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Hyperplastic callus formation in osteogenesis imperfecta
RADIOLOGIC-PATHOLOGIC CORRELATION
Hyperplastic Callus Formation in Osteogenesis Imperfecta Janez Lamovec, MD, Eva Moz˘ina, MD, and Bos˘tjan Baebler, MD A case of a child with the hyperplastic callus formation in association with osteogenesis imperfecta is presented. The soft tissue mass arising at the site of femoral fracture was clinically and radiologically suspected to be a hyperplastic callus, although a possibility of osteosarcoma could not be completely excluded. A drill biopsy of the soft tissue mass was performed which showed osteocartilaginous callus. The soft tissue mass disappeared following biopsy. This occurrence is also reported in previously described cases. Ann Diagn Pathol 7: 231-235, 2003. © 2003 Elsevier Inc. All rights reserved. Index Words: Osteogenesis imperfecta; hyperplastic callus; soft tissues
H
YPERPLASTIC callus formation is a rare complication of osteogenesis imperfecta (OI). It may occur after fracture or osteotomy of the affected bone, most frequently the femoral shaft, or even spontaneously. Clinically, and occasionally radiologically, such a lesion in OI may simulate osteosarcoma or osteomyelitis.1 Because osteosarcoma may also occur in OI,2 it is of critical importance to accurately diagnose the benign condition of hyperplastic callus that may occur in the latter condition. In this report, we present a case of an 11-year-old child with OI who has had multiple recurrent fractures over the years and who developed a hyperplastic callus in the soft tissues of the thigh after intramedullary fixation of one of the old fractures when he was 8 years old. Case Report The 8-year-old boy presented with a fracture of the femur that occurred after minor trauma. On x-ray, a fracture of a proximal diaphysis of the right femur with mild dislocation and angulation was seen (Fig 1). The fracture was surgically treated by
From the Department of Pathology, Institute of Oncology, Ljubljana, Slovenia; the Department of Radiology, University Clinical Center, Ljubljana, Slovenia; and the Department of Orthopedic Surgery, University Clinical Center, Ljubljana, Slovenia. Address reprint requests to Janez Lamovec, MD, Department of Pathology, Institute of Oncology, Zalosˇka 2, SI-1000 Ljubljana, Slovenia. © 2003 Elsevier Inc. All rights reserved. 1092-9134/03/0704-0004$30.00/0 doi:10.1016/S1092-9134(03)00051-0
Figure 1. Anteroposterior view of the right femur showing a fracture of the proximal diaphysis with mild dislocation and angulation.
Annals of Diagnostic Pathology, Vol 7, No 4 (August), 2003: pp 231-235
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cylinder, irregular trabeculae of woven bone were seen set in a loose connective tissue stroma (Figs 4 and 5). The lesion was diagnosed as hyperplastic callus in the soft tissue at the site of the fracture. Following biopsy, the lesion disappeared spontaneously as demonstrated radiologically 6 months after the procedure (Fig 6). The boy was born after an uneventful pregnancy and showed no deformities or developmental defects at birth. At 6 months of age, after vaccination into the thigh, he developed swelling of the thigh that was painful on palpation. On x-ray, a fracture of the midshaft of the femur with exuberant callus formation was seen. The fracture was treated conservatively at another institution and healed with no dislocation and in time. He was suspected to have OI, which was reinforced by numerous fractures of the long bones of lower extremities in the years to follow. In the course of the disease, the deformities of legs, predominantly lower ones, also developed, presenting as marked antecurvatures of both tibiae and fibulae with cortical thinning and osteopenia (Fig 7). In addition, a radiodense metaphyseal band immediately adjacent to the growth plate was also observed. The patient had no blue sclera, no hearing loss, and no dental deformities. His parents were of relatively short stature but not affected by the disease. Figure 2. Excessive and irregular new bone formation in the soft tissues is seen at the site of the fracture, 2 months after trauma and osteosynthesis.
internal fixation with intramedullary telescopic rod along with corrective osteotomy. Swelling of the right thigh appeared 2 months after these procedures. Roentgenologically, excessive and irregular new bone formation in the bone and soft tissue at the site of the fracture was seen (Fig 2). Computerized tomography of the same area showed a large, well-defined, ossified soft tissue mass with some ill-defined cortical destruction (Fig 3). The hyperplastic callus formation was suspected clinically and radiologically but because some questions were raised as to the possibility of an osteosarcoma, a drill biopsy of the lesion was performed. Histologically, the majority of the biopsy specimen of the soft tissue lesion was represented by slightly to moderately calcified cartilaginous tissue that was focally quite cellular, with plump nuclei, occasional binucleated cells, and extremely rare mitotic figures. In a deeper portion of the biopsy
Figure 3. Axial computed tomography image showing a large well-defined ossified soft tissue mass; some ill-defined cortical destruction is also seen. Evaluation of the medullary cavity is not possible because of artifacts of osteosynthetic material.
Hyperplastic Callus Formation in OI
233
and radiologists than among pathologists, who rarely encounter it. Although the morphology of the biopsied lesion is usually straightforward, the clinical and radiologic aspects may be more confusing.1,4,5 The callus formation usually follows trauma or osteotomy, but it may also occur in their absence. In a review of published cases on hyperplastic callus formation in OI till 1997, Nakamura et al4 found 47 cases; there was no sex predominance and no special tendency as to scleral color. Hyperplastic callus formation occurred more frequently with severe bone fragility but was also seen in those cases with milder fragility.4 The most common site of hyperplastic callus was femur, and in approximately one half of the cases, the lesion was recurrent.4
Figure 4. A low-power view of the soft tissue mass showing a lobule of a partly calcified cartilaginous callus.
His fractures were first treated conservatively and later surgically by internal fixation; numerous corrective surgical procedures were also performed with relatively good functional and structural results. No cytogenetic studies were performed; clinically, he was considered to probably have type IV of OI. The patient is now 11 years old and has some shortening of the left leg with a slight varus position and internal rotation of both lower legs and uses braces for their support. He has been treated with biphosphonates for the last 2 years. Discussion Hyperplastic callus formation in OI was first described almost a century ago.3 Since then, a number of reports have followed and a review of the literature in 1971 summarized 23 such cases.1 This lesion is better known among orthopedic surgeons
Figure 5. Higher-power view of the callus featuring relatively dense chondrocytes with plump nuclei and some binucleated cells. The cartilaginous matrix in the lower third of the figure is calcified.
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band was clearly seen and it may well be that it really belonged to type V of OI. Most recently, another two types of OI, not associated with defects in collagen I synthesis, were identified and named type VI and VII.9,10 The most important aspect of recognizing hyperplastic callus formation in OI is its differentiation from osteosarcoma arising in bones affected by this condition. The rare reports on occurrence of osteosarcoma in association with OI are on record. The most recent report on this association lists eight previously published cases in the English literature, adding the newest one.2 This complication is exceedingly rare, much more than hyperplastic callus formation, which is estimated to occur in up to 6% of patients with OI.5 In rare cases, the two conditions may be sufficiently similar as to necessitate biopsy.
Figure 6. Anteroposterior view of the right femur, 9 months following trauma. The hyperplastic callus has spontaneously disappeared.
Currently, OI is divided into four types.6 This syndrome is caused by mutations in the genes for type I collagen (COL1A1 and COL1A2) which is the major collagen of bone. The latter genes encode polypeptide chain that make up the type I collagen triple helix and over 250 mutations have been characterized in both of these genes.7 Most patients with hyperplastic callus formation were traditionally classified as type IV.6 It has recently been established that group IV is heterogeneous and suggested that many cases with hyperplastic callus formation belong to the new type V which is clinically similar to type IV but differs from it by some radiologic findings such as a dense narrow metaphyseal band adjacent to the growth plate and also genetically. This type does not appear to be associated with mutations for type I collagen.8 In our case, which was clinically supposed to be type IV, a radiodense metaphyseal
Figure 7. Lateral view of the right lower leg showing gracile and bowed long bones with cortical thinning and osteopenia– osteogenesis imperfecta.
Hyperplastic Callus Formation in OI
References 1. Banta JV, Schreiber RR, Kulik WJ: Hyperplastic callus formation in osteogenesis imperfecta simulating osteosarcoma. J Bone Joint Surg (A) 1971;53:115-122 2. Maiya S, Grimer RJ, Ramaswamy R, et al: Osteosarcoma occurring in osteogenesis imperfecta. Int Orthop 2002;26:126128 3. Battle WH, Shattock HG: A remarkable case of diffuse cancellous osteoma of the femur following a fracture, in which similar growths afterwards developed in connection with other bones. Proc R Soc Med 1908;1:83-102 4. Nakamura K, Kurokawa T, Nagano A, et al: Familial occurrence of hyperplastic callus in osteogenesis imperfecta. Arch Orthop Trauma Surg 1997;116:500-503 5. Rieker O, Kreitner KF, Karbowski A: Hyperplastic callus
235
formation in osteogenesis imperfecta: CT and MRI findings. Eur Radiol 1998;8:1137-1139 6. Silence D: Osteogenesis imperfecta: An expanding panorama of variants. Clin Orthop 1981;159:11-25 7. Glorieux FH: Osteogenesis imperfecta. A disease of the osteoblasts. Lancet 2001;358:S45 (suppl) 8. Glorieux FH, Rauch F, Plotkin H, et al: Type V osteogenesis imperfecta: A new form of brittle bone disease. J Bone Miner Res 2000;15:1650-1658 9. Glorieux FH, Ward LM, Rauch F, et al: Osteogenesis imperfecta type VI: A form of brittle bone disease with a mineralization defects. J Bone Miner Res 2002;17:30-38 10. Labuda M, Morissette J, Ward LM, et al: Osteogenesis imperfecta type VII maps to the short arm of chromosome 3. Bone 2002;31:19-25
Hyperplastic Callus Formation in Osteogenesis Imperfecta Janez Lamovec, MD, Eva Moz˘ina, MD, and Bos˘tjan Baebler, MD A case of a child with the hyperplastic callus formation in association with osteogenesis imperfecta is presented. The soft tissue mass arising at the site of femoral fracture was clinically and radiologically suspected to be a hyperplastic callus, although a possibility of osteosarcoma could not be completely excluded. A drill biopsy of the soft tissue mass was performed which showed osteocartilaginous callus. The soft tissue mass disappeared following biopsy. This occurrence is also reported in previously described cases. Ann Diagn Pathol 7: 231-235, 2003. © 2003 Elsevier Inc. All rights reserved. Index Words: Osteogenesis imperfecta; hyperplastic callus; soft tissues
H
YPERPLASTIC callus formation is a rare complication of osteogenesis imperfecta (OI). It may occur after fracture or osteotomy of the affected bone, most frequently the femoral shaft, or even spontaneously. Clinically, and occasionally radiologically, such a lesion in OI may simulate osteosarcoma or osteomyelitis.1 Because osteosarcoma may also occur in OI,2 it is of critical importance to accurately diagnose the benign condition of hyperplastic callus that may occur in the latter condition. In this report, we present a case of an 11-year-old child with OI who has had multiple recurrent fractures over the years and who developed a hyperplastic callus in the soft tissues of the thigh after intramedullary fixation of one of the old fractures when he was 8 years old. Case Report The 8-year-old boy presented with a fracture of the femur that occurred after minor trauma. On x-ray, a fracture of a proximal diaphysis of the right femur with mild dislocation and angulation was seen (Fig 1). The fracture was surgically treated by
From the Department of Pathology, Institute of Oncology, Ljubljana, Slovenia; the Department of Radiology, University Clinical Center, Ljubljana, Slovenia; and the Department of Orthopedic Surgery, University Clinical Center, Ljubljana, Slovenia. Address reprint requests to Janez Lamovec, MD, Department of Pathology, Institute of Oncology, Zalosˇka 2, SI-1000 Ljubljana, Slovenia. © 2003 Elsevier Inc. All rights reserved. 1092-9134/03/0704-0004$30.00/0 doi:10.1016/S1092-9134(03)00051-0
Figure 1. Anteroposterior view of the right femur showing a fracture of the proximal diaphysis with mild dislocation and angulation.
Annals of Diagnostic Pathology, Vol 7, No 4 (August), 2003: pp 231-235
231
232
Lamovec, Moz˘ina, and Baebler
cylinder, irregular trabeculae of woven bone were seen set in a loose connective tissue stroma (Figs 4 and 5). The lesion was diagnosed as hyperplastic callus in the soft tissue at the site of the fracture. Following biopsy, the lesion disappeared spontaneously as demonstrated radiologically 6 months after the procedure (Fig 6). The boy was born after an uneventful pregnancy and showed no deformities or developmental defects at birth. At 6 months of age, after vaccination into the thigh, he developed swelling of the thigh that was painful on palpation. On x-ray, a fracture of the midshaft of the femur with exuberant callus formation was seen. The fracture was treated conservatively at another institution and healed with no dislocation and in time. He was suspected to have OI, which was reinforced by numerous fractures of the long bones of lower extremities in the years to follow. In the course of the disease, the deformities of legs, predominantly lower ones, also developed, presenting as marked antecurvatures of both tibiae and fibulae with cortical thinning and osteopenia (Fig 7). In addition, a radiodense metaphyseal band immediately adjacent to the growth plate was also observed. The patient had no blue sclera, no hearing loss, and no dental deformities. His parents were of relatively short stature but not affected by the disease. Figure 2. Excessive and irregular new bone formation in the soft tissues is seen at the site of the fracture, 2 months after trauma and osteosynthesis.
internal fixation with intramedullary telescopic rod along with corrective osteotomy. Swelling of the right thigh appeared 2 months after these procedures. Roentgenologically, excessive and irregular new bone formation in the bone and soft tissue at the site of the fracture was seen (Fig 2). Computerized tomography of the same area showed a large, well-defined, ossified soft tissue mass with some ill-defined cortical destruction (Fig 3). The hyperplastic callus formation was suspected clinically and radiologically but because some questions were raised as to the possibility of an osteosarcoma, a drill biopsy of the lesion was performed. Histologically, the majority of the biopsy specimen of the soft tissue lesion was represented by slightly to moderately calcified cartilaginous tissue that was focally quite cellular, with plump nuclei, occasional binucleated cells, and extremely rare mitotic figures. In a deeper portion of the biopsy
Figure 3. Axial computed tomography image showing a large well-defined ossified soft tissue mass; some ill-defined cortical destruction is also seen. Evaluation of the medullary cavity is not possible because of artifacts of osteosynthetic material.
Hyperplastic Callus Formation in OI
233
and radiologists than among pathologists, who rarely encounter it. Although the morphology of the biopsied lesion is usually straightforward, the clinical and radiologic aspects may be more confusing.1,4,5 The callus formation usually follows trauma or osteotomy, but it may also occur in their absence. In a review of published cases on hyperplastic callus formation in OI till 1997, Nakamura et al4 found 47 cases; there was no sex predominance and no special tendency as to scleral color. Hyperplastic callus formation occurred more frequently with severe bone fragility but was also seen in those cases with milder fragility.4 The most common site of hyperplastic callus was femur, and in approximately one half of the cases, the lesion was recurrent.4
Figure 4. A low-power view of the soft tissue mass showing a lobule of a partly calcified cartilaginous callus.
His fractures were first treated conservatively and later surgically by internal fixation; numerous corrective surgical procedures were also performed with relatively good functional and structural results. No cytogenetic studies were performed; clinically, he was considered to probably have type IV of OI. The patient is now 11 years old and has some shortening of the left leg with a slight varus position and internal rotation of both lower legs and uses braces for their support. He has been treated with biphosphonates for the last 2 years. Discussion Hyperplastic callus formation in OI was first described almost a century ago.3 Since then, a number of reports have followed and a review of the literature in 1971 summarized 23 such cases.1 This lesion is better known among orthopedic surgeons
Figure 5. Higher-power view of the callus featuring relatively dense chondrocytes with plump nuclei and some binucleated cells. The cartilaginous matrix in the lower third of the figure is calcified.
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Lamovec, Moz˘ina, and Baebler
band was clearly seen and it may well be that it really belonged to type V of OI. Most recently, another two types of OI, not associated with defects in collagen I synthesis, were identified and named type VI and VII.9,10 The most important aspect of recognizing hyperplastic callus formation in OI is its differentiation from osteosarcoma arising in bones affected by this condition. The rare reports on occurrence of osteosarcoma in association with OI are on record. The most recent report on this association lists eight previously published cases in the English literature, adding the newest one.2 This complication is exceedingly rare, much more than hyperplastic callus formation, which is estimated to occur in up to 6% of patients with OI.5 In rare cases, the two conditions may be sufficiently similar as to necessitate biopsy.
Figure 6. Anteroposterior view of the right femur, 9 months following trauma. The hyperplastic callus has spontaneously disappeared.
Currently, OI is divided into four types.6 This syndrome is caused by mutations in the genes for type I collagen (COL1A1 and COL1A2) which is the major collagen of bone. The latter genes encode polypeptide chain that make up the type I collagen triple helix and over 250 mutations have been characterized in both of these genes.7 Most patients with hyperplastic callus formation were traditionally classified as type IV.6 It has recently been established that group IV is heterogeneous and suggested that many cases with hyperplastic callus formation belong to the new type V which is clinically similar to type IV but differs from it by some radiologic findings such as a dense narrow metaphyseal band adjacent to the growth plate and also genetically. This type does not appear to be associated with mutations for type I collagen.8 In our case, which was clinically supposed to be type IV, a radiodense metaphyseal
Figure 7. Lateral view of the right lower leg showing gracile and bowed long bones with cortical thinning and osteopenia– osteogenesis imperfecta.
Hyperplastic Callus Formation in OI
References 1. Banta JV, Schreiber RR, Kulik WJ: Hyperplastic callus formation in osteogenesis imperfecta simulating osteosarcoma. J Bone Joint Surg (A) 1971;53:115-122 2. Maiya S, Grimer RJ, Ramaswamy R, et al: Osteosarcoma occurring in osteogenesis imperfecta. Int Orthop 2002;26:126128 3. Battle WH, Shattock HG: A remarkable case of diffuse cancellous osteoma of the femur following a fracture, in which similar growths afterwards developed in connection with other bones. Proc R Soc Med 1908;1:83-102 4. Nakamura K, Kurokawa T, Nagano A, et al: Familial occurrence of hyperplastic callus in osteogenesis imperfecta. Arch Orthop Trauma Surg 1997;116:500-503 5. Rieker O, Kreitner KF, Karbowski A: Hyperplastic callus
235
formation in osteogenesis imperfecta: CT and MRI findings. Eur Radiol 1998;8:1137-1139 6. Silence D: Osteogenesis imperfecta: An expanding panorama of variants. Clin Orthop 1981;159:11-25 7. Glorieux FH: Osteogenesis imperfecta. A disease of the osteoblasts. Lancet 2001;358:S45 (suppl) 8. Glorieux FH, Rauch F, Plotkin H, et al: Type V osteogenesis imperfecta: A new form of brittle bone disease. J Bone Miner Res 2000;15:1650-1658 9. Glorieux FH, Ward LM, Rauch F, et al: Osteogenesis imperfecta type VI: A form of brittle bone disease with a mineralization defects. J Bone Miner Res 2002;17:30-38 10. Labuda M, Morissette J, Ward LM, et al: Osteogenesis imperfecta type VII maps to the short arm of chromosome 3. Bone 2002;31:19-25