Imaging of Multiple Myeloma: Usefulness of MRI and PET/CT

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Multiple myeloma is a heterogeneous hematologic disorder of plasma cells with varied bone marrow imaging appearances. With advancements in both treatment and use of advanced imaging over the last several decades, it is important for radiologists to recognize the imaging presentation of the disease and the staging implications of imaging. This paper reviews the staging as it relates to imaging, consensus recommendations for imaging, expected imaging appearances of myeloma, pitfalls, and complications associated with treatment that are demonstrable on imaging.

Introduction

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells. It is commonly associated with monoclonal protein, immunodeficiency, renal insufficiency, and osteolytic bone lesions.1, 2 The radiographic bone survey (RBS) for osteolytic lesions has long been considered the imaging gold standard, which contributes to the staging of multiple myeloma.3 With the knowledge that at least 30% of trabecular bone must be lost before an osteolytic lesion is readily visualized,4 it becomes apparent that a significant number of osteolytic lesions may be radiographically occult and may lead to the incorrect diagnosis of solitary plasmacytoma, monoclonal gammopathy of unknown significance (MGUS), or smoldering multiple myeloma (SMM, also called asymptomatic myeloma), all conditions with different treatment algorithms and clinical courses compared to symptomatic multiple myeloma.5, 6, 7, 8 Advanced imaging techniques like fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) are increasingly used for the initial diagnosis and staging of multiple myeloma.

In addition, there have been great advances in the treatment of multiple myeloma over the past 2 decades, which originated with the use of prednisone and melphalan.1 With the advent of new chemotherapeutic agents, including lenalidomide and bortezomib, and the use of autologous stem cell transplantation, the median survival has increased from 3-4 years to 5-7 years.9 Imaging plays an important role in staging and can play a role in the monitoring of disease progression, disease complications, and treatment response. While the skeletal survey is useful for initial staging, most osteolytic lesions would never heal, limiting the usefulness of conventional radiography for long-term monitoring.6 Additionally, the osteolytic lesions of multiple myeloma demonstrate increased osteoclast activity with decreased osteoblast activity, resulting in a low sensitivity of bone scan for detecting myeloma.6, 10 Owing to these limitations, the advanced imaging techniques of MRI and FDG-PET/CT are playing an increasingly important role in disease monitoring.

This article reviews disease epidemiology, diagnostic criteria, clinical manifestations, staging, treatment, and imaging of multiple myeloma with an emphasis on the role of advanced imaging techniques including MRI and FDG-PET/CT. Pretreatment and posttreatment imaging features are described and illustrated in the diagnosis and monitoring of multiple myeloma.

Section snippets

Epidemiology

Multiple myeloma is the most common primary malignancy of bone and accounts for approximately 10%-15% of hematologic malignancies.1, 11, 12 Worldwide, as of 2002, multiple myeloma accounted for 0.8% of all cancer diagnosis and 0.9% of cancer deaths.13

In the United States, from 2005-2009, the incidence of multiple myeloma was 7.4 per 100,000 men and 4.7 per 100,000 women.14 Between 1975 and 2009, there has been approximately a 1.2% increase in the disease incidence. In 2012, it is estimated that

Consensus Recommendations for Imaging in Plasma Cell Disorders

The most recent consensus recommendations for the treatment of multiple myeloma have been published in 2011 with a more thorough statement published in 2009.6, 19 We focus on the imaging findings in myeloma and treatment of myeloma. However, keep in mind that recommendations are changing in the laboratory side of managing plasma cell disorders. Specifically, a relatively new laboratory test, serum free light chain assay, if positive, demonstrates a higher risk of progression in patients with

Radiographic Bone Survey

RBS continues to be the mainstay of initial evaluation by imaging.19 Radiologic evidence of skeletal involvement can be detected in almost 80% of patients on skeletal survey, and there is a clear association between the extent of disease, in terms of number of lytic lesions seen at presentation and tumor burden at diagnosis.21 RBS should be performed in all newly diagnosed patients with a plasma cell disorder, unless cross-sectional imaging obviates its usefulness.19 This should include

Monitoring Response to Therapy

Based on currently available literature, imaging is not considered an important component in the assessment of disease response. The most recent document of uniform response criteria in myeloma utilizes laboratory parameters for the assessment of response and incorporates new lytic lesions as indicative of progression of disease.60 Nevertheless, a discussion of studies that have utilized imaging in the monitoring of disease progression is warranted.

Staging of Myeloma

The criteria for the diagnosis of multiple myeloma is based on paraprotein in serum or urine or both, the percentage of monoclonal plasma cells in bone marrow, and end-organ damage as evidenced by hypercalcemia, renal insufficiency, anemia, or lytic bone lesions.2, 6 An important distinction is made between several forms of plasma cell dyscrasia because of differences in prognosis and treatments (Table 1). MGUS is characterized by lower monoclonal plasma cells in a nonselective iliac crest

Recent Advances and Developing Trends

Both treatment and imaging utilization continue to evolve. Over the last 15 years, treatment of myeloma has evolved to more frequent use of novel therapies, such as lenalidomide and bortezomib.67 In the near future, antibody therapy may remove some or all of the osteoblastic inhibition induced by myeloma, which potentially could result in osteoblastic healing of lesions.68

In regard to imaging, new uses for FDG-PET/CT have been tested and novel tracers have been investigated. Mulligan et al.69

Treatment-Related Findings and Pitfalls

Imaging findings in patients with myeloma may be the direct result of pharmacologic, surgical, or radiation treatment. Treatment-related imaging findings include avascular necrosis (AVN; which can occur in the femoral or humeral heads), compression fractures, fatty marrow infiltration due to radiation therapy, osteonecrosis, infection, vertebroplasty, and potentially bisphosphonate-related jaw osteonecrosis or subtrochanteric fractures.10, 62 Vertebral and rib fractures are common in myeloma

Summary

The imaging recommendations and treatment of multiple myeloma continue to evolve. Advanced imaging with MRI and FDG-PET/CT has changed our sensitivity for detecting and staging disease. With continued evolution of treatments, these imaging modalities may become more important in the future monitoring of novel treatment strategies.

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