Benign Giant Cell Tumor Research Articles

Benign metastasizing giant cell tumors of bone. A DNA flow cytometric study.

Approximately 2% of histologically benign giant cell tumors (BGCT) of bone are complicated by lung metastases, which can progress despite their benign histologic appearance. Almost all BGCT studied by DNA flow cytometry (FCM) have been reported to be diploid. However, the very few cases with lung metastases previously analyzed were all aneuploid. To assess the usefulness of DNA FCM in predicting the metastatic potential of BGCT, seven metastasizing BGCT were studied by DNA FCM using paraffin-embedded tissue. Five were purely diploid, one was tetraploid, and one was aneuploid. The primary and the metastasis showed the same DNA distribution in all but the tetraploid case, in which the metastasis was purely diploid. A single patient, who was in the diploid group, had unresectable tumor in the lungs; she remains alive with stable disease at 30 months. The other six patients, who underwent complete resections of their lung metastases, are free of disease. These results suggest that DNA FCM is not a sensitive method for predicting the metastatic potential of BGCT since most metastasizing cases appear to be diploid.

"Benign" metastasizing giant cell tumor: evaluation of nuclear DNA patterns by flow cytometry.

Nuclear deoxyribonucleic acid (DNA) ploidy was determined by flow cytometry for nine histologically benign giant cell tumors that developed systemic metastases and for eight tumors that did not metastasize. Specimens from the primary tumor, local recurrences, and pulmonary metastases were evaluated. No feature of the DNA ploidy pattern was identified to distinguish giant cell tumors that metastasized from those that did not. The mean percentage of diploid (G0/G1 peak, 2C) cells was 81% in the metastasizing group and 80% in the nonmetastasizing group. The DNA ploidy pattern of the primary tumors was not different from that of their metastases. No DNA aneuploid patterns were observed among the benign tumors.

Benign Metastasizing Giant-Cell Tumor of Bone

Three cases of benign giant-cell tumor (GCT) of bone with pulmonary metastasis are reported. In addition, 28 cases from the literature are reviewed. The patients were followed for a mean of 7.8 years (range from two to 29 years). The interval to metastasis ranged from zero to ten years with a mean of 3.2 years. Metastasis was not related to the number of previous operations. The local recurrence rate in the tumors that metastasized was 63%, suggesting that GCTs that metastasize may be an aggressive form of the tumor. The overall mortality rate was 16%. Persistent pulmonary disease does not carry a poor prognosis; surgical resection of accessible pulmonary nodules is recommended to provide histologic confirmation of the diagnosis, and prevent future complications secondary to local growth of the implants, as well as provide a potential cure. Chemotherapy has not improved survival and is associated with significant morbidity and is thus not recommended. Adjuvant radiation is recommended only for control of surgically unresectable lesions because of its potential association with sarcomatous degeneration in GCT.

Giant-cell tumor of bone, stage II, displaying translocation t(12;19)(q13;q13)

A new case of giant-cell tumour (GCT) of bone with benign histological features, clinical stage II, has been reviewed with immunohistochemistry and electron microscopy. After short-term tissue culture the karyotype, using G-banding techniques, presented a consistent translocation t(12;19)(q13;q13). Nude mice xenografts of the tumour were unsuccessful after 6 months of follow-up. Presence of such chromosomal rearrangement may be related to locally aggressive, histologically benign giant-cell tumors of bone.

Giant-Cell Tumor of Bone With Pulmonary Metastases

Giant-cell tumor of bone rarely metastasizes to the lung. In three of six cases, lesions in lung tissue were histologically benign. In 39 such cases reported in the literature, the treatments were surgical extirpation, chemotherapy, and radiation therapy. Resection was indicated to definitely diagnose the pulmonary lesions as benign giant-cell tumors. Radiation therapy and/or chemotherapy may be beneficial as adjuvant treatment, especially where the lesions are anatomically inaccessible. Some pulmonary lesions spontaneously regress even in the absence of definitive treatment.

Management of skeletal giant cell tumors of the phalanges of the hand

Five cases of unicentric benign giant cell tumors of the phalanges of the hand are reported. Three patients were initially treated with curettage and bone grafting; two had recurrences that necessitated ray resection as the definitive treatment, and one was free of disease at 16 years' follow-up. The two patients who were primarily treated with ray resection were free of disease at follow-up of 2 and 1 years, respectively. Enneking's surgical staging system and Lodwick's x-ray grading of bone tumors were used to evaluate management methods.

Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients.

Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

The correlation between the radiologic staging studies and histopathologic findings in aggressive stage 3 giant cell tumor of bone.

The histologic features of aggressive Stage 3 benign giant cell tumor of bone were correlated with their radiologic staging studies. Our series includes 24 patients treated at the University of Florida, Department of Orthopaedic Oncology, from January 1979 to July 1983. Particularly in 13 cases, results of routine specimen histologic as well as of the histologic study of macrosections containing the entire resected specimen (the tumor and surrounding bone and soft tissue) were evaluated. Surgical staging studies including plain radiographs, bone scintigrams, computerized axial tomography scans, tomography, and angiography were used to delineate the anatomic location of the lesion. Within this group of giant cell tumors, the general histologic features resemble those of the classic giant cell tumor. However, certain aggressive features best demonstrated on the macrosections, such as cortical and subchondral invasion, capsular and reactive bony zone infiltration, "digital extension" of the tumor, and neovascularity correlated well with the anatomic localization and aggressiveness found on the staging studies. Those findings emphasize the value of staging studies in the delineation of the histologic potential of these benign aggressive lesions.

Metastases from histologically benign giant-cell tumor of bone.

Metastasis from a giant-cell tumor of bone that is histologically benign has become a recognized entity. To date, thirty-one pathologically proved cases have been reported in the world literature. To this, we add eight cases from our experience of more than 400 cases of histologically benign giant-cell tumor of bone. The lungs are the principal site of metastasis, the lesions being pathologically indistinguishable from the primary tumor. The metastatic process is unpredictable as to clinical aggressiveness, and the mortality rate is approximately 25 per cent. We advise aggressive attempts at complete extirpation of metastases.

Benign giant cell tumor complicating extensive Paget's disease

Benign giant cell tumor complicating extensive Paget's disease

The mechanism of metastasis in the so-called “benign giant cell tumor of bone”

A case of so-called “benign giant cell tumor of bone” with an incidental histologic finding of intratumor vascular invasion is reported. The mechanism and biology of metastasis are briefly discussed. For the purposes of this presentation, the mechanism of metastasis is divided into two types—active and passive. An active type of metastasis indicates malignancy, whereas a passive type denotes a benign process. The malignant features of the conventional or typical giant cell tumor of bone are demonstrated. It is proposed that this neoplasm be labeled malignant despite its seemingly benign histologic appearance. Relative to the degree of malignancy, a lesion of this nature may be classified as either a low or a high grade type of malignant giant cell tumor.

Diffuse Pigmented Villonodular Synovitis in Association with Paget??s Disease of Bone

A 73-year-old patient with Paget's disease of bone was found to have associated diffuse pigmented villonodular synovitis (PVNS) of the right knee joint. Paget's disease has been reported in association with bone sarcoma, benign giant-cell tumor of bone, myeloma and a single case of giant-cell tumor of tendon sheath. the tendency for Paget's disease to be associated with giant-cell-rich lesions of bone and joint, which includes PVNS, merits further investigation, particularly since the recent observation of intranuclear viral-like inclusions in the osteoclast of all patients with this disease.

Late recurrence of giant-cell tumor of bone: pharmacoangiographic evaluation.

Late recurrence (more than five years) of benign giant-cell tumor of bone is uncommon. Two patients were evaluated by angiography, including injection of vasoactive drugs, because of osteolytic lesions developing six and seven years after primary operation for benign giant-cell tumor. Angiography established a probable recurrence in both cases. Angiography also permitted accurate evaluation of tumor extension, facilitating pre-operative planning. Giant-cell tumors are predominantly hypervascular lesions. Angiographic evaluation is therefore recommended when a recurrent lesion is suspected.

Giant cell tumor of bone

Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned.

Premalignant tumors and conditions of bone

Most bone sarcomas arise in apparently normal bone. However, some sarcomas arise in preexisting benign bone tumors or in nonneoplastic conditions. Some of the lesions, such as multiple exostoses and Ollier's disease, have a propensity to develop chondrosarcoma. Rarely does a benign giant cell tumor become malignant without prior irradiation, malignant transformation of other benign tumors, such as osteoblastoma and chondroblastoma, is a medical curiosity. Among nonneoplastic conditions, radiation changes, long-standing chronic osteomyelitis, and Paget's disease have definite premalignant connotations. However, the risk of developing cancer in these conditions is still low.

Malignant giant cell tumor of bone

The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant.

Benign giant cell tumor of femur with bilateral multiple pulmonary metastases

This paper presents the unusual case of a patient with a histologically benign giant cell tumor of the femur that resulted in bilateral multiple pulmonary metastases having the appearance of benign giant cell tumor. An aggressive surgical approach was used to eradicate the pulmonary metastases; 25 nodules excised from the left lung and 33 nodules from the right lung were proved histologically to be benign giant cell tumors. Three years after bilateral thoracotomies, he remains well, without evidence of recurrent disease, and his lung function is almost normal.

Maxillary giant cell reparative granuloma

"Giant cell reparative granuloma" was introduced into medical literature by Jaffe in 1953. Prior to that time most authors considered this lesion to be a variant of the benign giant cell tumor of the long bones, or a giant cell variant of osteitis fibrosa. Bernier and Cahn established the subdivision between the rare central giant cell reparative granuloma and the common peripheral epulis. In the past, considerable emphasis has been placed on the importance of differentiating the true giant cell tumor from the giant cell reparative granuloma of the jaw bones. Most authors now believe the true giant cell tumor does not appear in the jaw bones except in rare cases associated with Paget's disease of the skull. Developing from membranous, rather than cartilaginous, ossification might account for this. Both peripheral and central intraosseous lesions, parathyroid osteopathy and the pathologic tissue of cherubism show no appreciable histologic difference. These tumefactions are histologically a proliferative fibroblastic lesion with multinucleated giant cells. The histopathology of the giant cell tumor of the long bones is probably identical to the histopathology of the giant cell reparative granuloma of the jaw bones. The diagnosis of giant cell reparative granuloma must be made by physical examination, history, laboratory, X-ray parameters and clinical follow-up. Localized maxillary swelling is the most important clinical feature. The swelling is smooth and palpation can reveal a rubbery, elastic sensation where bone has been thinned. There are no specific radiographic signs. Conservative surgical management is indicated and adequate for giant cell reparative granulomas. Radiation is not indicated because of long term risks. Steroids have not been proven useful.

Giant cell tumor of bone: fine structural localization of acid phosphatase.

The fine structural localization of acid phosphatase in the different cells in a benign giant cell tumor of bone has been studied. Stromal cells type 1 and 2 (fibroblast-like and macrophage-like, respectively) showed the presence of lead phosphate precipitate following incubation in a Gomori-type lead salt medium only in conventional lysosomes. In the multinucleated giant cells, the final product was deposited over lysosome-like organelles, and also over Golgi cisternae, vesicles, and vacuoles. Furthermore, evidence for presence of acid phosphatase was obtained in smooth-surfaced tubular, sausage-, horse-shoe-, and ring-shaped structures and over digestive vacuoles of autophagic or heterophagic origin. Finally, in these cells, many of the tubular and vacuolar elements located subjacent to areas of the plasma membrane with microvillous specializations (abortive brush borders?) were shown to carry acid phosphatase.

EXCISION OF TUMOURS OF HUMERUS AND FEMUR, WITH RESTORATION BY INTERNAL PROSTHESES

A personal experience is recounted of operations in cases of tumour involving the humerus or femur with restoration by endoprostheses. Twenty-four patients were treated in this way from 1950 to 1969 inclusive and have been followed up for between four and twenty-four years. The patients selected for treatment have presented chondrosarcoma (ten), so-called benign giant-cell tumour of bone, usually recurrent (nine), angiomatous osteolysis (two), seemingly single thyroid or renal metastasis (two), and ununited pathological fracture after irradiation of a tumour (one). Development of the prostheses from early beginnings is outlined. Some points in surgical management are referred to. The complications and results are recorded.