J Oral Maxillofac 50:761-764,
Surg
1992
Chondrosarcoma and Osteosarcoma Arising in Polyostotic Fibrous Dysplasia KOJI EBATA,
DDS, DMSc,* TAKESHI USAMI, DDS,* IWAI TOHNAI, AND TOSHIO KANEDA, DDS, PHDS
DDS, DMSc,t
Fibrous dysplasia is a bone disorder of unknown etiology. Three types are recognized: monostotic, polyostotic, and a polyostotic type that is accompanied by precocious puberty and skin pigmentation (Albright’s syndrome). Fibrous dysplasia itself is a benign condition, but recently some cases of malignant degeneration have been reported.lm7 Its incidence has been estimated at 0.4% to 6.7%.’ A review of the literature showed 89 cases of malignant degeneration occurring in fibrous dysplasia, the most common type being osteogenic sarcoma, occurring in 60.7% of the reported cases. Generally, only a single type of malignant tumor was involved. We report a case of polyostotic fibrous dysplasia in which two types of malignant tumor arose, a chondrosarcoma and an osteosarcoma. Report of a Case A 4%year-old woman visited our clinic in February 1990 complaining of swelling of her right buccal region. She reported that, in 1953, at 10 years of age, she became aware of a painless facial swelling that gradually increased in size. Over the years, the tumor was resected or irradiated at several hospitals. In 1966, at the age of 23, a diagnosis of fibrous dysplasia was made, and her mandible was partially ressected. She had no problems for 15 years after the operation, but in 198 1, at the age of 38, a rapidly growing swelling occurred in the mental region (Fig 1). A biopsy was performed and a diagnosis of chondrosarcoma was made (Fig 2). The tumor was excised surgically by mandibulectomy between the mandibular angles, and the patient had an uneventful postoperative course. Some 9 years later, at age 47, another diffuse swelling occurred in the right buccal region (Fig 3). The swelling was
Received from the Department of Oral Surgery, School of Medicine, Nagoya University, Nagoya, Japan. * Assistant Professor. t Associate Professor. $ Chief Professor. Address correspondence and reprint requests to Dr Ebata: Department of Oral Surgery, Nagoya University, School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466 Japan. 0 1992
American
Association
of Oral and Maxillofacial
Surgeons
FIGURE I. A, Appearance of rapidly growing tumor in the mental region. B. Radiograph of the lesion (arrows).
0278-2391/92/5007-0020$3.00/O
761
762
MALIGNANT DEGENERATION
OF FIBROUS DYSPLASIA
FIGURE 2. Photomicrograph of biopsy specimen showing chondroid appearance (hematoxylin-eosin stain, original magnification X200).
firm and elastic, but the overlying tissues were of normal color and texture. No abnormality was found intraorally. Magnetic resonance imaging (MRI) showed a lesion measuring approximately
5.5 X 4.5 X 3.5 cm (Fig 4). Its borders FIGURE 4. Appearance of the tumor (arrows) on magnetic resonance imaging.
were we11demarcated and the surrounding bony tissue was unaffected. There appeared to be fluid in the lesion. Based on this finding, the tumor was suspected to be a cyst. In March 1990, the lesion was excised under general anesthesia (Fig 5). The cystic fluid subsequently was examined biochemically and found to be composed of components resembling serum. However, microscopically, the lesion was diagnosed as an osteosarcoma (Fig 6) and immediate postoperative chemotherapy was considered. Adriamycin (ADR; 30 mg/d for 3 days) and cis-diamine dichroloplatinam (CDDP; 80 mg/d for 1 day) were delivered over 6 weeks, with a total of six courses of chemotherapy given. In the last two courses, Pirarubicin (THP-ADR, Meiji Seika Co, Ltd, Tokyo, Japan) was substituted for ADR. During the whole period of chemotherapy, no changes were found in the elec-
Table 1. Malignant Degeneration of Fibrous Dysplasia
Male Female OS FS cs Others Total
FIGURE 3. Rapidly growing tumor in the right buccal region (arrows) 9 years after initial treatment.
MFD
PFD
Alb
Total
20 19 18 13 5 3 39
17 22 29 4 5 1 39
3 8 7 4 0 0 11
40 49 54 21 10 4 89
Abbreviations: Alb, Albright’s syndrome; CS, chondrosarcoma; FS, fibrosarcoma; MFD, monostotic fibrous dysplasia; OS, osteosarcoma; PFD, polyostotic fibrous dysplasia.
763
EBATA ET AL
A
FIGURE 6. Photomicrograph of the tumor showing malignant cells and osteoid formation (hematoxylin-eosin stain, original magnification X200).
osteosarcoma, fibrosarcoma, and chondrosarcoma, with osteosarcoma being the most frequent type, accounting for 60.7% of the cases. Males and females are equally affected. The monostotic variety accounted for 39 cases, the polyostotic for 39 cases, and Albright’s syndrome for 11 cases (Table 1). The craniofacial region was the most common site (36 cases), followed by the femur (27 cases), tibia (13 cases), and pelvis (6 cases) (Table 2). In all sites, malignant degeneration was found at the border between the normal bone and
B FIGURE 5. A. Extirpated tumor. T,Tumor: C,condyle. B, Location of the two tumors. CS,chondrosarcoma; F’D,Fibrous dysplasia; OS, osteosarcoma.
trocardiogram (ECG) or creatinine clearance, but a leukocytopenia was induced by the THP-ADR, which improved with administration of granulocyte colony-stimulating factor (G-CSF). One year later, the tumor could not be found on MRI (Fig 7).
Discussion Malignant degeneration in fibrous dysplasia can occur and has been the subject of numerous reports. In an analysis of the 89 cases reported in the literature, histologic types of identified malignant tumors include
FIGURE 7. Postchemotherapy MRI showing disappearance of the tumor (compare with Fig 4).
764
MALIGNANT DEGENERATION
Table 2. Location of the Malignant Degeneration
have had any effect on the malignant transformation. Although it has been suggested that there is a relationship between surgery and malignant degeneration, this was not obvious in our case. It appears that fibrous dysplasia is a lesion that has an inherent tendency to undergo malignant degeneration, in comparison with other bone diseases, and that previous radiation therapy is only one of the factors that can contribute to malignant change. After surgical excision, chemotherapy using CDDP, ADR, and THP-ADR was given, with good results. The patient, however, will continue to be observed carefully for a period of at least 5 years.
Craniofacial Femur Tibia Pelvis Humerus Scapula Fibura Ulna Metatarsus Rib Vertebra Total
MFD
PFD
Alb
15 10 7 2 3
16 14 5 3 2 3
5 3
1 1
1 1 1 1 39
1 45
OF FIBROUS DYSPLASIA
11
Abbreviations: Alb, Albright’s syndrome; MFD, monostotic fibrous dysplasia: PFD, polyostotic fibrous dysplasia.
the fibrous dysplasia, so remodeling of the bone may have some relationship to the malignant degeneration. In addition, radiation therapy also should be considered as a possible important etiologic factor. Yabut et al reported that of the 83 cases they studied showing malignant transformation, 27.7% had been irradiated.5 Schwartz’ and Yashima’ also reported incidences of 39.3% and 34.9%, respectively, of malignant degeneration of previously irradiated fibrous dysplasia. In our case, radiation therapy had been given about 20 years previously, but the irradiation was carried out only once and the dose was less than 10 Gy, so that it may not
1. Yashima S, Ishikawa T, Nagahata H: Osteosarcoma arising in the mandibular fibrous dysplasia of polyostotic type: A case report and a review ofthe literature. Jpn J Oral Maxillfac Surg 3i:l15, 1985 2. Jose CC, Benjamin CS: Osteogenic saroma arising in polyostotic fibrous dysplasia. A case report. Aust Radio1 30: 134, 1986 3. Present D, Bertoni F, Enneking WF: Osteosarcoma of the mandible arising in fibrous dysplasia. Clin Orthop 204:238, 1986 4. Witkin GB, Guilford WB, Siegal GP: Osteogenic sarcoma and soft tissue myxoma in a patient with fibrous dysplasia and hemoglobins JBaltimorr and-S. Clin Orthop 204245,‘ 1986 5. Yabut SM, Kenan S. Sissons HA: Malignant transformation of fibrous dysplasia. Clin Orthop 228:281, 1988 6. Takonis WK: Osteosarcoma in fibrous dysplasia. Skeletal Radio1 17:163, 1988 7. Campanacci M, Bettoni F: Malignant degeneration in fibrous dysplasia. Ital J Orthop Traumatol 5:373, 1979 8. Schwartz DT, Alpert M: The malignant transformation of fibrous dysplasia. Am J Sci 247: 1, 1964
Surg
1992
Chondrosarcoma and Osteosarcoma Arising in Polyostotic Fibrous Dysplasia KOJI EBATA,
DDS, DMSc,* TAKESHI USAMI, DDS,* IWAI TOHNAI, AND TOSHIO KANEDA, DDS, PHDS
DDS, DMSc,t
Fibrous dysplasia is a bone disorder of unknown etiology. Three types are recognized: monostotic, polyostotic, and a polyostotic type that is accompanied by precocious puberty and skin pigmentation (Albright’s syndrome). Fibrous dysplasia itself is a benign condition, but recently some cases of malignant degeneration have been reported.lm7 Its incidence has been estimated at 0.4% to 6.7%.’ A review of the literature showed 89 cases of malignant degeneration occurring in fibrous dysplasia, the most common type being osteogenic sarcoma, occurring in 60.7% of the reported cases. Generally, only a single type of malignant tumor was involved. We report a case of polyostotic fibrous dysplasia in which two types of malignant tumor arose, a chondrosarcoma and an osteosarcoma. Report of a Case A 4%year-old woman visited our clinic in February 1990 complaining of swelling of her right buccal region. She reported that, in 1953, at 10 years of age, she became aware of a painless facial swelling that gradually increased in size. Over the years, the tumor was resected or irradiated at several hospitals. In 1966, at the age of 23, a diagnosis of fibrous dysplasia was made, and her mandible was partially ressected. She had no problems for 15 years after the operation, but in 198 1, at the age of 38, a rapidly growing swelling occurred in the mental region (Fig 1). A biopsy was performed and a diagnosis of chondrosarcoma was made (Fig 2). The tumor was excised surgically by mandibulectomy between the mandibular angles, and the patient had an uneventful postoperative course. Some 9 years later, at age 47, another diffuse swelling occurred in the right buccal region (Fig 3). The swelling was
Received from the Department of Oral Surgery, School of Medicine, Nagoya University, Nagoya, Japan. * Assistant Professor. t Associate Professor. $ Chief Professor. Address correspondence and reprint requests to Dr Ebata: Department of Oral Surgery, Nagoya University, School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466 Japan. 0 1992
American
Association
of Oral and Maxillofacial
Surgeons
FIGURE I. A, Appearance of rapidly growing tumor in the mental region. B. Radiograph of the lesion (arrows).
0278-2391/92/5007-0020$3.00/O
761
762
MALIGNANT DEGENERATION
OF FIBROUS DYSPLASIA
FIGURE 2. Photomicrograph of biopsy specimen showing chondroid appearance (hematoxylin-eosin stain, original magnification X200).
firm and elastic, but the overlying tissues were of normal color and texture. No abnormality was found intraorally. Magnetic resonance imaging (MRI) showed a lesion measuring approximately
5.5 X 4.5 X 3.5 cm (Fig 4). Its borders FIGURE 4. Appearance of the tumor (arrows) on magnetic resonance imaging.
were we11demarcated and the surrounding bony tissue was unaffected. There appeared to be fluid in the lesion. Based on this finding, the tumor was suspected to be a cyst. In March 1990, the lesion was excised under general anesthesia (Fig 5). The cystic fluid subsequently was examined biochemically and found to be composed of components resembling serum. However, microscopically, the lesion was diagnosed as an osteosarcoma (Fig 6) and immediate postoperative chemotherapy was considered. Adriamycin (ADR; 30 mg/d for 3 days) and cis-diamine dichroloplatinam (CDDP; 80 mg/d for 1 day) were delivered over 6 weeks, with a total of six courses of chemotherapy given. In the last two courses, Pirarubicin (THP-ADR, Meiji Seika Co, Ltd, Tokyo, Japan) was substituted for ADR. During the whole period of chemotherapy, no changes were found in the elec-
Table 1. Malignant Degeneration of Fibrous Dysplasia
Male Female OS FS cs Others Total
FIGURE 3. Rapidly growing tumor in the right buccal region (arrows) 9 years after initial treatment.
MFD
PFD
Alb
Total
20 19 18 13 5 3 39
17 22 29 4 5 1 39
3 8 7 4 0 0 11
40 49 54 21 10 4 89
Abbreviations: Alb, Albright’s syndrome; CS, chondrosarcoma; FS, fibrosarcoma; MFD, monostotic fibrous dysplasia; OS, osteosarcoma; PFD, polyostotic fibrous dysplasia.
763
EBATA ET AL
A
FIGURE 6. Photomicrograph of the tumor showing malignant cells and osteoid formation (hematoxylin-eosin stain, original magnification X200).
osteosarcoma, fibrosarcoma, and chondrosarcoma, with osteosarcoma being the most frequent type, accounting for 60.7% of the cases. Males and females are equally affected. The monostotic variety accounted for 39 cases, the polyostotic for 39 cases, and Albright’s syndrome for 11 cases (Table 1). The craniofacial region was the most common site (36 cases), followed by the femur (27 cases), tibia (13 cases), and pelvis (6 cases) (Table 2). In all sites, malignant degeneration was found at the border between the normal bone and
B FIGURE 5. A. Extirpated tumor. T,Tumor: C,condyle. B, Location of the two tumors. CS,chondrosarcoma; F’D,Fibrous dysplasia; OS, osteosarcoma.
trocardiogram (ECG) or creatinine clearance, but a leukocytopenia was induced by the THP-ADR, which improved with administration of granulocyte colony-stimulating factor (G-CSF). One year later, the tumor could not be found on MRI (Fig 7).
Discussion Malignant degeneration in fibrous dysplasia can occur and has been the subject of numerous reports. In an analysis of the 89 cases reported in the literature, histologic types of identified malignant tumors include
FIGURE 7. Postchemotherapy MRI showing disappearance of the tumor (compare with Fig 4).
764
MALIGNANT DEGENERATION
Table 2. Location of the Malignant Degeneration
have had any effect on the malignant transformation. Although it has been suggested that there is a relationship between surgery and malignant degeneration, this was not obvious in our case. It appears that fibrous dysplasia is a lesion that has an inherent tendency to undergo malignant degeneration, in comparison with other bone diseases, and that previous radiation therapy is only one of the factors that can contribute to malignant change. After surgical excision, chemotherapy using CDDP, ADR, and THP-ADR was given, with good results. The patient, however, will continue to be observed carefully for a period of at least 5 years.
Craniofacial Femur Tibia Pelvis Humerus Scapula Fibura Ulna Metatarsus Rib Vertebra Total
MFD
PFD
Alb
15 10 7 2 3
16 14 5 3 2 3
5 3
1 1
1 1 1 1 39
1 45
OF FIBROUS DYSPLASIA
11
Abbreviations: Alb, Albright’s syndrome; MFD, monostotic fibrous dysplasia: PFD, polyostotic fibrous dysplasia.
the fibrous dysplasia, so remodeling of the bone may have some relationship to the malignant degeneration. In addition, radiation therapy also should be considered as a possible important etiologic factor. Yabut et al reported that of the 83 cases they studied showing malignant transformation, 27.7% had been irradiated.5 Schwartz’ and Yashima’ also reported incidences of 39.3% and 34.9%, respectively, of malignant degeneration of previously irradiated fibrous dysplasia. In our case, radiation therapy had been given about 20 years previously, but the irradiation was carried out only once and the dose was less than 10 Gy, so that it may not
1. Yashima S, Ishikawa T, Nagahata H: Osteosarcoma arising in the mandibular fibrous dysplasia of polyostotic type: A case report and a review ofthe literature. Jpn J Oral Maxillfac Surg 3i:l15, 1985 2. Jose CC, Benjamin CS: Osteogenic saroma arising in polyostotic fibrous dysplasia. A case report. Aust Radio1 30: 134, 1986 3. Present D, Bertoni F, Enneking WF: Osteosarcoma of the mandible arising in fibrous dysplasia. Clin Orthop 204:238, 1986 4. Witkin GB, Guilford WB, Siegal GP: Osteogenic sarcoma and soft tissue myxoma in a patient with fibrous dysplasia and hemoglobins JBaltimorr and-S. Clin Orthop 204245,‘ 1986 5. Yabut SM, Kenan S. Sissons HA: Malignant transformation of fibrous dysplasia. Clin Orthop 228:281, 1988 6. Takonis WK: Osteosarcoma in fibrous dysplasia. Skeletal Radio1 17:163, 1988 7. Campanacci M, Bettoni F: Malignant degeneration in fibrous dysplasia. Ital J Orthop Traumatol 5:373, 1979 8. Schwartz DT, Alpert M: The malignant transformation of fibrous dysplasia. Am J Sci 247: 1, 1964
