Multiple Myeloma Diagnosis

Multiple myeloma (MM) is a blood cancer that affects the plasma cells found in bone marrow, a key component of the immune system. Distinct from blood plasma—the liquid portion of blood—bone marrow plasma cells produce antibodies (immunoglobulins) that help the immune system fight off infections. In MM, plasma cells undergo cancerous changes that cause them to multiply uncontrollably and produce abnormal immunoglobulins, which can accumulate in the bone marrow and form tumors (plasmacytomas).

Diagnosing multiple myeloma can be challenging because the condition usually does not cause noticeable symptoms in its early stages. As a result, it is often discovered incidentally during a routine blood test or urinalysis, which can detect harmful proteins produced by cancerous plasma cells. Because an early diagnosis and treatment are essential to achieve the best possible outcome and quality of life, those at heightened risk of developing multiple myeloma—which may be due to a preexisting plasma cell disorder or family history of MM—are encouraged to undergo regular screenings for abnormal plasma cell activity.

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Multiple myeloma is usually diagnosed through a multi-step process. In addition to a clinical evaluation, this may include:

Laboratory tests used for diagnosing multiple myeloma

The diagnostic process for MM may include one or more lab tests, such as:

Blood work for multiple myeloma

Specialized blood tests can help the physician detect abnormal protein levels, assess kidney function and evaluate blood cell counts, all of which can be affected by multiple myeloma. Options may include:

• Calcium blood test – Myeloma-related bone degradation can release excess calcium into the bloodstream, causing hypercalcemia.
• Complete blood count (CBC) – Multiple myeloma can cause low blood cell counts. CBC measures the levels of red blood cells, white blood cells and platelets in the blood.
• Serum protein electrophoresis (SPEP) – SPEP can detect abnormal monoclonal (M) proteins, which are produced by myeloma cells. An M-protein spike is a key indicator of MM.
• Serum-free light chain assay – This test measures the levels of free kappa and lambda light chains in the blood, which may be elevated in multiple myeloma and related disorders.
• Immunofixation electrophoresis (IFE) – If M proteins are found in the bloodstream, IFE can identify the specific type (IgG, IgA, IgM, IgD or IgE), which can influence cancer progression, response to therapy and overall prognosis.
• Beta-2 microglobulin (B2M) test – High blood levels of beta-2 microglobulin may indicate advanced multiple myeloma.
• Creatinine and blood urea nitrogen (BUN) tests – MM can impair kidney filtration due to protein buildup. BUN tests can help the physician evaluate kidney function.

Urinalysis for multiple myeloma

Urine testing can detect abnormal proteins excreted by myeloma cells as well as kidney damage caused by multiple myeloma. Options may include:

• 24-hour urine collection – This relatively simple test involves collecting all urine produced over 24 hours, which can be used to measure protein levels.
• Urine protein electrophoresis (UPEP) – UPEP can detect Bence Jones proteins, a type of free light chain associated with MM.
• Urine immunofixation electrophoresis (IFE) – If M proteins are detected in the urine, IFE can identify the specific type.

Bone marrow testing for multiple myeloma

Specialized lab tests can allow for a direct examination of bone marrow plasma cells, which can help the physician confirm an MM diagnosis, determine the extent of abnormal cell growth and identify small amounts of myeloma cells after treatment is complete (minimal residual disease). Bone marrow lab tests include:

Flow cytometry for multiple myeloma

This lab technique can be used to analyze a sample of bone marrow plasma cells in a blood sample or biopsy. By examining cell surface markers and protein expression, the physician can differentiate between healthy and abnormal plasma cells, determine the characteristics of myeloma cells and rule out other plasma cell disorders.

Cytogenetic analysis and fluorescence in situ hybridization (FISH) for multiple myeloma

Genetic testing can detect chromosomal abnormalities and mutations associated with MM, which can help the physician predict cancer progression and plan treatment. Cytogenetic testing involves the microscopic examination of plasma cell chromosomes to identify structural changes that may indicate aggressive cancer progression. FISH is a more advanced technique that uses fluorescent probes to identify specific genetic mutations linked to multiple myeloma.

Imaging tests used for diagnosing multiple myeloma

MM can weaken and damage bones, particularly the skull spine, ribs and pelvis. Imaging can help the physician identify bone lesions, fractures and other structural abnormalities that may be related to the cancer. It can also help the physician determine the stage of multiple myeloma and identify possible complications, such as spinal cord compression and organ involvement. Additionally, by comparing images captured before and after therapy, the physician can monitor the response to treatment.

Common ways of imaging used during the diagnostic process for multiple myeloma include:

X-rays (skeletal survey) for multiple myeloma

Often the first imaging test used to identify bone damage caused by MM, a skeletal survey is a series of radiographic images taken of the skull, spine, ribs, pelvis and long bones, which the physician can analyze to check for areas of bone loss (lytic lesions). Although X-rays may reveal severe bone damage, the images may not be refined enough to detect early-stage myeloma or small lesions that have not yet caused significant bone destruction.

Magnetic resonance imaging (MRI) for multiple myeloma

MRI scans can provide detailed visuals of bone marrow and soft tissues, which can help the physician detect a plasmacytoma before bone damage occurs and identify bone marrow infiltration, which can be a sign of smoldering multiple myeloma or early-stage MM. Magnetic resonance imaging can also be useful for evaluating spinal cord compression, a potentially serious complication of multiple myeloma that can occur if a myeloma-related tumor presses on a spinal nerve.

Computed tomography (CT) for multiple myeloma

CT scans create detailed cross-sectional images of bones and soft tissues, offering a more comprehensive view than X-rays. For instance, a low-dose whole-body CT scan may be used in place of a skeletal survey to detect bone lesions with higher accuracy. Computed tomography can also be used to guide a biopsy, where a sample of suspicious tissue is collected for microscopic examination by a pathologist, who can identify cancerous cells.

Positron emission tomography (PET) for multiple myeloma

Unlike X-rays, MRI and CT scans—which primarily show the structure of organs and tissues—PET scans show metabolic activity. This imaging test can help the physician identify active multiple myeloma lesions by detecting areas of the body with rapid cell growth. After a small amount of radioactive glucose is injected into the bloodstream, a PET scanner will highlight areas of the body where the glucose accumulates, which may suggest an active tumor. Because a PET scan can help the physician distinguish active MM from an inactive (healed) lesion, this imaging technique can be particularly useful for evaluating treatment response.

Procedures used for diagnosing multiple myeloma

In addition to laboratory tests and imaging studies, certain specialized procedures can help the physician confirm the presence of cancerous plasma cells, evaluate bone marrow involvement, detect abnormal proteins and determine the extent of organ and bone damage. These diagnostic procedures may include:

Bone marrow aspiration and biopsy for multiple myeloma

A critical procedure for diagnosing MM, bone marrow aspiration and biopsy allows for a direct examination of bone marrow plasma cells. During the procedure, the physician will insert a hollow needle into the hip bone (or possibly the sternum) to extract a small sample of liquid bone marrow (aspiration) and a core of solid bone marrow tissue (biopsy). The samples will then be microscopically analyzed in a laboratory to determine the percentage of plasma cells present and identify any genetic abnormalities or mutations that may influence treatment decisions. A high percentage of abnormal plasma cells in the bone marrow may point to multiple myeloma or a precursor condition, such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma.

Lumbar puncture (spinal tap) for multiple myeloma

A spinal tap may be performed if the physician suspects central nervous system (CNS) involvement in multiple myeloma, which is rare but possible in advanced cases. During this procedure, the physician will use a thin needle to collect a small amount of cerebrospinal fluid (CSF) from the lower spine. The fluid will then be microscopically examined by a pathologist, who can determine if cancer has spread to the CNS.

Next steps after a multiple myeloma diagnosis

If a diagnosis of MM is confirmed, the next steps may include:

• Staging the cancer – Additional tests, such as blood work, imaging scans and bone marrow analysis, can help the physician evaluate the extent of MM and classify it as smoldering myeloma, active myeloma or advanced-stage myeloma.
• Developing a treatment plan – A hematologist or oncologist can suggest a personalized treatment approach based on the stage of the cancer, its genetic markers and the patient’s overall health. Options may include radiation therapy, chemotherapy, immunotherapy and/or bone marrow transplantation.
• Managing symptoms – Bone pain, kidney dysfunction, anemia and immunosuppression caused by multiple myeloma can often be addressed with supportive therapies, such as bisphosphonates, blood transfusions and physical therapy.
• Considering clinical trials – Some patients may wish to explore clinical trial opportunities to access new and emerging treatments for multiple myeloma.
• Monitoring cancer progression – Through ongoing blood tests, imaging studies and bone marrow testing, the physician can assess the treatment response and cancer progression.

The patient may also want to discuss lifestyle adjustments, nutrition planning and emotional support options with their care team to enhance their quality of life during multiple myeloma treatment.

Benefit from world-class care at Moffitt Cancer Center

The Malignant Hematology Program at Moffitt includes physicians who specialize in the evaluation and treatment of multiple myeloma and other types of plasma cell cancer. We offer the latest therapies for MM, including radiation therapy, chemotherapy, immunotherapy and bone marrow transplantation, in addition to a robust portfolio for clinical trials and supportive care.

If you would like to learn more about the diagnostic process for multiple myeloma, you can request an appointment with a specialist in Moffitt’s Malignant Hematology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.