Diagnostic Radiology/Musculoskeletal Imaging/Tumors Basic/Multiple Myeloma

Multiple Myeloma is a neoplasm of differentiated plasma cells resulting from malignant clonal expansion and overproduction of monoclonal immunoglobulins. Common complications include recurrent bacterial infections, anemia, osteolytic lesions and renal insufficiency.

Etiology
The cause of multiple myeloma is unknown, but risk is increased with radiation exposure and patient's with monoclonal gammopathy of undetermined significance (MGUS). Long term follow-up (30years) has shown that multiple myeloma develops in up to 16% of patients with MGUS.

Clinical Presentation
Multiple myeloma occurs in older adults, with a median age of onset of 65 years. It is more common in men and in African American population. Patients can be asymptomatic. Presenting symptoms include bone pain, fatigue, and pathologic fractures. They have strong diagnostic value if accompanied by more than 10% atypical plasma cells in the bone marrow and either a monoclonal immunoglobulin in the serum or light chains in the urine.

Bone lesions, hypercalcemia and anemia correlate directly with tumor burden.

MRI can detect involvement of the vertebral marrow in 50% of patients with indolent myeloma (asymptomatic MM with fewer than 4 osteolytic lesions and normal renal function).

Myeloma cells can induce increased cytokine release, especially interleukin 6 which activate osteoclasts provoking bone resorption.

Treatment
High dose or low dose melphalan, cyclophosphamide and glucocorticoids with or without bone marrow/stem cell transplant. Bisphosphonates (pamidronate) have been used to treat hypercalcemia and appears to reduce the incidence of skeletal complications (pathologic fractures, need for irradiation, spinal cord compression) and bone pain.

Radiologic Images
Conventional radiography, bone scans, CT, MR, and PET can be utilized to study patients for myeloma. Typically, skeletal radiography and MR surveys of the axial skeleton are both used in documenting extent of disease and response to treatment. In addition, consequences of multiple myeloma, such as compression fractures can be determined.

Conventional Radiographs
On skeletal surveys, images are obtained as follows:
 * 1) Lateral skull
 * 2) AP and lateral total spine (including cervicothoracic and lumbosacral lateral views)
 * 3) AP pelvis
 * 4) AP humeri and femori

Well-defined lucent lesions within the bone are suspicious for myeloma. Approximately 50% of bone destruction is required for conventional radiographs to detect these lesions.

There are four distinct types of myeloma involvement:
 * 1) Solitary lesion (plasmocytoma) - typically involves the spine, pelvis, skull, ribs, sternum, and proximal appendages.
 * 2) Diffuse skeletal involvement - myelomatosis
 * 3) Diffuse skeletal osteopenia - no well defined lytic lesions; compression fractures are common.
 * 4) Sclerosing myeloma - associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).

The number of lytic bone lesions, along with other clinical factors (M protein, serum hemoglobin, serum calcium, renal function), are used to stage the patient and estimate tumor burden. The Durie-Salmon staging system for multiple myeloma separates patients into 3 stages. Radiographically, if a patient has 2 or more lytic lesions, they are stage III. If they have no bone destruction or a solitary plasmacytoma, they are stage I or II, depending on the other clinical factors.

MRI
Malignant plasma cells tend to distribute themselves in areas of normal active hematopoesis. In adults, this is in the axial skeleton; therefore, MR surveys tend to image the axial skeleton.

On T1-weighted sequences, focal plasmacytoma will appear hypointense relative to the hyperintense marrow. Diffuse involvement will demonstrate diffuse hypointensity of the marrow relative to musculature and disk spaces.

On T2-weighted or STIR sequences, focal plasmacytoma is hyperintense relative to the background marrow. Diffuse involvement will demonstrate diffuse marrow hyperintensity relative to musculature.

Case 1
This image demonstrates a typical "punched-out" lesion in the skull on plain film.

Case 2
This case demonstrates progression of myeloma with increasing lucency within the iliac wing lesion.



Case 3
Here are correlative images of myeloma in the spine on a plain film, CT, and MR (hypointense to marrow on T1, hyperintense on STIR).



Case 4
These images are a CT and MR (T1 and STIR) of a rib lesion.





Case 5
This is an example of myeloma in the ischium on plain film and MR (STIR).

Case 6
There is subtle lucency on the plain film of the proximal femur. The MR shows extensive myeloma involvement.