Benign Giant Cell Tumor Research Articles

Giant cell tumor of bone: oncological and functional results of long-term follow-up.

Giant cell tumor (GCT) of bone is a rare and unpredictable lesion. Its standard treatment has ranged from surgical curettage to wide resection and varying oncological and functional results have been reported. A retrospective review of 47 patients (17 males and 30 females) with GCT of bone was performed to evaluate the oncological and functional results. The patients were followed up for at least 5 years. The average age of the patients was 32 years (range 15-66 years). The tumor sites were distal femur in 15 cases, proximal tibia in 10, distal radius in five, spinal column in four, proximal femur in three, proximal humerus in three, proximal fibula in two, pelvis in two and others in three. Enneking's surgical stages were Stage 1 in three, Stage 2 in 34 and Stage 3 in 10 cases. In these 47 patients, 80 surgical procedures were performed. The rate of local recurrence was 75% in the 28 patients undergoing intralesional excision, 50% in those receiving excision and curettage and 0% in those receiving wide resection. Although there was no statistical significance, surgical stages tended to be correlated with the local recurrence rate (Stage 1, 0%; Stage 2, 53%; Stage 3, 70%). Functional evaluation was performed according to the most recent system of the Musculoskeletal Tumor Society. Functional results of the patients with extremity tumors were 28.2 (average) in those undergoing intralesional excision, 30 (average) in those receiving excision and curettage and 27.1 (average) in those receiving wide resection. Functional results were significantly correlated with the initial surgical stages (Stage 1, 30; Stage 2, 27.5; Stage 3, 24.4; Kruskal-Wallis test, P = 0.016). To preserve good function of the extremities and avoid local recurrence, we consider that intralesional excision with adjunctive therapy such as phenol cauterization should be employed for the treatment of benign GCT of bone.

Hydrogen Peroxide Inhibits Giant Cell Tumor and Osteoblast Metabolism In Vitro

This study investigates the efficacy of using hydrogen peroxide as adjuvant therapy after extended local curettage for benign giant cell tumors of bone. Hydrogen peroxide is used clinically as a chemical adjuvant for removal of residual tumor cells, presumably by effervescent cleansing with minimal damage to surrounding soft tissue and bone cells. This investigation examined the effects of hydrogen peroxide on giant cell tumor cells and osteoblasts grown in culture. Fresh fragments of histologically confirmed giant cell tumor tissue (six patients) and trabecular bone (one patient) were excised. Cells obtained from the fragments were grown in culture. Confluent cell cultures were exposed to saline (control) or hydrogen peroxide (0.1-1000 mm) for 2 minutes, and incubation was continued for 12, 24, or 48 hours without hydrogen peroxide. Protein content, deoxyribonucleic acid content, tartrate resistant acid phosphatase activity, and alkaline phosphatase activity were measured in the cell layers. The medium from the final 12 hours of each incubation period was used to evaluate lactate production. Cell lysis or death occurred after exposing giant cell tumor cells and osteoblasts to 100 mm and 30 mm hydrogen peroxide, respectively, concentrations substantially lower than the 3% (880 mm) hydrogen peroxide commonly used clinically. These results support the theory of using a minimal concentration of hydrogen peroxide as a chemical adjuvant in the surgical treatment of giant cell tumors of bone.

Benign giant-cell tumor of the patellar ligament

We report the symptoms, clinical findings, and treatment of a patient with an extra-articular benign giant-cell tumor of the patellar ligament. Between the years 1966 and 1996 no similar case has been found to be documented by a Medline search. On palpation, a soft, mobile lesion, the size of a pigeon's egg, was felt in the lateral region of the patellar ligament. There was no set of laboratory values to determine the diagnosis. In addition, there were no typical findings in diagnostic imaging procedures and it seems that the most important fact is that the clinician is aware of this type of synovial tumor. A clear diagnosis is only possible by means of a pathological investigation. The choice of therapy for giant-cell tumors is local excision. Arthroscopy is recommended exclusively for the diagnosis and therapy of a localized intra-articular giant-cell tumor. Arthroscopy 1998 Jan-Feb;14(1):94-8

Giant cell tumor of bone. Prognosis and treatment of pulmonary metastases.

Giant cell tumor of bone is a challenging clinicopathologic entity. Despite its benign designation, it has the capacity to recur locally and develop rare pulmonary metastases. Between 1945 and 1991, 104 patients with histologically benign giant cell tumors of bone, 5 of which metastasized to the lung, were treated at the authors' institution. In these cases, histologic materials from the lung were identical to those found in the primary bone lesion. The primary bone lesions were treated with local curettage (3), wide resection (1), and wide resection with prosthesis placement (1). The patients were observed for a mean of 12.6 years (range, 5-38 years). Four of the 5 patients experienced local recurrences (average time interval, 34 months), with 3 patients experiencing 2 or more recurrences. The average time to lung metastasis was 23 months; 1 patient presented initially with pulmonary findings. Four patients underwent surgical resection of pulmonary metastases. All 4 patients are alive with no disease progression, despite incomplete pulmonary resections in 2 patients. Locally aggressive disease and multiple recurrences appear to be risk factors for pulmonary metastases in benign giant cell tumor of bone. Pulmonary metastases occurred within the first few years after discovery of primary bone tumors. Radiographs and computed tomographs of the chest are recommended to rule out this complication in patients with local recurrences. Resection of pulmonary metastasis is recommended. Long term survival is not incompatible with persistent pulmonary lesions.

Expression of metalloproteinases and tissue inhibitors of metalloproteinases in giant cell tumor of bone: An immunohistochemical study with clinical correlation

The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumor's biological behavior, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded tissue was collected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had local recurrence. One showed metastasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 was strongly expressed in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy distribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 recurrent cases, TIMP-1 was expressed weakly by both giant and stromal cells. TIMP2 was variably expressed in the giant cells of the nonrecurrent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell positivity for TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in the giant cells. These results indicate that expression of MMPs and TIMPs differs in giant cells and stromal cells in the same tumor. More significantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in the recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Finally, these markers may prove useful in predicting behavior in these tumors.

Proliferation index and vascular density of giant cell tumors of bone: Are they prognostic markers?

The proliferation index (PI) and vascular density (VD) in giant cell tumors (GCT) of bone were studied to assess then value as prognostic markers. Formalin fixed, paraffin embedded tissue from 7 nonrecurrent (NR-GCT) and 13 recurrent (R-GCT) tumors were stained with MIB-1, a monoclonal antibody against Ki-67 (nuclear proliferation antigen), and QBEND-10, a monoclonal antibody against CD34 (endothelial antigen). A minimum of ten fields/case were analyzed on the SAMBA 4000 Image Analyzer. Only mononuclear cell nuclei were analyzed for MIB-1 staining. Mean values +/- 1 Standard deviation (SD) for PI (stained nuclear area/total nuclear area) were: NR-GCT, 10.98 +/- 3.70; R-GCT (initial presentation), 8.94 +/- 3.57; and R-GCT (first recurrence), 9.25 +/- 3.52. In addition, the mean PI +/- 1 SD for mononuclear round-ovoid cells was 8.71 +/- 3.47 and was 9.16 +/- 10 for mononuclear spindle cells. The mean values +/- 1 SD for VD (stained area/total area of structures) were: NR-GCT, 10.61 +/- 6.37; R-GCT (initial curettage), 9.40 +/- 4.94; and R-GCT, (first recurrence), 12.56 +/- 5.88. Comparing the means for PI and VD for both groups of tumors using Student's t test showed no statistically significant differences (P = 0.34). In one case of histologically benign GCT that metastasized to the lungs, the PI of the metastatic tissue was not significantly different from the primary tumor. This study presents evidence that the degree of tumor cell proliferation and vascularity are not useful parameters to predict the recurrence of GCT of bone and that there are no significant differences between the PI of mononuclear round-ovoid cells and mononuclear spindle cells.

Giant cell tumour of metacarpal with pulmonary and skeletal metastases

A case of giant cell tumour of the left fifth metacarpal with pulmonary and skeletal metastases is reported with follow-up of 14 years. The pulmonary metastases were treated by chemotherapy, but the size of the metastatic nodules continued to increase, and no further treatment was given. The pulmonary metastatic nodules started to regress 8 years after the diagnosis without any treatment, and had disappeared after 14 years. The skeletal metastases were unchanged at the latest follow-up. Both pulmonary and skeletal metastases have been asymptomatic for the 14 years after they were diagnosed. It is suggested that pulmonary metastases of benign giant cell tumour has a good long-term prognosis and these patients should be kept under observation only, avoiding extensive lobectomy, chemotherapy or radiotherapy.

Fine-Needle aspiration cytology of benign giant cell tumor of tendon sheath

Benign giant cell tumor of tendon sheath (GCTTS) also known as nodular tenosynovitis is a common soft tissue neoplasm of the extremities. Although the histopathology of this neoplasm is well described, cytologic reports are sparse. In this paper we describe the cytologic findings in three cases of GCTTS. Aspiration smears were moderately cellular. In two cases they contained several multinucleate osteoclast type giant cells dispersed haphazardly with a background of mononuclear cells. The mononuclear cells were polygonal with eccentrically located nucleus. The cytologic diagnosis was later confirmed by histopathology. We feel that GCTTS has characteristic cytologic findings that lead to its easy recognition.

Case report: Benign giant cell tumour associated with Paget's disease of bone

Case report: Benign giant cell tumour associated with Paget's disease of bone

Telomerase activity and oncogenesis in giant cell tumor of bone

Benign giant cell tumor of bone (GCT) is a primary skeletal neoplasm with an unpredictable pattern of biologic aggressiveness and cytogenetic findings characterized by telomeric associations and telomeric reduction. The role of maintaining telomeric integrity is performed by telomerase. To determine if telomerase activity is present, cell extracts from fibroblasts and tumor cells from five patients with GCT were analyzed and compared with HeLa (a positive control cell line). Telomerase activity was detected by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. Telomere reduction was assessed using southern blot analyses of the restriction enzyme Hinf I digested DNA with a radio-labeled telomere probe. Telomerase or telomerase-like activity was detected in the cell extracts from HeLa and tumor cells. However, GCT telomerase activity varied and was less than that observed in HeLa, but no activity was detected from fibroblasts. In addition, telomere reduction was seen in DNA isolated from both HeLa and GCT but not in fibroblasts or age-matched controls. Telomere reduction and telomerase activity may be oncogenic sustaining events required to maintain the transformed phenotype seen in GCT.

骨巨細胞腫３３例の臨床病理学的検討

Thirty-three cases of benign giant cell tumor of bone were analyzed clinicopathologically. The most common site of the tumor was around the knee. At the time of diagnosis, patients ranged in age from 20 to 74 years (mean 36.3 years). Nine patients had had local recurrences.One patient has had multiple pulmonary metastases one and half years after his initial surgery of curettage and packing with methylmetacrylate. The pulmonary lesion was confirmed by thoracoscopical biopsy as a metastatic giant cell tumor. The patient remains well and working without any symptoms one year after metastases. The lesions show no change in size and number.One of the most challenging differential diagnoses is the solid variant of aneurysmal bone cyst (SABC) or giant cell reparative granuloma.We compared giant cell tumors and a case of SABC roentgenologically and histologically. Focal aggregates of giant cells were present in both conditions in a similar fashion. X-rays and histology do not differentiate these lesions. Clinicopathologically, in some cases, a distinct differentiation of each lesion was impossible. We prefer the diagnosis of giant cell tumor rather than SABC when the lesion occurs in long bones and co-exists with dense aggregates of giant cells in small portions, even though in large areas the distribution of giant cells may be sparse.

C-myc oncogene amplification and cytometric DNA ploidy pattern as prognostic factors in musculoskeletal neoplasms.

The relationship between c-myc oncogene amplification in neoplastic cells as determined by means of Southern-blot analysis, and their nuclear DNA content as assessed by combined flow and image cytometry, was investigated in fresh tumor specimens from 33 patients with musculoskeletal neoplasms. Amplification, without rearrangement of the c-myc proto-oncogene, was detected in 4 out of 7 bone sarcomas and in 6 out of 26 soft-tissue sarcomas, but in none of 3 benign giant-cell bone tumors. Among the 10 cases with c-myc amplification, 2 were found to be cytometrically DNA diploid, 2 DNA tetraploid, and 6 DNA aneuploid. Conversely, there were 10 tumors displaying extremely aneuploid DNA patterns without c-myc oncogene amplification. Thus, there was no relationship between c-myc amplification and DNA ploidy; neither did the percentage of S-phase cells, as determined by means of image cytometry, correlate significantly with the occurrence of c-myc amplification. A surprising sex-bias was observed; all 6 cases of c-myc-amplified soft-tissue sarcomas occurred in females, whereas none of the 11 males with such sarcomas showed this amplification. When the clinical follow-up data of the patients were scrutinized, it was found that the DNA ploidy pattern of the neoplastic cell nuclei, in combination with the S-phase values, as well as the occurrence of c-myc amplification, yielded prognostic information, being statistically significant 2 years after the diagnosis.

Pulmonary Metastasis of Benign Giant Cell Tumor of Bone

Benign giant cell tumor of bone, despite being classified as benign, has the unusual ability to metastasize. Metastasis of such a tumor has been thought to be rare, with only approximately 50 such cases having been reported. However, as awareness of the metastatic potential of these tumors has increased, and methods of detection have improved, metastasis of benign giant cell tumor has been increasingly recognized. Six patients with pulmonary metastasis of giant cell tumor have been treated at a Los Angeles hospital since 1980. This represents 9.1% of all patients treated for benign giant cell tumor of bone over the same period at this institution, a higher rate than that encountered in previously published series. The early detection and treatment of this tumor is important, because those with complete resection of tumor have the best prognosis. The nature of these pulmonary metastases remains unpredictable, however, as evidenced by two of the cases in this series: one of spontaneous regression, and another of death caused by pulmonary failure.

설골에 발생한 양성 거대세포종양 치험 1례

설골에 발생한 양성 거대세포종양 치험 1례

Kotz modular femur and tibia replacement. 28 tumor cases followed for 3 (1-8) years.

In the period 1984-1991, 33 lower limb reconstructions were performed with an uncemented Kotz modular femur tibia reconstruction (KMFTR) prosthesis after resection of 32 malignant bone tumors and 1 benign giant cell tumors. Tumor localization was proximal femur in 12, distal femur in 17, and proximal tibia in 4. The mean age of the patients was 38 years. 28 patients with a minimum follow-up of 1 year were studied after 3 (1-8) years. 7 patients were reoperated because of complications. Good or excellent results were obtained in 6 of the 10 proximal and 13 of the 14 distal femur reconstructions. In 2 of the 4 patients undergoing combined distal femur and proximal tibia resection, a deep infection developed, and above-knee amputation was performed. One local recurrence occurred after proximal femur resection.

Malignant Giant Cell Tumor of the Tendon Sheath: An Autopsy Report and Review of the Literature

A case of malignant giant cell tumor of the tendon sheath of the right hip, which developed in a 72-year-old Japanese woman, is described. The tumor exhibited histological similarities to a benign giant cell tumor of the tendon sheath (localized nodular tenosynovitis). The resected tumor, measuring 9 x 9 x 11 cm, was located in the adductor muscle and invaded the proximal femur and acetabulum. The nodule was encapsulated with a thin membrane which was soft and gelatinous in consistency and varied in color from yellow to brown. The synovium of the hip joint was normal. The primary lesion was composed of plump polyhedral and spindle-shaped cells. The nuclei were large, irregular and hyperchromatic, and contained prominent nucleoli. A moderated number of multinucleated giant cells was scattered throughout the lesion. There was little stromal collagen. In the majority of the specimens, pseudoglandular or alveolar spaces were predominant. An ultrastructural study demonstrated three cell types: fibroblast-like, histiocyte-like and an intermediate. The patient underwent reconstructive surgery with a Dacron fabric-enveloped alumina ceramic pelvic prosthesis and total hip components after resection of the primary lesion. Unfortunately, because of a local recurrence, a hemipelvectomy was required 10 months after the initial operation. At that time the intestines were involved with the recurrent tumor, and the patient subsequently died of perforative peritonitis. An autopsy revealed distant metastases to the right pelvis, urinary bladder, right ureter, ilium, mesenterium and lungs.

Giant Cell Tumor of the Sacrum

Twenty-six patients (18 women and eight men) with giant cell tumors of the sacrum were treated from 1960 through 1986. The mean age of the patients was 29 years. The follow-up duration averaged 7.8 years. A neurologic deficit was present in 88%. Sixteen patients had not had a previous operation. Ten patients were referred for local recurrence. Twenty-one patients had radiation therapy; malignant transformation later occurred in three. Three benign giant cell tumors metastasized to the lungs. The local recurrence rate for patients treated by curettage was 33%. Three patients died of tumor-related complications. At the completion of this study, two patients were alive with disease. The suggested initial treatment is complete curettage. Radiation therapy should be reserved for incomplete resection and local recurrence. Occasionally, patients may require wide resection, which may cause a severe neurologic deficit and compromise spinal stability.

Benign giant-cell tumor of bone with pulmonary metastases: clinical findings and radiologic appearance of metastases in 13 cases.

Tumors that metastasize are considered "malignant" by definition. However, benign giant-cell tumor of bone is an exception because of the potential for histologically benign pulmonary metastases, a fact seldom emphasized in the radiologic literature. We therefore report our experience with 13 cases of pulmonary metastasis among 475 patients (prevalence, 3%) in whom benign giant-cell tumor of bone was diagnosed before 1990 at our institution. Five (38%) of the 13 primary bone tumors were located in the distal radius. Local recurrence at the site of the primary bone tumor tumor occurred in seven patients (54%) before pulmonary metastases developed. The mean interval from the diagnosis of the primary bone tumor to the onset of pulmonary metastasis was 3.8 years, with a maximum of 10.7 years. Fifty-four percent of the patients (7/13) had pulmonary metastases 3 years after diagnosis of the primary bone lesion, and 92% (12/13) had pulmonary metastases 7.5 years after diagnosis. Overall mortality rate directly due to giant-cell tumor and its metastases was 23%. On chest radiographs and CT scans, pulmonary metastases appeared as rounded, nodular opacities of homogeneous density, ranging from 0.5 cm to 8.0 cm in diameter. Peripheral regions of the lungs were involved in 85% of the cases and basilar regions in 62%. Our study shows that benign giant-cell tumor of bone can produce pulmonary metastases, that metastases most often occurred with recurrent local disease and distal radial lesions, that the prognosis was relatively favorable, and that such metastases had no distinguishing radiologic features.

Significance of chromosomal abnormalities in a malignant giant cell tumor of bone

Cytogenetic analysis of a malignant giant cell tumor of the sacrum from a 62-year-old female revealed the following chromosomal complement: 47,XX,−1,−11,+22,del(2)(p22),t(7;7) (p22;q32),+der(1)t(1;11;21)(p32;q13;q22),+der(19)t(19;?)(q13.4;?),der(8)t(8;?)(p11;?),der(7)t(17;?)(p13;?). Metaphase cells with 92–127 chromosomes sharing identical structural abnormalities detected in the near-diploid cells were also observed. Several of these abnormalities have previously been described in the benign giant cell tumors supporting a direct relationship between these benign and malignant neoplastic counterparts.

Benign giant cell tumour with metastases to bone and lung. One case studied over 20 years

We report a case of benign giant cell tumour which over a 20-year period has given rise to pulmonary and bony metastases. The indolent nature of these metastases is remarkable, with considerable implications for the long-term management of such cases.