Home Can Whole-body Low-dose Multidetector CT Exclude the Presence of Myeloma Bone Disease in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)?
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Can Whole-body Low-dose Multidetector CT Exclude the Presence of Myeloma Bone Disease in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)?

Posted Dec 31, 2011 Updated Apr 10, 2023
By Daniel Spira MD , Katja Weisel MD , Harald Brodoefel MD , Maximilian Schulze MD , Sascha Kaufmann MD , Marius Horger MD
8 min read

Rationale and Objectives

To determine the benefit of using whole-body low-dose computed tomography (WBLD-CT) in patients with monoclonal gammopathy of undetermined significance (MGUS) for exclusion of multiple myeloma (MM) bone disease.

Materials and Methods

Seventy-one consecutive patients with confirmed MGUS (as defined by the latest criteria of the International Myeloma Working Group) who underwent WBLD-CT for diagnosis were identified retrospectively by a search of our institution’s electronic medical record database (2002–2009). Patients were classified as low-risk or intermediate/high-risk and followed over a ≥2-year period with additional CT imaging and/or laboratory parameters. Presence of osteolysis, medullary, or extramedullary abnormalities compatible with involvement by MM was recorded. A diffuse or focal increase in medullary density to Hounsfield unit (HU) values >20 HU/>0 HU was considered suspicious for bone marrow infiltration if no other causes identifiable.

Results

The presence of osteolysis was excluded in all 71 patients with MGUS at initial diagnosis and patients were surveilled for ≥2 years. Lytic changes were observed at follow-up in1/71 patients that progressed to MM and were detectable via WBLD-CT at an early stage (even before a significant rise in M-protein was recorded). In 3/71 patients with MGUS (4%) suspicious bone marrow attenuation values were measured, disclosing disease progression to smoldering myeloma in another patient and false-positive results in 2/71 patients. Bone marrow attenuation assessment resulted in a specificity and negative predictive value of 97%, respectively. No significant difference with respect to bone marrow attenuation was observed in patients with low-risk MGUS versus intermediate- to high-risk MGUS. One of 71 patients showed serologic disease progression to active MM without bone abnormalities detectable.

Conclusion

WBLD-CT reliably excludes findings compatible with myeloma in MGUS and thereby complements hematologic laboratory analysis.

A total of 3.2% of the population age 50 years or older and 5.3% of persons older than 70 years present with a monoclonal gammopathy of undetermined significance (MGUS) . MGUS is defined as the presence of a monoclonal protein (M protein) in the serum at a concentration of <3 g/dL, an amount of <10% plasma cells in the bone marrow and no additional features of plasma cell disease, such as lytic bone lesions, anemia, hypercalcemia, or renal insufficiency . Because this premalignant condition consistently precedes multiple myeloma (MM) with an average 1% annual risk of progression, regular follow-up needs to be performed .

In MM the most widely used staging system is based on the Durie-Salmon criteria encompassing the presence of lytic bone lesions on radiographs, a decrease in hemoglobin, an increase in serum calcium, the amount of M protein, and renal function . However, because at least 30%–50% of the bone mass needs to be destructed for a lytic lesion to become apparent on a radiograph , a substantial number of MM lesions (both within bone and extraosseous) are missed by conventional radiography . Because low-dose computed tomography (CT) is a sensitive imaging tool for the detection of destructive bone lesions, we routinely perform a whole-body low-dose multidetector CT (WBLD-CT) at our institution to exclude lytic bone involvement in patients presenting with a monoclonal gammopathy . WBLD-CT enables an accurate assessment of osteolysis in the entire skeleton and allows for a concise evaluation of the appendicular and pelvic bone marrow including the less frequent extramedullary involvement . Several studies revealed focal bone marrow abnormalities in MGUS patients via magnetic resonance (MR) imaging leading to redivivus interest in the Durie-Salmon PLUS staging system , even though prediction of overall survival was not improved by the latter . No data exist in the current literature concerning the applicability and the relevance of WBLD-CT in patients with MGUS.

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Materials and methods

Population

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CT Protocol

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Image Analysis

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Laboratory Data

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Statistics

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Results

Population and Disease Course

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Bone Marrow Attenuation

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Figure 1, A 71-year-old female patient with stable monoclonal gammopathy of undetermined significance (MGUS; immunoglobulin A kappa). At initial whole-body low-dose computed tomography (a) , an unremarkable bone marrow attenuation was observed with values around -20 Hounsfield units (HU). Thirteen months later (b) , bone marrow attenuation values increased to 30 HU even though the M-protein remained stable. However, progressive anemia resulting from drug toxicity from antidepressant medication was recorded and explained the reactive increase in bone marrow attenuation. Sagittal reconstructions of the right femur at the respective points in time are shown (a,b) .

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Recognition of Osteolysis via WBLD-CT

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Figure 2, A 46-year-old male patient with progressive monoclonal gammopathy of undetermined significance (MGUS; immunoglobulin G lambda). At initial whole-body low-dose computed tomography (a) , no osteolysis was present in the left eighth rib. One year later (b) , a solitary, rudimentary osteolysis was recorded. However, the patient’s M-protein remained stable. Another year later (c) , the solitary osteolysis progressed and the M-protein increased to >3 g/dL. No increase in bone marrow attenuation of the long bones was observed over time (a–c) . Dexter, a magnification of the left eighth rib ( arrows ) is shown.

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Discussion

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Figure 3, A 78-year-old male patient with progressive multiple myeloma (immunoglobulin G kappa). At initial whole-body low-dose computed tomography (a) , mildly elevated bone marrow attenuation values were observed (around 22 Hounsfield units [HU], M-protein 1.3 g/dL). At 1.5 years later (b) , the patient progressed to high-grade multiple myeloma and bone marrow attenuation values increased to 60 HU (M-protein 3.4 g/dL). Dexter, a magnification of the left femur ( arrows ) is shown.

Figure 4, Confident exclusion of monoclonal gammopathy of undetermined significance (MGUS) in a 78-year-old male patient with progressive multiple myeloma (immunoglobulin G kappa; same patient as in Figure 3 ). At initial whole-body low-dose computed tomography (a) , solitary osteolytic changes in the left lateral mass of the sacral bone are demonstrated allowing reliable exclusion of the MGUS status and timely diagnosis of multiple myeloma (MM). The M-protein was unremarkable at that time (M-protein 1.3 g/dL) and only mildly elevated bone marrow attenuation values were observed (around 22 Hounsfield units [HU]; see Figure 3 ). At 1.5 years later (b) , the patient developed high-grade MM with multifocal osteolysis. Note the progressive destruction of the left sacral bone with medullary outgrowth into the sacral neuroforamina ( arrow ). Bone marrow attenuation values increased to 60 HU (see Figure 3 , M-protein 3.4 g/dL). In the lower row, a magnification of the sacral bone is shown and the lytic changes are indicated ( arrows ).

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Conclusion

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Academic Radiology, Volume 19, Issue 1
Journals General Radiology
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