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Patients usually will not experience pain from benign latent or active bone tumors, unless they are related to a pathological fracture (with the exception of the well-defined pain syndrome associated with osteoid osteoma). Pain associated with a bone tumor, therefore, generally is a symptom of an aggressive or malignant bone lesion.
Neoplastic bone pain is related to bone destruction and the resulting mechanical instability, as well as to intra-osseous and soft tissue pressure caused by rapid tumor expansion and malignant tumor cell proliferation. Aggressive and malignant bone tumors are also known to produce proteinases that may stimulate pain fibers. The inflammatory response to these tumors will release cytokines, which also produce pain.
Patients with painful bone tumors may complain of pain at rest, as well as worsening pain during mechanical loading. As the lesion enlarges, pain becomes more severe and the patient may be aware of a soft tissue mass surrounding the bone. Joint and limb function may be limited with very advanced lesions due to pain and extension of the lesion into the surrounding soft tissues.
Neoplastic bone pain may be mistaken for pain resulting from other causes. This is particularly true in the axial skeleton, where pain resulting from bone lesions of the spine, pelvis, or sacrum may be mistaken for mechanical back pain or sciatica.
Age is in important consideration when taking the history of a patient with possible neoplastic bone pain:
- In children, benign, aggressive bone lesions, such as osteoblastoma, aneurysmal bone cyst, and eosinophilic granuloma, may cause bone destruction and pain. Primary malignant bone tumors are rare; children primarily develop osteosarcoma and Ewing's sarcoma.
- In skeletally mature young adult patients, pain may be related to aggressive primary tumors of bone, or due to primary mesenchymal bone malignancies or lymphoma.
- As the patient reaches early middle age, metastatic lesions are much more likely to be the cause of pain than primary bone tumors.
- Evaluate possible evidence of systemic infection
- Ask about growth of a soft tissue mass at the site of pain
- Characterize the severity and the exacerbating features for the pain.
- Determine whether the pain is mechanical or present at rest.
- If the radiograph suggests osteoid osteoma, ask about characteristics of this type of lesion; for example, night pain and rapid relief with non-steroidal anti-inflammatory are typical.
- If the patient is middle aged or older, determine if there are historical features related to a possible remote primary cancer, including smoking history and risk factors for breast cancer or prostate symptoms.
A general physical examination should include evaluation of:
- The site of primary symptoms
- Evidence of primary malignancy at other sites (breast, thyroid, kidney, prostate, lymph nodes)
- Evidence of a soft tissue mass, inflammation, or joint involvement
- The presence of a pathological fracture (physical examination and X-ray)
- The presence of skeletal pain in other sites
The laboratory investigations should be ordered partly on the basis of the patient's age:
- In pediatric patients, the differential diagnosis always includes infection. Testing, therefore, should include a complete blood count (CBC) and erythrocyte sedimentation rate (ESR).
- In older patients at risk for metastatic and primary tumors, CBC (anemia is frequent in myeloma), ESR (elevated in infection, Ewing's, lymphoma, and myeloma), serum calcium and phosphorous (calcium may be elevated in metastatic disease and in myeloma), alkaline phosphatase (elevated in osteosarcoma and Paget's disease), serum immune electrophoresis for myeloma, and prostatic specific antigen (PSA) for prostate cancer should be included in the laboratory tests.
All patients with musculoskeletal pain should have a conventional radiograph of the affected site. Although plain Xray will occasionally fail to demonstrate the neoplastic cause of bone pain (especially in the axial skeleton where spine, pelvis, and sacral lesions may be difficult to visualize), it is advisable to obtain the radiograph to avoid the clinical disaster that occurs when patients are referred to physiotherapy for an undiagnosed bone tumor or undergo arthroscopic meniscectomy when the true cause of their knee pain was a bone tumor.
A technetium bone scan can help determine:
- Whether other lesions are present in the skeleton, such as synchronous or metastatic disease from a primary bone tumor, or, more commonly, metastatic bone cancer derived from a primary cancer originating elsewhere.
- Whether chronic pain may be related to occult neoplastic etiology. Small painful lesions such as osteoid osteoma may be difficult to identify in complex anatomical regions such as the spine or the pelvis. Increased uptake on bone scan may direct the clinician to order cross-sectional imaging through the site in search of a small occult lesion.
- Whether widening the clinician's anatomical perspective will change a diagnosis. Patients with sacral chordoma or primary pelvic tumors often present with back and leg pain that is misdiagnosed as sciatica due to a disc lesion when the true diagnosis is sciatica due to extra spinal nerve root irritation. Because these deep seated pelvic lesions are often impossible to detect on physical examination or on plain radiographs, bone scan may be critical to their diagnosis.
Cross-sectional imaging is useful in identification of a soft tissue mass. Both CT and MRI provide good approximation of the extent of the lesion into the soft tissues; however, MRI probably provides better visualization of the intra-osseous extent, as well as a better appreciation of the margin of the soft tissue mass and normal tissue. CT is advantageous in defining areas of cortical destruction and is, therefore, at least as useful as MRI in assessing bone destruction from an aggressive lesion such as a giant cell tumor. Gallium scan is used predominately to evaluate the extent of lymphoma in extra-osseous sites. Finally, chest CT is required to complete staging of a malignant primary bone tumor.
Older patients with bone pain and a probable malignant lesion on conventional radiographs are more likely to have metastatic disease than a primary bone cancer. If the patient is not discovered to have a primary cancer on history and physical examination, the following protocol is useful in attempting to identify the lesion prior to resorting to surgical biopsy:
- A total body bone scan is used to evaluate the extent of skeletal involvement
- CT of the chest is ordered to search for small lung primary tumors
- CT or ultrasound of the abdomen (to search out renal masses)
If the primary lesion is not identified on history, physical examination, or on these radiographic tests, a biopsy is undertaken with extensive use of immunohistochemistry to identify the primary tumor site. In many cases, a primary lesion is never identified and the patient is left with the diagnosis of metastatic carcinoma of unknown primary.
The final step of evaluation of the patient with a painful bone lesion is generally biopsy (unless a primary lesion has been discovered on the radiographic investigations described above). If the lesion is a probable metastasis (based on the patient's age and the presence of multiple lesions on bone scan), biopsy may be performed by the general orthopaedic surgeon. If, however, the painful lesion is a probable primary aggressive or malignant bone tumor, it is prudent to refer the patient to a sub-specialty musculoskeletal oncology unit prior to biopsy. Both the performance of the biopsy and the interpretation of the histological sample require sub-specialty expertise.
Pain is a negative feature when assessing bone tumors. It is important to emphasize the history and physical examination to determine whether the pain is the result of the bone lesion or due to other musculoskeletal etiology with the bone lesion representing an incidental finding. If the pain is the result of the bone lesion, the tumor is likely to be aggressive or malignant.
The Other Presenting Complaints