Journal Reading

Imaging of Multiple Myeloma:

Current concepts

Retno Manggalih 030.11.244

Bangun Said Santoso 030.12.047
Christopher Adhisasmita Yandoyo 030.12.055
 Core Tip

A comprehensive review about state-of-the art imaging of multiple

myeloma with a focus on whole body imaging techniques including: (CT),
MRI and PET/CT which are increasingly used for detection and
visualization of both osseous and extraosseous myeloma manifestations.
 Abstract

• Diagnosing MM vs other Monoclonal Plasma Cell Disease

• Medical Imaging = Crucial
• Conventional radiography :Reference standard for diagnosis, wide availability and
low cost and the limitation are Low sensitivity, limited specificity and inability to
detect extraosseous lesions.
• Newer: Whole-body low-dose CT, Whole-Body MRI, F-fluorodeoxyglucose (FDG)
Positron emission tomography (PET)/CT. Whole-boy low-dose CT : the usage >> ,
hinger sensitivity for extraosseous lesions.
• Highest sensitivity both bone marrow disease and extraosseous : Whole-body MRI &
F-FDG PET/CT.
• MRI is the most Sensitive for initial stage.
• F-FDG PET/CT monitoring of treatment of MM.
 Introduction

• Multiple myeloma (MM) :

• second most common (10%-15% of all) hematological
malignancies
• 1% of all malignant diseases
• 15%-20% of deaths from hematological malignancies
• 2% of all deaths from cancer
• Characterized by clonal proliferation of plasma cells
• It produce excessive amounts of monoclonal
• Immunoglobulins that can be detected in serum and urine.
• The proliferating plasma cells infiltrate the bone
marrow leading to replacement of the normal
myelopoiesis.
Characteristic Clinical
Symptoms

Anemia

Renal Insufficiency

Hypercalcemia

Pathologic Fractures

Extraosseous Manifestations
Differential Diagnosis

Monoclonal Plasma
Cell Disorders
 1
Role Imaging in Multiple Myeloma

International Myeloma Working Group (IMWG)

Conventional projection radiography

Durie-Salmon-Staging system

The Presence and number of osseous lesion – Staging of the disease -> Risk
stratification of MM

Newer staging system ex: Durie-Salmon-PLUS

MRI / F-fluorodeoxyglucose (FDG) PET/CT

More sophisticated (better define osteolytic lesions)

Computer Tomography (CT)

Magnetic Resonance Imaging (MRI)
Positron emission tomography (PET)
 2
Role Imaging in Multiple Myeloma

Two Patterns of oseeous involvement :

• Focal Lesions with confirmed Circumscriptive plasma cell of

the bone marrow
• Destruction of the inner cortical bone (scalloping)

• Diffuse bone marrow infiltration

• Mixture of monoclonal cells and physiologic hematopoietic cells
(spongiosa of the bone remains primarily intact.
 3
Role Imaging in Multiple Myeloma

 The two Patterns may occur:

• Isolated
• Synchronous
• Metachronous.

 Soft tissue and/ or organ involvement:

• May originate from primary extraosseous lesion
• Arise secondarily from osseous lesions
Treatment

Stem cell High dose

transplantation chemotherapy

Immunomodulatory Proteasome
drugs inhibitor
ROLE OF DIFFERENT IMAGING
MODALITIES FOR MM
 Conventional Projection
Radiography
• Represents the standard method
• Detection of bone lesions for initial staging and monitoring of
MM.
• Lytic lesions in the plate bone of the skull and pelvis =
stamped out lesions without a sclerotic rim.
• IMWG: Redomends complete conventional radiographic for
each newly diagnosed patient with MM.
• Long bone :
• Thining of the inner cortical bone (scalloping),
• discrete small lytic lesions up to 1 cm,
• “moth-eaten” patterns

The lesision = represent replacement of the physiological bone marrow by clinal expanding plasma cells
+ consecutive destruction of the bone.
 Conventional Projection
Radiography

Advantage Disanvantage

Wide availability Low sensitivity

Low Cost Can’t neither detect nor quantify a

diffuse bone marrow infiltration nor
extraossoue lesions.

Cover almost the entire skeletal system Can’t be used for therapy montoring
 Computed Tomography
CT

Advantage Disanvantage

Allows detection of smaller osseous lesions High radiation dose

Early Changes detectability Low-dose CT Protocols highlt specific for the

detection of osteolytic bone lesions

Higher sensitivity in superimposed area (Scapulae, Can’t be used for therapy montoring
ribs, and sternum)

Potential instabilities and risk of fractures Limited sensitivity:

For detection of diffuse bone marrow
infiltration
Bone marrow lesions without lytic reactions
Extraosseous lesions

Short imaging times

Allows detection of extraosseous manifestations of

MM
 Involvement of bone marrow
(MRI)

• Focal Lesions
• Homogenous diffuse bone marrow infiltration
• Mixed “Salt-and-pepper” pattern.

 Indication of using MRI :

• Suspicion of solitary plasmacytoma
• Suspicion of spinal chord / nerve root compression
• Painful myeloma manifestations for potential extent soft
tissue involvement
• Non-secretory myeloma
• Monitoring treatment
 MRI
Advantage Disanvantage

Clearly more sensitive than conventional radiography Relatively hight cost

Up to 50% inconspicupus conventional radiographic Relatively ling scanning time

imaging -> reveal focal lesions on a MRI

Improfed detection of lesions (Spine, pelvis, sternum, Risk of developing nephrogenic systemic fibrosis
skull, and scapulae)

Excellent depiction of:

• The spinal cord and nerve roots
• Detection of soft tissue manifestations
• Differentiate between physiological and
myeloma-infiltrated bonne marrow
 Newer MRI

• Limited published data

• Can also significantly detect the difference of apparent diffusion
Diffusion Weighted coefficients (Before and after therapy)
Imaging (DWI)

• Limited small studies

• One study, DCI MRI Reflected the degree of infiltration and vessel
Dynamic Contrast- density.
Enhanced (DCE) MR
Imaging.
• Can show significantly higher bine marrow plasmocytosis

Both MRI and DWI are promising techniques

Monitoring the response.
Further studies are needed to define their exact role.
 1
PET/CT

PET/CT + F-FDG as Radiotracer:

• Excellent depiction of osseous structure and lesions (CT) + High

sensitivity of PET for detection of isolated focal medullary lesions
without destruction of the osseous substance and for detection of
extraosseous manifestation.
• Initial staging and treatment monitoring of non-secretory myeloma.
• MGUS is typically PET negative.
• Detects 40-60% more osseous myeloma manivestation bs
conventional radiography
• Detects lesioin in false negative conventional radiography results.
• 40% patients with initially solitary plasmacytoma detected
• MRI still has higher sensitivity for detection of diffuse bone marrow
infiltration.
 2
PET/CT

• Allows estimation of the standardized uptake value (SUV)

• High SUV of lesion -> Faster disease progression -> worse prognosis
• More than 3 PET- Positive lesions -> major independent parameter
for predicting overall survival
• Negative posttherapy PET -> predictive for nonrelapse / a long
disease-free survival.
• C-atetate PET
• Diffuse bone marrow detection sensitivity = 100% vs FDG PET = 40%
• Detection of Bony myelomatous lesions (Via Amino Acid
Tracers)
• C-Choline PET/CT : 37 Lesions vs F-FDG PET/CT scans : 22 Bone
lesions
• Nakamoto et al = C-Methionine (MET) : 156 lesions vs FDG : 58
lesions
• FAMT vs FDG = Uptake still significantly higher on FDG PET.
 IMAGING FOR MONITORING OF TREATMENT OF MM

• Conventional radiography and CT cannot be adequately used for

treatment monitoring
• A recent study has addressed the value of MRI for monitoring
treatment of MM after stem cell transplantation
• F-FDG PET/CT can detect specific lesions after stem cell
transplantation
• MRI may often be false positive because of persistent non-viable
lesions in the post-treatment setting, indicating that PET/CT might
be more suitable than MRI for determination of remission status
 CONCLUSION

Medical imaging is of crucial importance for;

• Diagnosis
• Initial staging
• Differentiation of MM from other monoclonal
plasma cell diseases
 Conventional radiography
whole-body low-dose CT
- low sensitivity
- Low specificity High sensitivity for osseous lesions and the
- Inability to detect extraosseous lesions possibility to detect extraosseous lesions
- Wide availability
- Low costs

MRI A complementary CT

Has the highest sensitivity for osseous lesions and To assess the presence of osteolytic lesions and
detection of diffuse bone marrow involvement to evaluate stability

Whole-body MRI
F-FDG PET/CT
-Initial staging of MM due to its high sensitivity
-Detection of osseous and extraosseous lesion - Differentiate between active and inactive
- Sensitive detection of both focal and diffuse lesions
bone marrow infiltration - Enabling monitoring of MM treatment