Multiple myeloma (Kahler 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
- Neoplastic proliferation of plasma cells
- Overproduction of monoclonal immunoglobulin and/or light chains → dysproteinemia (a state of pathologically increased synthesis of immunoglobulins and/or their subunits) → kidney damage (e.g., myeloma cast nephropathy) and/or paraprotein tissue deposition (may cause amyloidosis) 
International Staging System (ISS) 
International Staging System for multiple myeloma
|Features||Stage I||Stage II||Stage III|
|Serum concentration|| |
|Median survival|| || || |
- 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.
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
Monoclonal gammopathy of undetermined significance (MGUS) 
- Definition: : characterized by complete or incomplete monoclonal immunoglobulins (of any class) detectable in patient serum without accompanying clinical symptoms
- Usually, an incidental finding on workup (e.g., protein electrophoresis) for other conditions such as vasculitis, hypercalcemia, skin rashes, peripheral neuropathy, increased ESR, and hemolytic anemia
- Screening may be considered in individuals ≥ 50 years of age with two or more affected first-degree relatives with multiple myeloma or related disorders (e.g., cryoglobulinemia, acquired von Willebrand syndrome, C3 glomerulonephritis, light-chain proximal tubulopathy)
- Risk of progression to myeloma and presence of associated disorders is determined by the following predictors: presence of non-immunoglobulin G-type M protein, M-protein concentration ≥ 1.5 g/dL, and abnormal serum free light chain (SFLC) ratio
- Laboratory studies
- Bone marrow biopsy is indicated in moderate-to-high risk of progression to malignancy or if there is evidence of transformation to another PCD. 
- Skeletal imaging is indicated in moderate-to-high risk of progression to malignancy or if there is evidence of transformation to another PCD (i.e., M-protein concentration ≥ 3 g/dL, findings of a severe PCD).
- Modality of choice: low-dose whole-body CT
- Skeletal survey is indicated if CT is not available.
- Whole-body MRI is indicated if CT results are inconclusive and multiple myeloma is suspected.
- Diagnostic criteria 
- Treatment: none required
- Multiple myeloma
- Light chain amyloidosis: can occur with all forms of MGUS
- Waldenstrom macroglobulinemia: only arises from IgM MGUS
- Increased risk of thrombosis (thromboprophylaxis is usually not required) and developing osteoporosis (bone densitometry should be performed at the time of diagnosis)
- Follow-up: Long-term follow-up involving complete blood count, serum calcium and creatinine, SPEP, and SFLC studies is recommended at 6 months and then every 2–3 years to monitor the risk of progression to lymphoplasmacytic malignancy.
Waldenstrom macroglobulinemia 
- Definition: : a type of non-Hodgkin lymphoma associated with abnormal production of monoclonal IgM antibodies
- Epidemiology: mostly occurs in old age
- 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)
- Prognosis: good, as it is a type of indolent lymphoma
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.
Dysproteinemia-associated kidney disease 
- (myeloma kidney)
- Monoclonal immunoglobulin deposition disease (MIDD)
Type I cryoglobulinemia
- An immune-mediated disorder characterized by the deposition of monoclonal immunoglobulins (IgG and IgM) within blood vessels.
- Most commonly associated with protein-secreting monoclonal gammopathies, including monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, and multiple myeloma.
- Type II cryoglobulinemia
- Immunotactoid glomerulopathy
- Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)
- Monoclonal gammopathy-associated C3 glomerulopathy
- Light-chain proximal tubulopathy
- Monoclonal IgM-mediated kidney disease
- Monotypic fibrillary glomerulonephritis
- Hypercalcemia-associated renal damage: leads to hypercalciuria and nephrocalcinosis
- Analgesic nephropathy: caused by long-term intake of NSAIDs for bone pain
- : Light chains can accumulate as amyloids and may lead to restrictive cardiomyopathy, renal insufficiency, macroglossia, and malabsorption syndromes.
- Secondary plasma cell leukemia 
- Hypercalcemic crisis: Osteolysis is associated with chronically elevated calcium levels, which can result in hypercalcemic crisis.
We list the most important complications. The selection is not exhaustive.