Bone Imaging

 

Accurate diagnosis of bone tumors requires a multimodality approach with clinical-radiologic-pathologic correlation. Appropriate diagnostic and staging evaluation should be performed before biopsy, as careful imaging and review of blood chemistry results may eliminate the need for a biopsy. Plain radiographs in two orthogonal views (anteroposterior and lateral) can help determine tumor morphology; patterns of bone destruction (i.e., lytic, blastic, mixed, moth-eaten, or permeated); lesion margins (i.e., from well-delineated sclerotic rim to ill-defined margin) and internal characteristics (i.e., nonmatrix-producing tumors, nonmineralized matrix-producing tumors, and mineralized matrix-producing tumors); type of host bone response (i.e., medullary, periosteal, or none); the location (i.e., femur, tibia, humerus, or others), site (i.e., metaphysis, diaphysis, or epiphysis), and position (i.e., central, eccentric, or periosteal) of the lesion in the skeletal system and in the individual bone; soft tissue involvement; and number of lesions. Plain radiographs also can help identify radiation-induced bone changes such as osteoradionecrosis (with its characteristically ill-defined cortical destruction) and avascular necrosis.

 

Computed tomography (CT) and magnetic resonance imaging (MRI) are useful for determining the extent of bone tumors. CT is particularly useful for the assessment of cortical invasion, periosteal reaction, soft tissue or lesion matrix calcification or ossification, and fracture fragment positioning or configuration, especially in complex anatomic sites such as the spine, pelvis, and hindfoot. Because bony anatomy is well defined on CT, CT scans can provide useful information regarding the best site for biopsy, such as in areas of cortical thinning. MRI can visualize the intraosseous extent of the lesion and the presence and dimensions of soft tissue masses. MRI is also useful for assessing the response of primary bone tumors to systemic treatment and for follow-up after surgical treatment.

Because bone scintigraphy visualizes local osteoblastic activity, it is useful for assessing the entire skeleton for the presence of metastases. However, not all lesions are “hot” (i.e., detectable on bone scans); one example is skeletal lesions from multiple myeloma, which should be evaluated by skeletal survey (whole-body radiography) rather thanbone scanning. Bone scintigraphy is also useful for documenting the presence or extent of the osteoblastic response necessary for the concentration of therapeutic radionuclides such as 89Sr or samarium 153 (153Sm)–lexidronam. Gallium scans are useful for evaluating primary and metastatic lesions of malignant fibrous histiocytoma when the tumor invades the skeletal system.

 

Another technique that has become widely available in recent years is18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which has also assumed an important role in oncologic evaluations. FDG-PET can be quite effective for diagnosing osseous metastases.Fujimoto and others retrospectively compared the diagnostic accuracy of PET with that of conventional bone scintigraphy for the diagnosis of bone metastases in 95 consecutive patients with a variety of types of cancer. In that study, findings from “whole-body” PET scans (from face to upper thigh) were compared with those from standard whole-body scintigraphic scans obtained within a month of one another. The diagnostic accuracy was comparable for both techniques, but PET had the advantage of being able to visualize the response ofbone lesions to treatment and the presence of soft tissue metastases. The limited field of view used for PET in this study precluded detection of solitary bone metastases in the skull or below the femoral diaphysis.

 

Cells to be used for transplantation can be obtained in one of two ways. In the traditional bone marrow harvest, the patient is anesthetized, and multiple marrow samples are collected by needle aspiration from the iliac crest or occasionally from the sternum. In the more common procedure, donors are given cytokines, with or without chemotherapy, to stimulate the production and release of stem cells from the marrow into the peripheral blood (i.e., stem cell mobilization). Stem cells are then removed from the peripheral blood by apheresis, and the remaining blood is returned to the donor.

The relationship of the donor to the recipient defines the type of marrow or stem cell transplant: autologous, syngeneic, or allogeneic. Each type is described briefly in the following paragraphs.

 

Types of Transplants

Autologous Transplants

In autologous transplants, the donor is also the recipient. In this procedure, stem cells are harvested from the patient and frozen, after which the patient undergoes a conditioning regimen involving ablative chemotherapy with or without irradiation. After the conditioning regimen has been completed, the frozen stem cells are thawed and reinfused. If the stem cells are thought to be contaminated by malignant cells, they may be purged before being reinfused. This process involves exposing the isolated stem cells to agents such as monoclonal antibodies in an attempt to remove any neoplastic cells.

 

Syngeneic Transplants

Syngeneic transplantation takes place between genetically identical twins. Some of the first successful transplants in humans were syngeneic. This type of transplant is rarely used because few patients have genetically identical twins.

 

Allogeneic Transplants

Allogeneic marrow or stem cell transplantation takes place between two nonidentical individuals of the same species (e.g., two humans) and can be subdivided into two broad categories: related and unrelated. Related allogeneic bone marrow transplantation occurs between two genetically related individuals. These transplants are further categorized according to the degree of human leukocyte antigen (HLA) matching. A completely matched donor and recipient transplant occurs between HLA-identical siblings, whereas a mismatched related transplant occurs between relatives who match at only three, four, or five of the six major HLA loci. The donor can be a parent, aunt, cousin, or other relatives having the appropriate HLA type.

Unrelated allogeneic marrow or stem cell transplantation takes place between two genetically unrelated people. Success with this type of transplant requires that the donor and recipient share most, if not all, of the six major HLA loci.

 

 

Uses of Marrow or Stem CellTransplantation

The use of marrow or stem cell transplantation has been increasing over time (Fig. 38-3) as success rates continue to improve, especially for leukemias and lymphomas. Most marrow or stem cell transplantations have been performed in patients with leukemia. Initially, transplantation was considered only for acute leukemias in refractory phases or after multiple relapses, but currently, many patients with high-risk acute leukemias are referred for transplantation during their first remission. Patients include children with Philadelphia chromosome–positive acute lymphocytic leukemia and adults with acute leukemia with high-risk features.

 

FIGURE38-3 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Numbers of patients undergoing allogeneic and autologous blood and marrow transplantation worldwide, 1970 to 1998. 

 

Patients with chronic leukemia did not routinely undergo transplantation in the early years because the natural history of the disease allowed many patients to live for years before succumbing to the disease. However, as bone marrow transplantation became safer, it was considered and used successfully for patients with chronic leukemias (especially chronic granulocytic leukemia). Currently, adult patients with chronic myelogenous leukemia routinely undergo transplantation while they are in early chronic-phase disease if an appropriate donor can be found.

Lymphomas make up the other major disease category for which transplantation is performed. Hodgkin and non-Hodgkin lymphomas have been successfully treated with autologous, syngeneic, or allogeneic bone marrow transplantation. Most patients with lymphomas are treated with standard chemotherapy or radiation, or both, and they are considered for marrow or stem cell transplantation only if the disease proves refractory to these therapies. Experimentally, peripheral blood stem cell infusions may be used to enhance marrow recovery after intensive chemotherapy. Some reports suggest that autologous marrow or stem cell transplantation can be appropriate front-line therapy for patients with certain aggressive lymphomas.

Bone marrow transplantation is used for noncancerous but otherwise fatal conditions, such as severe aplastic anemia and some congenital immunodeficiency disorders, and for some solid tumors. The most successful transplantations for treating solid tumors have been done for children with neuroblastoma or Ewing’s sarcoma.Transplantations for solid tumors in adults, especially autologous transplants for breast cancer, have been studied extensively but remain controversial.