JBJS | Osteosarcoma Associated with Osteochondritis Dissecans. A Case Report and Review of the Literature*

Introduction

Introduction | Case Report | Discussion | References

Sarcoma associated with a bone infarct is fairly unusual; we are aware of only forty-nine well documented cases (in forty-seven patients)^1-10,12-20. Of these forty-nine tumors, thirty were malignant fibrous histiocytomas; nine, osteosarcomas; five, fibrosarcomas; three, angiosarcomas; and two, poorly differentiated sarcomas. All occurred in a non-epiphyseal region of a long bone. In the present report, we describe the case of an elderly woman in whom an osteosarcoma was found incidentally on examination of bone that had been removed to perform a total knee replacement. The osteosarcoma was located within an area of osteochondritis dissecans in the medial femoral condyle. To our knowledge, we are the first to report a sarcoma arising from an area of osteochondritis dissecans.

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Funds were received in total or partial support of the research or clinical study presented in this article. The funding source was The Henry L. Guenther Foundation.

†Division of Orthopaedic Oncology, Orthopaedic Hospital, 2400 South Flower Street, Los Angeles, California 90007. Please address requests for reprints to Dr. Brien.

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Funds were received in total or partial support of the research or clinical study presented in this article. The funding source was The Henry L. Guenther Foundation.

†Division of Orthopaedic Oncology, Orthopaedic Hospital, 2400 South Flower Street, Los Angeles, California 90007. Please address requests for reprints to Dr. Brien.

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Fig. 1 Plain anteroposterior radiograph (top) showing slight narrowing of the joint space, and coronal T1-weighted magnetic resonance image (bottom) demonstrating a lesion with a peripheral rim of low signal intensity and a medial zone of intermediate (large arrow) to low (two small arrows) signal intensity. On histological examination, the rim of low signal intensity corresponded to a border of reactive osseous tissue surrounding an infarct. The area of intermediate signal intensity was found to be fibroblastic osteosarcoma, and the adjacent area of low signal intensity was found to correspond to a region of partially calcified subchondral infarction.

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Fig. 2 Histological specimen demonstrating that portions of the articular cartilage were thinned and had cracks consistent with fibrillation (signs of degenerative disease). The upper part of the photomicrograph demonstrates a bone infarct, including trabeculae with loss of osteocyte nuclei as well as saponified fat and acellular collagenous tissue (hematoxylin and eosin, x 40).

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Fig. 3 Photomicrograph showing articular cartilage and its tidemark zone (bottom). The upper two-thirds of the image shows disrupted and fractured trabeculae within infarcted tissues, features characteristic of osteochondritis dissecans (hematoxylin and eosin, x 40).

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Fig. 4 Low-power photomicrograph demonstrating the architecture of the lesion in Fig. 1 (bottom). Although the articular cartilage in this particular section is relatively intact, most of the subchondral aspect consists of disrupted bone trabeculae (arrow) and light-staining infarcted tissue (a) (similar to those shown in Figs. 2 and 3). The dark-staining region (b) along the top of the photomicrograph corresponds to an area of high-grade, anaplastic fibroblastic osteosarcoma as seen at higher magnification (Fig. 5). The intermediate-staining region between a and b is a transition zone consisting of infarcted tissue mixed with atypical, but not definitely anaplastic, spindle cells (hematoxylin and eosin, x 10).

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Fig. 5 High-power photomicrographs illustrating region b in Fig. 4. The photomicrograph on the left demonstrates that about 95 per cent of the tumor is composed of spindly, fibroblast-like cells with moderate-to-severe nuclear anaplasia and atypical mitotic figures (arrow) (hematoxylin and eosin, x 400). As shown in the image on the right, these malignant cells also produce primitive woven bone, which is diagnostic of a high-grade, fibroblastic-type osteosarcoma (hematoxylin and eosin, x 250).

Case Report

Introduction | Case Report | Discussion | References

A sixty-seven-year-old white woman had had increasing pain in the right knee for several months. There was only minimum relief of pain after the administration of non-steroidal anti-inflammatory medications and an injection of cortisone. The patient had no history of alcoholism or alcohol consumption; cardiac, pulmonary, renal, or hepatic disease; Gaucher disease; pancreatitis; or a dysbaric condition. Physical examination revealed a painful arc of motion and an antalgic gait, but there was no ligamentous laxity, joint-line tenderness, effusion, or mass. Pertinent laboratory data, including a complete blood-cell count and blood-chemistry levels, were normal. The white blood-cell count was 8.3 × 10⁹ per liter, the level of hemoglobin was 115 grams per liter, the erythrocyte sedimentation rate was twelve millimeters per hour, the serum calcium level was 2.22 millimoles per liter, the serum phosphate level was 1.00 millimole per liter, and the serum alkaline phosphatase level was seventy-six international units per liter. A plain radiograph of the right knee, made in March 1992, showed only mild narrowing of the joint space (Fig. 1). A T1-weighted magnetic resonance image of the lateral aspect of the medial femoral condyle revealed a 2.0-by-1.5-centimeter lesion with a mixed (low-to-intermediate) signal intensity surrounded by a low signal intensity peripherally (Fig. 1). A T2-weighted image of the center of the lesion demonstrated a bright signal surrounded by a rim of low signal intensity. The differential diagnosis considered at that time included osteochondritis dissecans, subchondral cyst, and low-grade infection. The patient had increasing pain, and a total knee replacement was done in August 1994. At the operation, a subchondral infarct was seen and a small osteosarcoma was found incidentally. Gross and histological examination revealed that the osteosarcoma approximated and extended to the margin of excision. The patient was advised to have an additional procedure or chemotherapy because the tumor involved the margin of excision, but she refused both. The knee became markedly swollen nine months after the total knee replacement. At that time, a plain radiograph showed osteolysis of the proximal aspect of the right tibia. The patient refused to have additional imaging studies to determine whether there had been local recurrence or distant metastasis. Seven months later, a plain radiograph demonstrated multiple nodules in the chest. The patient died in July 1996, twenty-three months after the total knee replacement.

Pathological Findings

The gross specimen consisted of multiple fragments of bone and articular cartilage from both the femoral condyle and the tibial plateau; the fragments measured ten by six by two centimeters in aggregate. The fragment from the femoral condyle was 2.5 by 0.6 centimeters, and firm, grayish, tumor-like tissue, 1.3 by 1.0 by 0.6 centimeters, was seen along one edge of the specimen. No flattening or cartilaginous separation was present. Histological examination demonstrated focal thinning and fibrillation of the articular cartilage surface overlying a region approximately 2.5 by 1.0 centimeters, which was occupied by a subchondral infarct consisting mostly of acellular bone and fibrous tissue (Fig. 2). Subchondral trabecular fractures were seen in the zone of infarction in some sections (Fig. 3). In one portion of the specimen, an interface could be seen between the normal bone and the area of infarction; the interface consisted of hypovascular, primitive, fibrocartilaginous, and woven-bone tissues. The opposing interface demonstrated a zone of transition from a poorly vascularized, loose, bland, fibroblastic tissue into a well vascularized, highly cellular, atypical, spindle-cell process (Fig. 4). The 1.3-centimeter area of grayish tumor-like tissue that was seen on gross examination was found, on high-power micrographs, to consist of a highly cellular area of spindle cells, demonstrating definite anaplasia with severe nuclear atypia (hyperchromatism with mitoses, most of which were atypical) (Fig. 5). Most of the lesion was a high-grade malignant spindle-cell neoplasm; however, a few areas showed production of woven bone by the malignant spindle cells (Fig. 5), which is diagnostic of a high-grade, fibroblastic-type osteosarcoma. The sarcoma was seen in a margin of the specimen.

Discussion

Introduction | Case Report | Discussion | References

Furey et al., in 1960, reported on two patients who had a bone infarct associated with fibrosarcoma, and Mirra et al.¹⁶, in 1974, reported on three patients who had a malignant fibrous histiocytoma and one who had an osteosarcoma-associated bone infarct. Torres and Kyriakos, in a review of the literature, reported thirty-eight fully documented cases (including the one in their patient) of sarcoma associated with a bone infarct. We are aware of nine subsequent fully documented cases of sarcoma associated with a bone infarct^1,3,13,18,19. Most of the patients had a single bone sarcoma arising in intimate association with one of multiple bone infarcts. A sarcoma arising in a single infarct, as in our patient, is a very rare event. Two case reports were unique in that there was multifocal, sarcomatous osseous involvement. Heater and Collins reported on a patient who had an osteosarcoma in the right femur followed by development of a malignant fibrous histiocytoma in the left tibia six years later. Heselson et al.^9,10 reported on a patient who had a malignant fibrous histiocytoma in the right tibia and then a malignant fibrous histiocytoma in the left tibia thirty-eight months later. The ages of these forty-eight patients (the forty-seven included in the previous reports and the patient reported on here) ranged from eighteen to eighty-two years, with a mean age of fifty-two years. The prevalence of sarcoma associated with a bone infarct is extremely low: Mirra et al.¹⁶ reported a prevalence of 0.6 per cent (three of 525 primary bone sarcomas), and Desai et al. found a prevalence of 1 per cent (four of 384 primary bone sarcomas).

To our knowledge, a sarcoma associated with a bone infarct has been found only in the extremities. Forty-six (92 per cent) of fifty tumors (including the tumor in our patient) were in the lower extremity: twenty-eight (56 per cent) were in the femur, and eighteen (36 per cent) were in the tibia. The remaining four tumors (8 per cent) were found in the upper extremity: three (6 per cent) were in the proximal part of the humerus and one (2 per cent) was in the distal aspect of the radius. Our review of the literature revealed no previous report of a sarcoma located within an infarct involving the epiphysis. An etiological relationship between a repair of an infarct and sarcomatous transformation has been previously proposed¹⁶. It was hypothesized that the sarcoma most likely arises from one of the cellular components of the repair tissues—namely, osteoblasts (osteosarcoma), fibroblasts (fibrosarcoma), histiocytes (malignant fibrous histiocytoma), or blood vessels (angiosarcoma or malignant hemangioendothelioma). To date, all of these sarcomas, and only these sarcomas, have been reported in association with a bone infarct.

In thirty-one (66 per cent) of the forty-seven patients described in the previous reports, the bone infarct had no definite etiology. In the remaining sixteen patients (34 per cent), a predisposing condition was identified; six patients had a dysbaric condition^4,12,14,16, three had sickle-cell hemoglobinopathy^5,15,19, three had a history of alcohol consumption^3,7,10, one had been managed with steroids¹⁷, two had hereditary bone dysplasia², and one had Gaucher disease¹⁸. In addition, it has been proposed that pancreatitis may predispose to a bone infarct associated with sarcoma²¹. The rates of survival of patients who have a sarcoma in association with a bone infarct have been poor. Torres and Kyriakos, in their study of thirty-eight patients, found that twenty-six (68 per cent) had died of the disease, eight (21 per cent) were alive and well for more than five years, one (3 per cent) was alive with metastases at thirty-three months, and three (8 per cent) had been lost to follow-up before five years.

Jaffe described osteochondritis dissecans as "a condition in which a small osteochondral body (composed of articular cartilage along with a fragment of aseptically necrotic subchondral bone) is delimited and loosened from an articular end of a bone (usually a femoral condyle) and often finally extended into the joint space." The classic site of osteochondritis dissecans is the lateral aspect of the medial femoral condyle, which was the location of the lesion in our patient.

It is possible that the bone infarct was related to the sarcoma in our patient. However, the pathological findings of extensive old, highly collagenized, scar tissue; the thinning and fibrillation of cartilage; the proximity of the lesion to the joint; and the subchondral trabecular fractures indicated that the lesion was fairly old. Therefore, we believe that the patient had an antecedent small, subchondral infarct consistent with Jaffe's definition of osteochondritis dissecans. After some indeterminate period of time, the subchondral infarct was followed by malignant transformation, most likely from the ischemic fibro-osseous repair tissue, organizing the periphery of the infarct. The histological evidence of an intimate association of bland and atypical fibro-osseous tissue along the periphery of the infarct, which also blended imperceptibly into the high-grade fibroblastic osteosarcoma, supports this contention.

In conclusion, we believe that we are the first to report an osteochondritis dissecans that was intimately associated with the development of a fibroblastic osteosarcoma, which was found incidentally. To our knowledge, our patient had the smallest infarct (2.5 by 1.0 centimeters) associated with the smallest sarcoma (largest dimension, 1.3 centimeters) documented to date.

NOTE: The authors thank Dr. Yvonne Lonni, Department of Pathology, Bellflower Kaiser Permanente Hospital, Los Angeles, California, for supplying all of the materials necessary to report this consultation case.

References

Introduction | Case Report | Discussion | References

1

Abdelwahab, I. F.; Kenan, S.; Klein, M. J.; and Lewis, M. M.: Case report: angiosarcoma occurring in a bone infarct. Clin. Radiol.,45: 412-414, 1992.45412 1992 [PubMed]

2

Arnold, W. H.: Hereditary bone dysplasia with sarcomatous degeneration. Study of a family. Ann. Intern. Med.,78: 902-906, 1973.78902 1973 [PubMed]

3

Desai, P.; Perino, G.; Present, D.; and Steiner, G. C.: Sarcoma in association with bone infarcts. Report of five cases. Arch. Pathol. and Lab. Med.,120: 482-489, 1996.120482 1996

4

Dorfman, H. D.; Norman, A.; and Wolff, H.: Fibrosarcoma complicating bone infarction in a caisson worker. A case report. J. Bone and Joint Surg.,48-A: 528-532, April 1966.48-A528 1966

5

Frierson, H. F., Jr.; Fechner, R. E.; Stallings, R. G.; and Wang, G. J.: Malignant fibrous histiocytoma in bone infarct. Association with sickle cell trait and alcohol abuse. Cancer,59: 496-500, 1987.59496 1987 [PubMed]

6

Furey, J. G.; Ferrer-Torells, M.; and Reagan, J. W.: Fibrosarcoma arising at the site of bone infarcts. A report of two cases. J. Bone and Joint Surg.,42-A: 802-810, July 1960.42-A802 1960

7

Gaucher, A. A.; Regent, D. M.; Gillet, P. M.; Péré, P. G.; Aymard, B. M.; and Clement, V.: Case report 656: malignant fibrous histiocytoma in a previous bone infarct. Skel. Radiol.,20: 137-140, 1991.20137 1991

8

Heater, K., and Collins, P. A.: Osteosarcoma in association with infarction of bone. Report of two cases. J. Bone and Joint Surg.,69-A: 300-302, Feb. 1987.69-A300 1987

9

Heselson, N. G.; Webber, B. L.; Goldberg, S.; and Mills, E. E.: Bone infarction complicated by sarcomatous change: a case report. South African Med. J.,50: 1942-1944, 1976.501942 1976

10

Heselson, N. G.; Price, S. K.; Mills, E. E. D.; Conway, S. S. M.; and Marks, R. K.: Two malignant fibrous histiocytomas in bone infarcts. Case report. J. Bone and Joint Surg.,65-A: 1166-1171, Oct. 1983.65-A1166 1983

11

Jaffe, H. L.: Certain disorders of individual epiphyses, apophyses, and epiphysoid bones. In Metabolic, Degenerative, and Inflammatory Diseases of Bones and Joints, pp. 584-631. Edited by H. L. Jaffe. Philadelphia, Lea and Febiger, 1972.

12

Kitano, M.; Iwasaki, H.; Yoh, S. S.; Kuruda, K.; and Hayashi, K.: Malignant fibrous histiocytoma at site of bone infarction in association with DCS. Undersea Biomed. Res.,11: 305-314, 1984.11305 1984 [PubMed]

13

Matsuno, T.; Kaneda, K.; and Takeda, N.: Development of angiosarcoma at the site of a bone infarct. A case report. Clin. Orthop.,327: 259-263, 1996.327259 1996 [PubMed]

14

Michael, R. H., and Dorfman, H. D.: Malignant fibrous histiocytoma associated with bone infarcts. Report of a case. Clin. Orthop.,118: 180-183, 1976.118180 1976 [PubMed]

15

Mirra, J. M.; Gold, R. H.; and Marafiote, R.: Malignant (fibrous) histiocytoma arising in association with a bone infarct in sickle-cell disease: coincidence or cause-and-effect?. Cancer,39: 186-194, 1977.39186 1977 [PubMed]

16

Mirra, J. M.; Bullough, P. G.; Marcove, R. C.; Jacobs, B.; and Huvos, A. G.: Malignant fibrous histiocytoma and osteosarcoma in association with bone infarcts. Report of four cases, two in caisson workers. J. Bone and Joint Surg.,56-A: 932-940, July 1974.56-A932 1974

17

Péré, P.; Adolphe, J.; Delgoffe, C.; Froment, N.; and Gaucher, A.: Ostéonécroses épiphysaires, infarctus osseux multiples et histiocytome fibreux malin. Rev. rhumat.,51: 427-430, 1984.51427 1984

18

Pins, M. R.; Mankin, H. J.; Xavier, R. J.; Rosenthal, D. I.; Dickersin, G. R.; and Rosenberg, A. E.: Malignant epithelioid hemangioendothelioma of the tibia associated with a bone infarct in a patient who had Gaucher disease. A case report. J. Bone and Joint Surg.,77-A: 777-781, May 1995.77-A777 1995

19

Resnik, C. R.; Aisner, S. C.; Young, J. W.; and Levine, A.: Case report 767. Osteosarcoma arising in bone infarction. Skel. Radiol.,22: 58-61, 1993.2258 1993

20

Torres, F. X., and Kyriakos, S. M.: Bone infarct-associated osteosarcoma. Cancer,70: 2418-2430, 1992.702418 1992 [PubMed]

21

Unni, K. K.: Malignant (fibrous) histiocytoma. In Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, pp. 217-224. Edited by K. K. Unni. Philadelphia, Lippincott-Raven, 1996.

Topics

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Fig. 1 Plain anteroposterior radiograph (top) showing slight narrowing of the joint space, and coronal T1-weighted magnetic resonance image (bottom) demonstrating a lesion with a peripheral rim of low signal intensity and a medial zone of intermediate (large arrow) to low (two small arrows) signal intensity. On histological examination, the rim of low signal intensity corresponded to a border of reactive osseous tissue surrounding an infarct. The area of intermediate signal intensity was found to be fibroblastic osteosarcoma, and the adjacent area of low signal intensity was found to correspond to a region of partially calcified subchondral infarction.

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Fig. 2 Histological specimen demonstrating that portions of the articular cartilage were thinned and had cracks consistent with fibrillation (signs of degenerative disease). The upper part of the photomicrograph demonstrates a bone infarct, including trabeculae with loss of osteocyte nuclei as well as saponified fat and acellular collagenous tissue (hematoxylin and eosin, x 40).

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Fig. 3 Photomicrograph showing articular cartilage and its tidemark zone (bottom). The upper two-thirds of the image shows disrupted and fractured trabeculae within infarcted tissues, features characteristic of osteochondritis dissecans (hematoxylin and eosin, x 40).

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Fig. 4 Low-power photomicrograph demonstrating the architecture of the lesion in Fig. 1 (bottom). Although the articular cartilage in this particular section is relatively intact, most of the subchondral aspect consists of disrupted bone trabeculae (arrow) and light-staining infarcted tissue (a) (similar to those shown in Figs. 2 and 3). The dark-staining region (b) along the top of the photomicrograph corresponds to an area of high-grade, anaplastic fibroblastic osteosarcoma as seen at higher magnification (Fig. 5). The intermediate-staining region between a and b is a transition zone consisting of infarcted tissue mixed with atypical, but not definitely anaplastic, spindle cells (hematoxylin and eosin, x 10).

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Fig. 5 High-power photomicrographs illustrating region b in Fig. 4. The photomicrograph on the left demonstrates that about 95 per cent of the tumor is composed of spindly, fibroblast-like cells with moderate-to-severe nuclear anaplasia and atypical mitotic figures (arrow) (hematoxylin and eosin, x 400). As shown in the image on the right, these malignant cells also produce primitive woven bone, which is diagnostic of a high-grade, fibroblastic-type osteosarcoma (hematoxylin and eosin, x 250).

1

Abdelwahab, I. F.; Kenan, S.; Klein, M. J.; and Lewis, M. M.: Case report: angiosarcoma occurring in a bone infarct. Clin. Radiol.,45: 412-414, 1992.45412 1992 [PubMed]

2

Arnold, W. H.: Hereditary bone dysplasia with sarcomatous degeneration. Study of a family. Ann. Intern. Med.,78: 902-906, 1973.78902 1973 [PubMed]

3

Desai, P.; Perino, G.; Present, D.; and Steiner, G. C.: Sarcoma in association with bone infarcts. Report of five cases. Arch. Pathol. and Lab. Med.,120: 482-489, 1996.120482 1996

4

Dorfman, H. D.; Norman, A.; and Wolff, H.: Fibrosarcoma complicating bone infarction in a caisson worker. A case report. J. Bone and Joint Surg.,48-A: 528-532, April 1966.48-A528 1966

5

Frierson, H. F., Jr.; Fechner, R. E.; Stallings, R. G.; and Wang, G. J.: Malignant fibrous histiocytoma in bone infarct. Association with sickle cell trait and alcohol abuse. Cancer,59: 496-500, 1987.59496 1987 [PubMed]

6

Furey, J. G.; Ferrer-Torells, M.; and Reagan, J. W.: Fibrosarcoma arising at the site of bone infarcts. A report of two cases. J. Bone and Joint Surg.,42-A: 802-810, July 1960.42-A802 1960

7

Gaucher, A. A.; Regent, D. M.; Gillet, P. M.; Péré, P. G.; Aymard, B. M.; and Clement, V.: Case report 656: malignant fibrous histiocytoma in a previous bone infarct. Skel. Radiol.,20: 137-140, 1991.20137 1991

8

Heater, K., and Collins, P. A.: Osteosarcoma in association with infarction of bone. Report of two cases. J. Bone and Joint Surg.,69-A: 300-302, Feb. 1987.69-A300 1987

9

Heselson, N. G.; Webber, B. L.; Goldberg, S.; and Mills, E. E.: Bone infarction complicated by sarcomatous change: a case report. South African Med. J.,50: 1942-1944, 1976.501942 1976

10

Heselson, N. G.; Price, S. K.; Mills, E. E. D.; Conway, S. S. M.; and Marks, R. K.: Two malignant fibrous histiocytomas in bone infarcts. Case report. J. Bone and Joint Surg.,65-A: 1166-1171, Oct. 1983.65-A1166 1983

11

Jaffe, H. L.: Certain disorders of individual epiphyses, apophyses, and epiphysoid bones. In Metabolic, Degenerative, and Inflammatory Diseases of Bones and Joints, pp. 584-631. Edited by H. L. Jaffe. Philadelphia, Lea and Febiger, 1972.

12

Kitano, M.; Iwasaki, H.; Yoh, S. S.; Kuruda, K.; and Hayashi, K.: Malignant fibrous histiocytoma at site of bone infarction in association with DCS. Undersea Biomed. Res.,11: 305-314, 1984.11305 1984 [PubMed]

13

Matsuno, T.; Kaneda, K.; and Takeda, N.: Development of angiosarcoma at the site of a bone infarct. A case report. Clin. Orthop.,327: 259-263, 1996.327259 1996 [PubMed]

14

Michael, R. H., and Dorfman, H. D.: Malignant fibrous histiocytoma associated with bone infarcts. Report of a case. Clin. Orthop.,118: 180-183, 1976.118180 1976 [PubMed]

15

Mirra, J. M.; Gold, R. H.; and Marafiote, R.: Malignant (fibrous) histiocytoma arising in association with a bone infarct in sickle-cell disease: coincidence or cause-and-effect?. Cancer,39: 186-194, 1977.39186 1977 [PubMed]

16

Mirra, J. M.; Bullough, P. G.; Marcove, R. C.; Jacobs, B.; and Huvos, A. G.: Malignant fibrous histiocytoma and osteosarcoma in association with bone infarcts. Report of four cases, two in caisson workers. J. Bone and Joint Surg.,56-A: 932-940, July 1974.56-A932 1974

17

Péré, P.; Adolphe, J.; Delgoffe, C.; Froment, N.; and Gaucher, A.: Ostéonécroses épiphysaires, infarctus osseux multiples et histiocytome fibreux malin. Rev. rhumat.,51: 427-430, 1984.51427 1984

18

Pins, M. R.; Mankin, H. J.; Xavier, R. J.; Rosenthal, D. I.; Dickersin, G. R.; and Rosenberg, A. E.: Malignant epithelioid hemangioendothelioma of the tibia associated with a bone infarct in a patient who had Gaucher disease. A case report. J. Bone and Joint Surg.,77-A: 777-781, May 1995.77-A777 1995

19

Resnik, C. R.; Aisner, S. C.; Young, J. W.; and Levine, A.: Case report 767. Osteosarcoma arising in bone infarction. Skel. Radiol.,22: 58-61, 1993.2258 1993

20

Torres, F. X., and Kyriakos, S. M.: Bone infarct-associated osteosarcoma. Cancer,70: 2418-2430, 1992.702418 1992 [PubMed]

21

Unni, K. K.: Malignant (fibrous) histiocytoma. In Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, pp. 217-224. Edited by K. K. Unni. Philadelphia, Lippincott-Raven, 1996.

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