Benign Giant Cell Tumor Of Bone Research Articles

Late Local Recurrence of Bone Giant Cell Tumors Associated with an Increased Risk for Malignant Transformation.

Simple SummaryIn giant cell tumor of bone (GCTB), an intermediate malignant bone tumor, approximately 4% of cases can undergo malignant transformation. We analyzed risk factors for malignant transformation of GCTB treated without radiotherapy and retrospectively reviewed medical files of 461 patients with GCTB of the extremities who had undergone surgery alone, with no radiotherapy or denosumab therapy. Malignant transformation occurred in 15 of 461 patients (3.3%) at a median follow-up period of 192 months. The median follow-up duration was 89.4 months. Multivariate analysis revealed that local recurrence was an independent prognostic factor for unfavorable malignant transformation. The interval between the last surgery to local recurrence and malignant transformation was longer than that to local recurrence of benign GCTB, with a median of 15.2 (IQR, 5.2–25.4) years versus 1.3 (IQR, 0.8–2.6) months, respectively (p < 0.001). Late local recurrence of GCTB is associated with a higher risk of malignant transformation.In giant cell tumor of bone (GCTB), an intermediate malignant bone tumor, approximately 4% of all cases undergo malignant transformation. Accordingly, we analyzed risk factors for malignant transformation of GCTB treated without radiotherapy. We retrospectively reviewed medical records of 530 patients with GCTB of the extremities, admitted and treated at two institutions between January 1980 and December 2019. Overall, 4 patients with primary malignant GCTB, 4 patients with missing data, 3 patients with a history of radiotherapy, 22 patients with a follow-up of less than 6 months, and 36 patients who received denosumab were excluded. Accordingly, 461 patients were included for further analysis. Malignant transformation was observed in 15 of 461 patients (3.3%) at a median follow-up period of 192 months. The median follow-up duration was 89.4 months. Multivariate analysis revealed that local recurrence was an independent prognostic factor for unfavorable malignant transformation (Hazard ratio [HR], 11.33; 95% confidence interval [CI] 2.33–55.13; p = 0.003 for once versus none and HR, 11.24; 95% CI, 1.76–71.96; and p = 0.011 for twice or more versus none). The interval between the last surgery to local recurrence and malignant transformation was longer than that to local recurrence of benign GCTB, with a median of 15.2 years (interquartile range [IQR], 5.2–25.4) versus 1.3 months (IQR, 0.8–2.6), respectively (p < 0.001). Late local recurrence of GCTB is associated with a higher risk of malignant transformation.

Malignancy in giant cell tumor of bone in the extremities

BackgroundMalignancy in giant cell tumor of bone (GCTB) is a rare tumor with relevant literature being sparse. In primary malignant GCTB, distinct areas of benign GCTB are juxtaposed with high-grade sarcoma, while in secondary malignant GCTB sarcoma occurs at the site of previously managed GCTB. This study assesses the distinguishing characteristics of patients with this condition, the time interval for development of secondary malignant GCTB, the outcome of treatment, and explores factors associated with oncologic outcomes. MethodsThis is a retrospective case series of patients from a prospectively collected institutional musculoskeletal oncology database. From January 1998 to December 2016, 1365 patients were managed for extremity GCTBs. 32 (2.3%) patients had malignant GCTB, including 12 with primary malignant GCTB and 20 with secondary malignant GCTB. The study population comprised 18 males and 14 females presenting at a mean age of 33.7 years (±13.0) and followed for a mean of 9.5 years (±7.4). Data were collected on patient and treatment-related factors, and the occurrence of local recurrence, metastasis, and death. The time from the diagnosis of GCTB to the secondary malignant GCTB was defined as the latent period. ResultsMalignant GCTB most commonly presents in the distal femur and proximal tibia with pain and swelling. Radiologically, they are aggressive Campanacci Grade III tumors with prominent bony destruction and soft tissue extension. In the 20 patients with secondary malignant GCTB, the tumors were osteosarcoma in 15, undifferentiated pleomorphic sarcoma in 4 patients and fibrosarcoma in one patient. The mean latent period in patients with secondary malignant GCTB was 7.9 year (±7.3). The median recurrence-free survival (RFS) of secondary malignant GCTB (latent period) and benign GCTB were 61.5 and 19 months respectively (p < 0.001), receiver operating curve analysis found 49.5 months to be the critical threshold, with a longer interval to recurrence being seen in malignant recurrence. The 5 and 10-year overall survival rate of malignant GCTB were 45.8% and 36.1% respectively. The 5-year survival rates of primary malignant GCTB and secondary malignant GCTB were 56.2% and 40.0% respectively (p = 0.188). Adequate surgical margins decreased the local recurrence (LR) rate (P = 0.006). Pulmonary metastasis developed in 69% of patients. The median distant metastasis-free survival between malignant GCTB and benign GCTB were 9 and 21 months (p = 0.002). Chemotherapy was associated with a longer pulmonary metastasis free survival (13 months Vs 6 months, P = 0.002), but not with increased overall survival (57.0% Vs 33.3%, P = 0.167). ConclusionsMalignant GCTB carries a poor prognosis. Accurate diagnosis is critical to avoid inadequate surgical margins when treating primary malignant GCTB. Aggressive tumors and pulmonary metastasis should raise suspicion for malignant GCTB. Secondary malignant transformation should be suspected in patients presenting with recurrence especially after 4 years. Adjuvant chemotherapy use did not benefit survival, but was associated with increased pulmonary progression-free survival.

Drivers underpinning the malignant transformation of giant cell tumour of bone.

The rare benign giant cell tumour of bone (GCTB) is defined by an almost unique mutation in the H3.3 family of histone genes H3‐3A or H3‐3B; however, the same mutation is occasionally found in primary malignant bone tumours which share many features with the benign variant. Moreover, lung metastases can occur despite the absence of malignant histological features in either the primary or metastatic lesions. Herein we investigated the genetic events of 17 GCTBs including benign and malignant variants and the methylation profiles of 122 bone tumour samples including GCTBs. Benign GCTBs possessed few somatic alterations and no other known drivers besides the H3.3 mutation, whereas all malignant tumours harboured at least one additional driver mutation and exhibited genomic features resembling osteosarcomas, including high mutational burden, additional driver event(s), and a high degree of aneuploidy. The H3.3 mutation was found to predate the development of aneuploidy. In contrast to osteosarcomas, malignant H3.3‐mutated tumours were enriched for a variety of alterations involving TERT, other than amplification, suggesting telomere dysfunction in the transformation of benign to malignant GCTB. DNA sequencing of the benign metastasising GCTB revealed no additional driver alterations; polyclonal seeding in the lung was identified, implying that the metastatic lesions represent an embolic event. Unsupervised clustering of DNA methylation profiles revealed that malignant H3.3‐mutated tumours are distinct from their benign counterpart, and other bone tumours. Differential methylation analysis identified CCND1, encoding cyclin D1, as a plausible cancer driver gene in these tumours because hypermethylation of the CCND1 promoter was specific for GCTBs. We report here the genomic and methylation patterns underlying the rare clinical phenomena of benign metastasising and malignant transformation of GCTB and show how the combination of genomic and epigenomic findings could potentially distinguish benign from malignant GCTBs, thereby predicting aggressive behaviour in challenging diagnostic cases. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Malignant Sarcomatous Transformation of Benign Giant Cell Tumor of Bone after Treatment with Denosumab Therapy: A Literature Review of Reported Cases.

Giant cell tumor of bone (GCTB) is a biologically benign and locally aggressive tumor that most often affects the epiphyseal and metaphyseal sites of long bones in the young adult population. Overexpression of receptor activator of nuclear factor kappa B ligand (RANKL) by cancerous mesenchymal stromal cells stimulates a signal transduction cascade that recruits and activates multinucleated osteoclast-like giant cells, resulting in pathologic bone resorption. Denosumab, an RANKL inhibitor that blocks the RANKL-mediated osteoclast activation, has been recently approved by the United States Food and Drug Administration (FDA) for the treatment of aggressive GCTB. Although uncommon, several studies reported drug-related malignant morphological transformation of benign GCTB following treatment with denosumab therapy. The aim of the article was to review the clinicopathological characteristics of all the reported cases of malignant sarcomatous transformation of GCTB after treatment with denosumab therapy in patients without any history of prior exposure to radiotherapy.

H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign and Malignant Giant Cell Tumor of Bone.

Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor. Having recently reported that H3.3 G34W mutations are characteristic of this tumor type, we have now investigated the sensitivity and specificity of the anti-histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors including histologic mimics of GCTB to assess its value as a diagnostic marker. We also determined the incidence of H3.3 G34 mutations in primary malignant bone tumors as assessed by genotype and H3.3 G34W immunostaining. A total of 3163 tumors were tested. Totally, 213/235 GCTB (90.6%) showed nuclear H3.3 p.G34W immunoreactivity. This was not the case for the rare variants, p.G34L, M, and V, which occurred most commonly in the small bones of the hands, patella, and the axial skeleton. If these sites were excluded from the analysis, H3.3 G34W expression was found in 97.8% of GCTB. Malignant bone tumors initially classified as osteosarcomas were the only other lesions (n=11) that showed G34W expression. Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation were not immunoreactive for the antibody. A total of 11/13 of these malignant H3.3-mutant tumors exhibited an osteoclast-rich component: when imaging was available all but one presented at a subarticular site. We propose that subarticular primary malignant bone sarcoma with H3.3 mutations represent true malignant GCTB, even in the absence of a benign GCTB component.

A solitary pleural metastasis of benign giant cell tumor of bone

Giant cell tumor of bone (GCTB) usually appears as a benign tumor. We describe an extremely rare case of a metastatic pleural tumor arising from a benign GCTB. The patient had undergone radial resection of a GCTB in his left wrist. After 6 years, he was sent to us for diagnosis of a large mass detected upon routine radiographic screening. We resected the tumor, which was found to be a solitary pleural metastasis of GCTB and had evidently spread arterially. To our knowledge, this is the first report of its kind.

Multicentric giant cell tumor of the fourth and fifth metacarpals with lung metastases.

Giant cell tumors of bone (GCTB) are generally benign neoplasms, but recently, some authors consider them to be low-grade malignant neoplasms because they have a relatively high rate of recurrence and at least some potential for metastases. The majority of GCTB are unifocal, and less than 1% are multicentric. We report a rare case of a multicentric GCTB arising simultaneously in the non-dominant fourth and fifth metacarpals of a 25-year-old female. The patient underwent ray amputation of the two involved digits, and the surgical margins were histologically negative for tumor. The tumor had the classic histologic appearance of a benign GCTB. A year after the amputation, the patient developed pulmonary metastasis which was treated with pulmonary lobe resection. She is currently over 2.5years postsurgical treatment of the primary lesion with no evidence of local recurrence or distant metastasis.

Updates in the Treatment of Bone Cancer

Although extremely rare, primary bone cancers are often curable with proper treatment. Effective management of primary bone tumors hinges on the involvement of a multidisciplinary team of physicians with expertise in this area, both in the realms of diagnosis and treatment. In her presentation at the NCCN 18th Annual Conference, Dr. J. Sybil Biermann reviewed the changes to the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for bone cancer, featuring the introduction of new sections on giant cell tumor of bone (GCTB) and chordoma. The benefits of denosumab for the benign GCTB and the unique challenges associated with the malignant chordoma are also explored.

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.

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.

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.

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.

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.

Central giant-cell reparative granuloma of mandible: Report of a case

This case report describes the occurrence of a relatively asymptomatic lesion in the bone of the mandible of a 46-year-old female patient. The roentgenographic appearance of the lesion was nonpathognomonic. Surgical treatment consisted of meticulous curettage of the lesion in conjunction with root canal fillings of four teeth in its immediate vicinity. Biopsy of a questionable bone lesion is always desirable prior to the institution of surgical intervention. However, our initial exploratory operation subsequently proved to be definitive therapy, for rapid healing resulted and further surgical intervention was unnecessary. Within 2 years complete regeneration of bone was noted radiographically, but we kept the patient under observation for 6 years to ascertain that there was no recurrence before publishing this report (Fig. 5). Microscopic examination of the tissue specimen revealed a giant-cell-containing lesion which at that time Gerald Shklar chose to classify as a benign giant-cell tumor of bone. Dr. Shklar 7 is ready to acknowledge now that, in view of the clinical behavior and postoperative healing of this particular lesion, a designation of giant-cell reparative granuloma would not be improper. In conclusion, it goes without saying that the patient is quite pleased to be free of the pathologic condition in her mandible and still retain her natural teeth. It behooves us, therefore, to stop and consider the psychologic impact of our recommendations upon a patient and to employ the most conservative management of a problem consistent with sound surgical principles.

Benign giant-cell tumor of bone: radiation dosage for each type.

THE PURPOSE of this paper is to bring some order out of the chaotic mass of published data and opinions concerning the role of irradiation in the treatment of benign giant-cell tumor (GCT) of bone. Material and Methods The study is based upon 57 cases of genuine benign giant-cell tumors: 11 treated by us and 46 from the literature.2 We eliminated from our own material 4 successfully irradiated probable giant-cell tumors because of lack of histologic corroboration and 9 successfully treated cases with long-term follow-up because of insufficient radiation dosage data. The latter lesions were irradiated in the 1930's with radium packs and intermediate voltage radiation. Treatment was often in multiple courses and dosage was uncertain. Many published cases were eliminated from this study for the following reasons: histologic confirmation was lacking; the histologic description was not consistent with genuine giant-cell tumor; irradiation dose data were either absent, inadequate, or presented in archaic terms preventing a reasonable estimation of tumor dose; irradiation and surgery were carried out simultaneously so that the effect of irradiation alone could not be evaluated. Although a follow-up period of five years is desirable for accurate evaluation, almost one third of the reported cases would have been rejected if this criterion had been applied. Therefore, we accepted cases with shorter follow-up periods because they provided data useful to this study. Classification There is insufficient data available for the ultimate classification of benign giant-cell tumor. It is practical and convenient to group these tumors according to combined clinical and radiotherapeutic considerations (Table I). The major parameters are: age (children up to fifteen years of age, young adults up to twenty-five years of age, and adults); anatomy (membranous bones, long bones, and spine); and miscellaneous types of GCT. Special consideration is given to tumors of the jaw. Central Giant-Cell Tumor of the Jaw in Children and Young Adults Central giant-cell tumor of the jaw is an innocent tumor with specific characteristics. It occurs chiefly in children and young adults. It is radiosensitive and is radiocurable with tumor doses considerably smaller than those required for typical GCT. These lesions are equally curable with surgery, but that is a more formidable procedure and sacrifices teeth (6). Figures 1 and 2 illustrate central giant-cell tumors of the upper and lower jaw in two females aged ten and twenty-two years. Tumor doses of 1,850 rads3 in twenty-two days and 3,000 rads in sixty days arrested the lesions and restored the involved teeth to normal function and position for four teen and thirteen years respectively. Our other two patients are listed in Table II. Figure 3 and Table II depict the doses given to 13 central giant-cell tumors of the jaw.

THE TREATMENT OF BENIGN GIANT-CELL TUMORS OF THE VERTEBRAE BY IRRADIATION.

The benign giant-cell tumors of the vertebrae merit discussion as a more or less distinctive group because their location contraindicates surgical removal. Treatment by irradiation is thus indicated, with an opportunity to evaluate its merits and demerits which are at present controversial. Although successful results of irradiation of benign giant-cell tumors of bone have been reported (1 3), Lichtenstein (4) has claimed that there is no well controlled, convincing series of patients so treated and followed for a sufficient period. The giant-cell tumors of bone are uncommon, occurring most frequently in the extremities with an incidence of about 90 per cent. Approximately 7 per cent occur in the vertebrae, including the sacrum. Table I shows the incidence of vertebral involvement in several large groups of cases gathered from the literature, and, as one can see, the number of vertebral giant-cell tumors in any one series is small. Furthermore, a tendency in the past to rely on roentgen findings alone wit...

Fibrosarcoma involving the thyroid gland of a sheep given I131 daily.

CancerVolume 10, Issue 3 p. 587-591 ArticleFree Access Fibrosarcoma involving the thyroid gland of a sheep given I131 daily Sidney Marks M.D., Sidney Marks M.D. Biology Operation, Hanford Laboratories, General Electric Company, Richland, WashingtonSearch for more papers by this authorLynn A. George Jr. D.V.M., Lynn A. George Jr. D.V.M. Biology Operation, Hanford Laboratories, General Electric Company, Richland, WashingtonSearch for more papers by this authorLeo K. Bustad M.S., D.V.M., Leo K. Bustad M.S., D.V.M. Biology Operation, Hanford Laboratories, General Electric Company, Richland, WashingtonSearch for more papers by this author Sidney Marks M.D., Sidney Marks M.D. Biology Operation, Hanford Laboratories, General Electric Company, Richland, WashingtonSearch for more papers by this authorLynn A. George Jr. D.V.M., Lynn A. George Jr. D.V.M. Biology Operation, Hanford Laboratories, General Electric Company, Richland, WashingtonSearch for more papers by this authorLeo K. Bustad M.S., D.V.M., Leo K. Bustad M.S., D.V.M. Biology Operation, Hanford Laboratories, General Electric Company, Richland, WashingtonSearch for more papers by this author First published: May/June 1957 https://doi.org/10.1002/1097-0142(195705/06)10:3<587::AID-CNCR2820100325>3.0.CO;2-TCitations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Barnes, C. M.; George, L. A. Jr., and Bustad, L. K.: Toxicity of I131 in sheep; XV, I131 uptake by fetal thyroid during various stages of gestation. In Biology Research-Annual Report, Document HW-35917. 1954; pp. 117– 123. (Unclassified.) 2 Buschke, F., and Cantril, S. T.: Roentgentherapy of benign giant-cell tumor of bone. Cancer 2: 293– 315, 1949. 3 Bustad, L. K.; George, L. A. Jr.; Marks, S.; Warner, D. E.; Barnes, C. M.; Herde, K. E., and Korberg, H. A.: Biological effects of I131 continuously administered to sheep. Radiation Research. In press. 4 Feldman, W. H.: Neoplasms of Domesticated Animals. Philadelphia. W. B. Saunders Co. 1932; p. 90. 5 Jones, T. C., and Maurer, J. D.: Personal communication. 6 Looney, W. B.; Hasterlik, R. J.; Brues, A. M., and Skirmont, E.: Clinical investigation of chronic effects of radium salts administered therapeutically (1915–1931). Am. J. Roentgenol. 73: 1006– 1037, 1955. 7 Marks, S.; Dockum, N. L., and Bustad, L. K.: Toxicity of I131 in sheep; XI, Histologic effects in thyroid gland at five μc/day level. In Biology Research-Annual Report, Document HW-30437. 1953; pp. 141– 148. (Unclassified.) 8 Marks, S.; Dockum, N. L., and Bustad, L. K.: Histopathology of thyroid gland of sheep in prolonged administration of I131. Am. J. Path. 33: 219– 250, 1957. 9 Wilson, H., and Brunschwig, A.: Irradiation sarcoma. Surgery 2: 607– 611, 1937. Citing Literature Volume10, Issue3May/June 1957Pages 587-591 ReferencesRelatedInformation

TREATMENT OF GIANT-CELL TUMOURS OF BONE

1. Twenty-five cases of benign giant-cell tumour of bone, treated at Westminster Hospital, London, are reported. 2. The diagnosis can often be made on clinical and radiographic grounds alone but biopsy is sometimes necessary and seldom, if ever, contra-indicated. 3. Some cases may best be treated by excision, but in general irradiation is the treatment of choice. 4. Details of treatment by irradiation are given.

Late Results in Benign Giant-Cell Tumor of Bone Obtained by Radiation Therapy

The principles of therapy of giant-cell tumor of bone have been, from the beginning, subordinated to the variation in pathologic and histogenetic interpretation. In the early days, when the lesion was commonly regarded as belonging to the group of true bone sarcoma, radical surgery canconstituted the mode of attack. In 1920, the Bone Tumor Registry of the American College of Surgeons, recognizing the benign character of most giant-cell-containing new growths of bone, placed them in a separate division under the name of “benign giant-cell tumor.” Since then the trend of therapy has been toward conservatism. Inasmuch as metastases were not to be feared, attention was centered on how to apply the treatment locally in the most advantageous manner. Where formerly amputation or resection was advocated, curettage, swabbing of the bony cavity with escharotics, intracavitary radium, etc., were applied, the aim being to save the limb and if possible to restore its normal function. Later, when it was found that the curetted bony cavity was often slow in filling in and when a certain number of cases recurred or became secondarily infected, irradiation was tried. Thus in its incipience, radiation therapy of giant-cell tumor of bone formed a supplement to surgical intervention, usually under most unfavorable circumstances. If one also considers the peculiar radiation reaction which is observed in this lesion, and which was not altogether understood at that time, there can be no doubt that the method was placed in a position of jeopardy even as to its merit in an auxiliary capacity. All too often the cases treated by such a combination had to be subjected in the end to amputation, a procedure which, in fact, signified complete failure of the local therapeutic effort. Additional study of the radiation behavior of this tumor became necessary when it was unexpectedly noted that some of the patients who, after presumably unsuccessful treatment by curettage and irradiation, refused to submit to more radical surgery turned up later entirely recovered from their former trouble with out further treatment. During the same time new concepts started to make a heavy inroad on the histogenetic interpretation of the lesion. The opinion was heard with increasing frequency that giant-cell tumors are merely the result of a foreign-body response or a repair process of the disturbed osseous structure and, since not all arise under the same circumstances, they may represent parts of a more complex agglomeration of tumors. It thus became apparent that radiation therapy in order to be of value must be carried out with a technic which would take into consideration special requirements. These factors have given impetus to a long series of clinical investigations which now are apparently leading to the establishment of irradiation, in the form of roentgen therapy, as the primary method of treatment in all cases of benign giantcell tumors and allied cystic conditions of bone.