The Patient with a Tumor or a Tumor-Like Lesion of Bone

Prevalence and Epidemiology

Prevalence and epidemiologic data, such as location and age of the patient, are important parameters in the analysis of a patient presenting with a possible osseous tumor (see Table 90-2 ). However, specific tumors do occur outside of their preferred locations, or age ranges. Although primary osseous neoplasm is rare in the general population, the incidence is significant in subpopulations. The incidence of primary osseous benign and malignant neoplasm is 2 to 3 cases per 100,000 population per year. The incidence of lung cancer and breast cancer are approximately 60 times higher than that of bone sarcoma. Bone sarcoma comprises only approximately 0.3% of newly diagnosed malignancies. Malignant primary bone tumors occur mainly in children and adolescents and have an annual incidence of 5 to 6 cases per 100,000 population of children younger than 15 years of age. Malignant lymphoma, including the more common extraskeletal lymphoma, is the most common, and bone sarcoma is the second most common solid malignant neoplasm in adolescence.

Myeloma, by far, is the most frequent osseous malignancy in adults, accounting for 45% of all malignant osseous tumors. Lymphoma is the other nonsarcomatous malignancy found in bone, accounting for 8% of malignant osseous tumors. These entities are discussed respectively in Chapters 92 and 93 . The most frequently encountered sarcomas, benign osseous tumors, and tumor-like osseous lesions are listed in Table 90-3 . Many benign lesions that are frequently asymptomatic, such as nonossifying fibroma, hemangioma, enchondroma, and fibrous dysplasia, are underreported and, therefore, much more frequently encountered as an incidental finding.

Many lesions present within a specific age range, and, therefore, age is an important parameter to consider when a lesion that may be a primary bone tumor is analyzed. Myeloma and metastases are much more frequent than primary bone sarcoma when a patient is older than 40 years of age. Multiple osseous lesions are frequently found in young children with neuroblastoma (see Chapter 97 ). Bone sarcoma and benign osseous tumors typically present in the second decade of life. There is a second smaller peak late in the sixth decade. Age distribution of the more common lesions is presented in Tables 90-4 and 90-5 .

In the next step of the analysis, the location within the body is considered. As shown in Table 90-6 , some tumors have a preference for certain locations within the body. Based on frequency distribution only, a tumorous lesion in the hand, and more specifically in the phalanges, is almost always an enchondroma because of the preference for this location in combination with the relatively high prevalence of enchondroma, in general. Adamantinoma is almost exclusively found in the tibia. However, a tumor in the tibia is more likely to be an osteosarcoma or nonossifying fibroma than adamantinoma, based on frequency distribution only. The reason is that osteosarcoma and, especially, nonossifying fibroma are relatively common and have a much higher prevalence than the extremely rare adamantinoma. Relatively common lesions are found much more frequently in aspecific or even uncommon locations than rare lesions are found in their preferential locations.

In the final step of analyzing epidemiologic data, one needs to determine whether the lesion is solitary or multifocal. This may be apparent from the beginning, for instance, when multiple lesions are seen on bone scintigraphy, on large field-of-view MRI, or on radiographs taken from symptomatic parts of the skeleton. It may also be necessary to start a search for other lesions using MRI, bone scintigraphy, or PET. The most important lesions that are typically, but not always, multifocal are myeloma and metastasis. If these are combined with age, it is fairly straightforward to suggest a differential diagnosis, without even analyzing the images, of myeloma or metastasis in a patient older than 40 years of age with multiple osseous lesions. Other lesions that may be multifocal are listed in Tables 90-7 and 90-8 .

Although some tumors have a higher incidence in males, gender does not play a critical role in diagnosing bone tumors. There are some exceptions to this. Multiple myeloma and osteoid osteoma occur two to three times more frequently in males than in females. Examples of conditions that occur slightly more often in females than in males are hemangioma and giant cell tumor.

Clinical Presentation

Radiographs, displaying findings that may reflect the presence of a tumor, are typically made because of local clinical symptoms, such as pain, dysfunction, and/or swelling. These clinical signs may be misleading in children because of referred pain. For instance, the patient may present with pain in the knee with or without a limp (dysfunction) secondary to a lesion in the hip region. The radiographic finding of a tumor may also be incidental or not related to the patient's symptoms.

Pain and/or local swelling are the most common, although nonspecific symptoms. Typically, pain has been present for several weeks or months. The onset is often gradual, and the patient may not recall when the pain started. Sudden onset of pain without adequate trauma occurs in pathologic fractures. In malignant tumors, pain may be rapidly progressive and may also be aggravating. When the tumor or tumor-like lesion is not fractured, pain is not related to physical activity and may be continuous or intermittent. Pain may be worse during the night. This is typically seen in osteoid osteoma in combination with good response to treatment with salicylates. When the tumor is located close to a joint or when it is extending into a joint, the symptoms may erroneously be attributed to joint disease. Posttraumatic sequelae in and around joints are clearly much more frequently encountered in this young age group. This may even tempt the clinician to choose arthroscopy rather than radiography as a first diagnostic test, for instance, when reactive synovitis is found at the clinical examination.

Fever and general malaise may be present in high-grade malignancies, especially in Ewing sarcoma. Because Ewing sarcoma may look radiographically like osteomyelitis, it is important to realize that, also clinically, the differentiation between infection and high-grade sarcoma may be challenging ( eFig. 90-9 ). Temperature, sedimentation rate, and blood cultures may be normal in patients with osteomyelitis and, with the exception of blood cultures, may be abnormal in patients with Ewing sarcoma.

During a physical examination, the soft tissue swelling is typically firm; it may be warm, but there is no discoloration of the skin. Specific skin abnormalities are seen during inspection in various syndromes, such as neurofibromatosis. Dysfunction of joints or muscles may be observed.

Pathophysiology

Imaging techniques may visualize the tumor, the host's response to the tumor, or both. Radiographs typically visualize the host's response. Parts of the tumor are only directly depicted using radiographs when there are calcifications within the tumor (e.g., in cartilaginous tumors), when tumor matrix is ossified (e.g., in osteosarcoma), or when there is a substantial soft tissue extension. Often more evident is the host's response, including osteoclast activity (osteolysis), osteoblast activity (sclerosis), and periosteal reaction. Of these, osteolysis is the hardest to detect, especially in the diaphysis where there is a paucity of trabecular bone. Osteolysis becomes visible only when there is marked destruction of cortical bone and/or when more than 40% to 50% of trabecular bone is destroyed. There is a complex and only partially understood interaction between tumor and host, using multiple signaling pathways, that initiates and maintains this dynamic process. The ensuing growth rate of the tumor has an important impact on the radiographic appearance (see the discussion on disease manifestations).

In addition to these radiographically detectable reactions, angiogenesis is an important part of this interaction between tumor and host that can be visualized using only MRI, ultrasonography, and early-phase bone scintigraphy.

Altered hemodynamics in the vicinity of the tumor and even in large parts of the affected extremity, cause increased tracer uptake, seen on ^99m Tc bone scintigraphy. Early cellular proliferation in the cambium layer of the periosteum that is not yet ossified can be observed on MRI and not on radiographs ( eFig. 90-10 ). Inflammatory response and edema surrounding the tumor may be best seen on MRI, but the intraosseous component of this may be seen as rarefaction on radiographs. Periosteal reaction and inflammatory reaction are usually found close to the tumor but may be quite extensive, resulting in periosteal reaction seen away from the tumor, for instance, in chondroblastoma. Extensive inflammatory reaction, as seen in osteoid osteoma and Langerhans cell histiocytosis, may even obscure the original lesion.

Imaging Techniques

Clinical findings and symptoms or a finding on another imaging study such as ^99m Tc bone scintigraphy or MRI are reasons to take radiographs. Good quality radiographs taken in two orthogonal directions, with important exceptions ( eTable 90-1 ), can be used to confidently diagnose or exclude the presence of a tumor. Sometimes, the cause of symptoms is not identified on radiographs also, when symptoms are secondary to pathology other than bone tumor, such as early osteomyelitis, intraarticular lesions, or soft tissue tumor.

The main reason to perform MRI in osseous lesions is local staging and monitoring of chemotherapy. In addition, dynamic gadolinium-chelate-enhanced MR can be used to differentiate benign from malignant cartilaginous tumors and to localize recurrent disease. Dynamic MR is a controversial topic because of mainly two reasons. First is improper indications. Dynamic MR is useful in monitoring chemotherapy, in assisting to differentiate between benign and malignant soft tissue tumors, and in differentiating between benign and malignant cartilaginous tumors. In general, it cannot be used to differentiate between benign and malignant osseous tumors. The second issue is improper technique. The temporal resolution should be at least 3 seconds. If the time interval between images acquired exceeds the 3-second margin, the parameter becomes useless. This is explained in the two- or three-compartment pharmacokinetic modeling described by Tofts.