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Multiple Myeloma

Wilmot Cancer Institute / Cancers We Treat / Multiple Myeloma / Diagnosis

 

Diagnosis

The symptoms of multiple myeloma vary significantly.  Sometimes, myeloma causes no symptoms and is found only on blood tests.  Other times, myeloma can cause debilitating symptoms for the patient.  The most common symptoms of myeloma include:

  • Bone pain, most often in the back, hips or skull
  • Broken bones
  • Easy bruising or bleeding
  • Fever
  • Fatigue
  • Frequent infections
  • Hypercalcemia, or high levels of calcium in the blood, which can cause many symptoms including loss of appetite, nausea or vomiting, feeling thirsty, frequent urination, constipation and confusion or trouble thinking.

How is multiple myeloma diagnosed?

Getting an accurate diagnosis is essential to getting the best treatment. Some types of blood cancer can be difficult to diagnose, but Wilmot has an in-house pathology team with expertise in blood disorders to provide a precise diagnosis. Tests to diagnose myeloma include:

Medical history and physical examination:  This includes a complete medical history, assessment of risk factors and symptoms, and a complete physical exam.

Blood tests:

  • Calcium level
  • Renal function
  • Red blood cells, white blood cells, and platelets
  • Protein electrophoresis:Detects the presence and amount of a monoclonal protein (M-spike)
  • Immunofixation:Identifies the type of monoclonal protein, which is an immunoglobulin composed of a heavy chain and a light chain
  • Free light chains:There are two types of light chains: kappa (κ) and lambda (λ).
  • Heavy chains:There are five types of heavy chains: G, A, D, E, and M.

Most myeloma patients have IgG myeloma, with either kappa or lambda light chains.  The next most common type is IgA myeloma.  IgD, IgE, and IgM myelomas are rare. 

Urine test: Urine may be collected and tested for the abnormal proteins made by plasma cells.

Bone marrow biopsy/aspiration:  Because most myeloma starts in the bone marrow, pathologists need to evaluate the bone marrow for the presence and extent of abnormal plasma cells.  For this procedure, doctors place a needle into a bone (usually the pelvis) and extract a small piece of tissue and bone marrow liquid. Pathologists examine the extracted material under a microscope.

Imaging:  This can include x-rays, CT scans, MRI, and/or PET/CT scans.  These tests are used to detect the presence of plasmacytomas and/or weakening of the bones caused by multiple myeloma.

Molecular testing: These tests can include:

  • Cytogenetics, which allows pathologists look at a patient’s chromosomes to determine if there any major abnormalities.
  • Fluorescent in situ hybridization, or FISH, which allows pathologists to use fluorescent dyes that only attach to certain genes or chromosomes, allowing them to find chromosome changes that are too small to be seen with a microscope.
  • Polymerase chain reaction, a test similar to FISH that can detect even smaller DNA changes within cells.

Staging

Once multiple myeloma has been diagnosed, tests are done to find out how the cancer has advanced.  This process, called staging, is important for determining treatment options and prognosis.

There are two systems of staging in multiple myeloma:

  • The Durie-Salmon Staging System factors in levels of hemoglobin, monoclonal immunoglobulin (M protein) in the blood and urine, blood calcium levels, and bone damage.
    • Stage I:
      • Hemoglobin > 10 g/dL (mild or no anemia)
      • At most, one area of bone damage on imaging
      • Normal calcium level
      • Relatively small amount of M-protein in blood or urine
    • Stage II:
      • A moderate number of myeloma cells are present, features are between Stage I and Stage III
    • Stage III:
      • Hemoglobin < 8.5 g/dL (moderate to severe anemia)
      • Calcium > 12 mg/dL
      • 3 or more areas of bone damage on imaging
      • Large amount of M-protein in blood or urine
  • The International Staging System (ISS) incorporates the levels of the serum beta 2-microglobulin and albumin.
    • Stage I:beta-2 microglobulin < 3.5 mg/L and albumin >3.5 g/L.
    • Stage II:Neither stage I or stage III
    • Stage III:beta-2 microglobulin > 5.5 mg/L.
  • The Revised Internal Staging System (R-ISS) adds prognostic information obtained from the serum lactate dehydrogenase (LDH) and high-risk chromosomal abnormalities detected by FISH.