Bone and Soft-Tissue Tumors

Bone and Soft-Tissue Tumors

Alexandre Arkader

Mark C. Gebhardt

John P. Dormans

Pediatric bone and soft-tissue tumors are rare. Although uncommon, these tumors may impact significantly in the child’s life, in terms of both survival and quality of life. Most musculoskeletal tumors seen in pediatric group are benign; however, malignancies do occur. The musculoskeletal primary malignancies that occur predominately in children are two bone sarcomas, namely osteosarcoma and Ewing sarcoma (EWS), and one soft-tissue sarcoma (STS), rhabdomyosarcoma (RMS). In addition, there are non-RMSs, such as congenital and infantile fibrosarcoma in young children and synovial sarcoma in adolescents. The orthopaedist must remain alert, because the malignant tumor is an unexpected event, and its infrequency can result in improper or delayed initial management. The orthopaedist who sees pediatric patients but is not prepared to manage a malignant or an aggressive benign musculoskeletal tumor needs to be comfortable with evaluating patients with these kinds of tumors and deciding which of them should be referred to an orthopaedic oncologist.

This chapter reviews the common bone and soft-tissue tumors of childhood; it discusses how the patients present, what physical findings to expect, and what the plain radiographs may show, and it suggests additional diagnostic and staging evaluations and treatment. This chapter is not intended to be a definitive text on musculoskeletal pathology, and tumor management, and includes only the most common tumors of childhood.


In the last 30 years, the use of adjuvant chemotherapy has led to dramatic improvement in the survival of children with previously lethal sarcomas. While 30 years ago, 80% of children with a primary bone sarcoma died, now at least that same number will survive (1, 2). One of the intriguing aspects of childhood sarcomas is that, despite similar histologies, stages, and prognostic factors, some patients respond well to treatment, whereas others seem to be resistant to chemotherapy. To date, patients with good prognoses cannot be distinguished from those with poor prognoses except by crude clinical characteristics, such as the presence of metastatic disease at diagnosis or the histologic response to preoperative chemotherapy (3). Recent molecular findings in sarcomas may shed light on their biologic behavior and their response to chemotherapy.

One method of looking for genetic alterations in tumors is to examine the chromosomes by karyotype analysis. The identification of recurrent chromosomal abnormalities provides clues regarding sites of potential gene mutations. Normally, there are 23 pairs of chromosomes in the nucleus of the human cell. Osteosarcomas in general have multiple, bizarre karyotypic abnormalities: some chromosomes are missing, some are duplicated, and some are grossly altered. To date, all studies of high-grade osteosarcomas have shown complex karyotypes and nonclonal chromosome aberrations superimposed on complex clonal events (4, 5). Low-grade juxtacortical osteosarcoma, on the other hand, is characterized by the presence of a ring chromosome accompanied by few other abnormalities or none at all (6). Although it is usually possible to distinguish high-grade from low-grade osteosarcoma by standard histology, the karyotype information may be diagnostically useful in the case of other tumors. In addition to possibly providing prognostic information, the specific chromosomal aberrations provide clues that assist molecular biologists who are looking for gene mutations (6).

In contrast to osteosarcoma, Ewing sarcoma (EWS)/peripheral neuroectodermal tumors (PNETs) and alveolar RMSs have single chromosomal translocations characteristic of their respective histologies. In these tumors, part of one chromosome is transposed to part of another chromosome through a breakpoint. A novel gene and gene protein product are created that presumably give the cell a growth advantage. The most common translocations for these tumors are listed in Table 13-1 (7, 8).

TABLE 13-1 Cytogenetic Findings in Pediatric Soft-Tissue Neoplasms









Clear cell sarcoma



Synovial sarcoma




Desmoid tumor, fibromatosis

Trisomy 20

Congenital fibrosarcoma




Dermatofibrosarcoma protuberans




8q rearrangement (8q11-q13)

Alveolar RMS





Alveolar soft parts sarcoma



EWS/PNET, Ewing sarcoma/peripheral (primitive) neuroectodermal tumor.

The demonstration of translocations has been useful in the differential diagnosis of round cell tumors. Under the light microscope, there is little to distinguish one of these tumor types from another, and although immunohistochemistry helps to a certain extent, it is at times difficult to be sure of the diagnosis. Demonstration of these characteristic karyotypic findings makes pathologists more secure in their diagnosis and has helped with the classification of these tumors. To perform a karyotype analysis, short-term cultures and metaphase spreads are necessary, but these are labor- intensive and require fresh tissue (7). Fluorescent in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) allow rapid analysis for the presence of translocations; these techniques can be performed on frozen tissue and sometimes even on paraffin-embedded tissue (8, 9 and 10). Therefore, it is important to give the pathologist appropriate fresh tissue to be snap frozen to preserve messenger ribonucleic acid (mRNA) and allow these studies to be performed (11).

These translocations have significance beyond merely establishing the diagnosis. These rearrangements lead to novel proteins that give the tumor cell a growth advantage. In EWS/PNET, for instance, a fragment of the EWS gene contains DNA-binding domains of the FLY1 gene. The protein acts by disrupting pathways that regulate DNA transcription (12). For several years, it was difficult to make the distinction between EWS and PNET, and clinicians were not sure whether to treat them differently. The observation that both EWS, a poorly differentiated mesenchymal tumor of uncertain cell lineage, and PNET, a tumor believed to be of neural crest origin, shared the same chromosomal translocation led pathologists to believe that both were related neuroectodermal tumors (13). As noted in Table 13-1, further studies revealed other translocations in several of these tumors, each such translocation specifying a different novel protein. There is debate regarding whether one or the other of these is associated with a better prognosis, but the treatment strategies used today are the same for both tumors. While some authors suggest that tumors with the type 1 transcript (EWS-FLY1) are associated with a better prognosis than those with other transcripts, others have disputed this (14, 15).

More recently, these markers have been used in staging and follow-up of high-risk patients (16). Using RT-PCR technology, one can detect small numbers of tumor cells in a bone marrow or a peripheral blood cell population (17). This makes the interpretation of bone marrow aspirates more precise and may provide a method for the earlier detection of relapses after treatment. It is hoped that the gene products of these translocations can also be used in treatment strategies. Because the novel genes formed from the translocation make a novel protein that normal cells do not make, antibodies or targeted T cells can be generated to specifically kill tumor cells. This is being tried in early-phase trials of relapsed patients with RMS and EWS/PNET, and if it works, it may be a way of treating patients who fail standard drug therapy.

Genetic alterations in the DNA of sarcomas have been well demonstrated. Mutations in genes, called oncogenes, give some evidence about the pathogenesis of these tumors and may have some prognostic and therapeutic import (4, 18, 19). Oncogenes are normal cellular genes (protooncogenes) that are necessary for the normal development and functioning of the organism (20). When they are mutated, they may produce a protein that is capable of inducing the neoplastic state. Oncogenes act through a variety of mechanisms to deregulate cell growth. This is obviously a very complex process and may involve more than one genetic event.

There are two categories of oncogenes: dominant oncogenes and tumor-suppressor genes (20). The cumulative effect alters proteins that function as growth factors and their receptors, kinase inhibitors, signal transducers, and transcription factors (12). The dominant oncogenes encode proteins that are involved in signal transduction, that is, in transmitting an external stimulus from outside the cell to the machinery that controls replication in the cell nucleus. Mutant cellular signal transduction genes keep the cell permanently “turned on.” The protein products of oncogenes also function as aberrant growth factors, growth factor receptors, or nuclear transcription factors. These types of genes seem to have less of a role in osteosarcomas. One exception is amplification of the HER-2/NEU/ERBB-2 protooncogene in patients with breast cancer, which confers a poorer prognosis. Patients with this amplification are treated with a monoclonal antibody to this protooncogene [MAb45D5, trastuzumab (Herceptin)]. Overexpression of HER2-NEU in osteosarcoma has been reported and is associated with advanced disease and poorer prognosis (21, 22). Although this has been disputed by some studies (23, 24), it provides the potential for treatment strategies in patients with osteosarcoma who have amplification of HER2-NEU.

A second class of genes are the tumor-suppressor genes, which encode proteins whose normal role is to restrict cell
proliferation (25, 26). They act as brakes rather than as accelerators of growth. Their normal role is to regulate the cell cycle and keep it in check. The retinoblastoma gene (RB) was the first gene recognized in this class (27). Osteosarcomas are very frequent in patients with hereditary retinoblastoma (1000× increased chance), both in the orbit and in the extremities, and are unrelated to irradiation. It was subsequently learned that osteosarcoma in these patients, as well as spontaneously occurring osteosarcomas, carries mutations or deletions of the RB gene. It was one of the first clues to the finding that osteosarcomas have a genetic cause. It is estimated that approximately 60% to 75% of sporadic osteosarcomas either have an abnormality of the RB gene or do not express a functional RB product (19). The RB gene is located on the long arm of chromosome 13 (13q14) and is 200 kb in length. Its product is a 105- to 110-kDa nuclear phosphoprotein (pRB) that appears to have a cell cycle regulatory role. The retinoblastoma protein acts as a signal protein, or a gatekeeper, to regulate the cell cycle through the transcription of genes that mediate the cell cycle. Deactivation of the RB gene or absence of pRB allows cells to enter the cell cycle in an unregulated fashion, a condition that imparts a growth advantage to the affected cell. It should be noted that one copy of the gene is sufficient for a normal phenotype. A child born with a normal allele and a mutant or an absent allele will not manifest retinoblastoma until some event occurs in retinoblasts to alter the normal allele. If both copies become deranged, the normal check on the cell cycle disappears, and the conditions for the neoplastic state are met. There are several other mechanisms by which the function of the RB protein can be altered; for instance, viral proteins may bind to the RB protein and inactivate it (5).

The second tumor-suppressor gene to be identified was the p53 gene (28, 29 and 30). Located on the short arm of chromosome 17 (17p), its product is a nuclear phosphoprotein that has a cell cycle-regulatory role similar to that of the RB protein. As in the case of RB, inactivation of p53 gives the cell a growth advantage, probably because of loss of cell cycle regulation. The p53 phosphoprotein may be inactivated by a variety of mutations, including a single base change (point mutation) that increases the half-life of the protein, allelic loss, rearrangements, and deletions of the p53 gene. Each of these mechanisms can result in tumor formation by loss of growth control. The p53 protein functions as an extremely important cell cycle checkpoint that blocks cells with DNA damage until they can be repaired or directs damaged cells into apoptosis (programmed cell death) if they cannot be repaired. Cells lacking this checkpoint can accumulate successive genetic abnormalities and possibly become malignant. It is estimated that approximately 25% of osteosarcomas have detectable mutations of the p53 gene (31).

The p53 protein is a transcription factor, meaning that it binds to regions of other genes (DNA) and controls the expression of genes responsible for cell cycle control (cell growth), apoptosis (programmed cell death), and other metabolic functions, such as control and repair of DNA damage. In concert with RB and a variety of other proteins, p53 acts to regulate the cell cycle through a complex cascade of enzymes, in which RB probably plays the central role. Apoptosis has recently become recognized as an important mechanism by which chemotherapy and radiotherapy kill cancer cells. p53 is involved in this process and appears to arrest cell division after sublethal damage (e.g., by radiation), to give the cell time to repair DNA defects before the next division (32, 33 and 34). If repair does not take place, the cell undergoes apoptosis and dies. If p53 is not functional, the cell may survive and accumulate genetic defects, leading to malignant transformation. Osteosarcomas have been shown to have a variety of mutations of the p53 gene (35, 36 and 37). Preliminary evidence suggests that overexpression of mutant p53 protein (detected by immunohistochemistry) or loss of heterozygosity of the p53 gene is related to human osteosarcoma (38, 39).

In sarcomas, genetic defects other than p53 and RB have also been detected. One example is a gene called mdm-2, which is a zinc finger protein that is amplified in some sarcomas (28, 40, 41). It inactivates p53 protein by binding to it, preventing its transcription factor activity. Cordon-Cardo et al. (42) studied 211 adult STSs by immunohistochemistry, using monoclonal antibodies to mdm-2 and p53, and demonstrated a correlation between overexpression of mdm-2/p53 and poor survival rates. Patients without mutations in either gene (mdm-2/p53-) had the best survival rates, those with one mutation (either mdm-2+/p53- or mdm-2-/p53+) had intermediate rates of survival, and those with mutations in both genes (mdm-2+/p53+) had the lowest survival rates. Another mechanism in which p53 protein can be inactivated is by viral proteins that bind and inactivate both RB and p53 protein (43).

Not only are genetic mutations found in the tumors of patients with sarcomas, but mutations may also be present in all somatic cells (germ-line mutations) in patients with heritable cancer (44, 45 and 46). Although such defects do not appear to be common in the general population, germ-line p53 mutations are present in patients who are part of a familial cancer syndrome. These families have a variety of cancers, often at an early age, and osteosarcomas and STSs are a fairly common occurrence in these kindred. Identification of patients with p53 germ-line mutations can be useful in determining which patients in an affected family are at risk for developing cancers, but much more work is needed in the area of genetic counseling to determine how best to use this information. One study showed that germ-line mutations were present in approximately 3% to 4% of children with osteosarcoma, and that the detection of these mutations was more accurate than family history in predicting the family’s susceptibility to cancer (47).

How is this information useful for treatment? One possibility is that the p53 mutations may be potential biologic markers of prognosis and response to treatment (chemotherapy). There is some preliminary evidence that p53 mutations in the tumor may portend a worse prognosis in osteosarcoma. More recently, the association of p53 with apoptosis has suggested possible strategies for chemotherapy, on the basis of the status of the p53 pathway (33, 34). Gene therapy (replacing the missing or mutated gene by transfection with viral carriers) is often discussed, but there are major technical hurdles to overcome before this technology can be used for treating cancers
in humans. However, it might be possible to make tumor cells more antigenic, or to make them more sensitive to antineoplastic drugs, by gene transfer. Another strategy would be to alter normal cells to make them less sensitive to damage by chemotherapeutic agents. Currently, these techniques pose technical challenges, but they offer realistic promise for the near future.

Another exciting area of research in the molecular biology of sarcomas is multidrug resistance (MDR). MDR probably explains why some patients respond to chemotherapy and others do not. Drug resistance may be intrinsic (present at diagnosis) or acquired (appearing after treatment of a tumor) (48, 49). At least four basic mechanisms of drug resistance are now recognized under the category of the MDR phenotype. They are (a) changes in glutathione metabolism, (b) alterations in topoi-somerase II, (c) non-P-glycoprotein (P-gp)-mediated mechanisms, and (d) P-gp-mediated mechanisms (6, 7, 48, 49 and 50). Recent evidence has suggested that P-gp may be of particular relevance to osteosarcoma. P-gp is a glycoprotein encoded by the MDR-1 gene on the long arm of chromosome 7 in humans (48, 49). MDR-1 is one member of the aneurysmal bone cyst (ABC) superfamily of genes that encode membrane transport proteins; these proteins function as unidirectional membrane pumps using adenosine triphosphate hydrolysis to work against a concentration gradient. P-gp is a 170-kDa protein that is located in the cell membrane and functions as an energy (adenosine triphosphate)-requiring pump that excludes certain classes (amphipathic compounds) of drugs from the cell. This physiologic mechanism is believed to be important in certain organ systems, such as the blood-brain barrier, placenta, liver, kidney, and colon, for ridding the cell of unwanted toxins, but it is also responsible for actively excluding chemotherapeutic agents, such as Vinca alkaloids, anthracyclines, colchicine, etoposides, and taxol (many of which are active in osteosarcoma protocols) from the cancer cell. Another feature of the P-gp mechanism that may have some relevance to therapeutic strategies is that some classes of drugs can reverse the MDR phenotype by blocking the action of the pump. These drugs include verapamil, cyclosporin A, tamoxifen, and others.

Several studies have demonstrated that some sarcomas (25% to 69%) display the MDR phenotype at diagnosis, and that relapsed sarcomas show higher incidence and intensity of MDR expression (48, 49, 51, 52). Because of the small numbers of patients in these studies, and the variety of the methods by which MDR expression was tested, comparisons of the studies and an accurate determination of the incidence of MDR expression are difficult to accomplish. In addition, the age of the patient and the type of sarcoma appear to be related to the incidence of detectable P-gp at diagnosis. One study showed that osteosarcomas have a higher incidence of MDR than other types of adult sarcomas (51). Serra et al. (53) demonstrated that overexpression of P-gp protein was evident in 23% of primary and 50% of metastatic osteosarcomas.

Baldini et al. (54) reported on 92 patients with non-metastatic osteosarcoma of an extremity who had been treated with chemotherapy and surgery. The study demonstrated that an immunohistochemically determined expression of P-gp predicted a decreased probability of the patient having an event-free survival, and was more accurate in prediction than histologic response to preoperative chemotherapy. Another study failed to find a relation between MDR-1 mRNA expression and outcome in patients treated for osteosarcoma (55).

Findings such as these are important in planning future protocols in human osteosarcoma. The drug-resistant tumor is becoming better identified as one that has a poor histologic response to preoperative chemotherapy and that expresses P-gp. Undoubtedly, it is more complex than this, and other mechanisms will pertain. Several caveats exist. One is the complexity of defining the resistant tumor. Preoperative chemotherapy requires 10 to 12 weeks to provide an estimate of histologic necrosis, unless ways can be found to accurately predict percentage of necrosis by positron emission tomographic (PET) scans, thallium scans, and/or gadolinium-enhanced magnetic resonance imaging (MRI). Detection of P-gp at diagnosis is difficult, and no one method has proven superior. It is probably not sufficient to demonstrate the presence of P-gp; also important is whether the pump is functioning to exclude cytotoxic agents from the tumor cell. Ideally, one would like to reverse the action of the P-gp mechanism but, just as there are no new agents to rescue patients who show poor histologic response, the agents currently available to reverse MDR are of limited benefit. They are potentially problematic in that they make normal cells less tolerant of chemotherapy, and thereby increase toxicity; and in other tumors they have not proven to be effective. The future probably lies in developing more effective reversing agents and in defining other drug-resistant mechanisms.


A thorough evaluation is necessary for any child presenting with a bone or soft-tissue mass. Although infection and trauma are much more common than a neoplastic process, the consequences of the mismanagement of a patient with a musculoskeletal tumor can be grave (Fig. 13-1).

Medical History.

Most children have no significant past medical history, but inquiries should be made. Has the child had a previous fracture? Has the child had other illnesses? Have radiographs been taken previously? Do not assume that the patient or the family will volunteer significant past medical history. Questions that should be asked include: How long has the mass been present? The longer the mass has been present, the more likelihood of a benign process. Especially worrisome are new masses that arise and grow over a short period of time. Is the mass getting bigger or is it stable in size? Masses that are rapidly growing indicate an active process that could be aggressive. Depending on the location, however, such as axial skeleton, some masses may not be noticed until they reach substantial size. Among younger patients, a parent usually notices the mass first, and although the parent will usually think that the mass has appeared overnight, this is rarely the
case. Teenagers may report the presence of a mass, but often only after a few weeks or months of waiting for it to resolve spontaneously. Is the mass associated with pain? Pain at the lesional site is a frequent complaint (see below). Active and aggressive tumors will usually present with pain. Painful soft-tissue masses are most often abscesses. Most soft-tissue tumors do not produce significant symptoms until they are large. Although most of the soft-tissue masses seen in children prove to be benign, all soft-tissue masses, even those in children, should be considered to be malignant tumors until proven otherwise. The consequences of mistaking a malignant soft-tissue tumor for a benign tumor can be devastating, whereas the consequences of approaching a benign tumor as if it were a malignancy are minimal. Is there a history of cancer? Depending on the age and the type of tumor, metastatic disease may be the main differential diagnosis.

FIGURE 13-1. Anteroposterior radiograph of the knee of a young man who complained of it “giving way.” The orthopaedist who saw the patient suspected a derangement, and the patient eventually had arthroscopic surgery. A radiolucent lesion can easily be seen in the lateral aspect of the proximal tibial metaphysis and epiphysis. This giant cell tumor of bone was missed because the physician did not consider this diagnosis when he was examining the patient or the radiograph.

Chief Complaint.

Generally, bone and soft-tissue tumors present in one of four ways:

  • Pain

  • Mass

  • Incidental finding on x-ray

  • Pathologic fracture

Pain is the most common presenting complaint of a child with a musculoskeletal tumor. The characteristics of the pain can help determine the diagnosis. Ask the patient: Where is the pain? How did it begin? Is it sharp, dull, radiating, or constant? Is it associated with activity? Is there a particular activity that makes the pain worse? What makes the pain better? Does it awaken you at night? Is the intensity of the pain increasing, staying the same, or diminishing?

Patients who have active or aggressive benign tumors (e.g., ABC, chondroblastoma, and osteoblastoma) usually have a mild, dull, slowly progressive pain that is worse at night and aggravated by activity. Patients with malignant musculoskeletal tumors complain of a more rapidly progressive symptom complex, not specifically related to activity, which often awakens them at night. Occasionally, the pain pattern is diagnostic. The classic example is the pain of an osteoid osteoma, which is a constant, intense pain that is worse at night, and is almost always relieved by aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). The pain caused by a Brodie abscess (subacute osteomyelitis) is similar to that of an osteoid osteoma, but is rarely relieved by aspirin.

Most children and parents date the onset of symptoms to a traumatic event. The specific nature of the trauma and the relation of the trauma to the current symptoms must be evaluated thoroughly. Trauma without a definitive fracture may be the explanation for an abnormal radiograph, but it should not be assumed to be the explanation, even for a periosteal reaction, unless the history is perfectly consistent. With the increased level of organized sports for children, there has been an increase in the incidence of fatigue or stress fractures, and these can sometimes be confused with neoplasias. Still, one should be cautious about ascribing a lesion to trauma.

The child presenting with a fracture should be questioned about the specifics of the injury that produced the fracture. Most lesions that lead to a pathologic fracture are easily recognized on a plain radiograph, but occasionally they may not be obvious. When the traumatic event seems insignificant, a pathologic fracture should be suspected. Patients should be asked about symptoms, no matter how minimal, that they experienced before the fracture. Most aggressive benign tumors and malignant tumors produce pain before the bone is weakened enough to fracture. Latent benign tumors such as unicameral bone cyst (UBC) and nonossifying fibroma (NOF) are often diagnosed following a trauma, as an incidental finding or a pathologic fracture.

A complete review of systems is mandatory. Ask specifically about fever, decreased appetite, irritability, and decreased activity. Most patients with musculoskeletal tumors do not have systemic symptoms at presentation, and their presence should alert the physician to the possibility of an underlying generalized disorder or osteomyelitis. Rarely, children with a malignant neoplasm, such as EWS, may present with fever, weight loss, and malaise, favoring an infectious etiology. Even
children with large primary malignant musculoskeletal tumors usually appear healthy.

Physical Examination.

All patients with musculoskeletal complaints, especially those in the pediatric age group, should have a complete physical examination. Not only can important information be gained about the specific disorder being evaluated, but also other significant abnormalities may be found. For example, café au lait lesions of the skin are a clue that the patient has fibrous dysplasia or neurofibromatosis (Fig. 13-2); numerous hard, nontender, fixed masses near the ends of long bones are suggestive of multiple hereditary exostosis (MHE).

The affected extremity should be examined carefully. The mass should be measured; larger tumors are usually more active and worrisome. Although there isn’t a specific number, soft-tissue masses over 5 cm and bone tumors over 8 cm have a higher likelihood of being malignant. The location is an important characteristic. STSs are usually located deep to the deep fascia, while bone sarcomas are usually located around the fastest growth areas (e.g., knee and shoulder). STSs are usually “fixed” to superficial or deep structures (no mobility) and firm to touch; soft, movable, nontender masses, especially those in the subcutaneous tissues, are usually benign. Transilluminate the mass, if light is transmitted more easily through the mass than through the surrounding tissue, the mass is a fluid-filled cyst. The gait pattern should be recorded; muscular atrophy measured, and the range of motion of the adjacent joint should be measured. The presence of erythema, tenderness, or increased temperature should be noted.

Neurovascular exam is essential. Often vascular malformations will be in the differential of soft-tissue tumors; check for pulsations or bruit. Detailed peripheral nerve check will assist in evaluating the proximity to these structures. Check for satellite lesions, the easiest lesion to miss is the second lesion. Examine the abdomen for hepatomegaly, splenomegaly, etc. Examine regional lymph nodes; although most musculoskeletal malignancies metastasize via hematogenous, some will do it via lymphatic. The most common ones are epithelioid sarcoma (16%), synovial sarcoma (15%), RMS (13%), and angiosarcoma (13%) (56).

FIGURE 13-2. Appearance of the abdomen of a 4-year-old girl who presented with several café au lait spots and angular deformity of the tibia. Based on physical examination, the diagnosis of neurofibromatosis could be made. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

Plain Radiograph Examination.

Plain radiographs are the single most useful image modality to assess a musculoskeletal tumor; all patients should have at least anteroposterior and lateral plain radiographs of the affected area. Often bone tumors are incidentally found after radiographs are taken for other reason. Pathologic fracture is also a common presentation, especially among some benign tumors such as UBC.

The entire lesion must be observed. The radiograph should be reviewed systematically. Look at the bone, all of it, and every bone on the radiograph. Ask yourself these questions: Is there an area of increased or decreased density? Is there endosteal or periosteal reaction, and if there is, what are the characteristics of the reaction? Is there cortical destruction? Is it localized or are there multiple defects? Is the margin in the tumor well defined or poorly defined? Is there a reactive rim of bone surrounding the lesion? Are there densities within a radiolucent lesion? Is the bone of normal, increased, or decreased overall density? Is the joint normal? Is there loss of articular cartilage? Is the subchondral bone normal, thick, or thin? Are there abnormalities in the bone on both sides of the joint? Are there intra-articular densities? Is there a soft-tissue mass? Are there calcifications or ossifications in the soft tissue? If one looks specifically for abnormalities, it is unlikely that an abnormality will be missed.

The pelvis and the scapula are exceptions to this rule. Large tumors involving the pelvis or the scapula, even those with marked destruction of bone, can be extremely difficult or impossible to see on a plain radiograph. If there is a suggestion that the patient has a pelvic or a scapular tumor, computerized axial tomography (CT) scan or magnetic resonance (MRI) is recommended.

Enneking (57) proposes that four sets of questions should be asked when looking at plain radiographs of a possible bone tumor.

  • Where is the tumor? This refers to the lesion’s anatomic location: long bone or flat bone; epiphyseal, metaphyseal, or diaphyseal; and medullary canal, intracortical, or surface. Based on the tumor location and the patient’s age, one can already formulate a differential list.

  • What is the tumor doing to the bone? Is there erosion of the bone, and if so, what is the pattern? This will determine the lesion aggressiveness.

  • What is the bone doing to the tumor? Is there periosteal or endosteal reaction? Is it continuous? Is it sharply defined? The periosteal reaction will reflect the efforts of the host bone to contain the lesion.

  • Are there any intrinsic characteristics within the tumor that indicate its histology? Is there bone formation by the tumor? Is there calcification? Is the lesion completely radiolucent?

TABLE 13-2 Most Common Pediatric Bone Tumors by Location

Tumor Location

Most Common Tumors


Chondroblastoma (growth plate open)

Giant cell tumor (growth plate closed)

Brodie abscess (subacute osteomyelitis)

Langerhans cell histiocytosis



Most benign and malignant bone tumors


Fibrous dysplasia

Osteofibrous dysplasia


Langerhans cell histiocytosis

Osteoid osteoma

Bone cyst

Ewing sarcoma



Anterior spine elements

Langerhans cell histiocytosis



Giant cell tumor



Posterior spine elements

Aneurysmal bone cyst


Osteoid osteoma


In addition to this list approach, always consider patient’s age and specific location of the tumor within the bone, as these characteristics will limit the differential diagnosis (Table 13-2). Most bone tumors can be diagnosed correctly after obtaining the history, performing a physical examination, and examining the plain radiograph. When the specific diagnosis is made from these examinations, additional studies are requested only if they are necessary for treatment. Often, specific treatment can be planned from only the history, physical examination, and plain radiographs. For example, a 12-year-old boy with a hard, fixed mass in the distal femur that has been present for several years and has not increased in size for more than 1 year complains of pain after direct trauma to this mass. Plain radiographs confirm the clinically suspected diagnosis of osteochondroma (Fig. 13-3). Further evaluation to make the diagnosis is not necessary.

When the specific diagnosis cannot be made, it should be possible to limit the differential to three or four diagnoses, and appropriate additional evaluations can be requested. CT, MRI, and nuclear bone scanning (technetium, gallium, thallium, or indium) may reveal findings that are diagnostic, or that provide the information required for planning a subsequent biopsy.

FIGURE 13-3. Anteroposterior radiograph of the distal femur of a 12-year-old boy with a hard, fixed mass that has been present for several years. Note the continuity of the cortex and the outline of the mass, as well as continuity of the intramedullary cavity and the interior of the mass. Also present are calcifications within the mass. The appearance is typical for a pedunculated osteochondroma. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

Additional Diagnostic Studies

Laboratory Examinations.

For the most part, serum and urine laboratory values are usually normal in musculoskeletal neoplasia. Nonetheless, a few musculoskeletal tumors are associated with abnormal laboratory values. The erythrocyte sedimentation rate (ESR) is nonspecific but sensitive. Patients with infections or malignant tumors usually have an elevated ESR, but patients with benign disease should have a normal value. A normal ESR value can increase the physician’s confidence that a suspected benign, inactive lesion is just that. Patients with active benign or malignant musculoskeletal tumors, particularly those with EWS, often have an elevated ESR, but it is rarely >80 mm/hour. A markedly elevated value (>180 mm/hour) favors a diagnosis of infection and may be just what is needed to justify an early aspiration of a bone or soft-tissue lesion. C-reactive protein (CRP) is another useful serum value that indicates systemic inflammation. Because it increases and returns to normal more quickly than ESR, CRP has been used as the main serum value to follow-up infection.

Serum alkaline phosphatase is present in most tissues in the body, but the bones and the hepatobiliary system are the predominant sources. In the pediatric age group, conventional high-grade osteosarcoma is associated with
elevated levels of serum alkaline phosphatase (58). Not all patients with osteosarcoma have elevated levels of serum alkaline phosphatase, and therefore a normal level does not exclude osteosarcoma from the diagnosis. A minimal elevation can be observed with numerous processes, even a healing fracture. Adults with elevated levels of serum alkaline phosphatase secondary to bone disease are most likely to have Paget disease of bone or diffuse metastatic carcinoma. Patients with a primary liver disorder have elevated levels of serum alkaline phosphatase as well, but they also have elevated levels of serum 5-nucleotidase and leucine aminopeptidase, and glutamyl transpeptidase deficiency. The levels of 5-nucleotidase and leucine aminopeptidase are not elevated in primary bone tumors. Two- to threefold increase in the alkaline phosphatase levels has been associated with worse prognosis in patients with osteosarcoma (58).

Serum and urine calcium and phosphorus levels should be measured, especially if a metabolic bone disorder is suspected. Serum lactate dehydrogenase (LDH) level is elevated in some patients with osteosarcoma. Patients with EWS or osteosarcoma with elevated LDH have a worse prognosis (15, 59, 60). Elevated LDH levels may also indicate relapse in a patient who has been treated for these tumors (59). Patients entering chemotherapy treatment protocols will need to have LDH levels determined in order to stratify them on the protocol. Other laboratory determinations are not helpful and are not recommended.

Radionuclide Scans.

Technetium bone scanning is readily available, safe, and an excellent method for evaluating the activity of the primary lesion. In addition, bone scanning is the most practical method of surveying the entire skeleton (Fig. 13-4). Technetium-99 attached to a polyphosphate is injected intravenously, and, after a delay of 2 to 4 hours, the polyphosphate, with its attached technetium, concentrates in the skeleton proportional to the production of new bone. A disorder that is associated with an increase in bone production increases the local concentration of technetium-99 and produces a “hot spot” on the scan. The technetium bone scan can be used to evaluate the activity of a primary lesion, to search for other bone lesions, and to indicate extension of a lesion beyond what is seen on the plain radiograph. The polyphosphate-technetium-99 compound also concentrates in areas of increased blood flow, and soft-tissue tumors usually have increased activity compared with normal soft tissues. The technetium-99 bone scan can be used to evaluate blood flow if images are obtained during the early phases immediately after injection of the technetium-99. The polyphosphate-technetium-99 is cleared and excreted by the kidneys, so the kidneys and the bladder have more activity than other organs. The technetium-99 scan is sensitive but nonspecific, whereas infectious processes will usually present with “hot scans.” The principal value of a radionuclide scan is as a means of surveying the entire skeleton for clinically unsuspected lesions. There are exceptions and false negative may occur, in approximately 25% of cases of Langerhans cell histiocytosis (LCH), the bone scan is normal, or there is decreased activity at the site of the lesion (42, 61, 62).

FIGURE 13-4. An anterior and posterior view of a whole-body technetium-99 bone scan. This was a 14-year-old girl with a right proximal tibia osteogenic sarcoma and there is increased activity in the lesional area. There were no other sites of disease based on the bone scan. Technetium-99 bone scanning is an efficient means of evaluating the entire skeleton of a patient with a bone lesion. It is important to have the entire skeleton scanned, rather than limit the scan to a small part of the skeleton. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

PET is being used more frequently in the evaluation of musculoskeletal tumors (42, 63). Fluoro-2-deoxy-D-glucose (FDG) PET is the type of PET used most frequently for the musculoskeletal system. Because there is a differential uptake of FDG between neoplastic tissue and normal tissue (neoplastic tissue has greater uptake), it is possible to identify neoplastic tissue on a PET scan. The role of PET in the evaluation and monitoring of patients with musculoskeletal neoplasia is under
investigation, especially among children. PET with fluorine-18-FDG has proved particularly useful in evaluating patients with lymphoma (64, 65).

Computerized Axial Tomography.

When introduced in the late 1970s, CT scan dramatically improved the evaluation of bone and soft-tissue tumors. The anatomic location and extent of the tumor could be determined accurately. The improved accuracy of anatomic localization means that less radical surgery can be performed safely.

The density of a bone or soft-tissue mass on a CT scan is called its “attenuation coefficient” and is measured in Hounsfield units (HU). The density of water is 0 HU; tissues more dense than water have a positive value, and tissues less dense than water have a negative value. The vascularity of a lesion can be evaluated by measuring the increase in the attenuation coefficient of a lesion after intravenous infusion of contrast, and comparing this increase to that in an adjacent muscle. Normal muscle has an attenuation coefficient of approximately 60 HU, and increases 5 to 10 HU with a bolus of intravenous contrast. Fat has an attenuation coefficient of approximately 60 HU, and cortical bone usually has a value of more than 1000 HU.

CT scan can be performed quickly and is less anxiety producing than closed MR, so sedation is less likely to be needed when compared with MRI. The main downside is the amount of radiation delivered in a CT scan, particularly among children (66). CT scan is most useful in the evaluation of small lesions in or immediately adjacent to the cortex (e.g., osteoid osteoma) and lesions with fine mineralization or calcifications (e.g., chondroblastoma). CT is still the gold standard for chest evaluation and to rule out lung nodules (Fig. 13-5). CT has also been used for percutaneous biopsies and treatment of several different lesions.

FIGURE 13-5. Axial cut of a CT scan of the chest of an 18-year-old male who had NF-1 and an MPNST of the shoulder girdle with metastatic involvement of the lung at presentation. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

Magnetic Resonance Imaging.

MRI does not expose the patient to radiation and has proved to be the most useful tool in the evaluation of soft-tissue lesions. MRI produces images of the body in all three planes (axial, sagittal, and coronal) as easily as in a single plane, and poses no known hazards to the patient.

The images are produced by a computer program that converts the reactions of tissue hydrogen ions in a strong magnetic field excited by radio waves. By adjusting excitation variables, images that are T1- and T2-weighted are obtained. A variety of techniques have been used to produce images of improved quality compared with routine T1- and T2-weighted images. The use of gadolinium as an intravascular contrast agent allows one to judge the vascularity of a lesion, thereby providing even more information about the tumor. Fat-suppression images with gadolinium enhancement are often especially useful in demonstrating a soft-tissue neoplasia. As with CT scan, it is important for the orthopaedist requesting MRI to discuss the case with the radiologist. The radiologist can then determine the optimal MRI settings required for visualizing the lesion.

MRI is the single most important diagnostic test after physical examination and plain radiography for evaluating a musculoskeletal lesion. The ability to view the lesion in three planes, determine its intraosseous extent, see the soft-tissue component clearly, and have an idea of the tissue type from one diagnostic test makes MRI a powerful tool. Unfortunately, variations in technique mean that it is important that the examination be planned carefully if the maximum information possible is to be obtained. T1-weighted (with and without gadolinium), T2-weighted, and fat-suppression techniques are the minimal images needed.


Patients with neoplasia can be separated into groups on the basis of the extent of their tumor and its potential or presence for metastasis. These groups are called stages. Grouping patients by their stage helps the physician predict a patient’s risk of local recurrence, metastasis, and outcome. This facilitates making treatment decisions about individual patients and helps in the comparison of treatment protocols. Staging systems are based on the histologic grade of the tumor, its size and location, and the presence of regional or distant metastases. The presence of a metastasis at the time of presentation is a bad prognostic sign and, regardless of other findings, puts the patient in the highest-risk stage. For patients without metastases at presentation, the histologic grade of the tumor is the principal prognostic predictor. Size is next in importance. Higher histologic grade and larger tumors are associated with the worse prognoses (67).

There are two common staging systems in use for musculoskeletal tumors. The task force on malignant bone tumors of the American Joint Commission on Cancer Staging and End Result Studies published a staging system for soft-tissue tumors in 1977, which was most recently revised in 2002 (68). This staging system is based on the histologic grade (G), local extent or size (T), whether the nodes are involved (N), and
metastases (M). The tumors are separated into three histologic grades (G1, low grade; G2, medium grade; G3, high grade) and two sizes (T1 for <8 cm (for bone) or 5 cm (for soft tissue), T2 for equal to or greater than that). Patients with nodal involvement are designated N1, and those without nodal involvement are designated N0. Patients with metastatic disease are designated M1, and those without metastatic disease are designated M0. There are four stages, with subclasses in each stage. Tumors at stage I are associated with the best prognosis, and tumors at stage IV with the worst prognosis.

Enneking et al. (69) also proposed a musculoskeletal staging system. This system is used more often by orthopaedists involved in the management of patients with musculoskeletal tumors. It was designed to be simple, straightforward, and clinically practical. The tumors are separated into only two histologic grades (I, low grade; II, high grade) and two anatomic extents (A, intracompartmental; B, extracompartmental). Patients with metastatic disease in either a regional lymph node or a distant site are grouped together as stage III. Each bone is defined as its own separate anatomic compartment. The soft-tissue anatomic compartments are defined as muscle groups separated by fascial boundaries. There are five stages in this system (Table 13-3).

Enneking et al. (69) also introduced four terms to indicate the surgical margin of a tumor resection. These terms are in common use, and provide a means of describing the relation between the histologic extent of the tumor and the resection margin. The surgical margins are defined as intralesional, marginal, wide, and radical. An intralesional margin is the surgical margin achieved when a tumor’s pseudocapsule is violated and gross tumor is removed from within the pseudocapsule. An incisional biopsy and curettage are two common examples of an intralesional margin. A marginal surgical margin is achieved when a tumor is removed by dissecting between the normal tissue and the tumor’s pseudocapsule. This is a surgical margin obtained when a tumor is “shelled out.” A wide surgical margin is achieved when the tumor is removed with a surrounding cuff of normal, uninvolved tissue. This is often referred to as en bloc resection and is the most common type of resection used for malignant tumors. A radical surgical margin is achieved when the tumor and the entire compartment (or compartments) are removed together. This usually is accomplished only with an amputation proximal to the joint that is just proximal to the lesion (e.g., an above-knee amputation for a tibial tumor). As a rule, benign lesions can be managed with an intralesional or a marginal surgical margin, but malignant tumors require a wide surgical margin. Radical surgical margins are reserved for recurrent tumors and the most infiltrative malignancies.

TABLE 13-3 Staging of Musculoskeletal Tumors



Site and Size



Intracompartmental (T1)



Extracompartmental (T2)



Intracompartmental (T1)



Extracompartmental (T2)


Any grade; regional or distant metastasis

Any site or size

T1, tumor <5 cm; T2, tumor ≥5 cm.

From Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980;153:106, with permission.


Biopsy is an essential part of tumor staging and management decision making for children with a bone or a soft-tissue tumor. Sometimes, a biopsy can be avoided and diagnosis made on basis of history, physical examination, and imaging studies. When a biopsy is required, the prebiopsy evaluation improves the chance that adequate and representative tissue will be obtained, the least amount of normal tissue will be contaminated, and the pathologist will make an accurate diagnosis. It is recommended that the surgeon consult with the radiologist and the pathologist before performing the biopsy to get their suggestions for the best tissue to obtain; furthermore, discussing the case preoperatively with the pathologist will allow the pathologist to be better prepared to make a diagnosis from a frozen section.

The purpose of the biopsy is to confirm the diagnosis suspected by the physician after the evaluation, or to determine which diagnosis, from among a limited differential diagnosis, is correct. In addition to providing confirmation for a specific diagnosis, the tissue obtained must be sufficient for histologic grading. It must be representative of the tumor and, because many musculoskeletal tumors are heterogeneous, the specific site from which the tissue is taken is important. Biopsy is not a simple procedure; the musculoskeletal tumor society has shown that an unplanned or erroneous biopsy can impact negatively the outcome, with higher incidence of unneeded surgery, including amputation and worse outcome (70).

There are two forms of biopsies: percutaneous (needle biopsy) and open (incisional and excisional). Percutaneous biopsy can be done via fine needle aspirate or core. It has the advantage of having low morbidity and sometimes can be done in clinic (older patients). Some of the disadvantages include a small amount of tissue and a higher chance for sampling error that may limit the ability to perform special stains and cytogenetics. The reported accuracy of a needle biopsy is around 85% (71).

Open biopsy has the advantage of obtainment of a larger tumor sample that allows the pathologist to perform all necessary studies and decreases the chance of sampling error. The accuracy of open biopsy is close to 96% (71). Furthermore, most children will require general anesthesia for a biopsy and therefore is important to obtain adequate sampling. Open incisional biopsy is the most commonly used technique. It entails obtaining a sizeable fragment of the tumor without attempting excision of the whole mass. Ideally, the treating surgeon will be the one performing the biopsy. That should avoid several possible complications that could impact in the ability of performing limb salvage and adequate tumor resection. Some of
the principles of open biopsy include drawing definitive limb salvage incision prior to start; avoiding transverse incisions on extremities; avoiding raising flaps or exposure of neurovascular structures; always performing an intraoperative frozen section to ensure acquisition of diagnostic tissue; if a drain is used, it should exit the skin in line with the incision; placing sutures within 5 mm of the incision; sending material for culture and sensitivity; achieving meticulous homeostasis (hematoma from the biopsy may contain tumor cells and will require resection if surgery is the treatment); and avoiding or judicious use of local anesthesia (72).

Occasionally an excisional biopsy, rather than an incisional biopsy, is indicated. Open excisional biopsy differs from incisional biopsy in that the entire tumor is excised and sent for analysis. An excisional biopsy is appropriate when the lesion is small and can be excised with a cuff of normal tissue. It is usually reserved for small (<3 cm) lesions that are likely benign. An excisional biopsy may be appropriate even when a major resection is required. If the preoperative evaluation strongly supports the diagnosis of a malignancy, particularly one for which a frozen section analysis will be difficult to do, an excisional biopsy should be considered. The advantages include single surgical procedure; however, a significant disadvantage is the need for extensive tissue sacrifice if re-excision is necessary (malignant tumor) to obtain appropriate margins (i.e., unplanned excision) (Fig. 13-6). An added advantage of an excisional biopsy is that the pathologist is able to examine the entire lesion, thereby improving the accuracy of the pathologic examination. An incisional biopsy exposes uncontaminated tissues to the tumor, and if the tumor proves to be a malignancy, the definitive resection is more complicated. If the lesion can be treated with curettage or a marginal excision, the incisional biopsy leads to the least functional loss. The final decision is made for each patient on the basis of not only the tumor’s characteristics but also the patient’s preference. Some patients want to take the fewest chances, and are willing to accept the possibility of slight overtreatment, whereas others choose to take one step at a time. It is the surgeon’s responsibility to explain the situation to the patient so that an informed decision can be made.

FIGURE 13-6. This 14-year-old girl had an unplanned excision of a “lipoma” of the dorsum of her foot, performed at an outside institution (A). The definitive diagnosis was consistent with a fibrosarcoma. The patient needed re-excision of the lesion with oncologic margins (B) and the soft-tissue defect created needed skin grafting (C). (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

A final note of caution is offered with regard to the biopsy: osteomyelitis is more common than bone tumors, especially in children, and osteomyelitis often mimics neoplasia. The reverse is also true; therefore, when performing a biopsy, even
when the diagnosis seems obvious, culture every biopsy and biopsy every culture.


This chapter is not designed to be a definitive musculoskeletal pathology text, and only those tumors that are commonly seen in the pediatric orthopaedic practice are discussed. The authors have tried to confine the discussion to pertinent information regarding the tumors, their evaluation, and particularly their treatment.


Bone-Forming Tumors

Osteoid Osteoma.

Osteoid osteoma is a benign active bone tumor that accounts for 11% of the benign bone tumors in Dahlin series from the Mayo Clinic (73). Osteoid osteoma most commonly affects boys (3:1 girl) between 5 and 24 years of age (80% of all patients). McLeod (74) is credited with the initial description, distinguishing it from a Brodie abscess, and from Garre osteomyelitis.

The classic presentation is pain at lesional site. The pain is not related to activity. Prostaglandins produced by the tumor are suspected to cause the pain, which is sharp, piercing, worse at night, and readily alleviated by aspirin or NSAIDs. If a patient has the typical pain for an osteoid osteoma, but there is no relief by aspirin, the diagnosis should be doubted. Patients with osteoid osteoma show few abnormalities on physical examination, with the exception of scoliosis in patients with osteoid osteoma of the spine. The child may walk with a limp and have atrophy of the extremity involved. If the lesion is superficial, it may be tender on palpation.

Although osteoid osteomas may arise in any bone, around 50% are found in the femur and tibia. The usual radiographic appearance is one of dense reactive bone with new bone periosteal formation, the actual lesion (a.k.a. nidus) is small (<15 mm in diameter), radiolucent, and of difficult visualization especially in the axial skeleton. The nidus may be on the surface of the bone, within the cortex, or on the endosteal surface. Lesions on the endosteal surface have less reaction than lesions within or on the cortex (Fig. 13-7).

Spine is a common location for “occult” osteoid osteoma. Since osteoid osteoma of the spine does not elicit a significant bony reaction, and it is usually located in the posterior elements, it is very difficult to make the diagnosis based on plain radiographs (Fig. 13-8A). When a child presents with painful scoliosis, with or without atypical curve pattern, osteoid osteoma should be considered (75, 76 and 77).

A technetium-99 bone scan is particularly useful to localize the lesion otherwise missed on the plain radiograph (78). CT is the best imaging modality for visualization of the nidus (79). The distance between the CT scan sections should be small (1 to 2 mm), so that the nidus is not missed (Fig. 13-8B). The window settings of the CT scanner should be adjusted so that the dense reaction around the lesion does not obscure the small, low-density nidus. MRI can be misleading and demonstrate excessive soft-tissue reaction favoring an infectious or a more aggressive diagnosis (79). Serum and urine laboratory values are normal.

FIGURE 13-7. Anterior-posterior radiograph of the humerus of a 5-year-old girl who presented with night pain that was readily relieved with NSAIDs. Note the intracortical lytic (nidus) lesion, surrounded by new bone formation, no periosteal reaction or soft-tissue mass (arrow). The nidus measured <1 cm and the lesion was consistent with an osteoid osteoma. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

On gross inspection, the nidus of an osteoid osteoma is cherry-red and surrounded by dense white bone. The nidus is small, <5 to 10 mm in diameter. A lesion that is identical histologically to the nidus of an osteoid osteoma, but larger than 2 cm, is called an osteoblastoma. The nidus is composed of numerous vascular channels, osteoblasts, and thin, lacelike osteoid seams (Fig. 13-9). Multinucleated giant cells may be seen, but are not common (75).

Natural history shows that osteoid osteoma may heal spontaneously although that may take several years (75, 80). Occasionally, a patient may use aspirin or NSAIDs to control the symptoms until the pain disappears, but most often the intensity of pain, the time it takes for the lesion to heal spontaneously, and the amount of medication required are not tolerable, and surgery is indicated.

FIGURE 13-8. This is a 13-year-old boy with lower neck pain, worse at night and torticollis; anterior-posterior (A) radiographs of the cervical spine is not diagnostic and only shows malalignment due to muscle spasm. Axial CT (B) shows the osteoid osteoma nidus located in the pedicle of C5 (arrow). (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

Kneisl and Simon (80) treated 24 patients with osteoid osteoma. Thirteen were operated on immediately, and all had complete relief of pain. Nine others were treated with NSAIDs. Of these, three subsequently elected to have surgery, but the six others also eventually became free of pain (an average of 33 months). Complete removal of the nidus relieves the patient’s pain. Partial removal may provide temporary relief, but the pain usually returns (80). Only the nidus needs to be excised. The reactive bone around the nidus does not have to be removed.

FIGURE 13-9. A: Typical histologic appearance of an osteoid osteoma. There is immature (woven) bone lined with osteoblast. Between the woven bone is a vessel-rich fibrous stroma. There is no atypia, and the few mitotic figures are normal (10× magnification). B: Higher magnification (40×) of the histology of the osteoid osteoma shown in A. The woven bone lined with osteoblast is easily seen. The red blood cells indicate the intense vascularity that is typical of this lesion.

Minimally invasive CT-guided techniques have become the preferred treatment for osteoid osteoma. The advantages include adequate visualization of the nidus, lower risk of recurrence, fast recovery, and its safety. Radiofrequency ablation is
one of the most common methods used. The procedure is performed under as an outpatient with general anesthesia. A needle biopsy is performed under CT guidance that is followed by placing the radiofrequency electrode with an internal thermistor and ablating the nidus. The success rate is of up to 90% (81).

Sometimes surgery is indicated, especially for recurrent tumors and spine lesions. Once identified, the nidus is curetted. Although this technique usually does not weaken the bone significantly, sometimes bone grafting is required; for spinal lesions, instrumentation may be needed. Failure in removing the entire nidus will cause recurrence of pain (77, 81). Preoperative planning and careful localization of the nidus is the most important means of ensuring that the nidus can be found during the operation. The reactive bone does not need to be removed.


Osteoblastoma is a benign active or aggressive tumor. It is histologically identical to osteoid osteoma, but larger. Osteoblastoma is less common than osteoid osteoma, accounting for <1% of the primary bone tumors in Dahlin series (73). Unlike osteoid osteoma, osteoblastoma is not surrounded by dense reactive bone.

It is most commonly seen in boys in the second decade of life (50% of the patients are between 10 and 20 years of age, although the age range is from 5 to 35 years). Pain at lesional site is the classic presentation; most patients have an average delay of 6 months from start of symptoms and diagnosis (82). The pain of an osteoblastoma is not as severe as the pain of an osteoid osteoma, and aspirin or NSAIDs do not have such a dramatic effect. At least one-third of the lesions are located in the spine, in those cases, scoliosis is present in almost half of the patients (82). Lesions of the extremities are usually diaphyseal; the patient often has a limp and mild atrophy, and complains of pain directly over the lesion, especially on palpation.

The appearance of osteoblastoma on a radiograph is variable. It is usually a mixed radiolucent, radiodense lesion, more lucent than dense. There is usually reactive bone formation but less intense than with osteoid osteoma. When the nidus can be observed, it measures over 2 cm. Lesions in the spine may be difficult or impossible to see when initially examining the plain radiograph, but when located by other studies, the subtle abnormality on the plain radiograph can usually be appreciated. Clues to look for on the plain radiograph to indicate the location of an osteoblastoma are an irregular cortex, loss of pedicle definition, and enlargement of the spinous process (83, 84). As with osteoid osteoma, a technetium-99 bone scan is the best method of localization. On a radionuclide scan an osteoblastoma shows increased uptake, and technetium-99 bone scanning is an excellent method of initially screening a patient suspected of having an osteoblastoma. CT scans are the best method of determining the diagnosis and extent of the lesion (Fig. 13-10A-C). On the CT scan, the lesion usually “expands the bone” and has intralesional stippled ossifications and a high attenuation coefficient (100 HU or more). Laboratory examinations of blood and urine show normal results.

The histology of an osteoblastoma is identical to the nidus of an osteoid osteoma. There should not be abnormal mitoses, although mitotic activity may be observed. There are osteoblasts, multinucleated giant cells, seams of osteoid, and a rich vascular bed. Schajowicz and Lemos (85) suggested that a subset of osteoblastoma be termed malignant osteoblastoma. They believe that this subset has histologic features that are worse than those of the usual osteoblastoma, is more aggressive locally, and is more likely to recur after limited surgery. Rarely, an osteoblastoma metastasizes (<1%) but still meets the histologic definitions of a benign tumor, although in those cases it should probably be classified as low-grade osteosarcoma.

Biopsy for diagnostic confirmation is usually indicated. The definitive treatment is surgical, as these lesions will continue to enlarge and damage the bone and adjacent structures. A wide surgical resection is theoretically preferred when practical, to reduce chance of recurrence. A four-step approach (extended curettage, high-speed burring, electrocauterization of cavity wall, and phenol 5% solution) has been shown to be effective with recurrence rates around 5% (82) (Fig. 13-10E,F). Children younger than 6 years tend to recur more frequently (82).

Osteochondroma and Multiple Hereditary Exostoses.

Also known as exostosis, osteochondroma is a benign latent or active cartilaginous tumor. Although the pathogenesis of this lesion is not known, an abnormality or injury to the periphery of the growth plate has been suggested as the cause (86). It has been shown in an experimental animal study that the periphery of the growth plate can be traumatized and a typical exostosis can be produced.

The patient with a solitary exostosis is usually brought in by a parent who has just noticed a mass adjacent to a joint. Often, the patient may have been aware of the mass for months or even years, and says that it has been slowly enlarging. Pain at presentation is unusual unless there is a trauma. Occasionally, there is loss of motion in the adjacent joint attributable to the size of the mass. Some patients have pain resulting from irritation of an overlying muscle, bursa formation, repeated trauma, pressure on an adjacent neurovascular bundle, or inflammation in an overlying bursa. Other symptoms may include “catching” or “popping” around the knee due to impingement to tendons and muscles.

On physical examination, the mass is nontender, hard, and fixed to the bone. The rest of the physical examination may show no abnormality. Complete neurovascular examination is important.

Osteochondromas can be diagnosed based on their radiographic appearance alone (Fig. 13-3). The mass is a combination of a radiolucent cartilaginous cap with varying amounts of ossification and calcification. The amount of calcification and bone formation increases with age. The base may be broad (sessile exostosis) or narrow (pedunculated exostosis). In both types, the cortex of the underlying bone opens to join the cortex of the exostosis, so that the medullary canal of the bone is in continuity. This can usually be appreciated on the plain radiograph itself, but if not, CT scan or MRI establishes this finding and confirms the diagnosis.

FIGURE 13-10. Osteoblastoma. Anteroposterior (A) and lateral (B) radiographs of a 13-year-old boy with a 3-month history of increasing thigh pain. There is abundant new bone formation and continuous periosteal reaction. A small lucency is seen in the posterior aspect of the femur (arrow). The bone scan (C) shows increased uptake in the lesional area, and CT axial cut

FIGURE 13-10. (continued) (D) demonstrates the well-defined nidus. Twelve months after a four-step approach (E and F), the bone has remodeled; there is no signs of recurrence, and the patient is pain free. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

In the pediatric age group, osteochondromas should be expected to grow. This is not a sign of malignancy. After skeletal maturity, continued growth of an exostosis is usually an indication for removal (87). The growth rate is not steady, and occasionally a lesion grows more rapidly than expected. Removal of the lesion in a child is indicated only for those patients who have symptoms attributable to pressure on a neurovascular bundle or irritation of the overlying muscle. Removal of the lesion in a young child may result in damage to the growth plate and recurrence of the lesion. Degeneration of the lesion into a malignancy is extremely rare in children and uncommon in adults. The definition of malignant degeneration of a solitary exostosis is confusing. Clinically, an exostosis is considered to be malignant in a patient as old as 30 years or older if there is an enlarging cartilage cap and when the cap is more than approximately 2 cm thick. This so-called malignant degeneration is more common in lesions of the scapula, the pelvis, and the proximal femur. The real incidence of malignant degeneration is not known. It is probably <2% (88).

Gross examination of an exostosis reveals a lesion that looks like a cauliflower. It has an irregular surface covered with cartilage. The cartilage is usually <1 cm thick, except in the young child, in which it may be 2 or 3 cm thick. Deep in the cartilaginous cap, there is a variable amount of calcification, enchondral ossification, and normal bone with a cortex and cancellous marrow cavity. Typically, the microscopic appearance of the cartilaginous cap is that of benign hyaline cartilage, which has the configuration of a slightly disordered growth plate (Fig. 13-11).

Some patients have multiple osteochondromas, a condition called multiple hereditary exostosis (MHE) (89, 90 and 91). A patient may have 3 or 4 lesions, but more often there are 10 to 15. Usually, the patient has exostoses of all shapes and
sizes. They are concentrated in the metaphysis of the long bones, but may be in the spine, the ribs, the pelvis, and the scapula. On physical examination, they are hard, fixed masses adjacent to joints. Patients with multiple exostoses are usually shorter than average but not shorter than the normal range. The affected joints show loss of range of motion, especially forearm rotation, elbow extension, hip abduction and adduction, and ankle inversion and eversion.

FIGURE 13-11. Low-power view of an osteochondroma cartilage cap, showing the very blend benign hyaline cartilage, low cellularity, no mitoses or pleomorphism. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

MHE is transmitted by an autosomal dominant gene with a variable penetrance, and there is an approximately 50% chance that a child of a parent with the heritable gene will show clinical manifestations of this condition (88, 89, 92, 93). Up to half of the cases are spontaneous mutation (88). The disease may manifest with extensive involvement in the parent, but with minimal involvement in the child, or vice versa (88). In most patients with MHE, the radiographic appearance of the proximal femur or the knees is diagnostic (Fig. 13-12).

Occasionally, one or more of the exostoses need to be removed in order to relieve the pain related to repeated local trauma, or to improve the motion of the adjacent joint. Lesions in the pelvis and the spine should be observed closely because they have the greatest risk of undergoing malignant degeneration. We do not recommend that these lesions be removed simply because they are present. MHE patients often need surgery for correction of angular deformities. Secondary chondrosarcoma is rare in the pediatric age group (94, 95). After the third decade, patients with MHE are at increased risk of developing secondary chondrosarcoma (96, 97). Among large series on chondrosarcoma in children, around 25% of the cases are secondary to a benign cartilaginous lesion (96, 97). We advise patients with exostosis, in particular MHE, to be examined at least yearly. Patients are told to report symptoms or increasing size immediately.


The origin of enchondroma is debatable; it may be the result of epiphyseal growth cartilage that does not remodel and persists in the metaphysis, or it may result from persistence of the original cartilaginous anlage of the bone (86). Both possibilities have been suggested as the cause of this common benign latent or active tumor. Most patients with a solitary enchondroma present with either a pathologic fracture through a lesion in the phalanx, which is the most common location (86, 98); or a history of the lesion having been an incidental finding on a radiograph taken for another reason (Fig. 13-13). Enchondromas are common lesions that account for 11% of benign bone tumors (99, 100), and they
do not necessarily need to be removed. However, they may be difficult to diagnose. Usually, the diagnosis can be made from the clinical setting and the plain radiograph. Forty percent of enchondromas are found in the bones of the hands or feet, usually a phalanx. An enchondroma should not produce symptoms unless there is a pathologic fracture. There are no associated abnormalities of blood or urine. The femur and proximal humerus are the next most common sites.

FIGURE 13-12. Clinical appearance (A) and anteroposterior radiograph (B) of a 12-year-old boy with MHE demonstrates several osteochondromas arising from distal femur and proximal tibia. (Reproduced with permission from The Children’ s Orthopaedic Center, Los Angeles, CA.)

FIGURE 13-13. A: This enchondroma of the fifth metacarpal is typical. The shaft is enlarged, and the lesion is radiolucent, with cortical thinning. This patient had been aware of this lesion since she was 10 years of age. She had sustained numerous pathologic fractures and decided to have it curetted. The curettage was done after the fracture had healed. B: Enchondroma can have varied histologic appearances with varying cellularity, but generally the cartilage, the amorphous material in the center of the image, has few chondrocytes. Typically, the cartilage is lined by a thin band of bone, and the adjacent marrow is normal. Often there is considerable calcification within the cartilage component of the lesion (10× magnification).

Enchondromas are located in the metaphysis and are central lesions in the medullary canal. The bone may be wider than normal, but this is caused by the lack of remodeling in the metaphysis rather than by expansion of the bone by the tumor. The cortex may be either thin or normal; the lesion is radiolucent in the pediatric age group, but at later stages it shows intralesional calcifications (101). There is usually no periosteal reaction. The appearance of an enchondroma on MRI is typical. The cartilage matrix has intermediate signal intensity on the T1-weighted image and high signal intensity on the T2-weighted image (102, 103). It has a sharp margin with the adjacent bone, without peripheral edema (102, 103).

When the findings are typical of an enchondroma, no biopsy is necessary. Repeat plain radiography and physical examination should be performed in approximately 6 weeks, then every 3 to 6 months for 2 years. Although there are reports of solitary enchondromas differentiating into chondrosarcomas, usually late in adult life, this does not occur frequently enough to justify the removal of all enchondromas. The patient should be advised that after age 30 years, if the lesion becomes painful or enlarges, it should be considered a low-grade chondrosarcoma and be surgically resected. Bone scan is also used to evaluate the tumor activity level and to help determining preferred treatment (101, 102 and 103).

Incisional biopsy is usually contraindicated. Pathologists have difficulty distinguishing between active enchondroma (most pediatric patients have active lesions) and low-grade chondrosarcoma. The clinical course is the best measure of the lesion’s significance, and an incisional biopsy alters the status of the lesion and makes subsequent evaluation difficult. If the patient or the patient’s parents insist on biopsy, it is best that the entire lesion be removed.

Patients with multiple enchondromatosis (Ollier disease) are far fewer than those with solitary enchondromas. Multiple enchondromatosis was originally described in the late 1800s by Ollier (104). Most patients with Ollier disease have bilateral involvement but with unilateral predominance. These patients have growth deformities, both angular and in length (Fig. 13-14). The deformities of the extremities should be managed surgically in order to maintain the function of the limbs, without specific regard to the enchondroma. Patients with Ollier disease have an increased risk of developing secondary chondrosarcoma later in life and should be so advised (105, 106). The incidence of secondary chondrosarcoma and other tumors in patients with Ollier disease is not known but may be as high as 25% (96, 107). The pelvis and the shoulder girdle are the most common locations of secondary chondrosarcoma.

FIGURE 13-14. Hip-to-ankle radiographs of a 5-year-old boy that presented for evaluation of angular deformity. Note the well-defined, mostly radiolucent lesion in the proximal femur and in the distal femur, with cortical thinning, no periosteal reaction, no soft-tissue mass and resultant valgus deformity of the femur. Ollier disease often predominates in one side of the body. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

Maffucci disease consists of multiple enchondromatosis and soft-tissue hemangiomas (108). Patients with this disorder have an even greater risk of developing malignant tumors than do patients with Ollier disease; more importantly, beside the risk of malignant degeneration, they have a great risk of developing carcinoma of an internal organ (96, 107, 109).


Chondroblastoma, or Codman tumor, is a benign active tumor. It was first described by Codman in 1931 as an “epiphyseal chondromatous giant cell tumor” (110); since Codman was particularly interested in the shoulder, he thought this lesion was found mostly in the proximal humerus (Fig. 13-15A). It has since become clear that chondroblastoma is found in many bones, but the proximal humerus is the most common site (approximately 20%) (99).

Chondroblastoma accounts for 1% of bone tumors (111, 112). The patient with a chondroblastoma is usually in the second decade of life, with an open growth plate, but the condition may occur in older patients as well. The initial symptom is pain in the joint adjacent to the lesion. The findings on physical examination also may suggest an intra-articular disorder because most patients have an effusion and diminished motion in the adjacent joint. Frequently, the patient is believed to have chronic synovitis; he or she does not have other symptoms or abnormal physical findings. The patient’s laboratory data are normal.

The lesion arises in the secondary ossification center. In children, it is the most common neoplastic lesion of the secondary ossification center (74); in adults, only giant cell tumor of bone involves the secondary ossification center more often. In children, osteomyelitis is the most common condition that can produce a lesion in the secondary ossification center.

On the plain radiograph, the lesion is radiolucent, usually with small foci of calcification (99). The calcification is best seen on a CT scan (Fig. 13-15B). There is usually a reactive rim of bone surrounding the lesion and, sometimes, metaphyseal periosteal reaction. The edema associated with chondroblastoma can be appreciated on MRI (Fig. 13-16). There is increased uptake on a technetium-99 bone scan. Chest radiography or CT scan should be performed because chondroblastoma is one of the benign bone tumors that can have lung implants and still be considered benign (<2% incidence) (113).

Chondroblastoma and osteochondritis dissecans can have similar appearances on plain radiographs, but they should not be confused with each other. Osteochondritis dissecans produces an abnormality in the subchondral bone; in chondroblastoma, on the other hand, the subchondral bone is almost always normal. Patients with chondroblastoma have more of an effusion than patients with osteochondritis dissecans, and their pain is constant and not related to activity as it is in patients with osteochondritis dissecans.

Histologically, the appearance of chondroblastoma is typical and is rarely confused with other diagnoses. It consists of small cuboidal cells (chondroblasts) closely packed together to give the appearance of a cobblestone street (114). In addition,
there are areas with varying amounts of amorphous matrix that often contains streaks of calcification, and usually there are numerous multinucleated giant cells. Chondroblastoma is not as vascular as osteoblastoma; there are few, if any, mitoses, and no abnormal ones (Fig. 13-17).

FIGURE 13-15. This is a 15-year-old boy with a chondroblastoma of the right proximal humerus epiphysis. Radiographs (A) at presentation shows a well-defined lytic lesion within the epiphysis and opened growth plate; coronal CT images (B) better define this lesion and demonstrate intralesional calcification; 12 months after a “four-step procedure” (C) the lesion is completely healed and the patient is pain free. (Reproduced with permission from The Children’s Orthopaedic Center, Los Angeles, CA.)

Chondroblastomas progress and invade the joint. They should be treated when found (111). Following biopsy for diagnostic confirmation, curettage is the treatment of choice, but it should be a thorough curettage and should extend beyond the reactive rim (four-step approach described above) (Fig. 13-15C). The lesion should be seen adequately at the time of the curettage, which usually means that the joint should be opened. Iatrogenic seeding of a joint is not a significant risk, and intra-articular surgical exposure is recommended if this facilitates visualization. Most recurrences are cured with a second curettage, but a rare lesion can be locally aggressive and requires a wide resection (111). Chondroblastoma of the pelvis frequently behaves more aggressively than that in long bones, and an initial wide excision is recommended if it can be done with limited functional loss and morbidity. Most patients are close to skeletal maturity when the diagnosis is made, and the risk of growth disturbance from the tumor or its treatment is usually minimal. When the patient is younger than 10 years old, care should be taken not to damage the growth plate. Intra-articular penetration and articular cartilage damage are real risks that should be avoided.

Chondromyxoid Fibroma.

Chondromyxoid fibroma is a rare benign active, rarely aggressive tumor. The patient is usually of the male sex (men are more frequently affected than women, at a ratio of 2:1) in the second or third decade of life (99, 115). The patient complains of a dull, steady pain that is usually worse at night. The only positive physical finding is tenderness over the involved area, and occasionally a deep mass can be detected.

Approximately one-third of chondromyxoid fibromas occur in the tibia, usually proximally. It is a radiolucent lesion that involves the medullary canal but is eccentric and erodes the cortex (100, 116) (Fig. 13-18). It may be covered by only periosteum, and is often mistaken for the more common ABC. The solid nature of chondromyxoid fibroma versus the cystic nature of an ABC, as seen on MRI, is a means of differentiating between these two lesions. The natural history is not known because the condition itself is infrequent and surgical treatment is nearly universal. Thorough curettage and bone grafting are recommended. Recurrence is a risk, and patients and parents should be so advised.

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Jul 21, 2016 | Posted by in ORTHOPEDIC | Comments Off on Bone and Soft-Tissue Tumors

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