Diagnosis and Criteria

A diagnosis of multiple myeloma is difficult to make on the basis of any single laboratory test result. To obtain an accurate diagnosis, several additional factors must be considered, including the findings on physical examination and a thorough history and evaluation of symptoms. Throughout your journey, you will hear these terms many times. Try to define your type of myeloma as early as possible.

Standards for diagnosis currently require confirmation of one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of myeloma.

Major Criteria

  • Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
  • 30% plasma cells in a bone marrow sample
  • Elevated levels of M protein in the blood or urine

Minor Criteria

  • 10% to 30% plasma cells in a bone marrow sample
  • Minor elevations in the level of M protein in the blood or urine
  • Osteolytic lesions (as demonstrated on imaging studies)
  • Low levels of antibodies (not produced by the cancer cells) in the blood

Tests can be done on specimens of blood, urine, bone, and bone marrow to determine if these criteria are present. These tests are done not only to determine if myeloma is present but also to assess the extent of disease. Thus, the tests are also valuable for classifying and staging the disease.

Diagnostic Tests on Blood

  • Complete blood count (CBC) is done to measure the number of red blood cells, white blood cells, and platelets in the blood, as well as the number or relative proportion of the different types of white blood cells present. The results of this test indicate the degree to which myeloma is affecting the production of normal blood cells. Learn more about a CBC and normal values.
  • A chemistry profile provides levels of such substances as albumin, blood urea nitrogen (BUN), calcium, creatinine, and lactate dehydrogenase (LDH). These levels help provide an assessment of the general health status and the extent of disease. Abnormal levels may indicate decreased kidney function and increased size and/or number of tumors.
  • The beta-2 microglobulin (ß2-M) level is considered to be a standard measure of tumor burden (the extent of disease).
  • The C-reactive protein level reflects the level of interleukin (IL)-6, a growth factor involved in the development of myeloma cells. As such, the level is an indirect measurement of the number of myeloma cells and/or size of the tumor(s).
  • Quantitive immunoglobulin (QIG) testing provides measurements of the levels of the different types of immunoglobulins (antibodies)—that is, IgG, IgA, and IgM—that are produced by myeloma cells.
  • Serum protein electrophoresis (SPEP) detects the presence and level of various proteins in the blood, including M protein. Higher levels of M protein indicate more extensive disease.  
  • Immunofixation electrophoresis (IFE) or immunoelectrophoresis provides more specific information than SPEP regarding the type of abnormal immunoglobulins (IgG, IgA, or IgM). 
  • Freelite™ testing can detect and quantify free light chains (those not associated with intact immunoglobulin). Evidence suggests that this test may be a more sensitive test and detect the presence of M protein or light chains in individuals with nonsecretory myeloma.

 Diagnostic Tests on Urine

  • Urinalysis is done to assess kidney function.
  • The measurement of the amount of Bence Jones protein in a 24-hour specimen of urine is done to determine the presence of disease; higher levels represent more extensive disease.
  • Urine protein electrophoresis (UPEP) is done to determine the presence and levels of specific proteins in the urine, including M protein and Bence Jones protein, both of which are indicators of myeloma.

Diagnostic Tests on Bone/Bone Marrow

  • A skeletal survey, a series of x-rays of the spine, arms, ribs, pelvis, and legs can demonstrate bone lesions and changes in bone structure.
  • Other imaging studies, such as magnetic resonance imaging (MRI), computerized tomography (CT), and positron emission tomography (PET), are additional tests that can assess changes in the bone structure and determine the number and size of tumors in the bone.
  • Evaluation of a biopsy specimen taken from either bone tissue or bone marrow can determine the number and percentage of normal and malignant plasma cells in the bone marrow. The diagnosis of myeloma is probable if 10% or more of the cells in the bone marrow sample are plasma cells.
  • Plasma cell labeling index (PCLI) defines the relative percentage of plasma cells that are actively growing.
  • Cytogenetic analysis (fluorescence in situ hybridization [FISH]) is done to evaluate the number and normalcy of chromosomes and identify the presence of chromosome translocations (a type of abnormality).

Classification of Myeloma

Myeloma is classified into one of three categories: monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (further subdivided into smoldering or indolent myeloma), and symptomatic myeloma. The classification is important because immediate disease-directed treatment is needed only for symptomatic myeloma. Delaying treatment can help avoid unnecessary side effects associated with chemotherapy. Even though treatment directed at the myeloma is postponed for most types of the disease, supportive care is given to prevent and/or manage symptoms and complications.

(Source: IMF, MMRF)