Abstracts of 2nd Scientific Meeting on Bone Disease in Multiple Myeloma
Imaging of Myeloma Bone Disease
Meletios A. Dimopoulos, MD: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece
Approximately 75% of patients with multiple myeloma have abnormal skeletal radiographs. The most common sites involved include the central skeleton, the skull and the femurs whereas involvement of distal bones is unusual. The most common abnormality consists of lytic lesions, usually as multiple, small, round lucencies. The osteolytic lesions of myeloma are well circumscribed and sclerosis of surrounding bone is usually absent. At autopsy these lesions are due to nodular replacement of marrow and bone by plasma cells. In approximately 15% of patients, generalized osteopenia is the only bone manifestation of myeloma. At autopsy these patients show diffuse replacement of marrow with plasma cells but have less severe bone resorption when compared to lytic lesions.
Technetium-99m is a bone seeking radiopharmaceutical adsorbed onto the hydroxyapatite of bone depending on the degree of osteoblastic activity. In multiple myeloma the osteoblastic response to the bone destruction is negligible. Thus, the uptake of technetium-99m is low and most studies have indicated that the sensitivity for detecting individual lesions with this radiopharmaceutical ranges from 40% to 60%. However, skeletal scintigraphs may be helpful in evaluating areas not well seen on standard radiographs such as the ribs and the sternum.
Unlike plain X-rays, where approximately 25 to 50% of bone trabeculae must be destroyed in order to detect bone destruction, computed tomography can detect small osteolytic lesions This modality can accurately depict the extent of associated soft tissue masses and can direct needle biopsy for histological diagnosis.
Magnetic resonance imaging (MRI) is a noninvasive technique which can sample a large volume of bone marrow. MRI depicts bone marrow abnormalities in multiple myeloma with greater sensitivity than radionuclide bone and marrow scans, conventional radiography and computed tomography. Myelomatous lesions of bone marrow can be classified in three patterns. The focal pattern consists of localized areas of abnormal marrow. On T1-weighted images, focal lesions are darker than yellow marrow and slightly darker or isoientense to red marrow. On T2-weighted images they are brighter than both red and yellow marrow; on enhanced T1-weighted images they enhance to various degrees depending on the vascularity of the underlying pathologic process. STIR and fat-saturation T2-weighted images provide increased contrast between focal lesions and uninvolved marrow. In the diffuse MR pattern of abnormal marrow, the normal bone marrow is completely replaced by malignant cells. The intervertebral discs appear brighter or isointence to the diseased marrow. On T1-weighted images, there is a diffuse decrease in the signal intensity of the marrow. On T2-weighted images a variable increase in the signal intensity of the abnormal marrow is observed. After the administration of intravenous contrast, the abnormal marrow enhances. The intervertebral discs appear darker than the enhanced spine. The variegated pattern consists of innumerable small foci of disease on a background of intact marrow. The small lesions of the variegated pattern are dark on T1-weighted images, bright on T2-weighted images, and they enhance after the administration of intravenous contrast.
MR imaging studies have been performed in several patients with monoclonal gammopathy of undertermined significance (MGUS). Such patients usually have normal MR studies. We believe that whenever a patient with a presumed MGUS has abnormal marrow findings on MRI, he should be considered to have asymptomatic myeloma.
Approximately 2% of patients with myeloma have a solitary bone plasmacytoma (SBP) without evidence of clonal plasma cells at other sites. MR imaging should be part of the staging procedures of patients with SBP, to better assess the extent of the local tumor for definition of radiation portals and to rule out occult lesions elsewhere. Coronal images of the central skeleton may increase the detection of unsuspected lesions.
Approximately 15% of patients who have low tumor mass multiple myeloma are free of symptoms at the time of diagnosis. Patients with asymptomatic myeloma should be followed without treatment until there is evidence of disease progression. Several series have included MR studies of such patients. An abnormal MRI has been noted in 30% to 50% of patients and this abnormality was associated with earlier progression to symptomatic myeloma.
Most patients with multiple myeloma requiring treatment have abnormal MRI studies. Patients with normal or focal patterns tend to have lower tumor burden than those with focal or diffuse marrow involvement. Patients with normal pattern respond better to treatment and survive longer than patients with an abnormal pattern.
Development of vertebral compression fractures in multiple myeloma may be caused by substitution of normal bone substrate by a growing tumor mass and/or by osteoclastic bone resorption related to the increased production of various osteoclast activating factors. Although several criteria have been proposed for the differential diagnosis of benign and malignant vertebral compressions, these should be applied with caution to patients with multiple myeloma: normal signal intensity within a compressed vertebral body on spinal MR images does not preclude the diagnosis of multiple myeloma. In patients with osteoporotic or posttraumatic vertebral compression of recent onset, MR imaging will usually show inhomogeneous signal alteration that parallels one of the end-plates, involves less than half of the vertebral body, does not extend to the pedicles, and enhances homogeneously after the administration of paramagnetic contrast intravenously. Diffusion-weighted MR imaging has been recently applied to the differential diagnosis of compression fractures with promising results.
MR imaging can be used to assess the effect of treatment. Changes of abnormal marrow after successful treatment differ for each MR pattern. MR patterns of complete response included complete resolution of marrow abnormality, persistent abnormality without enhacement or with peripheral rim enhacement only. Conversion of a diffuse to a variegated or focal MR pattern and a decrease in the extent of marrow abnormality with persistent homogeneous enhacement may be observed. Post treatment MR imaging of the bone marrow may provide important information for patients with equivocal clinical and laboratory results as well as for patients with nonsecretory myeloma. It appears that the survival of patients who achieved complete response by MR criteria (MR-CR) after high date therapy is significantly longer than the survival of patients who do not achieve MR-CR. We believe that a true complete response should require resolution of MR abnormalities in addition to disappearance of myeloma protein and normal marrow.