- Clinical science
Multiple myeloma (Kahler's disease) is a malignant proliferation and the diffuse infiltration of monoclonal plasma cells in the bone marrow. Plasmacytoma, an early-stage plasma cell dyscrasia, originates from the same type of malignant plasma cells but is characterized by solitary cell proliferation that forms a mass. Malignant plasma cells generally produce monoclonal proteins (also known as M proteins or paraproteins), such as abnormal antibodies (e.g., IgG or IgA) or immunoglobulin light chains (e.g., Bence Jones protein). The condition is most common in elderly patients, who present with unspecific symptoms (fever, night sweats, weight loss), bone pain, or back pain, although multiple myeloma may also be asymptomatic; in this case, it is often a coincidental finding of serum protein electrophoresis. Proliferating plasma cells suppress normal bone marrow function, which leads to clinical findings of anemia, bleeding and/or infection. Additionally, plasma cell proliferation may result in extensive skeletal destruction with hypercalcemia. Complications arising from multiple myeloma often affect the kidneys, leading to conditions such as myeloma cast nephropathy, light chain deposition disease, amyloid light-chain (AL) amyloidosis with renal involvement, and nephrocalcinosis. Younger patients in good general condition are treated with a combination of high-dose chemotherapy and autologous stem cell transplantation, whereas older or frail patients are treated with immunomodulatory drugs (bortezomib, thalidomide, lenalidomide) combined with conventional chemotherapy (melphalan).characterized by uncontrolled
- Plasma cell dyscrasia: a group of conditions characterized by the abnormal proliferation of the same type (=monoclonal) of a plasma cell that may also secrete a monoclonal immunoglobulin and/or immunoglobulin fragment (e.g., light chain)
- Plasmacytoma: an early-stage plasma cell dyscrasia characterized by a single lesion that affect bones (solitary plasmacytoma of bone) or soft tissue (solitary extramedullary plasmacytoma), or in rare cases multiple solitary lesions in soft tissue, bone or both (multiple solitary plasmacytoma)
- Multiple myeloma: a malignant plasma cell dyscrasia characterized by uncontrolled proliferation and the diffuse infiltration of monoclonal plasma cells in the bone marrow
- Sex: ♂ > ♀ (3:2) 
- Peak incidence: 50–70 years 
Epidemiological data refers to the US, unless otherwise specified.
- Neoplastic proliferation of plasma cells
- Overproduction of monoclonal immunoglobulin and/or light chains
- Often asymptomatic
- Mild fever, night sweats, weakness, and weight loss
- Bone pain, especially back pain (most common symptom)
- Symptoms of
- Spontaneous fractures
- Increased risk of infection
- Increased risk of petechial bleeding
- Foamy urine (caused by Bence Jones proteinuria)
Enlarged lymph nodes are not a typical finding.
International Staging System (ISS) 
International Staging System for multiple myeloma
|Features||Stage I||Stage II||Stage III|
|Serum concentration|| || || |
|Median survival|| || || |
Approach and diagnostic criteria 
- The following tests are required for patients with suspected MM
|Diagnostic criteria |
|Types||Main criterion||Plus at least one of the following “myeloma-defining events”|
CRAB indicates organ damage: Calcium increased, Renal insufficiency, Anemia, and Bone lesions.
- Peripheral blood smear: rouleaux formation
Electrophoresis and immunofixation
- Serum protein electrophoresis (best initial test): monoclonal gammopathy with M protein (M spike)
- Urine protein electrophoresis: Bence Jones proteins
- Indication: confirmatory test indicated for all patients with suspected MM
- Fluorescence in situ hybridization (FISH): detect translocations/deletions for risk stratification
- Cytology: clusters of plasma cells
- First choice: low‑dose whole body CT (WBLD-CT) 
- Asymptomatic patients: watch and wait, unless patients have ≥ 60% clonal cells, excessive free light chains or ≥ 1 bone lesion
- Symptomatic patients
- Supportive therapy
- Definition: : characterized by complete or incomplete monoclonal immunoglobulins (of any class) detectable in patient serum without accompanying clinical symptoms
- Diagnostic criteria
- Complications: multiple myeloma (approx. 1% of MGUS cases per year transform into multiple myeloma)
- Treatment: none required (monitor M-protein levels)
- Definition: : a type of non-Hodgkin lymphoma associated with abnormal production of monoclonal IgM antibodies. It mostly occurs in old age and has a good prognosis, as it is a type of indolent lymphoma.
- Peripheral neuropathy
- Impaired platelet function → hemorrhagic diathesis with petechial bleeding
- Normochromic anemia
- Formation of cold agglutinins (IgM) with hyperviscosity syndrome
- Lymph node enlargement possible
- Constitutional symptoms (e.g., fatigue)
Overproduction of monoclonal IgM suggests Waldenstrom macroglobulinemia rather than multiple myeloma!
- Definition: a rare plasma cell disorder that causes chronic overproduction of proinflammatory cytokines
- Diagnostic criteria
The differential diagnoses listed here are not exhaustive.
- : Light chains can accumulate as amyloids and may lead to restrictive cardiomyopathy, renal insufficiency, macroglossia, and malabsorption syndromes.
- Hypercalcemic crisis: Osteolysis is associated with chronically elevated calcium levels, which can result in hypercalcemic crisis.
- (myeloma kidney)
- Light chain deposition disease
- Renal involvement with AL amyloidosis
- Renal damage caused by hypercalcemia → hypercalciuria and nephrocalcinosis
- Analgesic nephropathy due to long-term intake of NSAIDs for bone pain
- Secondary plasma cell leukemia 
We list the most important complications. The selection is not exhaustive.