Evaluation and Treatment of Musculoskeletal Tumors
Wakenda K. Tyler, MD, MPH, FAOA
Dr. Tyler or an immediate family member serves as an unpaid consultant to Musculoskeletal Transplant Foundation and Taithera; has stock or stock options held in Taithera, Inc.; and serves as a board member, owner, officer, or committee member of the American Academy of Orthopedic Surgeons, the J. Robert Gladden Society, and the Musculoskeletal Tumor Society.
ABSTRACT
Understanding the basics of appropriate evaluation and management of patients with neoplasms of the musculoskeletal system is an essential component in the education of orthopaedic surgeons. Good diagnostic acumen and appropriate early management can result in life- and limb-sparing surgical care. A decrease in unnecessary testing and undue worry is also accomplished if accurate diagnosis can be achieved early. We will discuss the following topics that are critical to adequate diagnosis and management of patients presenting with a suspected musculoskeletal tumor.
Clinical presentation of patients with bone and soft-tissue tumors
Imaging modalities used to assess musculoskeletal tumors
Biopsy techniques and molecular diagnostics
Staging of malignant bone and soft-tissue tumors
Initial surgical management of patients with bone and soft-tissue tumors
Adjuvant therapies and their role in management of patients
The role of functional testing in musculoskeletal tumor patients
Keywords: biopsy; bone tumors; clinical presentation and imaging; oncology; sarcoma; soft-tissue tumors
Clinical Presentation
Patients with musculoskeletal tumors can present as an incidental asymptomatic finding to severely painful lesions with deformity and/or fractures. It is not infrequent for more aggressive tumors to present with significant pain and for more indolent tumors to be asymptomatic. Although, these are the general rules, many patients will fall outside of this norm. It is, therefore, imperative that the clinician assessing the patient incorporate all of the data available to determine a diagnosis. The presentation will vary depending on bone versus soft-tissue origin and often depending on age of the patient, as many very young children will not verbally express pain or discomfort.
Soft-Tissue Tumors
The vast majority of soft-tissue tumors will present without pain. Pain is not a determinant of a malignant versus benign process. In fact, more frequently, benign soft-tissue masses will present with pain. Examples of tumors that can present with pain are schwannomas and neurofibromas, which will often present with nerve-related pain, which will be sharp and shooting. Patients with nerve tumors will frequently have a Tinel’s sign on examination, which will manifest as electric shooting pain at the site of the tumor when it is tapped. Vascular malformations and angiolipomas are also tumors that frequently present with pain. Patients will have pain directly over the mass. It is hypothesized that the vessels within these tumors have nerve endings within them that can be triggered from trauma or thrombosis of the vessels within the tumor.1 Most malignant soft-tissue tumors will not cause pain unless they are directly invading a nerve, bone, or large vessel. Although possible, this is a rare event for most soft-tissue sarcomas.
Most soft-tissue sarcomas will present as growing masses. Rapid growth is often an ominous sign, but there are some sarcomas that will present with slower than expected growth, such as synovial sarcoma. Most benign soft-tissue tumors will often be slow growing or stable in growth. Some lipomas and fibromatosis can grow more rapid and still be benign. Vascular malformations may exhibit a waxing and waning pattern of growth with patients reporting rapid enlargement, followed by fairly rapid decrease in size. The lesion will rarely go away completely however.
Bone Tumors
Both benign and malignant bone tumors can present with pain. Unfortunately, the skeleton is a structure with a plethora of nerve endings throughout it components. Pain is a frequent finding in many active tumors, particularly when risk of fracture is present. When bone pain is present, patients often report pain at the site of the lesion and may describe this pain as achy and throbbing in nature (tooth ache-like). The patient may report feeling that the pain is deep seated. It is common for patients with bone pain to report night pain that will wake them from sleep. In situations where risk of fracture is imminent, patients will often report functional pain, such as pain with taking a step or getting up from a chair. Although many benign and malignant bone tumors will have pain associated with them, it is not uncommon for patients with inactive benign tumors to present with an incidental finding on imaging that was obtained for another reason, such as an acute transient injury or workup for some other process, such as arthritis or rotator cuff pathology.
Young children can be a challenge for assessing the presence of bone pain. Most young children will not report pain, but parents and caregivers may notice a limp or a sudden lack of use of a limb. In any child that presents in such a manner, a full workup, including thorough physical examination and imaging of any areas of concern is warranted. In one analysis of children diagnosed with malignancy, the number one presenting symptom was pain.2 This points to the importance of care in assessing what pain is in the young child.
Occasionally, in the instance of bone tumors, the first presenting sign may be deformity of the limb involved. Osteofibrous dysplasia is a good example of such a presentation, in which case the parents may notice anterior bowing deformity of the shin (Figure 1). Other conditions such as isolated large osteochondromas or multiple hereditary exostosis will also often present with what is perceived as painless lumps or limb deformity.
Imaging of Musculoskeletal Lesions
Radiographic features often play a key role in helping to diagnose many bone and soft-tissue tumors. Many tumors will have distinct radiographic features that are characteristic of a specific tumor. Such findings can often allow the clinician to limit further invasive and noninvasive testing. We will discuss the bone tumors and soft-tissue masses separately as radiographic classifications and diagnoses are very distinct for these two general groups.
Figure 1 Radiograph showing osteofibrous dysplasia of the tibia in a 2-year-old boy. Note the mild anterior tibial bowing, which will likely get slightly worse with growth. |
Bone Tumors
Plain Radiographs
Plain radiographs are often the starting and ending point for many bone tumors. When imaging bone tumors, the plain orthogonal radiographs should always include the whole bone in question (full-length radiographs), as this may help identify an isolated condition versus a multifocal process. The radiographic presentation is frequently all that is needed for a diagnosis in many specific bone lesions. In a recent Dutch study looking at a universal country-wide registry, delays in diagnosis were often found to occur at the primary care or generalist level. The authors of the study point to the need to educate the generalist on the importance of early plain radiographs in the management of patient with musculoskeletal pain, as most bone sarcomas will be readily detected on plain radiograph.3 The first question one should ask when assessing a plain radiographic lesion is whether the tumor has a matrix or not. This is often clearly seen on the plain radiographs. The two matrices one would see
will be cartilage or bone (Figure 2). There can also be a fibrous tissue matrix, but this can be harder to discern from other lytic processes on plain radiograph. The matrix can then either be defined as aggressive appearing as in the case of chondrosarcoma or non-aggressive, such as an enchondroma. If no matrix is present, then the lesion is often described as radiolucent or lytic. It is important to keep in mind that in the case of a lytic lesion, greater than 30% of the calcium matrix needs to be lost before it will be seen on a typical plain radiograph. The Enneking’s classification system for benign bone tumors is often a good starting point for classifying bone tumors4 (Table 1). Enneking described three types of bone lesions, which he defined as latent, active, or aggressive based on plain radiographic features5 (Figure 3). Latent tumors have clear and distinct borders, often with a sclerotic rim around the lesion. An example of a latent tumor is a nonossifying fibroma picked up as an incidental finding. Active lesions do not have a distinct border and will not have a sclerotic rim. They indicate a tumor that is growing, but not aggressively, such as unicameral bone cyst. Aggressive tumors will show expansion of the bone and destruction of one or more cortices with indistinct borders. Examples of aggressive tumors are frequently giant cell tumor of bone or aneurysmal bone cysts. Both active and aggressive imaging features can also be present in malignant bone tumors that are lytic, such as telangiectatic osteosarcoma.
will be cartilage or bone (Figure 2). There can also be a fibrous tissue matrix, but this can be harder to discern from other lytic processes on plain radiograph. The matrix can then either be defined as aggressive appearing as in the case of chondrosarcoma or non-aggressive, such as an enchondroma. If no matrix is present, then the lesion is often described as radiolucent or lytic. It is important to keep in mind that in the case of a lytic lesion, greater than 30% of the calcium matrix needs to be lost before it will be seen on a typical plain radiograph. The Enneking’s classification system for benign bone tumors is often a good starting point for classifying bone tumors4 (Table 1). Enneking described three types of bone lesions, which he defined as latent, active, or aggressive based on plain radiographic features5 (Figure 3). Latent tumors have clear and distinct borders, often with a sclerotic rim around the lesion. An example of a latent tumor is a nonossifying fibroma picked up as an incidental finding. Active lesions do not have a distinct border and will not have a sclerotic rim. They indicate a tumor that is growing, but not aggressively, such as unicameral bone cyst. Aggressive tumors will show expansion of the bone and destruction of one or more cortices with indistinct borders. Examples of aggressive tumors are frequently giant cell tumor of bone or aneurysmal bone cysts. Both active and aggressive imaging features can also be present in malignant bone tumors that are lytic, such as telangiectatic osteosarcoma.
Computer Tomography
CT utilizes multiple plain radiographs taken in different plains to generate a three-dimensional image of a particular body part being assessed. The benefits are that
one can see the three-dimensional nature of the bone, and in that, assess the true relationship of the tumor to other surrounding bone and soft tissue. CT scans can allow for assessment of the structural integrity of the bone and the matrix of the tumor. CT scans are also less expensive than MRI and therefore may be favored in circumstances where cost containment is important. It does not provide the soft-tissue detail that can be assessed by MRI however. The other downside to CT scan is that, because one is effectively using numerous x-rays to generate an image, the radiation exposure is significantly higher than the typical two to four views one may obtain for a typical long bone. CT scans can carry up to 200-times more radiation exposure than a single plain radiograph. For this reason, it is important to use CT scans with some prudence, particularly in younger children where the exposure to multiple CT scans has been shown to have a theoretical risk of future cancer development.6
one can see the three-dimensional nature of the bone, and in that, assess the true relationship of the tumor to other surrounding bone and soft tissue. CT scans can allow for assessment of the structural integrity of the bone and the matrix of the tumor. CT scans are also less expensive than MRI and therefore may be favored in circumstances where cost containment is important. It does not provide the soft-tissue detail that can be assessed by MRI however. The other downside to CT scan is that, because one is effectively using numerous x-rays to generate an image, the radiation exposure is significantly higher than the typical two to four views one may obtain for a typical long bone. CT scans can carry up to 200-times more radiation exposure than a single plain radiograph. For this reason, it is important to use CT scans with some prudence, particularly in younger children where the exposure to multiple CT scans has been shown to have a theoretical risk of future cancer development.6
Table 1 Enneking Staging for Benign Bone Tumors | ||||||||
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CT scans can be useful for certain tumors, particularly in situations where the three-dimensional nature of the cortical bone may need to be assessed. Osteoid osteomas, which are cortically based tumors, that frequently show a clear nidus on CT scan, are an example of a tumor for which CT scan can be extremely useful as a diagnostic tool. In other regions of the body where the complex nature of the bone is not well seen on plain radiographs, such as the sacrum and pelvis, a CT scan can be very helpful.
Magnetic Resonance Imaging
MRI can be a useful modality beyond plain radiographs, if plain radiographs do not definitively allow for determination of the lesion in question or if further information regarding soft-tissue involvement or marrow edema is warranted. It is often less informative about the structural integrity of the bone. When considering an MRI to assess a bone lesion, one should plan to order the MRI with intravenous gadolinium contrast, unless there is a contraindication. MRIs allow for detailed assessment of tumor-associated edema, which can be useful in distinguishing subtle pathologic fractures, as well as tumors showing aggressive behavior.
There is no better study than MRI when one is concerned about soft-tissue extension of a tumor and therefore should be considered when clear cortical disruption is seen on plain radiograph. The addition of gadolinium allows one to see more clearly the borders of a tumor and also allows for the distinction of a cystic versus a solid lesion. Gadolinium goes to sites of high vascularity and will also allow for determining the vascular nature of the tumor in question in some cases. This can be particularly important in the assessment of malignant tumors. An MRI of the whole bone in question is absolutely necessary for any malignant primary bone tumor. This is done to rule out metastases. MRI is unnecessary in the initial workup of an adult patient with presumed metastatic disease. Plain radiographs are usually adequate for assessing risk of fracture, and since
wide resection is rarely performed for metastatic disease, knowing the exact margins of the tumor is unnecessary. In instances of an adult patient presenting with an unknown lesion in the bone, a specific algorithm that can be found in the metastatic bone disease chapter should be followed.
wide resection is rarely performed for metastatic disease, knowing the exact margins of the tumor is unnecessary. In instances of an adult patient presenting with an unknown lesion in the bone, a specific algorithm that can be found in the metastatic bone disease chapter should be followed.
Bone Scans and Other Nuclear Imaging
Nuclear imaging is a modality that can often be helpful in the assessment of bone tumors, but are often more expensive tests and expose the patient to higher levels of radiation, so should be reserved for when a true need for further diagnostic assessment is determined. There are several different forms of nuclear imaging that can be used to assess bone tumors. The most common is a nuclear bone scan. This test utilizes a technetium-99 radiolabeled diphosphonate, which upon injection into the circulatory system will go to sites of rapid bone turnover. If a three-phase bone scan is performed, there will be three phases of image analysis, an initial perfusion phase, which allows for assessment of blood flow to the skeleton, followed by a blood pool phase, which can be helpful in distinguishing some inflammatory conditions. Finally there is a late phase, which assesses the osteoblastic activity within the skeleton.
A tagged white blood cell (WBC) scan is another nuclear imaging modality that allows for the assessment of WBC activity at a skeletal site. This can be helpful for determining the presence of an infection in bone. It should be noted that some inflammatory conditions, including some tumors, may also show increased uptake on a tagged WBC scan. Another nuclear test that we frequently see ordered by our medical oncology colleagues is positron emission tomography (PET) scan, which is a nuclear test that utilizes radiotracer labeled glucose (18F-fluorodeoxyglucose, FDG) to identify metabolically active areas of the entire body. This test is not just limited to the skeleton, but can detect high metabolic activity anywhere in the body. Tumors, as well as healing injuries and infections, will show increased FDG uptake, so this test can be very nonspecific and is usually reserved for patients with a known diagnosis of malignancy when one is in search of metastatic disease. Recent cost analysis comparing PET scan to other modalities, such as chest radiograph or chest CT scan to survey for recurrent or metastatic disease in primary bone sarcomas, found that PET was never found to be cost-effective.7 Therefore, ordering of a PET should be coordinated with the medical or pediatric oncology teams and not as a first-line test for assessing for bone or soft-tissue malignancy.
Soft-Tissue Tumors
Plain Radiographs
Plain radiographs are often less helpful for diagnostic purposes in soft-tissue masses. There are a few instances where plain radiographs can be diagnostic or at least narrow the diagnostic possibilities. Lipomas, particularly large ones, are examples of tumors that are often seen on plain radiograph (Figure 4). This is because fat has a lower density than muscle. On plain radiograph, one can see the contrast of the lower density fat adjacent to or within the higher density muscle and skin. Soft-tissue calcifications on plain radiographs can also be helpful in narrowing the diagnosis. Certain benign conditions, such as synovial chondromatosis, heterotopic bone, and the phleboliths (vascular calcifications) within vascular malformations, will all exhibit soft-tissue calcification. Several malignant conditions will also show calcifications within the soft tissue, such as synovial sarcoma and extra-skeletal osteosarcoma. Both of these latter conditions will often have other concerning features on MRI or CT.
CT Scans
CT scans for soft-tissue masses can be used to delineate a calcified body, such as the case of heterotopic bone (HO). In the case of HO, the calcifications will start at the periphery of the mass and progress centrally as the mass matures. This is in contrast to malignant conditions with calcification, which will often show a more haphazard and nonzonal pattern of calcification. When MRI is contraindicated, then a CT scan with contrast can allow for an assessment of the nature of the mass and its relationship to surrounding structures. A CT
scan will often not give as much detail, such as subtle fat plane between the tumor and a nerve or vessel, but still can be very useful when MRI is not an option.
scan will often not give as much detail, such as subtle fat plane between the tumor and a nerve or vessel, but still can be very useful when MRI is not an option.
Magnetic Resonance Imaging