The nature of giant cell tumor of bone

Giant cell tumor of bone (GCT) is a locally osteolytic tumor with variable aggressiveness. In rare cases, pulmonary metastasis can be observed. The lesion most frequently occurs in the epiphysis of long tubular bones of the knee region, predominantly affecting young adults after closure of the growth plate. The characteristic histological appearance of GCT displays a high number of osteoclast-like multinucleated giant cells, which resulted in the classification "osteoclastoma" or "giant cell tumor". Apart from the multinucleated giant cells, there are two mononuclear cell types in GCT. The first one has a round morphology and resembles monocytes. The second cell type is the spindle-shaped, fibroblast-like stromal cell. Cell culture experiments with GCT cells revealed the stromal cell to be the proliferating component of the GCT. The other two cell types, the monocyte and the multinucleated giant cell, were lost after a few cell culture passages. Furthermore, latest results from GCT reveal that the stromal cells secrete a variety of cytokines and differentiation factors, including MCP1, ODF, and M-CSF. These molecules are monocyte chemoattractants and are essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells. The multinucleated giant cell itself resembles a normal osteoclast that is able to resorb bone leading to extended osteolysis. This new model of GCT genesis supports the hypothesis that the stromal cell is the neoplastic component whilst the monocytes and the multinucleated giant cells are just reactive components of this tumor. Taking this into consideration, the nomenclature of the "giant cell tumor" needs to be reconsidered.     

Treatment options for recurrent giant cell tumors of bone

Background  Although the recurrence rate of giant cell tumors of bone (GCTB) is relatively high exact data on treatment options for the recurrent cases is lacking. The possible surgical procedures range from repeated intralesional curettage to wide resection. Methods  Two hundred and fourteen patients with histologically certified GCTB have been treated at the authors department from 1980 to 2007. Sixty-seven patients with at least one local recurrence were included in this study. The mean follow-up was 77.3 months. The data was evaluated according the re-recurrence rate with regard to the surgical procedure for the recurrence. Results  The mean time until the first local recurrence was 22.0 months; the mean number of recurrences per patient was 1.4. The recurrence occurred in 69.7% (46 out of 66 patients) within the first 2 years. If after intralesional procedures (curettage or intralesional resection) no adjunct was used the re-recurrence rate was 58.8% (10 out of 17 patients) and decreased to 21.7% (5 out of 23 patients) if a combination of all adjuncts (PMMA + burring) was used. The likelihood of re-recurrence was reduced by the factor 5.508 which was clearly significant (P = 0.016). In case of wide resection no re-recurrence occurred. Seven patients (10.5%) developed pulmonary metastases. Fourteen patients (20.9%) finally received an endoprosthesis; 12 due to tumor recurrence, 2 due to secondary arthritis. Conclusion  Recurrent GCTB can be treated by further curettage with additional burring and cementing with an acceptable re-recurrence rate of 21.7%. The rate of patients finally needing an endoprosthesis is 20.9%. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease. Ethical Board Review statement: Each author certifies that his or her institution has approved or waived approval for the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.     

Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma

Summary We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The finding of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor.     

骨巨细胞瘤中MMP-9的表达及其意义

目的　探讨基质金属蛋白酶 - 9(MMP- 9)的表达与骨巨细胞瘤血管新生、肿瘤增殖、转移及复发的关系。方法　采用免疫组化法检测 82例骨巨细胞瘤标本 MMP- 9的表达 ,并分析其与肿瘤细胞增殖、血管形成及转移复发的关系。结果　骨巨细胞瘤中 MMP- 9的阳性表达率为 6 5 .85 %。MMP- 9表达强度与微血管密度(MVD)值显著相关 (P<0 .0 5 ) ,不同 MMP- 9表达组骨巨细胞瘤的复发率、转移率有显著差异 (P<0 .0 5 ) ,多因素 L ogistic回归分析显示 MMP- 9及手术方式对肿瘤复发有显著影响 (P<0 .0 5 )。结论　 MMP- 9的表达与骨巨细胞瘤的血管生成、转移及复发有关 ,可作为判定转移及复发潜能的参考指标     

Giant cell tumor of the cervical spine treated by carbon ion radiotherapy: A case report

Introduction:Giant cell tumor (GCT) of the bone is a benign–malignant intermediate tumor with locally destructive growth and a relatively high local recurrence rate. Neurological symptoms may develop in patients with GCT of the spine, and surgical treatment is prioritized in cases where resection is possible. However, the local recurrence rate of GCT of the bone is higher than that of GCT at other sites owing to the associated surgical challenges, and treatment is often difficult. No study to date has reported long-term remission of recurrent tumors for more than 5 years by treatment with carbon ion beam radiotherapy after resection of GCT of the cervical spine.Patient concerns:A 14-year-old boy who experienced recurrence after surgery for GCT of the cervical spine.Diagnosis:The patient presented with cervical pain, and computed tomography revealed a mass of the C2 vertebral body. He underwent surgery for tumor resection and autologous bone grafting, and the final pathological diagnosis was GCT. The transplanted bone exhibited gradual progression of resorption, and recurrent tumors were observed on computed tomography and magnetic resonance imaging 1 year and 4 months after surgery.Interventions:The patient was started on denosumab at 15 years of age and received carbon ion beam therapy with 70.4 Gy administered in 32 sessions over 7 weeks.Outcomes:No progressive tumor growth was observed, there were no neurological symptoms such as paralysis or pain were noted, and the patient was in remission for 5 years after irradiation.Conclusion:These findings suggest that carbon ion radiotherapy is a safe and effective therapeutic option for patients with recurrent GCT of the cervical spine.     

腹腔内促纤维增生性小圆细胞肿瘤4例

目的:探讨腹腔内促纤维增生性小圆细胞瘤(intra-abdominal desmoplastic small round cell tumor,IDSRCT)的临床特点.方法:对我院于1996-06/2006-10收治的4例IDSRCT患者诊疗及预后进行回顾性分析.结果:本研究报道4例患者,均表现为腹水和/或腹部肿物收入院,剖腹探查术发现肿瘤腹腔内广泛种植,术后病理证实为IDSRCT.结论:腹腔内促纤维增生性小圆细胞瘤是一种罕见腹膜恶性肿瘤,诊断时患者已经出现广泛转移且预后不良.     

50例胸腔巨大肿瘤的外科治疗分析

目的探讨胸腔巨大肿瘤外科手术治疗以及术中、术后特殊疑难问题的处理经验。方法回顾分析2010年1月至2013年6月在中国人民解放军总医院第一附属医院胸心外科手术治疗的50例胸腔巨大肿瘤患者的临床资料。结果完整切除肿瘤43例,大部切除肿瘤7例,单纯肿瘤切除46例,联合上腔静脉、无名静脉成形术1例,肺切除3例;正中切口纵劈胸骨8例,胸部侧切口39例,单侧胸部侧切口+横断胸骨切口1例,单侧胸部侧切口+横断锁骨切口1例,颈部横切口1例;切除肿瘤重628~2 586 g,平均1 973 g,术中出血400~1 500 ml。采用预防复张性肺水肿措施后术后并发肺水肿2例,其中1例因合并DIC死亡,1例治愈出院;其余患者术后均治愈出院。结论胸腔巨大肿瘤患者往往症状较重,内科保守治疗效果差,手术能彻底改善症状;手术切口要以接近瘤体、同时便于伸延为原则,要充分显露术野;术中可采用完整、分块、大部切除等手术技巧,注意术中避免大出血;术后尽早采用预防复发性肺水肿措施。     

Wegener’s granulomatosis and giant cell tumor of tendon sheaths: casual or causal combination? First case report

Giant cell tumor of tendon sheath (GCTTS) and Wegener’s granulomatosis (WG) are rare conditions both characterized by polyclonal cellular proliferation and multinucleated giant cells formation. Here, we report the case of a 27-year-old Caucasian woman affected by WG who experienced the metachrone appearance of two different GCTTSs at the right hand within a time of 3 years. To our knowledge, the combination of GCTT with WG is exceptional and this could probably be the first case reported. The subsequent appearance of two rare diseases both characterized by giant cell formation apparently points to similarities in their pathogenesis. However, at present no pathogenic relationship between GCTTS and WG is demonstrable and their simultaneous occurrence has to be considered coincidental. Actually, an emerging opinion is to consider GCTTS as a mixed lesion in which both tumoral and non-tumoral inflammatory cells play a central pathogenic action. On this view, the proposed case could support the evidence about the crucial role of a chronic inflammatory injury in enhancing GCTTS appearance.     

口腔颌面部恶性肿瘤肺转移的临床分析——附24例临床病例报道

目的探讨口腔颌面部恶性肿瘤肺转移的诊断及治疗方法。方法从我科2003年1月至2008年12月期间收治的220例口腔颌面部恶性肿瘤患者的临床资料中选取发生肺转移的案例24例,分析肺转移类型,相应的诊疗方法和临床疗效。结果24例肺转移患者中,孤立肺转移10例,双肺多发转移14例;4例患者放弃治疗,20例行全身化疗;所有患者随访6—36个月,其中6～12个月死亡4例,12～24个月死亡16例,4例生存超过24个月。结论早期肺转移患者多无明显呼吸道症状,故x线胸片及胸部CT检查是主要的诊断手段。对于局限性肺转移者可选择X线刀、适形放疗及全身化疗,对于弥散性肺转移者全身化疗是主要治疗手段。     

吻合血管腓骨近端移植治疗桡骨远端骨巨细胞瘤瘤段切除术后骨缺损

目的计价桡骨远端骨巨细胞瘤切除后腓骨近端重建修复腕关节的方法及效果。方法对23例桡骨远端骨巨细胞瘤患者行瘤段切除、吻合血管腓骨近端移植重建腕关节。按改良Campanacci影像学分级系统对全部病例进行分级,其中Ⅱ级7例,Ⅲ级16例。采用肌肉骨骼肿瘤学会保肢评分标准评定术后功能。结果全部病例均有随访,平均随访32个月,所有患者均无肿瘤局部复发和肺转移,无明显的腕关节脱位或半脱位及腕关节退变。腓骨与桡骨截骨端均达到骨性愈合,平均愈合时间为12周。腕关节平均活动度为掌屈36°、背伸43°、桡偏16°、尺偏26°,MSTS评分平均为85％。结论吻合血管腓骨近端移植呕建腕关节是桡骨远端肿瘤切除后骨缺损的一种良好的选择。     

Comprehensive treatment outcomes of giant cell tumor of the spine: A retrospective study

There is no consensus on a treatment strategy for spinal giant cell tumor of bone (GCTB) because of the difficulty in their treatment. Treatment options often include the use of the controversial denosumab, an antibody therapy aimed at tumor shrinkage, different curettage techniques, resection, or a combination of these therapies. The current study aimed to identify treatment methods associated with favorable outcomes in patients with spinal GCTB.We retrospectively reviewed 5 patients with spinal GCTB, including patients with tumors of the sacrum, treated at our hospital between September 2011 and November 2020. Two men and 3 women were included in the study. The median follow-up period was 74 months (range: 14–108 months). We surveyed the tumor site, treatment method, denosumab use, and outcomes.The median age was 17 years (range: 17–42 years). There were 2 cases of sacral GCTB and 1 case each of lumbar, cervical, and thoracic vertebral GCTB. The comorbidities observed included hepatitis, malignant lymphoma, atopic dermatitis, and asthma. The treatment method included zoledronic acid after embolization and denosumab, denosumab only, curettage and posterior fusion, and curettage resection after embolization and anterior and posterior fusion. Denosumab was used in all cases. Three patients were continuously disease-free, 1 patient with no evidence of disease, and 1 patient alive with disease.Aggressive treatment, especially surgical treatment, may lead to good results in spinal GCTB.     

Detection of disseminated tumor cells in bone marrow of gastric cancer using magnetic activated cell sorting and fluorescent activated cell sorting

Background and Aim: Magnetic activated cell sorting (MACS) and fluorescent activated cell sorting (FACS) were employed to enrich and detect the gastric cancer cells from a cell line in a model system, and to enrich and detect disseminated tumor cells (DTCs) from bone marrow (BM) of patients with gastric cancer. Methods: Fifteen patients with benign gastric lesions and 35 patients with gastric cancer who received curative operations between December 2002 and June 2003 were selected. Mononuclear cells were separated from their BM. Cells from cell line OCUM‐2M were seeded with 10‐grade ratio into mononuclear cells from patients with benign gastric lesion. After labeling by MACS minibeads conjugated with cytokeratin (CK) 7/8 antibodies, anti‐CK‐fluorescein isothiocyanate (FITC), and anti‐CD45‐perdinin chlorophyll protein (PerCP), the samples were enriched twice using an MS+/RS+ positive separation column. The FACS analysis was conducted on these samples before and after MACS enrichment. The results were analyzed using clinopathological parameters. Results: Disseminated tumor cells were detected in the BM of 25 (71.43%) patients with gastric cancer. The frequencies of DTCs were 1.38 × 10^?8–2.40 × 10^?5, 2.19 × 10^?7–3.70 × 10^?5, 4.01 × 10^?6–8.57 × 10^?5 in patients with well, moderately, and poorly differentiated carcinoma, respectively (P = 0.026). Disseminated tumor cells in BM had close correlation with tumor tumor‐node‐metastasis (TNM) stage (P = 0.034) and cancer‐free survival (P = 0.035). Conclusion: Disseminated tumor cells are very common in the BM of gastric cancer patients. Poor histological differentiation and more advanced TNM stage have more DTCs in the BM of gastric cancer patients. Patients with DTCs tend to have a poor prognosis.     

脊柱骨巨细胞瘤影像学分析及鉴别诊断

目的分析脊柱骨巨细胞瘤的影像学表现,提高术前诊断水平。 方法对36例经手术病理证实的脊柱骨巨细胞瘤的X线、CT和MRI资料进行回顾性分析。 结果发生于颈椎7例,胸椎16例,腰椎6例,骶椎7例。合并动脉瘤样骨囊肿9例。影像学表现为偏心性、膨胀性骨质破坏25例,27例首次手术患者伴发病理性骨折12例,椎管狭窄21例,周围软组织肿块形成20例,囊变17例。9例复发者均合并软组织肿块及椎管狭窄,病灶边界不清,囊变、出血7例。MRI多表现为T1WI呈等、低信号,T2WI呈等、低或混杂高信号。合并动脉瘤样骨囊肿者表现为多囊状高信号,内可见液-液平面。 结论脊柱骨巨细胞瘤影像学表现具有一定的特征性,CT和MRI结合分析,可以提高术前诊断率,对临床分期、手术方案制定及术后评估具有重要价值。     

Biological characterization of human bone tumors

Summary Seven giant cell tumors of bone and four malignant fibrous histiocytomas were studied immunohistochemically with different monoclonal antibodies to the mononuclear phagocyte system (MPS), to HLA-DR antigens, and to a proliferation-associated nuclear antigen (KI-67), in order to clarify the role of macrophages in these tumors. A part of the mononuclear cells stained positive with antibodies against the MPS. Antibody 25-F-9 against mature tissue macrophages showed the strongest reaction. The osteoclast-like giant cells also stained positive with this antibody. Fibroblast-like stromal cells, however, showed negative reactions to all antibodies against MPS cells. A double-labeling immunohistological technique was used to detect the proliferating cell population in these tumors. The fibroblast-like cells that were negative for MPS markers, were positively labeled with the monoclonal antibody Ki-67 against a proliferation-associated nuclear antigen, whereas a negative reaction to Ki-67 was seen in cells positive with antibodies to the MPS. These results support the concept that macrophages are a reactive population in these tumors, whereas the fibroblast-like mesenchymal cells are the proliferating tumor cells.Supported by Deutsche Forschungsgemeinschaft, grant no. 648 1/2     

Giant-cell tumor of bone with pathological evidence of blood vessel invasion

Giant cell tumor of bone is a rare but aggressive benign tumor that arises at the end of long tubular bones. The tumor rarely metastasizes; however, we report a case in which a giant cell tumor of bone presented with progressive pulmonary metastases. There has been no clear pathologic evidence of the definitive cause or route of metastasis. In our case, the primary tumor site was located in the left femur with pathological evidence of blood vessel invasion. The histological and pathological features of this entity are discussed in this letter to the editor.     

High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 m L of peripheral venous blood drawn using a Cell Search kit and a Cell Tracks Auto Prep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells(CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 m L of peripheral blood(median of 1724). These values were much higher than common gastric cancers(2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d(median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance(Y = 234.6- 0.03 X, P = 0.085).CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.     

Giant colonic diverticulum,clinical presentation,diagnosis and treatment: Systematic review of 166 cases

AIM: To investigate the clinical presentation,diagnosis,and treatment of giant colonic diverticulum(GCD,by means of a complete and updated literature review).GCD is a rare manifestation of diverticular disease of the colon.Less than 200 studies on GCD were published in the literature,predominantly case reports or small patient series.METHODS: A systematic review of the literature was performed using the Embase and PubM ed databases toidentify all the GCD studies.The following MESH search headings were used: "giant colonic diverticulum"; "giant sigmoid diverticulum".The "related articles" function was used to broaden the search,and all of the abstracts,studies,and citations were reviewed by two authors.The following outcomes were of interest: the disease and patient characteristics,study design,indications for surgery,type of operation,and postoperative outcomes.Additionally,a subgroup analysis of cases treated in the last 5 years was performed to show the current trends in the treatment of GCD.A GCD case in an elderly patient treated in our department by a sigmoidectomy with primary anastomosis and a diverting ileostomy is presented as a typical example of the disease.RESULTS: In total,166 GCD cases in 138 studies were identified in the literature.The most common clinical presentation was abdominal pain,which occurred in 69% of the cases.Among the physical signs,an abdominal mass was detected in 48% of the cases,whereas 20% of the patients presented with fever and 14% with abdominal tenderness.Diagnosis is based predominantly on abdominal computed tomography.The most frequent treatment was colic resection with en-bloc resection of the diverticulum,performed in 57.2% of cases,whereas Hartmann's procedure was followed in 11.4% of the cases and a diverticulectomy in 10.2%.An analysis of sixteen cases reported in the last 5 years showed that the majority of patients were treated with sigmoidectomy and en-bloc resection of the diverticulum; the postoperative mortality was null,morbidity was very low(1 patient was hospitalized in the intensive care unit for postoperative hypotension),and the patients were discharged 4-14 d after surgery.CONCLUSION: Giant colonic diverticulum is a rare manifestation of diverticular diseases.Surgical treatment,consisting predominantly of colonic resection with en bloc resection of the diverticulum,is thepreferred option for GCD and guarantees excellent results.     

Malignant giant cell tumor of the rib with lung metastasis in a man

Malignant giant cell tumor of bone (MGCTB) accounts for 0.07% of all cases of primary bone tumor. The rarity and complexity of this tumor give rise to some arguments about its histological differentiation, diagnosis, treatment and prognosis. In this paper, we present a 57-year-old man who has a large MGCTB in his rib with lung-targeted metastasis at the time of initial diagnosis. He underwent an operation followed by radiotherapy. The man has been free of recurrence or metastasis for 18 months.     

无功能性胰岛细胞瘤34例的诊治与预后分析

目的提高胰岛细胞瘤的诊断与治疗水平。方法对1986年1月～2001年10月间我院收治的34例无功能性胰岛细胞瘤病例进行回顾性分析。结果34例无功能性胰岛细胞瘤多以腹部包块和腹痛为首发症状。良性肿瘤28例，恶性6例。术前B超、CT及MRI检查可作肿瘤定位，其中30例肿瘤来源于胰腺。手术治疗33例，采用肿瘤切除术、远端胰腺切除加脾切除术、或Whipple手术，肿瘤恶性者术后辅以放、化疗。随访24例，其中良性18例，均存活；恶性6例中1例于术后6年死亡，5例存活，至目前已生存1年者2例，3年者2例，9年者1例。结论无功能性胰岛细胞瘤早期缺乏临床症状，不易发现。B超、CT及MRI是有效的影像学诊断方法。肿瘤对周围组织浸润和肿瘤转移是恶性胰岛细胞瘤最可靠的诊断标准。手术切除是无功能性胰岛细胞瘤的主要治疗方法，恶性者辅以放、化疗，预后一般较好。