(Radiographics. 1999;19:873-885.)
© RSNA, 1999
Skeletal Complications in Pediatric Oncology Patients1
Derek J. Roebuck, MB, BS, FRACR
1 From the Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, New Territories, Hong Kong. Received October 27, 1997; revision requested April 7, 1998 and received August 26; accepted August 26. Address reprint requests to the author.
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Abstract
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Pediatric oncology patients are at risk for the development of numerous skeletal complications, and radiologic studies are important in the identification and evaluation of these conditions. Methotrexate osteopathy manifests as osteopenia, dense provisional zones of calcification, pathologic fractures, and sharply outlined epiphyses. Hypertrophic osteoarthropathy may occur with nasopharyngeal carcinoma or tumors of the lungs or pleura and manifests as cortical thickening, lamellar periosteal new bone formation, and soft-tissue swelling. Biomechanical abnormalities are often seen at bone scintigraphy in patients who have undergone surgery for bone tumors. Growth plate injury may manifest as marked deformity, sclerotic metaphyseal bands, metaphyseal fraying, and longitudinal striations. Radiation "osteitis" is seen as an initial decrease in bone density with subsequent development of a mixed radiolucent and sclerotic appearance. Ischemic necrosis of the femoral heads is best demonstrated at magnetic resonance (MR) imaging and has low signal intensity on T1-weighted images and a high-signal-intensity rim on T2-weighted images. Bone infarcts are seen as well-demarcated, often ring-shaped areas of decreased signal intensity on T1-weighted MR images and as areas of increased signal intensity on short-inversion-time inversion recovery images. Radiographic signs of infection include bone destruction, periosteal new bone formation, and sclerotic changes. Short-inversion-time inversion recovery MR imaging is particularly useful in evaluating posttherapy changes in bone marrow. Osteochondroma may demonstrate a cartilaginous cap at MR imaging, whereas the most important finding in radiation-induced sarcoma is a soft-tissue mass. Radiologists who work with children with cancer need to be familiar with these complications and their imaging appearances.
Index Terms: Bones, effects of irradiation on, 30.47, 40.47 • Bone marrow, effects of irradiation on, 30.47, 40.47 • Children, skeletal system • Radiations, injurious effects, complications of therapeutic radiology, 30.47, 40.47
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INTRODUCTION
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In children with cancer, various abnormalities of the skeleton may develop that are related to the disease itself or to complications of its treatment. Most of these abnormalities are diagnosed on the basis of radiologic findings. Although some abnormalities have characteristic appearances, others may present a diagnostic challenge. Some of these conditions have been observed with increasing frequency because of more intensive therapeutic regimens and increased detection facilitated by means of advanced imaging technologies. It is therefore important for radiologists who work with children with a history of cancer to be able to distinguish these skeletal complications from each other and from metastatic disease and recurrent tumor.
This article presents the imaging features of disease-related skeletal changes and complications of medical cancer therapy. Metastatic disease, direct neoplastic involvement of bone, and complications of surgery are not considered.
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OSTEOPENIA
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Diffuse osteopenia may be due to the malignancy or its treatment. Osteopenia is a well-recognized feature of acute lymphoblastic leukemia at presentation (probably due to leukemic marrow infiltration) and may also occur with other malignancies, especially liver tumors (1), apparently as a paraneoplastic phenomenon. Osteoporosis may occur in children who have functioning tumors of the adrenal cortex (2).
Methotrexate, a dihydrofolate reductase inhibitor, is most often used in children for treatment of acute lymphoblastic leukemia or osteosarcoma. Methotrexate osteopathy, a syndrome that consists of bone pain, osteopenia, and pathologic fractures, was first recognized in children who underwent long-term, low-dose treatment with methotrexate for acute lymphoblastic leukemia (3). The radiographic findings are similar to those in scurvy: osteopenia, dense provisional zones of calcification, pathologic fractures (most often metaphyseal), and sharply outlined epiphyses (4) (Fig 1), but no massive subperiosteal hemorrhage. There may also be impaired healing of fractures. The same syndrome has also been described in children with brain tumors (5) and osteosarcoma (6) treated with a high dose of methotrexate.
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Figure 1. Methotrexate osteopathy. Frontal radiograph shows dense metaphyseal bands (straight white arrows) with sharply outlined epiphyses (arrowhead). There are also metaphyseal "corner" fractures in the distal part of the femur (black arrow) and proximal part of the fibula (curved arrow). (Courtesy of Jack Lawson, MD, Yale University School of Medicine, New Haven, Conn.)
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Osteopenia is also seen in children who have osteoporosis related to prolonged treatment with corticosteroids. Pathologic fractures may be seen, especially in the spine. Osteoporosis is particularly common after bone marrow transplantation, in which chronic graft-versus-host disease may also be a contributing factor (7).
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RICKETS
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Ifosfamide, an isomer of cyclophosphamide, is an alkylating agent used in children for the treatment of solid tumors, including rhabdomyosarcoma and Wilms tumor. Nephrotoxicity due to ifosfamide is caused by renal tubular dysfunction and may lead to clinically and radiologically apparent hypophosphatemic rickets (8) (Fig 2). This finding is most common in young patients and in those patients with a preexisting renal abnormality or a history of nephrectomy (9).
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Figure 2a. Ifosfamide rickets in an 11-year-old girl with Ewing sarcoma. (a) Frontal radiograph shows widening of the growth plates of the distal parts of the radius and ulna with mildly frayed metaphyses. (b) Frontal radiograph shows osteopenia of the tibia with an insufficiency fracture (arrow) and healing rickets.
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Figure 2b. Ifosfamide rickets in an 11-year-old girl with Ewing sarcoma. (a) Frontal radiograph shows widening of the growth plates of the distal parts of the radius and ulna with mildly frayed metaphyses. (b) Frontal radiograph shows osteopenia of the tibia with an insufficiency fracture (arrow) and healing rickets.
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Hypophosphatemic rickets may also occur as a paraneoplastic phenomenon associated with a mesenchymal tumor or tumorlike lesion (10). The hypophosphatemia appears to be caused by an unknown humoral factor that causes renal loss of phosphate (10). Associated lesions in children are usually benign (most frequently, nonossifying fibroma), although malignant tumors have been reported to cause osteomalacia in adults. The biochemical abnormality is cured with radiation therapy or surgical removal of the lesion.
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PERIOSTEAL NEW BONE FORMATION
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Hypertrophic osteoarthropathy is uncommon in pediatric oncology patients but may occur with nasopharyngeal carcinoma or primary or secondary tumors of the lungs or pleura (11,12). Radiographic findings include cortical thickening, lamellar periosteal new bone formation, and soft-tissue swelling. Skeletal scintigraphy shows symmetric increased activity along the shafts of the long bones (11).
Grissom et al (13) reported the case of a 4-year-old boy who underwent treatment with 13-cis-retinoic acid (a vitamin A analogue) for neuroblastoma; periosteal new bone formation developed along the shafts of the ulnae. This is a typical radiologic finding of hypervitaminosis A in childhood (14). In adults, 13-cis-retinoic acid appears to cause radiologic changes that resemble diffuse idiopathic skeletal hyperostosis.
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FRACTURES
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Bone scintigraphy often reveals biomechanical abnormalities including stress fractures in patients who have undergone surgery for bone tumors, osteosarcoma in particular (15). On occasion, these changes are present at diagnosis.
Less often, insufficiency fractures may develop in pediatric oncology patients (15) (Fig 2b). These findings may be related to several factors, including treatment with ifosfamide (Fig 2b), methotrexate (5,6), and corticosteroids. Pathologic fracture through an area of irradiated bone is uncommon in children.
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ABNORMAL SKELETAL MATURATION AND GROWTH RETARDATION
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Accelerated skeletal maturation may be seen in patients with paraneoplastic precocious puberty. This rare finding usually occurs in boys with hepatoblastoma or germ cell tumors (16) but is occasionally present in girls with germ cell (Fig 3) or adrenal cortical tumors. It may also be seen in children with central precocious puberty due to a brain tumor.
Delayed skeletal maturation may be present after bone marrow transplantation. Short stature is common in children with cancer (17), especially those younger than 5 years of age at the time of treatment. Irradiation of the brain in patients with cerebral tumors or acute lymphoblastic leukemia (with consequent deficiency of growth hormone) is probably the most important etiologic factor. Methotrexate and corticosteroids may have a direct inhibitory effect on bone growth (17). Total body irradiation and chronic graft-versus-host disease may contribute to the severe growth retardation seen in patients who have undergone bone marrow transplantation (18).
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GROWTH DEFORMITY
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A radiation dose of as little as 1.3 Gy received during childhood may cause impairment of growth at a growth plate (19). The severity of this effect is dependent on both the radiation dose and the patient's age at irradiation. Higher doses may lead to marked epimetaphyseal deformity (Fig 4). Injury to the growth plate may have other radiographic manifestations including sclerotic metaphyseal bands (Fig 5a), metaphyseal fraying (Fig 5b), and longitudinal striations (20). Slippage of an upper femoral or humeral epiphysis may occur, usually after doses of more than 25 Gy (21), and this finding may be associated with ischemic necrosis of the femoral or humeral head.
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Figure 4a. Growth deformity and osteochondroma in a teenage girl who had undergone radiation therapy for Langerhans cell histiocytosis several years earlier. (a) Frontal radiograph shows marked deformity of the femoral head with reciprocal deformity of the acetabulum, which has a markedly sloping roof. (b) Frontal radiograph shows that a small osteochondroma has developed on the medial aspect of the femoral shaft.
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Figure 4b. Growth deformity and osteochondroma in a teenage girl who had undergone radiation therapy for Langerhans cell histiocytosis several years earlier. (a) Frontal radiograph shows marked deformity of the femoral head with reciprocal deformity of the acetabulum, which has a markedly sloping roof. (b) Frontal radiograph shows that a small osteochondroma has developed on the medial aspect of the femoral shaft.
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Figure 5a. Metaphyseal radiation changes in a 5-year-old girl who underwent treatment for Ewing sarcoma of the left scapula. (a) Frontal radiograph shows that 1 year after radiation therapy there is a sclerotic metaphyseal band in the proximal left humerus. (b) Frontal radiograph shows that 5 years after radiation therapy there is patchy metaphyseal sclerosis and areas of hyperlucency with mild fraying (arrow) and irregularity of the epiphysis.
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Figure 5b. Metaphyseal radiation changes in a 5-year-old girl who underwent treatment for Ewing sarcoma of the left scapula. (a) Frontal radiograph shows that 1 year after radiation therapy there is a sclerotic metaphyseal band in the proximal left humerus. (b) Frontal radiograph shows that 5 years after radiation therapy there is patchy metaphyseal sclerosis and areas of hyperlucency with mild fraying (arrow) and irregularity of the epiphysis.
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When the spine is included in the radiation field, scoliosis that is concave to the irradiated side may result (22). This scoliosis may occur even if the full width of the vertebral column is irradiated and has been reported to occur after doses of less than 15 Gy (23). There is usually impairment of growth of the paraspinal muscles and failure of vertical growth in the vertebral bodies (Fig 6) (24). Anterior beaking and kyphosis are less common complications. Impairment of spinal growth appears to be most marked when radiation therapy is performed during early childhood or during the adolescent growth spurt (24).
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Figure 6. Growth deformity in a 22-year-old woman who as a child had received treatment for Wilms tumor with chemotherapy, radiation therapy, and left nephrectomy. Frontal radiograph obtained during excretory urography shows that the left ilium (arrows) is small owing to inclusion of the iliac crest in the radiation field. The lumbar vertebrae are flattened, and the end plates are slightly irregular. The right kidney shows compensatory hypertrophy.
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RADIATION OSTEITIS
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The typical pattern of radiation "osteitis" seen in adults is uncommon in children. When it occurs, this complication is seen as an initial decrease in bone density with subsequent development of a mixed radiolucent and sclerotic appearance (25,26). Radiolucency is the dominant effect, with disorganization of the trabecular pattern but no periosteal reaction (25). There is a narrow zone of transition between the affected area and normal bone tissue (25). Unlike changes caused by metastatic disease or disuse osteopenia, these changes are confined to the radiation field (25,26). Radiation-induced changes that occur in the metaphysis (Fig 5) are common in childhood and are related to injury to the growth plate. Bone scintigraphy may show decreased uptake in the radiation field (27). Magnetic resonance (MR) imaging can be used to exclude an associated soft-tissue mass that would raise the possibility of recurrent tumor or radiation-induced sarcoma.
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ISCHEMIC NECROSIS AND BONE INFARCTS
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Ischemic (avascular) necrosis of bone tissue is a well-described complication of therapy in children with cancer (28,29). An apparent recent increase in the prevalence of this complication may be due partly to changes in therapy and partly to greater recognition associated with more frequent use of MR imaging. Ischemic necrosis is seen most often in patients with leukemia or lymphoma (especially those who have undergone bone marrow transplantation or prolonged corticosteroid therapy) and after radiation therapy (28,29). The most frequently affected regions are the hips, shoulders, and knees (27–30). Often, more than one joint is involved (28). Children appear to be at less risk than adults who have undergone similar treatment.
Ischemic necrosis of subarticular bone may be disabling, and early diagnosis is important because therapy can be modified to attempt to minimize disability (28). Radiographs may show a radiolucent subchondral crescent (Fig 7) with prominent sclerosis and collapse of subchondral bone occurring only as late signs (Fig 8).
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Figure 7. Ischemic necrosis of the femoral head in a teenage girl who underwent treatment for Hodgkin disease followed by bone marrow transplantation for myelodysplastic syndrome. Frontal radiograph of the right hip demonstrates a prominent subarticular radiolucent line (arrows) with mild sclerosis of the femoral head.
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Figure 8a. Ischemic necrosis of the femoral heads and bone infarcts in an 11-year-old girl with acute lymphoblastic leukemia as a second malignancy after head and neck rhabdomyosarcoma. (a) Frontal radiograph shows sclerosis, fragmentation, and slippage of the left femoral head and mild sclerosis and a subchondral area of hyperlucency on the right side. (b) Coronal T1-weighted MR image (repetition time msec/echo time msec = 519/16) shows loss of signal intensity in the left femoral head (arrows) due to ischemic necrosis. A band of decreased signal intensity appears in the right femoral capital epiphysis. Numerous bands of decreased signal intensity seen elsewhere in medullary bone are due to bone infarcts. (c) Frontal radiograph obtained 11 months later shows advanced changes of ischemic necrosis of the right femoral head and conspicuous bone infarcts in both proximal femora.
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Figure 8b. Ischemic necrosis of the femoral heads and bone infarcts in an 11-year-old girl with acute lymphoblastic leukemia as a second malignancy after head and neck rhabdomyosarcoma. (a) Frontal radiograph shows sclerosis, fragmentation, and slippage of the left femoral head and mild sclerosis and a subchondral area of hyperlucency on the right side. (b) Coronal T1-weighted MR image (repetition time msec/echo time msec = 519/16) shows loss of signal intensity in the left femoral head (arrows) due to ischemic necrosis. A band of decreased signal intensity appears in the right femoral capital epiphysis. Numerous bands of decreased signal intensity seen elsewhere in medullary bone are due to bone infarcts. (c) Frontal radiograph obtained 11 months later shows advanced changes of ischemic necrosis of the right femoral head and conspicuous bone infarcts in both proximal femora.
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Figure 8c. Ischemic necrosis of the femoral heads and bone infarcts in an 11-year-old girl with acute lymphoblastic leukemia as a second malignancy after head and neck rhabdomyosarcoma. (a) Frontal radiograph shows sclerosis, fragmentation, and slippage of the left femoral head and mild sclerosis and a subchondral area of hyperlucency on the right side. (b) Coronal T1-weighted MR image (repetition time msec/echo time msec = 519/16) shows loss of signal intensity in the left femoral head (arrows) due to ischemic necrosis. A band of decreased signal intensity appears in the right femoral capital epiphysis. Numerous bands of decreased signal intensity seen elsewhere in medullary bone are due to bone infarcts. (c) Frontal radiograph obtained 11 months later shows advanced changes of ischemic necrosis of the right femoral head and conspicuous bone infarcts in both proximal femora.
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Radiography is a relatively insensitive method for detection of early ischemic necrosis, and if clinical suspicion is high, either MR imaging or bone scintigraphy (Fig 9a) should be performed. MR imaging is more sensitive for detection of ischemic necrosis of the femoral heads and is probably a better technique in the context of pediatric malignancy (28).
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Figure 9a. Ischemic necrosis and osteomyelitis in a 15-year-old girl who underwent bone marrow transplantation for acute lymphoblastic leukemia and in whom right knee symptoms developed. (a) Bone scintigram shows photopenia of both femoral heads, a finding consistent with ischemic necrosis. Scintigraphy demonstrated only nonspecific changes in both knees (not shown). (b) Technetium-99m-labeled white cell scintigram shows foci of activity in the distal right femur (arrow), which proved at surgery to be due to Streptococcus pneumoniae osteomyelitis. Diffuse periarticular activity is also seen, a finding consistent with synovitis.
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Figure 9b. Ischemic necrosis and osteomyelitis in a 15-year-old girl who underwent bone marrow transplantation for acute lymphoblastic leukemia and in whom right knee symptoms developed. (a) Bone scintigram shows photopenia of both femoral heads, a finding consistent with ischemic necrosis. Scintigraphy demonstrated only nonspecific changes in both knees (not shown). (b) Technetium-99m-labeled white cell scintigram shows foci of activity in the distal right femur (arrow), which proved at surgery to be due to Streptococcus pneumoniae osteomyelitis. Diffuse periarticular activity is also seen, a finding consistent with synovitis.
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T1-weighted MR images show decreased signal intensity in the femoral heads, often in a bandlike configuration (Fig 8b) (31). T2-weighted images may show the "double-line" sign of a high-signal-intensity rim (31).
At bone scintigraphy, ischemic necrosis may be seen as a photopenic area (Fig 9a) or recognized from the "doughnut sign," a ring of increased activity around a photopenic center (27) that may be the scintigraphic equivalent of the double-line sign.
Metaphyseal and diaphyseal lesions (bone infarcts) also occur in children with cancer (28, 30) (Fig 8c) but are usually asymptomatic. They are seen as well-demarcated, often ring-shaped areas of decreased signal intensity on T1-weighted MR images (28) (Fig 8b) and as areas of increased signal intensity on short-inversion-time inversion recovery images.
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INFECTION
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Most infections in children with cancer are respiratory (32). Osteomyelitis and septic arthritis appear to be relatively uncommon complications. Murphy and Greenberg (33) found nine cases of osteomyelitis in a group of 673 children with leukemia. All of their patients were infected with Staphylococcus species, Escherichia coli, or Pseudomonas species. Other organisms reported to cause osteomyelitis in patients with pediatric leukemia include Salmonella and fungi.
Children with unexplained fever (especially very young children) may not have localizing signs, which may contribute to diagnostic difficulty (34). Murphy and Greenberg (33) noted that seven of their nine patients with osteomyelitis had abnormal findings at radiography, which suggests that the diagnosis had been delayed.
Radiographic signs include bone destruction, periosteal new bone formation, and sclerotic changes (33,34). Scintigraphy with gallium-67 citrate (34) or technetium-99m–labeled white cells (Figs 9b, 10a) may help localize suspected but clinically occult infection or confirm the nature of abnormalities seen on other images. MR imaging is excellent for distinguishing soft-tissue from skeletal infection, a distinction with important implications for management, and for evaluating the extent of bone involvement (Fig 10b).
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Figure 10a. Osteomyelitis in an 8-year-old girl with relapsed acute lymphoblastic leukemia who presented with left hip symptoms. (a) Three-hour image from a technetium-99m-labeled white cell scan shows focal uptake in this region (arrow). (b) Short-inversion-time inversion recovery MR image (2,014/60; inversion time msec = 80) shows abnormally high signal intensity involving the greater trochanter and adjacent soft tissues as well as the intertrochanteric region (arrow), findings that are typical of osteomyelitis. Surgery revealed Pseudomonas infection.
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Figure 10b. Osteomyelitis in an 8-year-old girl with relapsed acute lymphoblastic leukemia who presented with left hip symptoms. (a) Three-hour image from a technetium-99m-labeled white cell scan shows focal uptake in this region (arrow). (b) Short-inversion-time inversion recovery MR image (2,014/60; inversion time msec = 80) shows abnormally high signal intensity involving the greater trochanter and adjacent soft tissues as well as the intertrochanteric region (arrow), findings that are typical of osteomyelitis. Surgery revealed Pseudomonas infection.
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EFFECTS OF THERAPY ON BONE MARROW
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Dissection (35) and MR imaging (36) show that there is a normal redistribution of red (hematopoietic) marrow during childhood. At birth, red marrow is present throughout the skeleton, but by early in the 3rd decade of life it is restricted to the skull, vertebral column, pelvis, ribs, sternum, and proximal femoral and humeral metaphyses (37,38) and is replaced elsewhere by yellow (fatty) marrow. On T1-weighted MR images, yellow marrow has high signal intensity similar to that of subcutaneous fat, whereas red marrow has low signal intensity similar to that of skeletal muscle and marrow metastases. Short-inversion-time inversion recovery sequences are particularly sensitive to the presence of red marrow and tumor tissue, which typically have higher signal intensity than does yellow marrow (39,40).
After therapy, certain patterns of bone marrow signal intensity may be identified at MR imaging and must be distinguished from metastatic disease or leukemic infiltration. Fatty transformation of bone marrow may be detected with MR imaging as early as 2 weeks after therapeutic irradiation (41) or even earlier with short-inversion-time inversion recovery sequences (42,43). In the long term, this fatty transformation manifests as an increase in signal intensity on T1-weighted images (Fig 11), an increase that may be irreversible (41). Marrow regeneration is more likely to occur in children than adults and when a large volume of marrow is irradiated than when radiation therapy is localized (44). Diffuse low signal intensity on T1-weighted images of the skull, spine, and pelvis has been reported after bone marrow transplantation, a finding that presumably reflects the presence of red marrow (45). Focal areas of low signal intensity, especially in the pelvis, may be due to marrow fibrosis or necrosis (46) or hypocellularity, which can be caused by chemotherapy alone (47).
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Figures 11, 12. (11) Radiation-induced fatty marrow change in a 14-year-old girl who underwent
radiation therapy for thoracolumbar paravertebral neuroblastoma 9 years previously. Sagittal T1-weighted MR image
of the spine shows high signal intensity in the irradiated vertebral bodies with central areas of low signal intensity. (12) Reconversion to red marrow in a 15-year-old boy who underwent treatment for intracranial mixed
germ cell tumor with chemotherapy and a hematopoietic growth factor.
(a) Sagittal T1-weighted MR image of the lumbar spine shows normal conditions before therapy.
(b) MR image obtained after treatment shows
numerous rounded areas of decreased signal intensity that probably represent centers of regenerating hematopoietic
marrow. Tumor markers were not elevated.
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Reconversion to red marrow may occur after marrow stress (38), especially in children who undergo treatment with hematopoietic growth factors (39,40). This effect may be seen in the axial (Fig 12) or appendicular skeleton. Although typically symmetric in the extremities, this process can be asymmetric or unilateral (40) and may mimic metastatic disease, even to the extent of showing increased uptake at bone (48) or thallium (49) scintigraphy. Metastatic tumor usually has higher signal intensity than reconverted red marrow on short-inversion-time inversion recovery images, but the signal intensity characteristics alone may not always be sufficient to exclude tumor. Bone marrow scintigraphy may be helpful, but biopsy is occasionally required (37).
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Figures 11, 12. (11) Radiation-induced fatty marrow change in a 14-year-old girl who underwent
radiation therapy for thoracolumbar paravertebral neuroblastoma 9 years previously. Sagittal T1-weighted MR image
of the spine shows high signal intensity in the irradiated vertebral bodies with central areas of low signal intensity. (12) Reconversion to red marrow in a 15-year-old boy who underwent treatment for intracranial mixed
germ cell tumor with chemotherapy and a hematopoietic growth factor.
(a) Sagittal T1-weighted MR image of the lumbar spine shows normal conditions before therapy.
(b) MR image obtained after treatment shows
numerous rounded areas of decreased signal intensity that probably represent centers of regenerating hematopoietic
marrow. Tumor markers were not elevated.
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Figures 11, 12. (11) Radiation-induced fatty marrow change in a 14-year-old girl who underwent
radiation therapy for thoracolumbar paravertebral neuroblastoma 9 years previously. Sagittal T1-weighted MR image
of the spine shows high signal intensity in the irradiated vertebral bodies with central areas of low signal intensity. (12) Reconversion to red marrow in a 15-year-old boy who underwent treatment for intracranial mixed
germ cell tumor with chemotherapy and a hematopoietic growth factor.
(a) Sagittal T1-weighted MR image of the lumbar spine shows normal conditions before therapy.
(b) MR image obtained after treatment shows
numerous rounded areas of decreased signal intensity that probably represent centers of regenerating hematopoietic
marrow. Tumor markers were not elevated.
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RADIATION-INDUCED TUMORS
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Both benign and malignant bone tumors may develop after radiation therapy. Osteochondromas appear to be particularly common in patients who receive total body irradiation before bone marrow transplantation at an early age (20) and usually arise after a shorter latency period than radiation-induced sarcomas. Radiologic features may be typical (Fig 4b). MR imaging may show a cartilaginous cap, which may help differentiate these lesions from radiation-induced sarcomas. Other benign bone tumors are rare complications of radiation therapy.
Radiation-induced sarcoma (Fig 13) is a grave late effect but fortunately is uncommon. Children are probably at greater risk than adults. The probability of sarcoma may not be directly related to local radiation dose and may increase with chemotherapy. The mean latency period is a little over 10 years (range, approximately 2–50 years). Most second malignancies that arise in bone are osteosarcomas, although fibrosarcomas, malignant fibrous histiocytomas (Fig 13), and other sarcomas may occur (50). Patients with bilateral or familial retinoblastoma are at especially high risk for the development of osteosarcoma as a second tumor; about 70% of these tumors arise in the radiation field.
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Figure 13a. Second malignant tumor in a 19-year-old woman who had undergone radiation therapy and chemotherapy for esthesioneuroblastoma several years earlier. (a) Frontal radiograph of the skull shows destruction of the right superior orbital margin (arrows) within the radiation field. (b) Coronal contrast-enhanced T1-weighted MR image shows a soft-tissue mass (arrow). Results of biopsy revealed malignant fibrous histiocytoma.
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Figure 13b. Second malignant tumor in a 19-year-old woman who had undergone radiation therapy and chemotherapy for esthesioneuroblastoma several years earlier. (a) Frontal radiograph of the skull shows destruction of the right superior orbital margin (arrows) within the radiation field. (b) Coronal contrast-enhanced T1-weighted MR image shows a soft-tissue mass (arrow). Results of biopsy revealed malignant fibrous histiocytoma.
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Radiation-induced sarcomas must be distinguished from recurrent primary tumor, metastatic disease, benign radiation changes, and infection. Bone destruction (Fig 13a) is common, although bone expansion and a sclerotic pattern may also be seen (50). The most important finding is a soft-tissue mass, which is best assessed with MR imaging (Fig 13b).
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CONCLUSIONS
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Pediatric oncology patients are at risk for the development of numerous skeletal complications. Imaging plays an important role in identifying these conditions and distinguishing them from one another and from recurrent or metastatic tumor tissue. It is important for radiologists who work with children with cancer to be familiar with these complications and their imaging appearances.
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Footnotes
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CME FEATURE This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician's Recognition Award. To obtain credit, see the questionnaire on pp 1029–1036.
LEARNING OBJECTIVES After reading this article and taking the test, the reader will:
• Be familiar with skeletal complications commonly encountered in pediatric oncology patients.
• Recognize the causes of skeletal complications in these patients.
• Be able to diagnose most skeletal complications on the basis of clinical and radiologic findings.
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Abstract
INTRODUCTION
