Currettage and thermo- or chemocauterization was applied to 8 patients, a subtotal sacrectomy was done in 11 patients, and total sacrectomy and lumbopelvic stabilization was done in 3 patients. The surgical margins were wide in all patients with GCT. The surgical margins were wide in 3 patients and wide contaminated in 1 patient with chordoma. The 2 patients with chondrosarcoma had high sacral lesions and were managed with total sacrectomy and lumbopelvic fixation. The surgical margin was wide in 1 patient and wide contaminated in the other, who relapsed locally and systemically in the 30th postoperative month. Three patients with aggressive aneurysmal bone cyst and 1 patient with simple bone cyst were managed by curettage and thorough debridement. One patient with low sacral Ewing sarcoma was managed by subtotal sacrectomy with wide margins. The two osteoblastomas were localized to the posterior elements of the sacrum. None of the patients relapsed. Most of the tumors of the sacrum are benign aggressive lesions or low grade malignancies. Intralesional resections in the form of curettage, with the addition of chemo- or thermocauterization, provide a complete cure for benign lesions. In contrast, wide resections are necessary for complete disease control in radio- and chemoresistant malignancies. Nerve root dissection should be performed in order to achieve wide margins.     

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。     

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.