Pictorial review of Multiple Myeloma on whole body MRI and PET-CT. Z Haque, S Alam, T Ashraf

Department of Radiology, Pilgrim Hospital

United Lincolnshire Hospitals NHS trust, UK

Introduction:

Multiple myeloma (MM) is a neoplastic disorder of plasma B cell, characterised by bone marrow infiltration and overproduction of

monoclonal immunoglobulins [1]. It is a common malignancy in patients above 40 (70% of cases are diagnosed between ages 50 and

70) with a male predilection (M:F 2:1) [4].The disease evolves from an asymptomatic premalignant stage, monoclonal gammopathy

of undetermined significance (MGUS), over smouldering multiple myeloma (SMM), to symptomatic MM with end-organ damage

[2,3]. Conventional radiographs used to be the gold standard [6], however with recent advancement, magnetic resonance imaging

(MRI), low dose multi-detector computed tomography (MDCT) and 18F-fluoro-deoxyglucose positron emission tomography ( 18F-

FDG PET-CT) play important role in assessing lytic bone lesions, early bone marrow infiltration as well as initial staging of the

disease, detection of complications, and assessing patient’s response to treatment [7]. We are presenting a pictorial review of few

cases of multiple myeloma and their imaging appearances mainly related to whole body MRI and PET-CT which we encountered in

our department in a six-month period.

NICE guideline (updated October, 2018) :

Imaging for people with suspected myeloma: 1.3.1Offer imaging to all people with a plasma cell disorder suspected to be myeloma. 1.3.2Consider whole body MRI as first line

imaging. 1.3.3Consider whole body low dose CT as first line imaging if whole body MRI is unsuitable or the person declines it. 1.3.4Only consider skeletal survey as first line

imaging if whole body MRI and whole body low dose CT are unsuitable or the person declines them. 1.3.5Do not use isotope bone scans to identify myeloma related bone disease in

people with a plasma cell disorder suspected to be myeloma.

Imaging for people with newly diagnosed myeloma: 1.3.6For people with newly diagnosed myeloma or smouldering myeloma who have not had whole body imaging with 1 of the

following, consider whole body imaging to assess for myeloma related bone disease and extra medullary plasmacytomas with one of: MRI, CT or FDG PET-CT. 1.3.7For guidance

on imaging for people with suspected spinal cord compression, see the NICE guideline on metastatic spinal cord compression. 1.3.8Consider baseline whole body imaging with MRI

or FDG PET CT for people who have non secretory myeloma or suspected or confirmed soft tissue plasmacytomas and have not already had either of these tests.

Imaging techniques:

Plain radiography demonstrates lytic lesions in the bone at presentation. Lytic lesions become apparent on conventional radiography

when 30–50% of the bone mineral density is already lost [9]. Its high false-negative rate of 30–70% leads to significant underestimation

in diagnosis and staging of patients with multiple myeloma [7-9]. CT has a higher sensitivity than plain radiography at detecting small

lytic lesions [5]. CT demonstrates punched-out lytic lesions, expansile lesions with soft tissue masses, diffuse osteopenia, fractures, and,

rarely, osteosclerosis [11]. It is mainly used in cases where MR is contraindicated or patient unable to lie inside MR scanner. MRI is the

most sensitive imaging modality at detecting diffuse and focal multiple myeloma in the spine, as well as the extra-axial skeleton [9-11].

The number and pattern of lesions detected on MRI correlates very well with treatment outcome and overall survival [10]. It is

important to note that MRI predominately reflects marrow infiltration, which may or may not be associated with bone destruction.

Multiple sequences are being used in identifying focal or diffuse disease. These include spin-echo (T1-weighted and T2-weighted),

STIR (short time inversion recovery), and contrast-enhanced spin-echo (with and without fat suppression) sequences [11]. DWI and

dynamic contrast enhanced MRI are increasingly being studied in Multiple Myeloma nowadays. Typical myeloma lesions are low

signal intensity on T1-weighted images and a high signal intensity on T2-weighted sequences and STIR images and generally show

enhancement on gadolinium-enhanced images. Four patterns (normal, focal, diffuse and variegated) of marrow involvement have been

identified in MRI. PET/CT is being used in patients with multiple myeloma to evaluate extent of active disease, detect extramedullary

involvement and assess treatment response [12].

References: 1. S. H. Landis, T. Murray, S. Bolden, and P. A. Wingo, “Cancer statistics, 1998,” Ca-A Cancer Journal for Clinicians, vol. 48, no. 1, pp. 6–29, 1998. 2. R. Desikan, B. Barlogie, J. Sawyer et al., “Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions

and superior survival in the absence of chromosome 13 abnormalities,” Blood, vol. 95, no. 12, pp. 4008–4010, 2000. 3. B. G. M. Durie and S. E. Salmon, “A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting

clinical features, response to treatment, and survival,” Cancer, vol. 36, no. 3, pp. 842–854, 1975. 4. Yochum TR, Rowe LJ. Essentials of Skeletal Radiology. Philadelphia, Pa. : Lippincott Williams & Wilkins, c2005. (2004) ISBN:0781739462 5. A Baur-Melnyk, S. Buhmann, C. Becker et al., “Whole-body MRI versus whole-body MDCT for staging of multiple myeloma,” American Journal of

Roentgenology, vol. 190, no. 4, pp. 1097–1104, 2008. 6. I. Snapper and A. Khan, Myelomatosis: Fundamentals and Clinical Features, University Park Press, Baltimore, Md, USA, 1971. 7. S. Lütje, J. W. J. Rooy, S. Croockewit, E. Koedam, W. J. G. Oyen, and R. A. Raymakers, “Role of radiography, MRI and FDG-PET/CT in diagnosing,

staging and therapeutical evaluation of patients with multiple myeloma,” Annals of Hematology, vol. 88, no. 12, pp. 1161–1168, 2009. 8. M. Dimopoulos, E. Terpos, R. L. Comenzo et al., “International myeloma working group consensus statement and guidelines regarding the

current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma,” Leukemia, vol. 23, no. 9, pp. 1545–1556, 2009. 9. D. J. Dinter, W. K. Neff, J. Klaus et al., “Comparison of whole-body MR imaging and conventional X-ray examination in patients with multiple

myeloma and implications for therapy,” Annals of Hematology, vol. 88, no. 5, pp. 457–464, 2009. 10. A.H. Mahnken, J. E. Wildberger, G. Gehbauer et al., “Multidetector CT of the spine in multiple myeloma: comparison with MR imaging and

radiography,” American Journal of Roentgenology, vol. 178, no. 6, pp. 1429–1436, 2002. 11. A. Baur-Melnyk, S. Buhmann, H. R. Dürr, and M. Reiser, “Role of MRI for the diagnosis and prognosis of multiple myeloma,” European Journal of

Radiology, vol. 55, no. 1, pp. 56–63, 2005. 12. M. A. Bredella, L. Steinbach, G. Caputo, G. Segall, and R. Hawkins, “Value of FDG PET in the assessment of patients with multiple

myeloma,” American Journal of Roentgenology, vol. 184, no. 4, pp. 1199–1204, 2005.

Conclusion:

Imaging plays an important role in diagnosing multiple myeloma. Radiographic skeletal survey is recommended for all patients with suspected

multiple myeloma and advanced imaging for those having normal radiographic findings. MR whole-body imaging and PET/CT provide

valuable complimentary information which help assessing not only morphological disease activity, but also functional disease activity, response

to treatment as well as tailoring treatment modalities to individual patients.

Case-1: Plain radiograph of skull demonstrates multiple punched

out lytic lesions. CT scan of lumbosacral spine shows a large

expansile lytic lesion in sacrum and few smaller lesions in L4

and L5 vertebrae which are better appreciated in subsequent MR

images in T1 weighted and STIR sequences.

Case-3: An elderly male patient presented with swelling in left parietal

region. MRI with contrast reveals an enhancing expansile mass

involving left parietal skull with surrounding soft tissue component

which showed increased FDG uptake in PET scan.

Case-4: CT scan of an elderly patient shows multiple lytic

lesions of variable sizes in the pelvis. MRI was not

performed due to patient`s noncompliant. FDG-PET scan

demonstrates intense uptake in the lesions of left and mild

uptake in the lesions of the right iliac bone.

Case-5: Whole body MRI

demonstrates- multiple T1 hypo

and STIR hyperintense lesions

in spine and pelvis .

Case-8: Abnormal signal change noted in T6 vertebra as evidenced by T1 hypo and STIR hyperintensity suggesting multiple myeloma deposit. The lesion shows FDG uptake in PET scan.

Case-2: MRI of lumbosacral region shows large expansile

lesions involving L5 and S1 vertebrae which appear as

hypointense in T1-weighted and hyperintense in STIR images.

FDG-PET of the same patient demonstrates intense FDG uptake

suggesting metabolically active lesion.

Case-9: FDG-PET

shows multiple

foci of intra and

extramedullary

metabolic activity.

Case-6: Follow-up PET scan of a multiple myeloma deposit in sternal region shows significant regression of the lesion following treatment.

Case-7: Micronodular multiple myeloma demonstrates salt-and-pepper appearance in STIR MR image.