Coupon Accepted Successfully!


Multiple Myeloma

Plasma Cell Dyscrasias
These are a group of disorders characterized by the expansion of a single clone of immunoglobulin (Ig) secreting cells and are associated with increase in levels of homogenous Ig or its fragments. 

Examples of Monoclonal Gammopathies
  1. Myeloma -
    1. Multiple myeloma
    2. solitary plasma cytoma
  2. Waldenström’s macroglobulinemia
  3. Heavy chain disease (γ, α, μ)
    1. Gamma Chain (Franklin disease) – Seen in elderly resemble lymphoma.
      Franklin disease is a gamma heavy chain disease. It characterized by elevated levels of a gamma heavy chain of immunoglobulins in blood and urine. 
    2. Alpha chain (Seligmann’s disease) - It is the most common type of heavy chain disease.
    3. mu chain – Rarest form, seen in patients with CLL.
  4. Primary or immunocyte associated amyloidosis
  5. Monoclonal gammopathy of undetermined significance (benign IgG, IgA, IgD, IgM, and rarely free light chains, biclonal gammopathies, idiopathic Bence Jones proteinuria) 
Multiple Myeloma
It is a malignant neoplasm of plasma cells.
Peak age group : 60 years and above

Light chain disease: No serum M component; only Bence Jones proteinuria
Immunopathology: In myeloma, the transformation of B – lymphocytes to plasma cells manufacturing immunoglobulins is defective resulting in the production of abnormal monoclonal immunoglobulin.Q

Variant Forms of Myeloma (Ref. Hari. 18th, ed., Pg- 936)
  1. Smoldering myeloma (SMM M – protein level > 3 gm/dl in the serum, > 10% atypical plasma cells in the bone marrow but no anemia, renal insufficiency or skeletal lesions). No lytic lesion, Serum Calcium is normal.
  2. Plasma cell leukemia (> 20% plasma cells in the peripheral blood and absolute plasma cell count is around 2000/mL).
  3. Nonsecretory myeloma – All features of MM except there is no M protein in serum or in urine.
  4. IgD myeloma (M – protein is smaller, and Bence – Jones proteinuria is of gamma type. Extramedullary plasmacytomas, plasma cell leukemia, and amyloidosis are common). They present with small band or no evident M-spike on serum protein electrophoresis. Higher incidence of renal insufficiency, amyloidosis and proteinuria than IgG/ IgA myeloma. Higher incidence of extramedullary involvement and inferior survival rates.
  5. Osteosclerotic myeloma (associated with the acronym POEMS – Polyneuropathy, Organomegaly, Endocrinopathy, M – protein, Skin changes)
  6. Solitary plasmacytoma

Extra Edge:


Bence Jones Protein

  1. A Bence Jones protein is a monoclonal globulin protein found in the blood or urine. 
  2. Causes:
    1. Multiple myeloma
    2. Waldenström's macroglobulinemia
  3. The proteins are immunoglobulin light chains (paraproteins) and are produced by neoplastic plasma cells. They can be kappa (most of the time) or lambda. 
  4. The light chains can be immunoglobulin fragments or single homogeneous immunoglobulins. 
  5. The light chains can be detected by heating or electrophoresis of concentrated urine. Light chains precipitate when heated to 50 - 60 degrees C and redissolve at 90 -100 degrees C. 

Clinical Features of Multiple Myeloma 
  1. The major feature of myeloma is the demonstration of an abnormal monoclonal protein (M protein) in the blood, urine, or both. This M protein usually consists of either one or a combination of heavy chains (lgG and IgA) and light chains (K and λ). 
  2. Complications occur due to: Infiltration of the marrow by large numbers of plasma cells, which are usually abnormal
    1. Anaemia: normocytic and normochromic (Note: leukopenia and thrombocytopenia are rare feature) 
    2. Weakness, fatigue, infection, and bleeding due to marrow failure
    3. Osteolytic lesions (Activation of osteoclast activating factor by IL-6 ) resulting from myeloma-induced bone resorption with subsequent pain (m/c symptom) and fracture. Bone involvement in MM is as follows:
      Vertebral column > ribs > Skull > Pelvis > Femur > Clavicle > Scapula
    4. Renal abnormalities due to myeloma infiltration of the kidney, hypercalcemia, toxic effects of light chains on tubules, amyloid deposition, and hyperuricemia. Urine cast is made up of light chain only (Not a complete immunoglobulin). Proteinuria can occur. (LQ 2012)
      In MM patient may developed CRF with enlarge kidney size. Other conditions where patient may have CRF with enlarge kidney size are –
      1. Diabeties,
      2. Polycystic kidney
      3. Amyloidosis
      4. Bilateral hydronephrosis (PGI Dec 2008)
    5. Recurrent infections due to acquired hypogammaglobulinemia and leukopenia
    6. Hypercalcemia due to myeloma-stimulated osteoclast activity. Osteoporosis can occur.
      i. Metastatic calcification occurs
      ii. Dystrophic calcifications do not occur.
Note: Metastatic calcification occurs but dystrophic calcifications do not occur. (LQ 2012)
  1. Hyperviscosity due to a high concentration of the M protein which tends to aggregate can cause visual disturbance. (LQ 2012)
  2. Systemic AL amyloidosis.
Compilations of MM
In MM there is no hepatomegaly, no splenomegaly and no lymph adenopathy.
  1. Hypercalcemia
  2. Spinal cord compression
  3. Hyperviscosity syndrome
  4. Renal failure
Note: CHF is not a feature of MM:


Table - Clinical Features of Multiple Myeloma (Ref. Hari. 18th ed., Pg- 938, table 111.1)
Clinical Finding Underlying Cause and Pathogenetic Mechanism
Hypercalcemia, osteoporosis, pathologic fractures, lytic bone lesions, bone pain Tumor expansion, production of osteoclast activating factor by tumor cells, osteoblast inhibitory factors
Renal failure Hypercalcemia, light chain deposition, amyloidosis, urate nephropathy, drug toxicity (nonsteroidal anti-inflammatory agents, bisphosphonates), contrast dye
Easy fatigue-anemia Bone marrow infiltration, production of inhibitory factors, hemolysis, decreased red cell production, decreased erythropoietin levels
Recurrent infections Hypogammaglobulinemia, low CD4 count, decreased neutrophil migration
Neurologic symptoms Hyperviscosity, cryoglobulinemia, amyloid deposits, hypercalcemia, nerve compression, anti-neuronal antibody, POEMS syndrome, therapy-related toxicity
Nausea and vomiting Renal failure, hypercalcemia
Bleeding/clotting disorder Interference with clotting factors, antibody to clotting factors, amyloid damage of endothelium, platelet dysfunction, antibody coating of platelet, therapy-related hypercoagulable defects
Pathology of MM:
Cells type
  1. Plasma cell
  2. Flame cell (Cell with cherry red cytoplasm)
  3. Mott cell (Cells with multiple blue grape like cytoplasmic droplet)
Inclusion body:
  1. Russell body (intracytoplasmic) found in plasma cell
  2. Dutcher body (nuclear)
  3. Inclusion of fibril crystalline Rods & globular)

Test Your Skills Now!
Take a Quiz now
Reviewer Name