Bone tumors may be benign or malignant. Malignant tumors may be primary or metastatic.
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 about 100 times more common than primary malignant tumors. Excluding marrow cell tumors (eg, multiple myeloma), there are only about 3900 cases of primary malignant bone tumors in the US each year among children and adults (1).
Synovial tumors are extremely rare in both children and adults. Tenosynovial giant cell tumors (pigmented villonodular synovitis [PVNS]) are benign but at times contain destructive synovial cells. Synovial sarcoma is a malignant soft tissue tumor that arises in different types of soft tissue but is not of synovial origin and seldom occurs inside of a joint. It is a monomorphic blue spindle cell soft tissue cancer with variable degree of epithelial differentiation characterized by the specific SS18-SSX/1/2/4 fusion gene but is often biphasic with both spindle cell and glandular–like components.
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. The American Cancer Society: Cancer Facts & Figures 2022
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 without weight bearing (pain at rest), particularly at night. Some tumors (eg, leukemia, lymphoma, Ewing sarcoma) can cause fever and/or other constitutional symptoms.
Diagnosis of Bone and Joint Tumors
Plain x-rays
MRI, usually initially without and then with contrast, and sometimes CT
Whole-body bone scan or whole-body PET-CT (positron emission tomography combined with CT) if multicentric or metastatic tumors are suspected
Biopsy unless imaging studies clearly show benign characteristics 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. Some pelvic bone tumors can cause pelvic or proximal buttock pain, mimic sciatica or, rarely, cause true sciatica by compressing the sciatic nerve.
Plain x-rays are the first test to identify and characterize a bone tumor. Lesions suggestive of tumors, including those found incidentally on x-rays done for other reasons, usually require further assessment, often with additional imaging studies (eg, CT or MRI) and a biopsy. However, tumors with x-ray findings classic for benign lesions do not require bone scan, CT, or MRI unless the patient has pain in the region of the lesion.
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, especially if multicentric or metastatic tumors are suspected. 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.
There are times where gadolinium contrasted MRI is necessary and other times where contrast is not necessary. 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 should make the final decision whether a contrasted MRI should follow the noncontrasted MRI study and what additional MRI sequences are needed.
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 suggest cancer include the following:
A lytic, destructive lesion
Ill-defined, permeative appearance of bone loss
Irregular tumor borders
Loculated areas of bone destruction (moth-eaten appearance)
Cortical destruction
Soft tissue extension
Pathologic fracture
A lytic appearance is characterized by areas of bone destruction that are sharply demarcated. A permeative appearance is characterized by a faint, gradual loss of bone or an infiltrating pattern without clear borders. Certain tumors have a characteristic appearance. For example, Ewing sarcoma typically shows permeative-type bone destruction, including a large soft tissue mass with aggressive periosteal onion-skin reactive bone often before there is an extensive, lytic, destructive appearance, and a giant cell tumor has a cystic 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 shaft of a long bone, osteosarcoma usually appears in the metaphyseal-diaphyseal region toward the end of a long bone, and a giant cell tumor usually occurs in the epiphysis.
Bone marrow affected by childhood leukemia and lymphomas sometimes causes abnormalities on bone x-rays. In adults, metastatic lung, breast, prostate, and renal cancer may manifest with multiple bony lesions.
Some benign conditions, however, 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 x-ray. 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.
Bone infection can manifest with pain and a destructive lesion on x-rays.
Other testing
The primary cancer location can be identified over 85% of the time with a quality history and physical examination, CT of the chest/abdomen/pelvis, mammography in females, and prostate-specific antigen (PSA) in males. CT and MRI may help define the location and extent of a bone tumor and sometimes suggest a specific diagnosis. MRI is usually done if cancer is suspected. If tumors are suspected of being metastatic or involving multiple foci (multicentric), then radioisotopic technetium-99m whole-body bone scanning should be done to search for additional tumors. Positron emission tomography (PET) imaging may be done, often combined with CT (PET-CT). For possibly metastatic tumors, mammography in females and PSA in males may help identify the primary cancer.
Biopsy is usually essential for diagnosis of malignant tumors, unless the imaging studies have a classically benign appearance. 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 needed 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. Diagnostic and surgical errors occur more frequently in hospitals that infrequently encounter patients with malignant primary bone tumors.
Key Points
In children, most bone tumors are primary and benign, some are primary and malignant, and very few are metastatic.
In adults, especially those age > 40, metastatic tumors (eg, from breast, lung, prostate, or renal cancer) are about 100 times more common than primary malignant bone tumors.
Assessment begins with plain x-rays but typically requires MRI and often other studies.
General radiographic findings suggesting cancer include a destructive appearance (particularly with multiple foci), irregular 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.
