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Of 327 patients who had a giant-cell tumor of bone and were seen at the Istituto Rizzoli, 293 were treated at the Institute, and 280 of these were followed for two to forty-four years. The distribution according to sex and age of the patient and site of the tumor was similar to the distributions in major reports of large series. The tumor usually involved the metaphysis and the epiphysis, but was occasionally limited to the metaphysis, and in only 2 per cent of the patients was it adjacent to an open growth plate. The tumor on occasion invaded the articular space, also involving the ligaments and the synovial membrane. Extension to an adjacent bone through the joint occurred in 5 per cent of the tumors. Our radiographic grading, which is roughly comparable with the staging system of Enneking et al., was Grade I in 4 per cent, II in 74 per cent, and III in 22 per cent of 266 patients before treatment. A pathological fracture was apparent on the first radiograph in 9 per cent of the patients. In the 280 patients with adequate follow-up, 331 surgical procedures were performed. The rate of local recurrence was 27 per cent in the 151 intralesional procedures, 8 per cent in the 122 marginal excisions, and zero in the fifty-eight wide or radical procedures. These results did not correlate with the radiographic grade of the lesion. Of the fifty-one local recurrences that were seen after treatment at our institution, 90 per cent appeared in the first three years after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

All seventy-five cases recorded as giant-cell tumor of bone in the Swedish Cancer Registry for the years 1958 through 1968 were analyzed. At reexamination, fifty-three cases constituted genuine giant-cell tumor of bone and twenty cases were so-called "giant-cell variants". The genuine giant-cell tumors showed a significantly higher incidence in the urban than in the rural population. The recurrence rate was 42 per cent. Patients under the age of twenty-five rarely had recurrences. A high recurrence rate was found among patients with tumors located in the distal end of the femur and the proximal end of the tibia. Tumors penetrating through the bone cortex were more aggressive than those located entirely within bone, regardless of tumor size and presence or absence of spontaneous fracture. A malignant course was found in 11.3 per cent of cases, predominantly in patients with tumors in the femur. Histopathological grading was of no prognostic value. Primary en bloc resection with or without prosthetic replacement is recommended in patients over the age of twenty-five.

The presence of more than one distinct giant-cell tumor in the same patient is rare; seven cases have been reported in the literature. The present series involves eleven patients with thirty-five individual tumors. Multifocal giant-cell tumors may pose a diagnostic problem. It is difficult to distinguish a multicentric giant-cell tumor from a primary giant-cell tumor with metastatic spread. This problem is magnified when the second lesion is not noted at the onset or is metaphyseal in location. Moreover, these lesions present a therapeutic challenge to the surgeon. Multiple lesions tend to exhibit the same aggressive clinical behavior as a solitary giant-cell tumor. A high recurrence rate after curettage indicates that aggressive surgical management is necessary.

Unlabelled: Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow., Clinical Relevance: Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents...

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.