Pediatric Radiology
Pediatr. Radiol. 8, 110-112 (1979)
9 by Springer-Verlag1979
Case Reports
Osteosarcoma Arising in Osteogenesis Imperfecta B a r b a r a S. R e i d a n d J. D . H u b b a r d Departments of Pathology and Radiology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Abstract. W e
r e p o r t a case of o s t e o s a r c o m a a r i s i n g i n osteogenesis imperfecta. The characteristic radiographic and pathological findings are discussed and emp h a s i z e d to w a r r a n t a b i o p s y .
Key words: O s t e o s a r c o m a - O s t e o g e n e s i s i m p e r f e c t a - H y p e r t r o p h i c cells
formation consistent with a rapidly developing process. Hyperplastic callus formation and hemorrhage (pseudotumor) were favored clinically. He was lost to follow-up until August 1977 when he presented to the Emergency Room unable to walk because of severe pain. The distal thigh at this time was very swollen, hot and tender. The skin was taut with multiple dilated veins. The fracture at this time was more impacted with further cortical destruction of the medial, posterior and lateral aspects of the distal femur. There
O s t e o s a r c o m a o c c u r r i n g i n o s t e o g e n e s i s i m p e f f e c t a is a r a r e e n t i t y . C o n v e r s e l y , h y p e r t r o p h i c callus i n osteogenesis imperfecta which can resemble osteos a r c o m a clinically o c c u r s m o r e f r e q u e n t l y . T h e r e a r e t h r e e d o c u m e n t e d cases of o s t e o s a r c o m a o c c u r r i n g i n patients with osteogenesis impeffecta in the English l i t e r a t u r e . W e r e p o r t a 4 t h case w i t h e m p h a s i s o n t h e radiographic and pathological characteristics. The radiographic characteristics should not be confused w i t h h y p e r t r o p h i c callus, a b e n i g n p r o c e s s .
Case Report A. A. (7-19-49) a 14 year old boy had been followed since 3 years of age with the diagnosis of osteogenesis impeffecta tarda (familial). He had had at least 16 documented fractures of the extremities. Between December 1976 and April 1977 the patient had three fractures of the proximal femur located about a Jewett nail and plate placed for a prior fracture in 1975. Radiographs in December 1976 and March 1977 showed a demineralized but otherwise normal distal left femur typical of osteogenesis imperfecta. Radiographs in April 1977 showed a loss of the cortex of the distal medial aspect of the left femur. No fracture was evident. The patient was a poor historian and could not remember when he first noted pain in the distal portion of the left femur. In June 1977, he was seen with pain and swelling of the left distal thigh. Radiographs (Fig. 1) showed a fracture through the distal left femoral metaphysis with destructive changes in the cortex particularly the medial surface with sunray appearance of periosteal new bone
00301-0449/79/0008/0110/$01.00
Fig. 1. Lateral view of the distal left femur shows destruction of the cortex anteriorly with typical sunray appearance of periosteal new bone formation consistent with a rapidly developing process. There is an associated soft tissue mass
B, S, Reid and J. D. Hubbard: Osteosarcoma Arising in Osteogenesis Imperfecta
111
Fig. 2. AP view with pathological fracture evident. There is destruction of medial and lateral aspects of distal left femur with increased poorly defined caMfic densities in the soft tissue mass
were more poorly defined calcific densities within the large soft tissue mass giving it a wooly appearance (Fig. 2). Approximately 5 months after the lesion was initially seen, a large wedge biopsy was performed. The biopsy (CS 2810-77) of the subcutaneous tissue of the mass showed shiny soft, gray-white tissue mixed with fat. Histologically, most of the tissue was composed of fairly regular stellate cells separated by extracellular mucin. Several microscopic cysts containing mucin were present. Only rare osteoid foci were present. Tumor giant cells were numerous but only rare mitoses were found. The diagnosis of osteosarcoma, chrondromyxoid type, was made. The biopsy site broke down and because of pain and increasing size of the leg an amputation was performed October 7, 1977. This specimen (CS2930-77) showed evidence of previous surgery. The lower end of the femur was replaced by a large mass obliterating the bone outline of most of the knee joint. In several areas, the periosteum was preserved. A large tumor plug was pre9sent in the popliteal vein and extensive invasion of the proximal femur and soft tissues up to the mid-shaft were present. Histologically, the soft tissue portion was similar to the biopsy. The intrafemoral tumor showed extensive osteoid formation as well as the chondromyxoid pattern. The amputation margin was grossly uninvolved but histologically a 2 ram. vein at the resection line contained tumor thrombus. Prior to the amputation, the patient developed multiple pulmonary metastases.
Discussion The first case of osteosarcoma in osteogenesis imperfecta was reported by Jewell and Lofstrom in 1940 [1]. The next 2 documented cases were reported by
Klenerman and Ockendon in 1967 [2]. Fairbank and Baker [3] reported the death of a patient who had originally been reported by Brailsford [4] in his article describing the scope of osteogenesis imperfecta. However, there is no record that the lesions in the leg or lungs were examined histologically and thus this may not have been osteosarcoma occurring in a patient with osteogenesis imperfecta. Hyperplastic callus formation occurring in osteogenesis imperfecta has been well recognized. It has occurred most often in the femur. It has been reported to occur in the presence or absence of a prior recognizable fracture. Hyperplastic callus formation may be an isolated incident, absent in earlier fractures and not forming in later fractures. The clinical history has been that of progressive enlargement of the leg with severe pain. The skin has been described as taut with dilated veins. The mass has been tender and hot to touch. The patient has usually had a low grade fever, increased sedimentation rate and an increased alkaline phosphatase. The usual course has been one of progressive increase in size and pain for 2-6 months after the initial clinical recognition. Following this, the pain has receded, but the mass has remained the same or decreases only slightly in size. The clinical picture of hyperplastic callus formation is indistinguishable from an osteosarcoma. An
112
B. S. Reid and J. D. Hubbard: Osteosarcoma Arising in Osteogenesis Imperfecta
o s t e o s a r c o m a as a complication of osteogenesis imperfecta is rare, w h e r e a s hyperplastic callus f o r m a tion is a m o r e frequent entity. Radiographically, hyperplastic callus usually shows swirls of new b o n e with distinct edges. T h e massive n e w b o n e usually parallels the shaft of the b o n e but does n o t cross the joint space. Transverse radiating striations have not b e e n n o t e d in cases of hyperplastic callus. D e s p i t e the extensive n e w b o n e formation, the cortex remains intact. B e c a u s e of the similar clinical a p p e a r a n c e of this b o y ' s t u m o r and the m o r e c o m m o n hyperplastic callus formation, biopsy was delayed. T h e radiographic findings of cortical b o n e destruction with transverse radiating striations of new b o n e and the later develo p m e n t of a " w o o l y " a p p e a r a n c e warrants a biopsy. It is possible, however, that a small biopsy (i. e. needle biopsy) of hyperplastic callus could yield tissue insufficient for diagnosis. T h e diagnosis in o u r case was m a d e o n a relatively superficial biopsy as the t u m o r was far advanced. Inclusion of cortical b o n e in biopsies of less a d v a n c e d cases should minimize the risk of i n a d e q u a t e tissue. In cases where the
radiographic suspicion of s a r c o m a is based o n a small area, care must be taken to include that area in the bioPsY.
References
1. Jewell, F. C., Lofstrom, J. E.: Osteogenic sarcoma occurring in fragilitas ossium. A case report. Radiology 34, 741 (1940) 2. Klenerman, L., Ockendon, B. G., Townsend, A. C.: Osteosarcoma occurring in osteogenesis imperfecta. Report of two cases. J. Bone Joint Surg. 49, 314 (1967) 3. Fairbank, H. A. T., Baker, S. E.: Hyperplastic callus formation with or without evidence of a fracture in osteogenesis imperfecta. With an account of the histology. Br. J. Surg. 36, 1 (1948) 4. Brailsford, J. F.: Osteogenesis imperfecta. Br. J. Radiol. 16, 129 (1943) Date of final acceptance: July 6, 1978 B. S. Reid, M. D. Department of Radiology Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine Pittsburgh, PA 15 213 USA
Note added in proof. In July 1978, patient expired with radiographic evidence of extensive pulmonary metastases. An autopsy was not
performed.
Pediatr. Radiol. 8, 110-112 (1979)
9 by Springer-Verlag1979
Case Reports
Osteosarcoma Arising in Osteogenesis Imperfecta B a r b a r a S. R e i d a n d J. D . H u b b a r d Departments of Pathology and Radiology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Abstract. W e
r e p o r t a case of o s t e o s a r c o m a a r i s i n g i n osteogenesis imperfecta. The characteristic radiographic and pathological findings are discussed and emp h a s i z e d to w a r r a n t a b i o p s y .
Key words: O s t e o s a r c o m a - O s t e o g e n e s i s i m p e r f e c t a - H y p e r t r o p h i c cells
formation consistent with a rapidly developing process. Hyperplastic callus formation and hemorrhage (pseudotumor) were favored clinically. He was lost to follow-up until August 1977 when he presented to the Emergency Room unable to walk because of severe pain. The distal thigh at this time was very swollen, hot and tender. The skin was taut with multiple dilated veins. The fracture at this time was more impacted with further cortical destruction of the medial, posterior and lateral aspects of the distal femur. There
O s t e o s a r c o m a o c c u r r i n g i n o s t e o g e n e s i s i m p e f f e c t a is a r a r e e n t i t y . C o n v e r s e l y , h y p e r t r o p h i c callus i n osteogenesis imperfecta which can resemble osteos a r c o m a clinically o c c u r s m o r e f r e q u e n t l y . T h e r e a r e t h r e e d o c u m e n t e d cases of o s t e o s a r c o m a o c c u r r i n g i n patients with osteogenesis impeffecta in the English l i t e r a t u r e . W e r e p o r t a 4 t h case w i t h e m p h a s i s o n t h e radiographic and pathological characteristics. The radiographic characteristics should not be confused w i t h h y p e r t r o p h i c callus, a b e n i g n p r o c e s s .
Case Report A. A. (7-19-49) a 14 year old boy had been followed since 3 years of age with the diagnosis of osteogenesis impeffecta tarda (familial). He had had at least 16 documented fractures of the extremities. Between December 1976 and April 1977 the patient had three fractures of the proximal femur located about a Jewett nail and plate placed for a prior fracture in 1975. Radiographs in December 1976 and March 1977 showed a demineralized but otherwise normal distal left femur typical of osteogenesis imperfecta. Radiographs in April 1977 showed a loss of the cortex of the distal medial aspect of the left femur. No fracture was evident. The patient was a poor historian and could not remember when he first noted pain in the distal portion of the left femur. In June 1977, he was seen with pain and swelling of the left distal thigh. Radiographs (Fig. 1) showed a fracture through the distal left femoral metaphysis with destructive changes in the cortex particularly the medial surface with sunray appearance of periosteal new bone
00301-0449/79/0008/0110/$01.00
Fig. 1. Lateral view of the distal left femur shows destruction of the cortex anteriorly with typical sunray appearance of periosteal new bone formation consistent with a rapidly developing process. There is an associated soft tissue mass
B, S, Reid and J. D. Hubbard: Osteosarcoma Arising in Osteogenesis Imperfecta
111
Fig. 2. AP view with pathological fracture evident. There is destruction of medial and lateral aspects of distal left femur with increased poorly defined caMfic densities in the soft tissue mass
were more poorly defined calcific densities within the large soft tissue mass giving it a wooly appearance (Fig. 2). Approximately 5 months after the lesion was initially seen, a large wedge biopsy was performed. The biopsy (CS 2810-77) of the subcutaneous tissue of the mass showed shiny soft, gray-white tissue mixed with fat. Histologically, most of the tissue was composed of fairly regular stellate cells separated by extracellular mucin. Several microscopic cysts containing mucin were present. Only rare osteoid foci were present. Tumor giant cells were numerous but only rare mitoses were found. The diagnosis of osteosarcoma, chrondromyxoid type, was made. The biopsy site broke down and because of pain and increasing size of the leg an amputation was performed October 7, 1977. This specimen (CS2930-77) showed evidence of previous surgery. The lower end of the femur was replaced by a large mass obliterating the bone outline of most of the knee joint. In several areas, the periosteum was preserved. A large tumor plug was pre9sent in the popliteal vein and extensive invasion of the proximal femur and soft tissues up to the mid-shaft were present. Histologically, the soft tissue portion was similar to the biopsy. The intrafemoral tumor showed extensive osteoid formation as well as the chondromyxoid pattern. The amputation margin was grossly uninvolved but histologically a 2 ram. vein at the resection line contained tumor thrombus. Prior to the amputation, the patient developed multiple pulmonary metastases.
Discussion The first case of osteosarcoma in osteogenesis imperfecta was reported by Jewell and Lofstrom in 1940 [1]. The next 2 documented cases were reported by
Klenerman and Ockendon in 1967 [2]. Fairbank and Baker [3] reported the death of a patient who had originally been reported by Brailsford [4] in his article describing the scope of osteogenesis imperfecta. However, there is no record that the lesions in the leg or lungs were examined histologically and thus this may not have been osteosarcoma occurring in a patient with osteogenesis imperfecta. Hyperplastic callus formation occurring in osteogenesis imperfecta has been well recognized. It has occurred most often in the femur. It has been reported to occur in the presence or absence of a prior recognizable fracture. Hyperplastic callus formation may be an isolated incident, absent in earlier fractures and not forming in later fractures. The clinical history has been that of progressive enlargement of the leg with severe pain. The skin has been described as taut with dilated veins. The mass has been tender and hot to touch. The patient has usually had a low grade fever, increased sedimentation rate and an increased alkaline phosphatase. The usual course has been one of progressive increase in size and pain for 2-6 months after the initial clinical recognition. Following this, the pain has receded, but the mass has remained the same or decreases only slightly in size. The clinical picture of hyperplastic callus formation is indistinguishable from an osteosarcoma. An
112
B. S. Reid and J. D. Hubbard: Osteosarcoma Arising in Osteogenesis Imperfecta
o s t e o s a r c o m a as a complication of osteogenesis imperfecta is rare, w h e r e a s hyperplastic callus f o r m a tion is a m o r e frequent entity. Radiographically, hyperplastic callus usually shows swirls of new b o n e with distinct edges. T h e massive n e w b o n e usually parallels the shaft of the b o n e but does n o t cross the joint space. Transverse radiating striations have not b e e n n o t e d in cases of hyperplastic callus. D e s p i t e the extensive n e w b o n e formation, the cortex remains intact. B e c a u s e of the similar clinical a p p e a r a n c e of this b o y ' s t u m o r and the m o r e c o m m o n hyperplastic callus formation, biopsy was delayed. T h e radiographic findings of cortical b o n e destruction with transverse radiating striations of new b o n e and the later develo p m e n t of a " w o o l y " a p p e a r a n c e warrants a biopsy. It is possible, however, that a small biopsy (i. e. needle biopsy) of hyperplastic callus could yield tissue insufficient for diagnosis. T h e diagnosis in o u r case was m a d e o n a relatively superficial biopsy as the t u m o r was far advanced. Inclusion of cortical b o n e in biopsies of less a d v a n c e d cases should minimize the risk of i n a d e q u a t e tissue. In cases where the
radiographic suspicion of s a r c o m a is based o n a small area, care must be taken to include that area in the bioPsY.
References
1. Jewell, F. C., Lofstrom, J. E.: Osteogenic sarcoma occurring in fragilitas ossium. A case report. Radiology 34, 741 (1940) 2. Klenerman, L., Ockendon, B. G., Townsend, A. C.: Osteosarcoma occurring in osteogenesis imperfecta. Report of two cases. J. Bone Joint Surg. 49, 314 (1967) 3. Fairbank, H. A. T., Baker, S. E.: Hyperplastic callus formation with or without evidence of a fracture in osteogenesis imperfecta. With an account of the histology. Br. J. Surg. 36, 1 (1948) 4. Brailsford, J. F.: Osteogenesis imperfecta. Br. J. Radiol. 16, 129 (1943) Date of final acceptance: July 6, 1978 B. S. Reid, M. D. Department of Radiology Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine Pittsburgh, PA 15 213 USA
Note added in proof. In July 1978, patient expired with radiographic evidence of extensive pulmonary metastases. An autopsy was not
performed.
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