How Multiple Myeloma Is Diagnosed

In multiple myeloma, a white blood cell known as the plasma cell becomes cancerous. Unlike breast cancer or lung cancer, which form solid tumors, multiple myeloma is a blood cancer that packs the bone marrow with these abnormal plasma cells. 

The diagnosis depends on bone marrow tests and markers that can be detected in blood and sometimes in urine, all in addition to any signs and symptoms that may be present. Imaging of the bones can also detect spots that suggest multiple myeloma.

How multiple myeloma is diagnosed
Verywell / Cindy Chung 

Self-Checks/At-Home Testing

Home self-checks and home testing do not currently have a role in the diagnosis of multiple myeloma. Bone pain is a very common finding in multiple myeloma, but there is nothing akin to a breast or testicular cancer self-exam that you can do at home. That said, persistent fatigue and pain that is presumed to be from something else, but does not respond to treatment, especially in an older person, should not be ignored.

Early signs and symptoms of multiple myeloma can easily be confused for other conditions.

In about one-third of cases, multiple myeloma is detected via routine blood screening when a person is being evaluated for some unrelated problem. In another one-third, multiple myeloma is diagnosed after it causes a so-called pathologic fracture, often involving the vertebrae of the lower back. 

Labs and Tests

The diagnosis of multiple myeloma depends on a variety of different tests, including blood tests, bone marrow tests, and imaging of the bones.

Plasma cells are part of the immune system, and their main job is to make large volumes of antibody, to help fight infection. In multiple myeloma, there is a malignant "clone" of plasma cells, with many copies of the same plasma cell present, all producing an identical protein (a monoclonal protein, or M protein), which is abnormal. This M-protein is helpful in the diagnosis of multiple myeloma, however not all cases of multiple myeloma secrete M-protein, and not all M-protein is from multiple myeloma.

Blood Tests

Like cervical cancer and colon cancer, in myeloma, there can be pre-cancerous conditions that lead to full-fledged malignancy. Abnormal plasma cell conditions range from pre-cancerous ones such as MGUS (monoclonal gammopathy of undetermined significance), to ones that are cancerous but non-active (or, so-called smoldering multiple myeloma) to the symptomatic/active multiple myeloma that requires treatment.

Laboratory tests to initially screen for multiple myeloma include a complete blood count, along with a count of the specific, different types of blood cells, and examination of a sample of your blood, or a smear, under the microscope. Tests of your blood chemistry will measure calcium and other substances and markers that can help evaluate your risk (creatinine, albumin, lactate dehydrogenase, beta-2 microglobulin, and C-reactive protein).

The workup for suspected myeloma also includes blood tests that provide information about the types and quantities of the different antibodies you have in your blood. In some cases, these tests look for small pieces of a whole antibody, or immunoglobulin light chains. The official names of these antibody-protein tracking tests are as follows:

  • Serum free monoclonal light chain (FLC) analysis
  • Serum protein electrophoresis (SPEP) with immunofixation and quantitation of immunoglobulins. 

Urine Tests

Since the protein markers of interest in myeloma can sometimes pass to the urine, tests may be done on your urine as well.

Viscosity Testing

With excess protein from the myeloma, sometimes blood can become too thick, or viscous, like too much flour in the batter. When this happens, it is called hyperviscosity. So, your blood viscosity will also be measured if the M-protein concentration is high (greater than 5 g/dL) or there are symptoms suggestive of hyperviscosity (such as bleeding in mucous membranes, bloody nose or bleeding gums; nervous symptoms such as headache, vision changes, double vision, dizziness, hearing loss).

Bone Marrow Aspiration and Biopsy

If you have multiple myeloma, there will be an excess of plasma cells in your bone marrow. The test used to check the bone marrow is called a bone marrow biopsy and aspiration, and it can either be done at the doctor's office or at the hospital. In the case of a bone marrow biopsy, a small piece of the involved section of bone marrow will be removed and examined under a microscope. It’s considered a simple surgery, performed under a general anesthetic. The sample of your bone marrow is then used for many different tests (immunophenotyping, conventional cytogenetics, and fluorescence in situ hybridization, or FISH) that reveal information about your malignancy, its markers, and, potentially, actionable information in terms of its treatment.

A bone marrow evaluation is indicated for all patients with multiple myeloma at diagnosis, and for patients suspected of MGUS (monoclonal gammopathy of undetermined significance) or smoldering myeloma in order to rule out the diagnostic of multiple myeloma.

Imaging

Imaging is done to see if multiple myeloma may be affecting your bones. Depending on what kinds of imaging tests are available to you, a variety of techniques, or different scans, may be used. 

Radiographic Skeletal Survey

Traditionally, a skeletal survey is performed, which consists of x-rays of the skull, spine, arms, ribs, hips, and thighs. 

PET/CT or MRI

Today, many facilities use whole body imaging, with positron emission tomography (PET/CT) or MRI. 

In a PET scan, a form of radioactive sugar (known as FDG) is injected into the blood. Many times, cancer cells in the body are growing quickly and absorb large amounts of the sugar, creating an image showing radioactivity in the body in areas of cancer involvement. The image is not detailed like a CT or MRI scan, but it provides useful information about the whole body. Often PET and CT scans will be combined at the same time (PET/CT scan) to allow areas of higher radioactivity on the PET scan to be compared with the more detailed appearance of that area on the CT scan.

Each imaging technique has its own strengths and limitations, and, depending on your particular case, one may be preferred over another.

Echocardiography

Another imaging test that may be done in some patients with multiple myeloma is an echocardiogram. Sometimes, and more frequently, as patients with multiple myeloma are living longer and longer, the excess protein in the blood leads to a condition called amyloidosis. Since amyloidosis often affects the heart, an echocardiogram (ECHO) may be ordered. This test is basically an ultrasound of the heart muscle to show how well it is working. If the heart muscle is affected by amyloidosis, it looks different from normal heart muscle.

Differential Diagnoses

It is important to distinguish multiple myeloma from benign causes that have the same findings, and from other plasma cell malignancies, in order to formulate the prognosis and treatment plan.

When bone or back pain and fatigue lasts more than two to four weeks in an older person, despite treatment for that pain, it should prompt further evaluation for multiple myeloma, as well as several other conditions. 

However, lower back pain is extremely common in the general population such that the vast majority of people with lower back pain do not have multiple myeloma.

Among the conditions that might cause persistent bone pain and fatigue are vitamin D deficiency, hyperparathyroidism, an autoimmune disorder called polymyalgia rheumatica, and bone metastasis from a different cancer.

Among the top conditions that may appear to be active myeloma but are not:

  • MGUS (monoclonal gammopathy of undetermined significance)
  • Bone involvement from a different cancer in a person with MGUS
  • Smoldering multiple myeloma
  • Solitary plasmacytoma (just one isolated area of myeloma, not multiple)
  • Waldenström macroglobulinemia 
  • AL (amyloid light chain) amyloidosis not due to multiple myeloma
  • POEMS syndrome (aka osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) 

Updated Diagnostic Criteria

In 2014, the revised International Staging System (R-ISS) for myeloma was introduced, with updates including specific biomarkers in addition to the established markers of end-organ damage. It used to be that, in order to receive treatment, a person had to have the so-called CRAB symptoms of myeloma: CRAB (hyperCalcemia, Renal insufficiency, Anemia, or new Bone lesions).

CRAB symptoms still qualify as active multiple myeloma, but today, if CRAB symptoms are absent, you can still be considered high enough risk to receive treatment for active multiple myeloma.

The international expert myeloma group added biomarkers associated with “near inevitable development” of CRAB features were added to the criteria (bone marrow plasma cells (BMPCs) greater than or equal to 60 percent; involved/uninvolved serum free light chain ratio greater than or equal to 100; diagnostic imaging showing osteolytic bone destruction with more than one focal lesion, with each lesion greater than 5 mm). 

The diagnostic criteria for smoldering multiple myeloma are: a serum M protein level of 3 g per dL (30 g per L) or more, 10 percent or more bone marrow plasma cells, and no related organ or tissue impairment (no end-organ damage, including bone lesions) or symptoms. 

A Word From Verywell

To be diagnosed with multiple myeloma is life-changing. For now, focusing on feeling better and forging the path forward is key. Though multiple myeloma is not the most common blood cancer, thousands are walking in your footsteps as you read this.

In addition to anticipated future advances in the diagnoses of myeloma, you can also take heart that, if you are being diagnosed today, the treatment options you and your health care providers have at your disposal are vastly superior to those available even 5 or 10 years ago. Not only are there aggressive options that allow younger, fitter patients to battle the disease with all they’ve got, but also highly effective yet lower-toxicity regimens that aim to extend life without as much sacrifice to the quality of life.

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Article Sources
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  • Rajkumar SV, Kumar S. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2016;91(1):101-119. DOI: 10.1016/j.mayocp.2015.11.007