Evaluation and Management of Pediatric Bone Lesions.
Pediatric bone lesions are commonly identified on radiographs secondary to either painful symptoms or a new mass appreciated by the patient or a family member. Patients may attribute symptoms to recent athletic injuries, prompting radiographic evaluation. The incidence of malignancy in children has been documented at 4 to 5 cases per million for osteosarcoma and 3 per million for Ewing sarcoma and primitive neuroectodermal tumor (PNET). (1) Rates of bone and joint cancer have grown by 13% in past 10 years. (2) Benign bone lesions such as metaphyseal fbrous deffects are much more common and are seen in up to 3% of children. (2) Cirakli et al. (3) retrospectively reviewed patients with benign bone lesions and documented that 30% of the diagnosable lesions were osteochondromas, 28% bony cysts, 12% en-chondromas, 11% osteoid osteomas, and 6% non-ossifying fibromas. Large epidemiologic studies are hard to perform on these benign lesions because many can remain asymptomatic and are therefore never diagnosed.
Because of the asymptomatic nature of many of these benign lesions, patients may have sizable tumors by the time they are eventually discovered. Dang et al. (4) in their review found that pediatric bone tumors on average had a delay of diagnosis from 8 to 21 weeks after symptom onset. This delay was often attributed to either parental delay or inappropriate physician workup. (4) Other studies have found that older children and children who are first seen by a primary care provider are more likely to have longer delays in diagnosis. (5)
Slow growing and stable-sized lesions are less concerning for malignancy than rapidly growing lesions. Pain may also be a sign of a malignant lesion, especially nighttime pain. Patients with osteosarcoma will describe bone pain 79% of time and may exhibit symptoms for up to 3 to 6 months. (6) Raab et al. (6) found that pain at rest with unexplained periods of pain relief are quite common in patients with Ewing's sarcoma. However, not all painful lesions are malignant. Osteoid osteomas have typical painful symptoms resolved with NSAIDS and are benign and easily treatable. Interestingly, pathologic fractures are more commonly associated with benign tumors, such as unicameral bone cysts (UBC). (7)
Subjective symptoms such as weight loss, fatigue, and fever should always raise concerns for infection or malignancy and should not be missed during the clinical investigation. The clinician should also inquire about the patient's past medical history as well as the family history in order to identify risk factors. A known patient or family history of p53 germline mutation increases the risk of osteosarcoma. Patients with multiple hereditary exostoses (MHE) and Ollier's or Mafuci's syndromes have a significantly increased risk of developing chondrosarcoma. (8)
A detailed physical exam is imperative during the workup of a pediatric patient with a suspected bone lesion. Tenderness in the vicinity of the lesion and range of motion deficits are important to note. Raab et al. (6) found that 79% of patients with osteosarcoma present with bony pain and tenderness on physical examination. A gait abnormality may be appreciated, which may be a sign of the mass abutting neurovascular structures or impeding joint range of motion. Neurovascular involvement can be seen in cases when osteochondromas place pressure on a nerve as well as when more aggressive malignancies encompass these structures.
Some patients will present with multiple lesions. Multiple bone lesions may be a sign of a benign process such as osteochondromas. Simultaneous sites of disease may also represent more concerning pathology such as osteosarcoma with skip lesions or other metastatic bone disease. The location of the lesion is important to note as most malignancies, such as osteosarcoma or Ewing's, occur in the lower extremity about the knee, the pelvis, or the spine (9) (Table 1).
The examiner should note any associated skin lesions or superfcial deffects as can be seen in cases of pathologic fracture, infection, and malignancy. Benign lesions are less likely to involve skin or present with superfcial exam findings. (10) Local infammation and erythema may be present in cases of Ewing's sarcoma, eosinophilic granuloma (EG), and infections. Although not part of the physical examination, laboratory analyses, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count (CBC) with differential, should also be performed in patients with multiple bone lesions, which are more concerning for malignancy or infection. For example, white blood cell count and inflammatory markers may be elevated in patients with Ewing's sarcoma and lymphoma, while alkaline phosphatase is elevated in 50% of osteosarcomas. (11)
Radiographs should always be a part of the initial imaging evaluation. Often the radiographic appearance of the lesion can provide a diagnosis and no further imaging will be required in cases such as non-ossifying fibromas, enchondromas, and some osteochondromas (Figs. 1 and 2). (12) In assessing radiographs, it is important to consider Enneking's basic principles of the evaluation of bone lesions (Table 1). (13) The physician should note whether the lesion is located in the epiphysis, metaphysis, or diaphysis of the bone (Table 2). Bony expansion, erosion, and permeation are aggressive findings. Some lesions may cause the bone to fracture and may be lytic or blastic in nature. The bone may react to the lesion with a periosteal reaction or sclerosis. Often the radiograph will provide clues as to the matrix of the lesion. The lesion may be radiolucent in cases of cysts or may show stippled calcification in cases of cartilage. Some tumors will exhibit smoke-like or sclerotic lesions in cases of bone and intermediate radiolucency in cases of soft tissue tumors. The examiner should also note the size of the lesion. Larger lesions greater than 5 cm are more prone to represent aggressive or malignant etiologies. It should also be noted if there is any soft tissue involvement of the lesion. Ewing's sarcoma and in some cases osteosarcoma may expand into the soft tissue, which may be appreciated on radiographs.
Often the examiner can determine whether these bone lesions are malignant or benign with reasonable accuracy based on radiographic findings. Characteristics of benign lesions include well-defined or sclerotic borders, sharp transitions zones, and lack of a periosteal reaction. More aggressive lesions will show poor defnition, bony destruction, periosteal reaction, and sometimes a soft tissue component. (7) Lesions that are unchanged over 3 to 6 months can be monitored and are less likely to be aggressive. Enchondromas and non-ossifying fibromas, which are commonly diagnosed with only radiographs, are benign lesions. These pathologies require serial radiographs every 3 to 6 months to prove stability. (14)
Lesions that cannot be adequately identified on plain radiographs should be further investigated with advanced imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI), (Fig. 3). Small enchondromas, non-ossifying fibromas, and bone infarcts do not require these studies. Use of CT and MRI may also be warranted post-treatment for follow-up and assessment of disease response. (15)
Computed tomography is the best modality to appreciate bony anatomy, especially for lesions in the pelvis and spine. Computed tomography has the ability to assist diagnosis of lesions, such as osteochondromas, in which medullary stalks can be appreciated on axial sequencing. Axial CT cuts are the imaging modality of choice to identify osteoid osteoma. Kaste et al. (16) suggest that both CT and MRI are useful tools for surgical planning in order to identify appropriate levels of bony resection. Murrell's group state that CT should still be the gold standard for evaluation for pulmonary metastasis. Pulmonary lesions between 5 to 10 mm in setting of primary malignancy are generally considered sites of metastasis. (17)
While MRI can also be used to appreciate bony anatomy, it more accurately details soft tissue structures. In our practice, we typically obtain an MRI for any concerning bony lesions associated with clinical symptoms, radiographic irregularity, rapid growth, or an apparent soft tissue component. Magnetic resonance imaging can help the physician identify the type of tissue that may be contained within the lesion and assist with diagnosis. In cases of enchondroma or chondrosarcoma, the lesion will most often be bright on T2 sequencing. Aneurysmal bone cysts and telangiactatic osteosarcoma often demonstrate fluid-fluid levels (Fig. 4). Simple cystic lesions will be fluid flled and with contrast will show rim-enhancement. Magnetic resonance can also show any soft tissue mass associated with bony malignancy and can display the extent of a cartilage cap in large osteochondromas. Larger or irregularly shaped cartilage caps in these cases are concerning for malignant degeneration. (12)
Magnetic resonance imaging is also useful for the evaluation of marrow involvement, which is nonspecific but can be a general sign of an aggressive lesion. Khanna et al. (18) showed that malignant lesions, such as osteosarcoma and Ewing's, as well as benign finding, such as osteoid osteoma and stress fractures, may show marrow edema or peritumoral edema. Magnetic resonance imaging can elucidate neurovascular structures and help guide operative approach. Magnetic resonance should be performed prior to biopsy so that postprocedural soft tissue and bony changes do not confound the imaging interpretation. (18)
Although these imaging modalities can enhance the diagnosis and treatment of bone lesions, they are not without their negative attributes. Computed tomography scans evaluating pediatric bone lesions do expose children to radiation. Obtaining an MRI can also be difficult in a child as the child may need to be sedated. Both of these imaging modalities also incur a cost burden to the health care system.
Whole body MRI has been utilized for evaluation of pediatric malignancies. However, this modality is very expensive, time consuming, and may require sedation. Future studies in PET-MRI may show it to be a superior technique for evaluating malignancies. (19) In our clinical practice, we do not use PET scans, however that may change in the future as new literature arises.
Bone Scan, PET Imaging
Bone scans have been commonly used to diagnose potentially malignant or concerning bone lesions. This modality has also proven useful in cases of pediatric infection and trauma. Because bone scans evaluate the entire skeletal system, they are able to elucidate skip lesions and sites of bony metastasis in malignant disease. (20) Unfortunately, bone scans expose children to significant amounts of radiation. In our clinical practice, we try to avoid bone scans in children for this reason and prefer other imaging options when available.
PET-CT is a relatively new modality with many uses for oncologic workup. This modality is also offered in new low-dose protocols that decrease the radiation burden to the patient. (12,16) This test can be more sensitive in identifying sites of increased metabolic activity and possible malignancy than bone scans. PET-CT is superior to MRI or CT alone in evaluating tumor response to chemotherapy or radiation and is quite valuable in identifying sites of metastasis. However, McCarville (21) found that some benign pediatric conditions, as well as brown fat, will be metabolically active on PETCT. Our practice routinely uses PET-CT in order to look for sites of metastasis. We have found this imaging modality to be useful for detecting peripheral sites of disease and for monitoring response to treatments.
Lesions that cannot be diagnosed with imaging alone, including all suspected malignant lesions, require a formal tissue biopsy for histologic evaluation. This concept remains true for bony and soft tissue lesions. (10) Any lesion that does require a biopsy for diagnosis should be referred to an orthopedic oncologist in order to obtain that biopsy. Studies have shown that lesions biopsied by a care team other than the defnite musculoskeletal oncology team had 12 times more complications than those biopsied by the oncology team. These complications included diagnostic errors, repeat biopsies, additional chemotherapy or radiation, additional surgical resections, and unnecessary amputations. (22) A review from The Netherlands showed that pediatric mesenchymal pathology was correctly diagnosed only 60% of the time when not properly evaluated by a multidisciplinary team of musculoskeletal oncologists, radiologists, and pathologists. (23) When the musculoskeletal oncologist performs the biopsy, he or she should adhere strictly to the standard principles in biopsy. The surgeon should plan the biopsy at the planned site of definitive treatment to avoid seeding a separate biopsy tract. There is less risk of this complication with core needle biopsy compared to open biopsy. (24) The surgeon should maintain hemostasis to prevent a hematoma from contaminating the surgical bed. The surgeon should remain unicompartmental, only use longitudinal incisions, place any drains through or in line with the incision, and avoid exposing neurovascular structures.
Common, benign entities such as enchondromas, nonossifying fibromas, simple osteochondromas, and infections can be diagnosed and treated definitively by most orthopedic surgeons. Malignancies as well as more complex benign entities, such as giant cell tumor of bone and aneurysmal bone cysts, should be referred to an orthopedic oncologist. Any condition requiring a biopsy should be referred to ensure that a multidisciplinary team with experience in musculoskeletal oncology can provide treatment. (25) Multidisciplinary oncology teams should be utilized in cases of malignancy to optimize patient outcomes. (26)
Most Common Benign Tumors Encountered Osteochondroma
Osteochondromas are benign chondrogenic lesions derived from aberrant cartilage. These lesions may present with pain, swelling, and a slowly growing mass. They most commonly occur near the knee. When osteochondromas grow near neurovascular structures, they may present with neurologic symptoms. For example, the common peroneal nerve may be affected by osteochondromas about the fbular head.
Osteochondromas may occur as a single lesion or as one of many lesions seen in patients with multiple hereditary exostoses (MHE). A family history of similar lesions may clue the examiner to familial conditions such as MHE. This condition puts patients at a 5% to 12% lifetime risk of developing chondrosarcoma, which is caused by mutation in a tumor suppressor gene. Saglik et al. (27) showed a 2% chance of malignant degeneration with a solitary lesion compared to 12% in cases of MHE.
Radiographs show sessile or pedunculated lesions with cortical and medullary continuity to native bone. Larger or irregular lesions may be better assessed with CT or MRI. There remains some academic debate over the importance of the size of the cartilage cap and its association with malignancy. Studies have shown that rapid growth of the lesion especially after puberty and irregular cap appearance are better predictors of malignancy. (27) In our practice, we treat these uncomplicated lesions with observation every 3 to 6 months if asymptomatic or by marginal excision at base of stalk if symptomatic.
Nonossifying Fibroma (NOF)
Nonossifying fibromas (NOFs) are benign fbrogenic lesions caused by an abnormal area of ossifcation and represent one of the most common benign bone tumors in children between 5 to 15 years of age. They are usually asymptomatic and found incidentally on radiographs. In rare cases, these lesions are associated with neurofibromatosis or Jafe-Campannaci syndrome, a congenital condition of multiple NOFs, mental delay, and heart, eye, and gonadal involvement. More commonly NOFs are isolated lesions.
Radiographs demonstrate metaphyseal, bubbly lesions and are often diagnostic.
Observation is the first line of treatment in asymptomatic lesions (Fig. 5). Repeat imaging can be obtained in 3 to 6 months to observe for rare lesions that progress. The majority of these lesions will resolve with time. In rare cases of large lesions and impending pathologic fracture, a biopsy may be required prior to definitive treatment with curettage and bone grafting. In these operative cases, the lesion usually is greater than 5 cm or 50% of cortical diameter. (28)
Langerhans Cell Histiocytosis and Eosinophilic Granuloma (EG)
This condition exists on a spectrum of disease of the reticuloendothelial cell system involving both bony and non-bony lesions. Eosinophilic granuloma is most often a single bony lesion in very young patients, often less than 5 years old. Hand-Schuller-Christian Disease and Letterer-Siwe Disease are more global and life-threatening diseases. A younger age of presentation and more sites of disease represent more aggressive conditions. However, EG has shown 100% survival with minimal or no therapy in some studies. (8)
Eosinophilic granuloma often presents with pain, swelling, or antalgic gait in very young patients between the age of 1 and 4 years. Radiographs are inconclusive because this lesion can appear similar to many other lesions, hence its nickname "the great mimicker" (Figs. 6 and 7). These bone tumors can also present in any anatomic location. Advanced imaging may reveal a soft tissue component to the tumor. (8) Histologic evaluation demonstrates a lack of nuclear atypia with a majority of mononuclear histiocyte-type cells described as having "cofee bean" shaped nuclei. Classically described "tennis racket shaped" Birbeck granules are seen on electron microscopy.
Treatment of these single lesions can be with observation, corticosteroid injection, or curettage and grafting in cases of impending fractures. Radiation and chemotherapy have been used with some success in more difuse disease or areas harder to treat. (29) Our practice has seen good success rates with observation or curettage in more aggressive single lesions.
Aneurysmal Bone Cyst (ABC) and Unicameral Bone Cyst (UBC)
Aneurysmal bone cysts (ABC) are benign, expansile bone lesions flled with blood and separated by fbrous septae. They may present with pain, a growing fullness in the extremity, or pathologic fracture. The workup of these lesions should include plain radiographs, MRI, and biopsy. Characteristic fluid-fluid levels on MRI are appreciated in ABCs (Fig. 4). This hallmark MRI finding can also be appreciated in telangiectatic osteosarcoma and, therefore, requires a skilled pathologist to differentiate between these two conditions. (7) In some cases, ABCs will go on to pathologic fracture, in which case curettage and bone grafting should be performed once the fracture heals. Some investigators also recommend the use of adjuvant therapeutic options in these lesions. (30)
Unicameral bone cysts (UBC) are simple bone cysts caused by a failure of medullary bone formation that causes a serous flled cyst. These lesions are most often diagnosed in the proximal humerus metaphysis in patients in the second decade of life. Unicameral bone cysts commonly present with a pathologic fracture after a minor injury. Radiographs show a central, lytic metaphyseal lesion expanding the cortices (Fig. 8). In cases of fracture, plain films will demonstrate a typical "fallen leaf" sign, which represents fractured cortex that has fallen into the lesion. Histologic evaluation will demonstrate cysts with fbrous lining without any cellular atypia.
Appropriate treatment of UBCs should consist of observation in asymptomatic lesions not at risk for fracture. In cases with pathologic fracture, the extremity should be splinted and the fracture allowed to heal. If the lesions still persist after bony union, treatment may continue with a steroid injection or curettage and bone grafting. Aboulafa et al. (28) found that most UBCs will heal with noninvasive treatment after fracture.
Osteosarcoma is a malignant neoplasm of bone with an incidence in children and adolescence of approximately four to five per million. Cases are most often diagnosed in the second decade of life. (1) Many tumors are diagnosed after an initial complaint of a sport-related injury in active children.
Plain radiographs as well as MRI should be obtained during workup and should include the entire involved bone in order to evaluate for skip lesions. (8) This malignancy commonly presents around the knee or shoulder. Plain radiographs can exhibit both lytic and blastic characteristics. A periosteal reaction such as a sunburst appearance or Codman's triangle may be present (Fig. 9).
On MRI sequencing, the lesion will usually be low-signal on T1 and high-signal on T2, STIR, and post-contrast images. When there is a high suspicion of a malignant neoplasm, such as osteosarcoma, a biopsy should be obtained. Biopsy should always be performed by a fellowship trained musculoskeletal oncologist. (8,22) After histologic confrmation of malignancy, a metastatic workup may proceed.
Treatment of osteosarcoma consists of wide surgical resection combined with preoperative and postoperative chemotherapy. (31) At time of diagnosis, approximately 90% of patients will have metastatic disease, most often to the lung. (31) With modern chemotherapy regimens as well as advanced surgical planning, long-term survival rates have been documented at 60% to 70% in patients with local disease compared to 20% to 30% for those with metastatic disease. (32)
Ewing's sarcoma is a small round blue cell tumor that is most commonly diagnosed in the second decade of life but can occur in patients up to age 40. (8) Patients with this tumor may present with pain or a growing mass, most commonly in the lower extremities but occasionally in the pelvis or spine. On radiographs, these lesions may appear lytic and permeative with some sclerotic characteristics, such as the classic onion skin appearance (Fig. 10).
Magnetic resonance imaging is the preferred modality to appreciate Ewing's sarcoma and will appear low signal on T1 and high signal and show contrast enhancement on T2 and STIR imaging. (8) As with osteosarcoma, these lesions require biopsy for definitive diagnosis. A bone marrow biopsy in addition to the standard metastatic evaluation is required for staging if diagnosis is confrmed. (25) Treatment of Ewing's sarcoma consists of chemotherapy and wide surgical resection. Children under the age of 15 have shown long-term survival rates of approximately 70%.
Bone lesions are frequently encountered in pediatric patients who present with musculoskeletal complaints. Many of these findings are first appreciated when imaging is obtained for an athletic injury. Without significant experience evaluating these lesions, they may be inadvertently mismanaged. Obtaining a thorough clinical history and physical exam helps set the stage as to whether radiographic findings indicate malignancy. Patients with mild clinical symptoms that have been consistent for many months are more likely to be diagnosed as having benign pathology. Plain radiographs, always the first step in evaluation, may be diagnostic in cases such as osteochondromas, unicameral bone cysts, and non-ossifying fibromas. These benign, common conditions can safely be treated by pediatric and general orthopedists. However, many lesions may be nonspecific on radiographs and may require further diagnostic imaging. The information provided in this review may provide assistance to orthopedists as an algorithm when bone lesions are suspected in children. Many lesions that require more sophisticated imaging beyond plain radiographs may also require a biopsy to confrm diagnosis. In these cases, we would recommend referring the patient to a musculoskeletal oncologist. Studies have demonstrated improved patient outcomes when the biopsy is performed at the center for definitive care. Although we discuss briefy the workup and treatment of malignant conditions, such as osteosarcoma and Ewing's sarcoma, we would only recommend biopsy and treatment of these conditions by a musculoskeletal oncologist. Orthopedic subspecialists and generalists alike encounter numerous bony lesions in pediatric patients every year. Understanding which lesions require further workup, which studies to obtain, and which lesions to treat are important steps in the evaluation and care of these patients.
None of the authors have a financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.
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Alan T. Blank, MD, MS, Norman Y. Otsuka, MD, and Timothy B. Rapp, MD
Alan T. Blank, MD, MS, Midwest Orthopedics at Rush, Chicago, Illinois USA. Norman Y. Otsuka, MD, Children's Hospital at Montefore, Bronx, New York, USA. Timothy B. Rapp, MD, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York, USA.
Correspondence: Alan T. Blank, MD, MS, Midwest Orthopedics at Rush, 1611 West Harrison Street, Suite 300, Chicago, Illinois 60612, USA; email@example.com.
Blank AT, Otsuka NY, Rapp TB. Evaluation and management of pediatric bone lesions. Bull Hosp Jt Dis. 2018;76(1):62-70.
Caption: Figure 1 Proximal tibial non-ossifying fibroma in a skeletally immature patient.
Caption: Figure 2 Distal femoral enchondroma in a skeletally immature patient.
Caption: Figure 3 Imaging algorithm in the evaluation of pediatric bone lesions.
Caption: Figure 4 Calcaneal aneurysmal bone cyst demonstrating fluidfluid levels.
Caption: Figure 5 Distal tibial enchondroma in a skeletally immature patient.
Caption: Figure 6 Eosinophilic granuloma of the humerus in a skeletally immature patient.
Caption: Figure 7 Eosinophilic granuloma of the vertebral body demonstrating vertebra plana.
Caption: Figure 8 Unicameral bone cyst of the proximal humerus in a skeletally immature patient demonstrating a pathological fracture.
Caption: Figure 9 Osteosarcoma of the distal femur in a skeletally immature patient.
Caption: Figure 10 Ewing's sarcoma of the distal femur in a skeletally immature patient.
Table 1 Enneking's Four Questions for Evaluating Bone Lesions 1. Where is the tumor? 2. What is the tumor doing to the bone? 3. What is the bone doing to the tumor? 4. Are there any intrinsic clues as to histologic diagnosis? Table 2 Common Locations of Pediatric Bone Lesions Epiphyseal Lesions Metaphyseal Lesions Diaphyseal Lesions Chondroblastoma Enchondroma Osteoid Osteoma Aneurysmal Bone Cyst Aneurysmal Bone Cyst Eosinophilic Granuloma Osteomyelitis Fibrous Dysplasia Osteofbrous Dysplasia Giant Cell Tumor of Bone Osteochondroma Ewing's Sarcoma (older) Unicameral Bone Cyst Nonossifying Fibromas Osteomyelitis Osteosarcoma
Please Note: Illustration(s) are not available due to copyright restrictions.
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|Author:||Blank, Alan T.; Otsuka, Norman Y.; Rapp, Timothy B.|
|Publication:||Bulletin of the NYU Hospital for Joint Diseases|
|Date:||Jan 1, 2018|
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