Case 8-2005 — A 10-Year-Old Boy with Pain in the Right Thigh
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《新英格兰医药杂志》
Presentation of Case
A 10-year-old boy was seen in the clinic because of pain in the upper portion of his right thigh. The pain had begun six months earlier and was made worse by walking and by exercise. His parents noticed a slight limp. He had not been playing sports because of the pain. The pain was relieved by lying down, but occasionally it awoke him from sleep. It was only slightly relieved by acetaminophen. He did not have fever, malaise, trauma, or other musculoskeletal pain.
At the age of 13 months, the patient had had a two-week episode of difficulty in walking; a diagnosis of toxic synovitis of the hip was made, and the condition had resolved. He had had no other musculoskeletal or developmental problems. He lived with his parents and two siblings in the Boston area. He had not traveled or been exposed to tuberculosis.
On physical examination, he was a healthy-appearing child in no acute distress. The height was 143 cm (between the 50th and 75th percentiles for his age) and the weight was 45 kg (between the 75th and 95th percentiles). There was tenderness over the anterolateral region of the right upper thigh, but there was no palpable mass or inguinal lymphadenopathy. There was pain on abduction and with internal and external rotation of the right hip. The Trendelenburg's test was positive; the patient walked with an abductor lurch and an antalgic gait because of the pain. The remainder of the physical examination was normal. Laboratory test results are listed in Table 1.
Table 1. Laboratory Test Results on Admission.
Radiographs of the right hip (Figure 1) revealed an area of periosteal reaction along the right proximal femur in the right subtrochanteric region, adjacent and inferior to the greater trochanter. Faint calcifications were noted adjacent to the inferior margin of the greater trochanter. Magnetic resonance imaging (MRI) of the right leg (Figure 2) showed an area of increased signal on T2-weighted images that extended from the level of the growth plate to approximately 12 cm down the femoral shaft and into the surrounding soft tissues. The bright signal on T2-weighted images corresponded to an area of abnormal contrast enhancement. A technetium-99m–labeled methylene diphosphonate radionuclide bone scan revealed an area of increased uptake in the right proximal femur, without other foci of abnormal isotope uptake, that corresponded in location to the abnormalities visualized on MRI. These findings suggested a differential diagnosis that included malignant round-cell neoplasms and infection. A biopsy was recommended. Computed tomographic (CT) scanning of the thorax performed without the intravenous administration of contrast material revealed no abnormalities.
Figure 1. A Plain Radiograph Obtained with the Patient in the "Frog-Lateral" Position.
There is a small area of calcification along the anterior and lateral surface of the femur (arrow).
Figure 2. MRI of the Leg.
A T1-weighted, fat-suppressed coronal image (Panel A) that was obtained after the administration of intravenous contrast material shows an area of increased signal within the bone marrow that extends from the level of the growth plate to approximately 12 cm down the femoral shaft and into the surrounding soft tissues. A T2-weighted axial image (Panel B) shows a large area of abnormal soft tissue anterior to the femur.
A CT-guided needle biopsy was attempted with the use of local anesthesia and intravenously administered conscious sedation. Although a sample of soft tissues was obtained, biopsy of the bone was impossible because of the patient's agitation. A review of the CT scan obtained at the time of the attempted biopsy (Figure 3) showed a small, lucent lesion in the anterior cortex of the proximal femur with a central focus of mineralization. There was an overlying periosteal reaction with an area of possible heterotopic bone in the soft tissues.
Figure 3. CT Scan of the Leg.
A CT scan obtained at the time of the initial biopsy attempt (Panel A) shows a small lytic focus within the anterior femur (black arrow). There is periosteal new bone formation and a small amount of soft-tissue ossification anterior to the lesion. An ill-defined area of low attenuation is present that corresponds in location to the abnormality seen on MRI, and which probably represents edema (white arrow). A CT scan shows the location of the electrode (Panel B).
Two weeks after the CT scan, a diagnostic and therapeutic procedure was performed.
Differential Diagnosis
Dr. Mark C. Gebhardt: May we review the radiologic studies?
Dr. Daniel I. Rosenthal: An anteroposterior radiograph of the femur obtained at the time of presentation appears normal. In the "frog-lateral" view of the hip, however, one can see a focal area of very faint calcification in the soft tissues adjacent to what appears to be an intact cortex (Figure 1). The MRI studies show an area of increased T2-weighted signal within the subtrochanteric part of the femur (Figure 2). There is also increased T2-weighted signal in the soft tissues anteriorly and laterally, resulting in an apparent focal soft-tissue abnormality. A bone scan showed a corresponding area, 12 cm in length, of increased uptake in the proximal femur.
A CT scan obtained at the time of the attempted biopsy reveals a lytic lesion, 8 mm in length, in the cortex of the femur that had not been noticed before (Figure 3). It contains punctate internal densities and is surrounded by edematous tissue. The key to the diagnosis in this case is the recognition that the actual lesion is the rounded lytic focus within the bone and that the large abnormality within the marrow as visualized on MRI and bone scanning is an extensive tissue reaction.
The differential diagnosis of a small lytic lesion in the cortex surrounded by periosteal new bone and edema of the bone marrow and soft tissues includes infection,1 several benign neoplasms including osteoid osteoma, chondroblastoma, eosinophilic granuloma, hemangioma, periosteal chondroma, and the very rare cancer, intracortical osteosarcoma.
The lytic lesions caused by infection are usually larger and more irregular in shape than this one. Chondroblastoma may be indistinguishable from an osteoid osteoma on imaging. However, in most cases, chondroblastoma is found in the epiphysis or apophysis of the bone rather than in the shaft. It has a lobulated, rather than a rounded, boundary and is usually larger than this lesion. Similarly, eosinophilic granuloma is rarely this small at presentation, is sometimes multifocal, and often exhibits an irregular margin.
Periosteal chondroma usually sits on the surface of the bone, producing a superficial indentation that has been described as similar to an egg in a cup. In very rare instances, a chondroma may be purely intracortical and may resemble an osteoid osteoma. Periosteal chondromas occur in a slightly older population and, although painful, cause fewer symptoms than osteoid osteoma. Cortical hemangiomas may also closely simulate osteoid osteomas, but they are usually less painful. In a typical case, neither chondromas nor hemangiomas cause edema in the surrounding tissues.
Osteoid osteoma is usually a small spherical or oval lytic lesion (1 mm to 15 mm), surrounded by a variable amount of reactive bone and soft-tissue edema. Reactive bone may take the form of medullary sclerosis or periosteal new bone. Edema may occur in the marrow or adjacent soft tissues and may include a joint effusion if the lesion is found within a joint. The lesions are usually cortical or periosteal in origin. Only about 20 percent arise within the marrow. Ossification within the lesion varies from undetectable to almost complete filling of the area of lysis. Osteoid osteomas are considerably more common than the other entities mentioned.2
Osteoid osteomas are generally well visualized on CT scans but can be difficult to identify on MRI because the lesion is obscured by the surrounding edema.3 This difficulty has become more important in recent years, because the initial choice for imaging most musculoskeletal conditions has become MRI, as it was in this case. Visualization of the lesion can be greatly improved by early imaging after the injection of contrast material. The lesion enhances optimally within 30 seconds of the injection, whereas surrounding reactive tissues enhance more slowly. This type of early imaging is not performed routinely, and it was not done in this case. On conventional delayed contrast-enhanced images, the tumor is actually less well visualized than on noncontrast images.4
Dr. Gebhardt: The approach to a patient such as this with a suspected infection or tumor of bone includes a careful history and physical examination, laboratory studies, and imaging.5 Laboratory studies, including a complete blood count and measurement of the erythrocyte sedimentation rate, are obtained primarily to rule out infection, and in this patient the results of both studies were normal.6
If the imaging is diagnostic, benign bone tumors may be identified; these can be observed without treatment, since some, such as bone cysts and nonossifying fibromas, resolve spontaneously over time. Lesions such as osteochondromas or enchondromas are not likely to progress to malignancy and do not usually weaken the bone. Other lesions require biopsy or surgical treatment, either to establish the diagnosis or to treat the lesion and prevent pathologic fracture. The decision whether to pursue an open biopsy or a needle biopsy is complex and related to the location and nature of the lesion and the expertise of the treatment team. Open biopsy yields a diagnosis in most cases but is associated with surgical morbidity.7 Needle biopsy with CT or ultrasound guidance was shown to be accurate in 80 percent of cases with the use of fine-needle aspiration and in 93 percent with the use of core needles in a recent series of bone tumors.8
In this case, the findings on imaging were ultimately characteristic of osteoid osteoma. Osteoid osteoma is a relatively common benign bone tumor that occurs primarily in children and young adults (age range, 8 months to 70 years, with a mean of 18.8 years) and has a male-to-female ratio of 2:1. The lower extremity is the location that is most often involved, with the femur and tibia the most common regions, but the tumor is also often located in the posterior elements of the spine.9
The main symptom is pain, which is characteristic and often described as a sharp, penetrating pain, frequently worse at night. The pain may or may not be worsened by activity, as it was in this case. Nonsteroidal antiinflammatory agents nearly always relieve the pain, and patients awaken at night after the effects of the drugs wear off. This patient's lesion was less responsive to antiinflammatory medications than most osteoid osteomas, but the pain did awaken him at night. The symptoms can mimic other conditions, depending on the location of the osteoid tumor. In the spine, an osteoid osteoma can mimic the radiculopathy of a disc herniation. When the tumor is located near a joint, the symptoms are similar to those of a synovitis. Some patients have been wrongly given a diagnosis of a psychiatric illness because the presence of the lesion was not detected. Findings on physical examination are also numerous and variable. In the arms and legs, atrophy is often present, because of disuse of the limb. Osteoid osteomas in the spine may present as a painful scoliosis.10 Osteoid osteomas near a growth plate can lead to limb-length discrepancy or gigantism. In this patient, the location of the lesion in the cortex of a long bone and the pain that was partially relieved by nonsteroidal antiinflammatory drugs and that awoke him at night are typical of osteoid osteoma.
Dr. Nancy Lee Harris (Pathology): Could we have the medical students' diagnosis?
A Medical Student: The length of the abnormal bone seen on the MRI and the isotope scan led us to think about the possibility of malignant bone tumors, including Ewing's sarcoma and osteosarcoma. We also considered the possibility of infection, because of the history of transient synovitis. On the basis of the CT scan and the partial improvement in pain that resulted from antiinflammatory medication, our final diagnosis was osteoid osteoma.
Dr. Rosenthal: The next procedure was a CT-guided biopsy that was performed while the patient was under general anesthesia. Although biopsy of most bone lesions can be performed with local anesthetic, penetration of an osteoid osteoma with a needle is very painful. Perhaps that is why, in this case, the initial biopsy was unsuccessful and general anesthesia was needed.11
Clinical Diagnosis
Osteoid osteoma.
Dr. Mark C. Gebhardt's Diagnosis
Osteoid osteoma.
Pathological Discussion
Dr. Paula M. Arnell: The needle-core biopsy showed two abnormal areas: an area of thickened trabeculae of lamellar bone and an adjacent irregular, lace-like deposit of osteoid and woven bone with intervening loose fibrovascular tissue (Figure 4A and Figure 4B). These features are typical of an osteoid osteoma.
Figure 4. Pathology of Osteoid Osteoma.
A low-magnification view of a CT-guided-needle-biopsy specimen (Panel A) shows thickened trabeculae of lamellar bone (thick arrow) and a zone of fibrovascular tissue (long, thin arrow) surrounding a nidus of woven bone (short, thin arrow). At higher magnification, osteoid and woven bone with intervening loose fibrovascular tissue are present, indicative of the nidus of an osteoid osteoma (Panel B). A specimen from an en bloc resection of an osteoid osteoma from another patient (Panel C) shows three different zones of tissue: the central nidus (N), fibrovascular zone (dotted line), and outer peripheral sclerotic bone (solid line).
Photographs courtesy of Drs. Andrew E. Rosenberg and Gunnlaugur P. Nielsen, Department of Pathology, Massachusetts General Hospital.
An osteoid osteoma is a benign, bone-forming tumor characterized by three zones: a central area called the nidus that is composed of osteoid and woven bone, surrounded by fibrovascular tissue with a peripheral sclerotic rim of thickened lamellar bone (Figure 4C). The term "nidus" is misleading; it suggests that the area referred to is the center of the tumor, whereas actually this area constitutes the entire tumor. The zones of fibrovascular tissue with sclerotic bone are merely reactive and probably form as a response to cytokines secreted by the tumor. The nidus is well circumscribed, less than 1.5 cm in diameter, and has a variable degree of mineralization.12 There has been debate about whether osteoid osteomas are reactive lesions or true neoplasms. A recent study that showed clonal alterations and abnormalities involving chromosome 22 in two cases of osteoid osteoma supports the latter hypothesis.13
The pathophysiology of the characteristic pain of osteoid osteoma is becoming better understood. Immunohistochemical studies, prompted by the clinical response to nonsteroidal antiinflammatory drugs, have shown that osteoblasts within osteoid osteomas contain prostaglandins.14,15 Similar results have been found in other benign and malignant bone tumors, such as fibrous dysplasia and osteosarcoma, however, so prostaglandins alone probably do not account for the distinctive pain profile of osteoid osteoma. Additional immunohistochemical studies in which antibodies are used against nerve fibers have shown that osteoid osteomas have an increased density of nerve fibers, particularly in the fibrovascular zone, as compared with other benign and malignant bone neoplasms, including osteoblastomas.16 Therefore, the pain of osteoid osteomas may result from an interaction between prostaglandins and nerve fibers.
Discussion of Management
Surgical Treatment of Osteoid Osteoma
Dr. Gebhardt: The natural history of osteoid osteoma differs from that of most other skeletal tumors in that osteoid osteoma does not grow appreciably. This is an important distinction from osteoblastoma, another benign bone tumor that may have a similar appearance.17 Malignant transformation has not been reported. Since the lesions do not progress and do not become malignant, the primary goal of treatment is pain control. If pain can be controlled by medication, and if the medication is well tolerated, the symptoms may ultimately resolve.18,19 Spontaneous regression is a well-recognized phenomeon, but it is unclear what proportion of these lesions will eventually disappear, because the number of cases that have been followed to resolution is small.20 In one series of nine cases, six regressed after an average observation period of almost three years.21 When regression has been reported, the duration of symptoms appears to range from about 2 to 7 years, but symptoms have been reported to persist for as long as 18 to 20 years.
Intervention may be indicated for reasons other than pain control. Muscle atrophy is common in osteoid osteoma, and weakness and diminished reflexes in the deep tendons of the affected limbs may simulate a neuropathy.22,23 Lesions within joints may result in a synovitis and an increased risk of degenerative arthritis24 as well as restricted motion, which may become permanent.25,26,27 Tumors adjacent to an open growth plate may cause a growth disturbance (overgrowth or premature epiphyseal fusion). Scoliosis caused by spinal tumors may also become permanent over time.28 When life activities are compromised by the lesion, medical management appears inappropriate. In this case, the severe pain was preventing the patient from participating in important activites, and treatment was indicated.
The traditional surgical treatment option for this patient would be en bloc surgical excision of the lesion. It can be difficult to localize the nidus because of the surrounding reactive bone, and a large portion of bone must be excised to ensure the complete removal of the nidus. Radiographic evaluation of a specimen can help to identify the nidus, but it is difficult to document the presence of the lesion by examining intraoperative frozen sections, because of the bony reaction. The resultant bony defect frequently requires bone grafting or internal fixation and carries the potential for intraoperative blood loss. Prolonged hospitalization and the need for cast immobilization or further hospitalization for the removal of hardware make this option less than ideal. Currently, excision is used primarily for osteoid osteomas of the spine, because they are often too close to the spinal cord to be treated safely with radiofrequency ablation.29
Curettage of the lesion by means of a small incision is another accepted surgical approach that might be appropriate for this child and in general would be preferred to en bloc excision for a small lesion located in the leg, such as this. This procedure removes less bone than the en bloc excision, and the nidus can be visualized, curetted, and treated with a high-speed burr to ensure complete removal. The intraoperative use of tetracycline fluorescence or bone scintigraphy has been proposed to aid in locating the lesion.30,31,32 The specimen can also be imaged to help the pathologist find the nidus, and postoperative imaging will ensure that the lesion has been completely excised. Because the reactive bone around the nidus is not completely removed, the need for internal fixation is less frequent than after en bloc resection, although fractures after curettage have been reported. The success of curettage compared favorably with that of en bloc excision in a recent study.33
CT-guided approaches to remove the nidus have been proposed. One technique is to remove the nidus with a trocar that has been placed percutaneously with CT guidance.34 The advantage of this method is a small incision and limited removal of normal bone.
Currently, the technique of radiofrequency ablation has proved to be a simple and effective way to treat most osteoid osteomas, and I recommended this approach for the patient under discussion.35
Radiofrequency Treatment of Osteoid Osteoma
Dr. Rosenthal: The use of radiofrequency energy to treat osteoid osteoma was first described in 1989,36 and I believe that osteoid osteoma was the first type of tumor treated in this way. Radiofrequency energy is at the low-energy end of the electromagnetic spectrum, with longer wavelengths and lower energies than microwaves but somewhat similar properties. An alternating electrical potential is applied to an electrode that is insulated, except for about 5 to 8 mm at the tip. The flow of current between the electrode and a ground results in oscillations of electrically charged ions. The energy is absorbed locally and converted to heat. The temperature can be monitored continuously by the emitting electrode.
For a given amount of power input, there is an initial temperature rise, followed by a steady state in which power input is balanced by thermal diffusion and the cooling effect of blood flow. Once the steady state is reached, the tissue temperature falls at a rate that is inversely proportional to the fourth power of the distance from the electrode. Because of the very steep slope of this curve, the transition between complete cell death and no damage occurs over a very small distance on the relevant scale. For an electrode maintained at 90°C, this transition occurs at approximately 5 mm from the electrode, resulting in a spherical volume of tissue death of approximately 1 cm in diameter.
An osteoid osteoma is an ideal candidate for thermal ablation, because it is usually small enough so that a single treatment can eliminate the entire lesion. When lesion tissue extends more than 5 mm from the exposed portions of the electrode, more than one treatment (in the same session) may be required. Spinal tumors must be approached with caution because of potential hazards to nerve roots. Thus far, a number of spinal lesions have been treated successfully,37,38,39 and thermal damage to spinal cord or nerve roots has not been reported. Similar considerations may apply to the rare lesions of the hand.
Clinical success (defined as no symptoms, no need for medications, and no additional procedures for a minimum of two years) has been achieved in 90 percent of the 300 patients whom we have treated with this approach.40 Seven percent of the patients have had recurrences, and another 3 percent have had outcomes that are ambiguous. Many other centers have reported similar success rates.41,42,43 Similar results can be accomplished with the use of laser energy,44 which can be applied through fiberoptic devices that are even smaller than those currently used for thermal ablations. However, the use of laser energy for tissue heating is more difficult to control and more expensive than is the case with radiofrequency ablation, and it is not possible to obtain adequate biopsy-specimen material through very small needles.
The procedure we chose can be performed on an outpatient basis under CT control and with the use of general anesthesia. We treated this patient with radiofrequency ablation immediately after we performed the CT-guided needle biopsy. After the sample of tissue was taken, an electrode was introduced into the tumor. The position was documented by CT scanning (Figure 3B), after which the lesion was heated to 90°C for six minutes. The patient left the hospital in the afternoon after a morning procedure, and he required narcotic analgesia in the recovery room and for the night after the procedure. Most patients are able to discontinue all medications (including nonsteroidal antiinflammatory drugs) within a few days, as was this patient. All daily activities can be resumed immediately, but patients with lesions in weight-bearing bones, such as this patient, are advised to avoid activities that involve long-distance running for three months.
The patient remained free of symptoms for eight months, but then pain in the right thigh recurred, and he began to limp. CT of the right leg showed heterotopic ossification adjacent to the inferior femoral neck and a persistent or recurrent lytic lesion. Five months later, a second biopsy and radiofrequency treatment were performed. The biopsy confirmed recurrent osteoid osteoma. The patient remains free of pain six years after the second treatment.
Anatomical Diagnosis
Osteoid osteoma.
Source Information
From the Department of Orthopedics, Beth Israel Deaconess Medical Center (M.C.G.); the Departments of Radiology (D.I.R.) and Pathology (P.M.A.), Massachusetts General Hospital; and the Departments of Orthopedic Surgery (M.C.G.), Radiology (D.I.R.), and Pathology (P.M.A.), Harvard Medical School — all in Boston.
References
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A 10-year-old boy was seen in the clinic because of pain in the upper portion of his right thigh. The pain had begun six months earlier and was made worse by walking and by exercise. His parents noticed a slight limp. He had not been playing sports because of the pain. The pain was relieved by lying down, but occasionally it awoke him from sleep. It was only slightly relieved by acetaminophen. He did not have fever, malaise, trauma, or other musculoskeletal pain.
At the age of 13 months, the patient had had a two-week episode of difficulty in walking; a diagnosis of toxic synovitis of the hip was made, and the condition had resolved. He had had no other musculoskeletal or developmental problems. He lived with his parents and two siblings in the Boston area. He had not traveled or been exposed to tuberculosis.
On physical examination, he was a healthy-appearing child in no acute distress. The height was 143 cm (between the 50th and 75th percentiles for his age) and the weight was 45 kg (between the 75th and 95th percentiles). There was tenderness over the anterolateral region of the right upper thigh, but there was no palpable mass or inguinal lymphadenopathy. There was pain on abduction and with internal and external rotation of the right hip. The Trendelenburg's test was positive; the patient walked with an abductor lurch and an antalgic gait because of the pain. The remainder of the physical examination was normal. Laboratory test results are listed in Table 1.
Table 1. Laboratory Test Results on Admission.
Radiographs of the right hip (Figure 1) revealed an area of periosteal reaction along the right proximal femur in the right subtrochanteric region, adjacent and inferior to the greater trochanter. Faint calcifications were noted adjacent to the inferior margin of the greater trochanter. Magnetic resonance imaging (MRI) of the right leg (Figure 2) showed an area of increased signal on T2-weighted images that extended from the level of the growth plate to approximately 12 cm down the femoral shaft and into the surrounding soft tissues. The bright signal on T2-weighted images corresponded to an area of abnormal contrast enhancement. A technetium-99m–labeled methylene diphosphonate radionuclide bone scan revealed an area of increased uptake in the right proximal femur, without other foci of abnormal isotope uptake, that corresponded in location to the abnormalities visualized on MRI. These findings suggested a differential diagnosis that included malignant round-cell neoplasms and infection. A biopsy was recommended. Computed tomographic (CT) scanning of the thorax performed without the intravenous administration of contrast material revealed no abnormalities.
Figure 1. A Plain Radiograph Obtained with the Patient in the "Frog-Lateral" Position.
There is a small area of calcification along the anterior and lateral surface of the femur (arrow).
Figure 2. MRI of the Leg.
A T1-weighted, fat-suppressed coronal image (Panel A) that was obtained after the administration of intravenous contrast material shows an area of increased signal within the bone marrow that extends from the level of the growth plate to approximately 12 cm down the femoral shaft and into the surrounding soft tissues. A T2-weighted axial image (Panel B) shows a large area of abnormal soft tissue anterior to the femur.
A CT-guided needle biopsy was attempted with the use of local anesthesia and intravenously administered conscious sedation. Although a sample of soft tissues was obtained, biopsy of the bone was impossible because of the patient's agitation. A review of the CT scan obtained at the time of the attempted biopsy (Figure 3) showed a small, lucent lesion in the anterior cortex of the proximal femur with a central focus of mineralization. There was an overlying periosteal reaction with an area of possible heterotopic bone in the soft tissues.
Figure 3. CT Scan of the Leg.
A CT scan obtained at the time of the initial biopsy attempt (Panel A) shows a small lytic focus within the anterior femur (black arrow). There is periosteal new bone formation and a small amount of soft-tissue ossification anterior to the lesion. An ill-defined area of low attenuation is present that corresponds in location to the abnormality seen on MRI, and which probably represents edema (white arrow). A CT scan shows the location of the electrode (Panel B).
Two weeks after the CT scan, a diagnostic and therapeutic procedure was performed.
Differential Diagnosis
Dr. Mark C. Gebhardt: May we review the radiologic studies?
Dr. Daniel I. Rosenthal: An anteroposterior radiograph of the femur obtained at the time of presentation appears normal. In the "frog-lateral" view of the hip, however, one can see a focal area of very faint calcification in the soft tissues adjacent to what appears to be an intact cortex (Figure 1). The MRI studies show an area of increased T2-weighted signal within the subtrochanteric part of the femur (Figure 2). There is also increased T2-weighted signal in the soft tissues anteriorly and laterally, resulting in an apparent focal soft-tissue abnormality. A bone scan showed a corresponding area, 12 cm in length, of increased uptake in the proximal femur.
A CT scan obtained at the time of the attempted biopsy reveals a lytic lesion, 8 mm in length, in the cortex of the femur that had not been noticed before (Figure 3). It contains punctate internal densities and is surrounded by edematous tissue. The key to the diagnosis in this case is the recognition that the actual lesion is the rounded lytic focus within the bone and that the large abnormality within the marrow as visualized on MRI and bone scanning is an extensive tissue reaction.
The differential diagnosis of a small lytic lesion in the cortex surrounded by periosteal new bone and edema of the bone marrow and soft tissues includes infection,1 several benign neoplasms including osteoid osteoma, chondroblastoma, eosinophilic granuloma, hemangioma, periosteal chondroma, and the very rare cancer, intracortical osteosarcoma.
The lytic lesions caused by infection are usually larger and more irregular in shape than this one. Chondroblastoma may be indistinguishable from an osteoid osteoma on imaging. However, in most cases, chondroblastoma is found in the epiphysis or apophysis of the bone rather than in the shaft. It has a lobulated, rather than a rounded, boundary and is usually larger than this lesion. Similarly, eosinophilic granuloma is rarely this small at presentation, is sometimes multifocal, and often exhibits an irregular margin.
Periosteal chondroma usually sits on the surface of the bone, producing a superficial indentation that has been described as similar to an egg in a cup. In very rare instances, a chondroma may be purely intracortical and may resemble an osteoid osteoma. Periosteal chondromas occur in a slightly older population and, although painful, cause fewer symptoms than osteoid osteoma. Cortical hemangiomas may also closely simulate osteoid osteomas, but they are usually less painful. In a typical case, neither chondromas nor hemangiomas cause edema in the surrounding tissues.
Osteoid osteoma is usually a small spherical or oval lytic lesion (1 mm to 15 mm), surrounded by a variable amount of reactive bone and soft-tissue edema. Reactive bone may take the form of medullary sclerosis or periosteal new bone. Edema may occur in the marrow or adjacent soft tissues and may include a joint effusion if the lesion is found within a joint. The lesions are usually cortical or periosteal in origin. Only about 20 percent arise within the marrow. Ossification within the lesion varies from undetectable to almost complete filling of the area of lysis. Osteoid osteomas are considerably more common than the other entities mentioned.2
Osteoid osteomas are generally well visualized on CT scans but can be difficult to identify on MRI because the lesion is obscured by the surrounding edema.3 This difficulty has become more important in recent years, because the initial choice for imaging most musculoskeletal conditions has become MRI, as it was in this case. Visualization of the lesion can be greatly improved by early imaging after the injection of contrast material. The lesion enhances optimally within 30 seconds of the injection, whereas surrounding reactive tissues enhance more slowly. This type of early imaging is not performed routinely, and it was not done in this case. On conventional delayed contrast-enhanced images, the tumor is actually less well visualized than on noncontrast images.4
Dr. Gebhardt: The approach to a patient such as this with a suspected infection or tumor of bone includes a careful history and physical examination, laboratory studies, and imaging.5 Laboratory studies, including a complete blood count and measurement of the erythrocyte sedimentation rate, are obtained primarily to rule out infection, and in this patient the results of both studies were normal.6
If the imaging is diagnostic, benign bone tumors may be identified; these can be observed without treatment, since some, such as bone cysts and nonossifying fibromas, resolve spontaneously over time. Lesions such as osteochondromas or enchondromas are not likely to progress to malignancy and do not usually weaken the bone. Other lesions require biopsy or surgical treatment, either to establish the diagnosis or to treat the lesion and prevent pathologic fracture. The decision whether to pursue an open biopsy or a needle biopsy is complex and related to the location and nature of the lesion and the expertise of the treatment team. Open biopsy yields a diagnosis in most cases but is associated with surgical morbidity.7 Needle biopsy with CT or ultrasound guidance was shown to be accurate in 80 percent of cases with the use of fine-needle aspiration and in 93 percent with the use of core needles in a recent series of bone tumors.8
In this case, the findings on imaging were ultimately characteristic of osteoid osteoma. Osteoid osteoma is a relatively common benign bone tumor that occurs primarily in children and young adults (age range, 8 months to 70 years, with a mean of 18.8 years) and has a male-to-female ratio of 2:1. The lower extremity is the location that is most often involved, with the femur and tibia the most common regions, but the tumor is also often located in the posterior elements of the spine.9
The main symptom is pain, which is characteristic and often described as a sharp, penetrating pain, frequently worse at night. The pain may or may not be worsened by activity, as it was in this case. Nonsteroidal antiinflammatory agents nearly always relieve the pain, and patients awaken at night after the effects of the drugs wear off. This patient's lesion was less responsive to antiinflammatory medications than most osteoid osteomas, but the pain did awaken him at night. The symptoms can mimic other conditions, depending on the location of the osteoid tumor. In the spine, an osteoid osteoma can mimic the radiculopathy of a disc herniation. When the tumor is located near a joint, the symptoms are similar to those of a synovitis. Some patients have been wrongly given a diagnosis of a psychiatric illness because the presence of the lesion was not detected. Findings on physical examination are also numerous and variable. In the arms and legs, atrophy is often present, because of disuse of the limb. Osteoid osteomas in the spine may present as a painful scoliosis.10 Osteoid osteomas near a growth plate can lead to limb-length discrepancy or gigantism. In this patient, the location of the lesion in the cortex of a long bone and the pain that was partially relieved by nonsteroidal antiinflammatory drugs and that awoke him at night are typical of osteoid osteoma.
Dr. Nancy Lee Harris (Pathology): Could we have the medical students' diagnosis?
A Medical Student: The length of the abnormal bone seen on the MRI and the isotope scan led us to think about the possibility of malignant bone tumors, including Ewing's sarcoma and osteosarcoma. We also considered the possibility of infection, because of the history of transient synovitis. On the basis of the CT scan and the partial improvement in pain that resulted from antiinflammatory medication, our final diagnosis was osteoid osteoma.
Dr. Rosenthal: The next procedure was a CT-guided biopsy that was performed while the patient was under general anesthesia. Although biopsy of most bone lesions can be performed with local anesthetic, penetration of an osteoid osteoma with a needle is very painful. Perhaps that is why, in this case, the initial biopsy was unsuccessful and general anesthesia was needed.11
Clinical Diagnosis
Osteoid osteoma.
Dr. Mark C. Gebhardt's Diagnosis
Osteoid osteoma.
Pathological Discussion
Dr. Paula M. Arnell: The needle-core biopsy showed two abnormal areas: an area of thickened trabeculae of lamellar bone and an adjacent irregular, lace-like deposit of osteoid and woven bone with intervening loose fibrovascular tissue (Figure 4A and Figure 4B). These features are typical of an osteoid osteoma.
Figure 4. Pathology of Osteoid Osteoma.
A low-magnification view of a CT-guided-needle-biopsy specimen (Panel A) shows thickened trabeculae of lamellar bone (thick arrow) and a zone of fibrovascular tissue (long, thin arrow) surrounding a nidus of woven bone (short, thin arrow). At higher magnification, osteoid and woven bone with intervening loose fibrovascular tissue are present, indicative of the nidus of an osteoid osteoma (Panel B). A specimen from an en bloc resection of an osteoid osteoma from another patient (Panel C) shows three different zones of tissue: the central nidus (N), fibrovascular zone (dotted line), and outer peripheral sclerotic bone (solid line).
Photographs courtesy of Drs. Andrew E. Rosenberg and Gunnlaugur P. Nielsen, Department of Pathology, Massachusetts General Hospital.
An osteoid osteoma is a benign, bone-forming tumor characterized by three zones: a central area called the nidus that is composed of osteoid and woven bone, surrounded by fibrovascular tissue with a peripheral sclerotic rim of thickened lamellar bone (Figure 4C). The term "nidus" is misleading; it suggests that the area referred to is the center of the tumor, whereas actually this area constitutes the entire tumor. The zones of fibrovascular tissue with sclerotic bone are merely reactive and probably form as a response to cytokines secreted by the tumor. The nidus is well circumscribed, less than 1.5 cm in diameter, and has a variable degree of mineralization.12 There has been debate about whether osteoid osteomas are reactive lesions or true neoplasms. A recent study that showed clonal alterations and abnormalities involving chromosome 22 in two cases of osteoid osteoma supports the latter hypothesis.13
The pathophysiology of the characteristic pain of osteoid osteoma is becoming better understood. Immunohistochemical studies, prompted by the clinical response to nonsteroidal antiinflammatory drugs, have shown that osteoblasts within osteoid osteomas contain prostaglandins.14,15 Similar results have been found in other benign and malignant bone tumors, such as fibrous dysplasia and osteosarcoma, however, so prostaglandins alone probably do not account for the distinctive pain profile of osteoid osteoma. Additional immunohistochemical studies in which antibodies are used against nerve fibers have shown that osteoid osteomas have an increased density of nerve fibers, particularly in the fibrovascular zone, as compared with other benign and malignant bone neoplasms, including osteoblastomas.16 Therefore, the pain of osteoid osteomas may result from an interaction between prostaglandins and nerve fibers.
Discussion of Management
Surgical Treatment of Osteoid Osteoma
Dr. Gebhardt: The natural history of osteoid osteoma differs from that of most other skeletal tumors in that osteoid osteoma does not grow appreciably. This is an important distinction from osteoblastoma, another benign bone tumor that may have a similar appearance.17 Malignant transformation has not been reported. Since the lesions do not progress and do not become malignant, the primary goal of treatment is pain control. If pain can be controlled by medication, and if the medication is well tolerated, the symptoms may ultimately resolve.18,19 Spontaneous regression is a well-recognized phenomeon, but it is unclear what proportion of these lesions will eventually disappear, because the number of cases that have been followed to resolution is small.20 In one series of nine cases, six regressed after an average observation period of almost three years.21 When regression has been reported, the duration of symptoms appears to range from about 2 to 7 years, but symptoms have been reported to persist for as long as 18 to 20 years.
Intervention may be indicated for reasons other than pain control. Muscle atrophy is common in osteoid osteoma, and weakness and diminished reflexes in the deep tendons of the affected limbs may simulate a neuropathy.22,23 Lesions within joints may result in a synovitis and an increased risk of degenerative arthritis24 as well as restricted motion, which may become permanent.25,26,27 Tumors adjacent to an open growth plate may cause a growth disturbance (overgrowth or premature epiphyseal fusion). Scoliosis caused by spinal tumors may also become permanent over time.28 When life activities are compromised by the lesion, medical management appears inappropriate. In this case, the severe pain was preventing the patient from participating in important activites, and treatment was indicated.
The traditional surgical treatment option for this patient would be en bloc surgical excision of the lesion. It can be difficult to localize the nidus because of the surrounding reactive bone, and a large portion of bone must be excised to ensure the complete removal of the nidus. Radiographic evaluation of a specimen can help to identify the nidus, but it is difficult to document the presence of the lesion by examining intraoperative frozen sections, because of the bony reaction. The resultant bony defect frequently requires bone grafting or internal fixation and carries the potential for intraoperative blood loss. Prolonged hospitalization and the need for cast immobilization or further hospitalization for the removal of hardware make this option less than ideal. Currently, excision is used primarily for osteoid osteomas of the spine, because they are often too close to the spinal cord to be treated safely with radiofrequency ablation.29
Curettage of the lesion by means of a small incision is another accepted surgical approach that might be appropriate for this child and in general would be preferred to en bloc excision for a small lesion located in the leg, such as this. This procedure removes less bone than the en bloc excision, and the nidus can be visualized, curetted, and treated with a high-speed burr to ensure complete removal. The intraoperative use of tetracycline fluorescence or bone scintigraphy has been proposed to aid in locating the lesion.30,31,32 The specimen can also be imaged to help the pathologist find the nidus, and postoperative imaging will ensure that the lesion has been completely excised. Because the reactive bone around the nidus is not completely removed, the need for internal fixation is less frequent than after en bloc resection, although fractures after curettage have been reported. The success of curettage compared favorably with that of en bloc excision in a recent study.33
CT-guided approaches to remove the nidus have been proposed. One technique is to remove the nidus with a trocar that has been placed percutaneously with CT guidance.34 The advantage of this method is a small incision and limited removal of normal bone.
Currently, the technique of radiofrequency ablation has proved to be a simple and effective way to treat most osteoid osteomas, and I recommended this approach for the patient under discussion.35
Radiofrequency Treatment of Osteoid Osteoma
Dr. Rosenthal: The use of radiofrequency energy to treat osteoid osteoma was first described in 1989,36 and I believe that osteoid osteoma was the first type of tumor treated in this way. Radiofrequency energy is at the low-energy end of the electromagnetic spectrum, with longer wavelengths and lower energies than microwaves but somewhat similar properties. An alternating electrical potential is applied to an electrode that is insulated, except for about 5 to 8 mm at the tip. The flow of current between the electrode and a ground results in oscillations of electrically charged ions. The energy is absorbed locally and converted to heat. The temperature can be monitored continuously by the emitting electrode.
For a given amount of power input, there is an initial temperature rise, followed by a steady state in which power input is balanced by thermal diffusion and the cooling effect of blood flow. Once the steady state is reached, the tissue temperature falls at a rate that is inversely proportional to the fourth power of the distance from the electrode. Because of the very steep slope of this curve, the transition between complete cell death and no damage occurs over a very small distance on the relevant scale. For an electrode maintained at 90°C, this transition occurs at approximately 5 mm from the electrode, resulting in a spherical volume of tissue death of approximately 1 cm in diameter.
An osteoid osteoma is an ideal candidate for thermal ablation, because it is usually small enough so that a single treatment can eliminate the entire lesion. When lesion tissue extends more than 5 mm from the exposed portions of the electrode, more than one treatment (in the same session) may be required. Spinal tumors must be approached with caution because of potential hazards to nerve roots. Thus far, a number of spinal lesions have been treated successfully,37,38,39 and thermal damage to spinal cord or nerve roots has not been reported. Similar considerations may apply to the rare lesions of the hand.
Clinical success (defined as no symptoms, no need for medications, and no additional procedures for a minimum of two years) has been achieved in 90 percent of the 300 patients whom we have treated with this approach.40 Seven percent of the patients have had recurrences, and another 3 percent have had outcomes that are ambiguous. Many other centers have reported similar success rates.41,42,43 Similar results can be accomplished with the use of laser energy,44 which can be applied through fiberoptic devices that are even smaller than those currently used for thermal ablations. However, the use of laser energy for tissue heating is more difficult to control and more expensive than is the case with radiofrequency ablation, and it is not possible to obtain adequate biopsy-specimen material through very small needles.
The procedure we chose can be performed on an outpatient basis under CT control and with the use of general anesthesia. We treated this patient with radiofrequency ablation immediately after we performed the CT-guided needle biopsy. After the sample of tissue was taken, an electrode was introduced into the tumor. The position was documented by CT scanning (Figure 3B), after which the lesion was heated to 90°C for six minutes. The patient left the hospital in the afternoon after a morning procedure, and he required narcotic analgesia in the recovery room and for the night after the procedure. Most patients are able to discontinue all medications (including nonsteroidal antiinflammatory drugs) within a few days, as was this patient. All daily activities can be resumed immediately, but patients with lesions in weight-bearing bones, such as this patient, are advised to avoid activities that involve long-distance running for three months.
The patient remained free of symptoms for eight months, but then pain in the right thigh recurred, and he began to limp. CT of the right leg showed heterotopic ossification adjacent to the inferior femoral neck and a persistent or recurrent lytic lesion. Five months later, a second biopsy and radiofrequency treatment were performed. The biopsy confirmed recurrent osteoid osteoma. The patient remains free of pain six years after the second treatment.
Anatomical Diagnosis
Osteoid osteoma.
Source Information
From the Department of Orthopedics, Beth Israel Deaconess Medical Center (M.C.G.); the Departments of Radiology (D.I.R.) and Pathology (P.M.A.), Massachusetts General Hospital; and the Departments of Orthopedic Surgery (M.C.G.), Radiology (D.I.R.), and Pathology (P.M.A.), Harvard Medical School — all in Boston.
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