Molecular imaging in myeloma precursor disease

Abstract

Multiple myeloma (MM) is consistently preceded by its pre-malignant states, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). By definition, precursor conditions do not exhibit end-organ disease (anemia, hypercalcemia, renal failure, skeletal lytic lesions, or a combination of these). However, new imaging methods are demonstrating that some patients in the MGUS or SMM category are exhibiting early signs of MM. Although MGUS/SMM patients are currently defined as low-risk versus high-risk based on clinical markers, we currently lack the ability to predict the individual patient's risk of progression from MGUS/SMM to MM. Given that the presence of gross lytic bone lesions is a hallmark of MM, it is reasonable to believe that less severe bone changes defined by more sensitive imaging may be predictive of MM progression. Indeed, since bone disease is such an essential aspect of MM, imaging techniques directed at the detection of early bone lesions, have the potential to become increasingly more useful in the setting of MGUS/SMM. Current guidelines for the radiological assessment of MM still recommend the traditional skeletal survey, although its limitations are well documented, especially in early phases of the disease when radiographs can significantly underestimate the extent of bone lesions and bone marrow involvement. Newer, more advanced imaging modalities, with higher sensitivities, including whole-body low-dose computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are being employed. Also various imaging techniques have been used to provide an assessment of bone involvement and identify extra-osseous disease. This review emphasizes the current state of the art and emerging imaging methods, which may help to better define high-risk versus low-risk MGUS/SMM. Ultimately, improved imaging could allow more tailored clinical management, and, most likely play an important role in the development of future treatment strategies for high-risk precursor disease.

Figure 1

X-ray demonstrates bone lytic lesions in the occipital area of the skull consistent with myeloma involvement.

Figure 2

MRI scan demonstrates hypointense signal on T1 weighted image and hyperintense signal on STIR sequence in the cervical vertebra, C6, consistent with myeloma involvement.

Figure 3

A patient diagnosed with SMM (i.e. without lesions on skeletal survey). Due to local pain, an ¹⁸F-FDG PET scan was conducted. The ¹⁸F-FDG PET (a) scan demonstrates increased uptake in the right distal femur, which shows a lytic lesion at the corresponding region on the low-dose CT (b), better visualized on the PET/CT fusion image (c). ¹⁸F-FDG PET also shows two additional areas of increased uptake in anterior aspect of the femur, without evidence of bone changes on CT, most likely representing early lytic changes. Reprinted with permission: Mailankody S, Mena E, Yuan CM, Balakumaran A, Kuehl WM, Landgren O. Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myeloma. Leuk Lymphoma. 2010 Oct 20 [Epub].

Figure 4

¹⁸F-FDG PET/CT scan demonstrates intense hypermetabolic ¹⁸F-FDG activity in the base of the skull on the PET image (a), and a bone lytic lesion on the CT scan (b). The combined PET/CT fusion (c) visualizes both functional and morphologic changes of bone myeloma involvement.

Figure 5

¹⁸F-FDG PET/CT scan demonstrates a low grade metabolic activity in the right sacrum (a), consistent with a lytic lesion on the corresponding low-dose CT (b). The combined PET/CT fusion (c) better visualizes the area of myeloma involvement.