Bone tumors may be benign or malignant. Malignant tumors may be primary (start in the bone) or metastatic (spread to the bone).
In children, most bone tumors are primary and benign; some are malignant primary tumors (eg, osteosarcoma, Ewing sarcoma). Very few are metastatic tumors (eg, neuroblastoma, Wilms tumor). Bone marrow also can be affected by childhood leukemia and lymphomas and can cause abnormal radiographs.
In adults, especially those over age 40, metastatic tumors are far more common than primary malignant tumors. Excluding marrow cell tumors (eg, multiple myeloma), there are estimated to be only about 3900 cases of primary malignant bone tumors in the United States each year among children and adults (1).
Joint tumors, or tumors of the synovial space, are extremely rare in both children and adults. Tenosynovial giant cell tumor (formerly known as pigmented villonodular synovitis [PVNS]) is benign but can be locally destructive to native cartilage. Synovial sarcoma is a malignant soft tissue tumor (sarcoma) that arises in different types of soft tissue but is not of synovial origin and seldom occurs inside of a joint.
Multiple myeloma is often considered a marrow cell tumor within the bone rather than a primary malignant bone tumor because it is of hematopoietic derivation (see also Multiple Myeloma).
Reference
1. American Cancer Society: Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2025.
Symptoms and Signs of Bone and Joint Tumors
Bone tumors typically cause unexplained, progressive pain and swelling. Pain can occur with the mechanical stress of weight bearing or pain at rest due to local bone destruction, particularly at night. Some tumors (eg, leukemia, lymphoma, Ewing sarcoma) can cause fever and/or other constitutional symptoms.
Diagnosis of Bone and Joint Tumors
Radiographs
Magnetic resonance imaging (MRI), with and without contrast, and/or computed tomography (CT)
Whole-body nuclear medicine bone scan or whole-body PET-CT (positron emission tomography combined with CT) if multicentric or metastatic tumors are suspected
Biopsy unless imaging studies are diagnostic of a benign entity or if there are multiple bony lesions consistent with metastatic disease in a patient with a confirmed active primary cancer
The most common reason that diagnosis of bone tumors is delayed is that physicians fail to suspect the tumor and order appropriate imaging studies. Bone tumors should be considered in patients who have unexplained bone pain, particularly pain at night or at rest. Persistent or progressive unexplained pain of the trunk or extremities, particularly if associated with a mass, is suggestive of a bone tumor. A patient who has been appropriately treated for some presumed injury or arthritic/inflammatory condition without symptomatic improvement should be considered for further evaluation. Some pelvic bone tumors can cause pelvic or proximal buttock pain, mimic sciatica or, rarely, cause true sciatica by compressing the sciatic nerve.
Radiographs are the first test to identify and characterize a bone tumor. Lesions suggestive of tumors, including those found incidentally on radiographs done for other reasons, usually require further assessment, often with additional cross-sectional imaging studies (eg, CT or MRI) and a biopsy. However, tumors with radiographic findings classic for benign lesions (eg, osteochondroma, enchondroma) do not require further evaluation unless the patient has pain in the region of the lesion that cannot be explained by any other process.
Magnetic resonance imaging (MRI) is the typical advanced imaging modality preferred in the extremities for its ability to demonstrate anatomic detail regarding soft tissue involvement, as well as bone marrow replacement. There are times where gadolinium-contrasted MRI is beneficial. In general, contrast should be ordered when malignancy is on the differential diagnosis. Contrast is not necessary for evaluating lipomas or other known or highly suspected benign lesions. Adequacy of renal function should be documented before adding MRI contrast, because there may be renal toxicity in patients with reduced renal capacity. The MRI radiologist can aid in the final decision whether a contrasted MRI should follow the noncontrasted MRI study and what additional MRI sequences are needed.
Computed tomography (CT) is another cross-sectional imaging modality that shows bone detail to a far higher degree in comparison to MRI. CT is often useful for determining the extent of any cortical destruction when determining fracture risk, or in assessing whether an unknown lesion possesses any calcifications to suggest a chondroid neoplasm. Lastly, CT is often used to assess a tumor when MRI may be contraindicated (eg, pacemaker or cochlear implant).
Whole-body bone scan in general, rather than just a scan of a selected area, should be done routinely to identify other areas of abnormality in the setting of a multicentric or metastatic tumor. Whole-body scan is usually preferred to ensure that other skeletal lesions are identified, particularly because the patient has already received the full dose of radionuclide, and the whole-body component only requires limited additional time. Whole-body PET-CT is an alternative to whole-body bone scan.
Pearls & Pitfalls
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Characteristic findings
Some tumors (eg, nonossifying fibroma, fibrous dysplasia, enchondromas) and tumor-like conditions (eg, Paget disease of bone) may have characteristic radiographic findings and can be diagnosed without biopsy.
Radiographic findings that may be more suggestive of a malignancy include:
An osteolytic, destructive lesion
Ill-defined, permeative or moth-eaten appearance of bone loss
Cortical destruction
Soft tissue extension
Pathologic fracture
A geographic appearance is characterized by an area of bone destruction that is sharply demarcated. A permeative appearance is characterized by a faint, gradual loss of bone or an infiltrating pattern without clear borders (ie, poor demarcation between the tumor and normal bone). A "moth-eaten" appearance is similar but has generally larger foci of destruction at the margin. Certain tumors have a characteristic appearance. For example, Ewing sarcoma typically shows bone destruction with a large soft tissue mass with an aggressive onion-skin periosteal reaction. On the other hand, a giant cell tumor has a very geographic destructive appearance without a sclerotic interface between the tumor and normal bone.
The tumor’s location may also suggest a diagnosis. For example, Ewing sarcoma commonly appears in the diaphysis (eg, shaft) of a long bone, osteosarcoma usually appears in the metaphyseal region toward the end of a long bone, and a giant cell tumor usually occurs in the epiphysis. It is common for tumors to extend out of one of these segments and involve more than one.
Bone marrow affected by childhood leukemia and lymphomas can also cause abnormalities on radiographs. In adults, metastatic carcinomas manifest with multiple bony lesions, along with multiple myeloma and lymphoma. The most common primary malignancies to metastasize to bone are breast, prostate, lung, renal, thyroid and gastrointestinal. However, all cancers are capable of doing so.
Some benign conditions can mimic a malignant tumor:
Heterotopic ossification (myositis ossificans) and exuberant callus formation after fracture can cause mineralization around bony cortices and in adjacent soft tissues, mimicking malignant tumors.
Langerhans cell histiocytosis (histiocytosis X, Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma) can cause solitary or multiple bone lesions that are usually distinguishable on radiograph. In solitary lesions, there may be periosteal new bone formation, suggesting a malignant bone tumor.
Osteopoikilosis (spotted bones, multiple bone islands) is an asymptomatic condition of no clinical consequence but can mimic osteoblastic bone metastases of breast or prostate cancer. It is characterized by multiple small, round, or oval foci of bony sclerosis, usually in the tarsal, carpal, or pelvic bones or the metaphyseal-epiphyseal regions of tubular bones.
Osteomyelitis (bone infection) can manifest with pain and a destructive lesion on radiographs.
Other testing
In patients who are older than 40, a destructive bone lesion is most often related to a diagnosis of metastatic carcinoma. When this is suspected and the patient has no known cancer diagnosis, it is referred to as a metastatic lesion of unknown origin. The primary cancer location can be identified over 85% of the time by history and physical examination, CT of the chest/abdomen/pelvis, whole body bone scan, and laboratory evaluation including prostate-specific antigen (PSA) in males (1). CT and MRI may help define the location and extent of a bone tumor and sometimes suggest a specific diagnosis. MRI is usually done in order to properly stage the local extent of the malignancy and also to plan surgical resection, if indicated. Positron emission tomography (PET) imaging often combined with CT (PET-CT) may also provide benefit for helping to identify a tumor site when the primary is still not found after the aforementioned extensive evaluation (2). However, as the yield is imperfect, it is still recommended that this approach be completed after performing mammography in females, head/neck exam, and consideration of upper and lower endoscopy to identify a primary source.
Biopsy is usually essential for diagnosis of malignant tumors. The pathologist should be given pertinent details of the clinical history and should review imaging studies. Histopathologic diagnosis may be difficult and requires sufficient viable tissue from a representative portion of the tumor (usually the soft portion). The best results are obtained in centers with extensive experience in bone biopsies. Prompt, accurate, definitive diagnosis is possible in > 90% of cases. Special immunohistologic staining and sometimes cytogenetic studies facilitate accurate diagnosis.
Biopsy may be needed to confirm the diagnosis of suspected metastatic disease in an isolated, single lesion. However, biopsy may not be necessary if there are multiple metastatic lesions in a patient with a confirmed active primary cancer.
If a malignant diagnosis is suspected on frozen section histology, often the surgeon will wait for the results of permanent histology before treating definitively unless the pathologist is able to definitively state this appears to be a carcinoma. Diagnostic and surgical errors occur more frequently in hospitals that infrequently encounter patients with malignant primary bone tumors.
Diagnosis references
1. Rougraff BT, Kneisl JS, Simon MA. Skeletal metastases of unknown origin. A prospective study of a diagnostic strategy. J Bone Joint Surg Am. 1993;75(9):1276-1281. doi:10.2106/00004623-199309000-00003
2. Lawrenz JM, Gordon J, George J, et al. Does PET/CT Aid in Detecting Primary Carcinoma in Patients with Skeletal Metastases of Unknown Primary?. Clin Orthop Relat Res. 2020;478(11):2451-2457. doi:10.1097/CORR.0000000000001241
Key Points
In children, most bone tumors are benign, some are malignant, and very few are metastatic.
In adults, especially those age > 40, metastatic tumors are far more common than primary malignant bone tumors.
Assessment begins with history, physical examination, and radiographs but typically requires laboratory evaluation and advanced imaging.
General radiographic findings suggesting cancer include a destructive appearance, ill-defined borders, cortical destruction, soft tissue extension, and pathologic fracture.
Biopsy is required for diagnosis of malignant tumors, which should be suspected in patients with unexplained persistent bone pain.
