Multiple myeloma is a complex blood cancer originating from plasma cells, a type of white blood cell responsible for producing antibodies. Plasma cells are typically located within the bone marrow. In this disease, abnormal plasma cells multiply uncontrollably, crowding out healthy blood-forming cells and producing an ineffective antibody called M protein. The disease is defined by the presence of these malignant plasma cells and related complications.
Understanding Multiple Myeloma’s Systemic Nature
The concept of multiple myeloma “spreading” often relies on the model of solid tumors, which metastasize from a single mass. Multiple myeloma, however, is inherently a systemic disease, meaning it is widespread throughout the bone marrow from diagnosis. It is a multifocal proliferation of plasma cells in areas where active bone marrow is present.
This systemic nature is why the condition is called “multiple” myeloma, as it affects many sites simultaneously. The malignant cells most commonly accumulate in the bones of the axial skeleton, which includes the spine, pelvis, ribs, and skull. Their presence in these locations leads to the destruction of bone tissue, creating characteristic small holes known as lytic lesions. This widespread involvement makes the disease a blood and bone cancer, distinct from localized solid tumors.
Progression from Precursor Conditions
The development of multiple myeloma follows a continuum of increasing severity, representing a progression in cell burden rather than a physical spread. The disease typically begins with Monoclonal Gammopathy of Undetermined Significance (MGUS). MGUS involves a small amount of M protein in the blood and has a low risk of progressing to active cancer, about one percent per year.
MGUS can progress to Smoldering Multiple Myeloma (SMM), characterized by a higher concentration of M protein and a greater percentage of plasma cells in the bone marrow, but still without symptoms. The risk of progression to active myeloma for SMM patients is about ten percent per year in the first five years.
The transition to active multiple myeloma is defined by myeloma-defining events (MDEs), which indicate damage to the body. These MDEs include the classic CRAB criteria:
- Elevated Calcium levels
- Renal failure
- Anemia
- Bone lesions
Updated diagnostic criteria also include biomarkers for high-risk SMM, such as having 60% or more clonal plasma cells in the bone marrow or a highly abnormal ratio of serum free light chains.
When Myeloma Moves Outside the Bone
Movement outside the bone marrow and bone structures is known as Extramedullary Disease (EMD). EMD is a less common, more aggressive manifestation that occurs when myeloma cells escape the bone marrow microenvironment and form tumors, called plasmacytomas, in soft tissues or organs. This process aligns with the concept of cancer spreading to non-skeletal sites.
The abnormal plasma cells use the bloodstream to migrate and form masses in various locations. These sites include the liver, lungs, kidneys, lymph nodes, and skin. EMD is present in 7 to 15 percent of patients at initial diagnosis, and 6 to 20 percent of patients who have relapsed after initial treatment.
The presence of EMD indicates a more challenging disease course because the cells have adapted to grow independently of the bone marrow. These soft tissue masses can cause symptoms depending on their size and location, such as pain or organ dysfunction. Defining EMD is crucial for treatment planning, as it often necessitates more intensive therapeutic strategies.
Localized Myeloma: Solitary Plasmacytoma
A Solitary Plasmacytoma (SP) is a highly localized condition involving a single tumor mass of plasma cells. This tumor may form within a bone (solitary bone plasmacytoma, or SBP) or outside the bone in soft tissue (extramedullary plasmacytoma, or EMP). For an SP diagnosis, the bone marrow must show minimal involvement of clonal plasma cells, and there must be no evidence of the systemic CRAB criteria.
SP is often treated with radiation therapy to eliminate the single tumor, offering a high rate of local control. While this localized form is distinct from multiple myeloma, it carries a significant risk of progression.
Approximately 65 to 84 percent of patients with SBP will eventually develop systemic multiple myeloma within ten years, typically within two to five years. Extramedullary plasmacytomas have a lower rate of progression to multiple myeloma than SBP.