Diagnostic protocols and tests (multiple myeloma diagnosis)
Since most cases are found incidentally, it is essential to rule out several diseases before making a final assumption. In the diagnostic considerations of multiple myeloma, we should also think about similar problems, such as a primary lymphoma of the bone, or a metastatic bone disease, which also have pathologic fractures and behaves similarly in many cases. We should also rule out Waldenstrom macroglobulinemia, a lymphoproliferative disorder that also affects B lymphocytes. Still, instead of monoclonal paraprotein, we have a very high level of immunoglobulin M, also known as macroglobulin.
After suspecting a case of multiple myeloma, most patients require several studies to evaluate what type of blood cancer it is and how far it has reached to compromise the patient’s health.
The most important exams in the workup include:
They are naturally part of the workup, and many patients are actually diagnosed after a routine blood test. Complete Blood Counts are important to evaluate the number of blood cells, which is typically depleted. Coagulation is also abnormal, and the erythrocyte sedimentation rate is generally increased.
It is sometimes vital for the diagnosis and should be evaluated in a 24-hour collection. That’s the only way to accurately quantification a substance called Bence Jones protein, as well as creatinine and protein clearance. Having a very high protein level in the urine (higher than 1 gram in 24-hour urine) can help diagnose the disease.
This study can be useful to determine the presence of Bence Jones proteins in the urine. It also detects M proteins in the blood, and serum concentrations of 30 g/L and higher are important for diagnosing multiple myeloma.
Multiple myeloma may feature suppression of specific immunoglobulins. Thus, detecting immunoglobulin levels is important to diagnose the disease.
C-reactive protein and Beta-2 microglobulin
C-reactive protein reflects very well the activity of interleukin-6, a substance that promotes growth in plasma cells. Beta-2 globulin levels can be used as a tumor marker, and it is also increased in renal insufficiency.
This measurement is particularly important in patients with epistaxis (nosebleeds) and those who have been found with very high levels of M protein.
Using radiography is very helpful to find pathological fractures and other lesions in the bones. It is an integral part of the differential diagnosis because we should always rule out metastasis to the bones. Plain radiography is often enough to make a diagnosis. Still, we should perform a complete series of X-rays to cover the entire body and evaluate the presence of small pathological fractures and bone degradation areas (lytic lesions).
Magnetic Resonance Imaging
This imaging technique is advantageous to evaluate spinal cord compression and lumbar lesions in the spine. It detects abnormalities in asymptomatic patients with apparently regular X-rays, so it is imperative in the workup.
Positron Emission Tomography
It is potentially useful in combination with MRI to evaluate the patient and provide more accurate follow-ups. However, it is not yet a part of the standard practice in multiple myeloma.
Biopsies and aspiration
This is an important test for diagnosing multiple myeloma because the disease is characterized by an increase in the proportion of plasma cells in the bone marrow. Bone aspiration is also useful, but not as accurate as a biopsy.
Cytogenetic analysis of the bone marrow
It offers a prognosis of multiple myeloma because it shows which genes are compromised. A deletion of 17p13 is so far the most severe abnormality associated with a higher risk and shorter survival.
In blood histological studies, we will find giant plasma cells, which are up to 3 times larger than usual. They have particular characteristics that contribute to the diagnosis.
After testing the patient and performing a physical exam, we can make an accurate conclusion by using multiple myeloma diagnostic criteria. These criteria are divided into two groups:
- I: Plasma cell accumulation in soft tissues, examined by biopsy
- II: More than 30% of plasma cells in the bone marrow
- III: Spikes in monoclonal globulin measures (IgG greater than 3.5 g/dL or IgA greater than 2 g/dL)
- A: 10-30% of plasma cells in the bone marrow
- B: Spikes of monoclonal globulin, but lower than the above
- C: Bone degradation and lesions
- D: Residual levels of IgG (less than 600 mg/dL), IgM (less than 50 mg/dL) or IgA (less than 100 mg/dL)
Using the above criteria, we can diagnose multiple myeloma when we have:
- B, C, or D plus I or II
- A, C, or D plus III
- A, B, and C
- A, B, and D
We also have two staging systems to evaluate and stratify the patient according to the severity of the disease. They are the Salmon-Durie staging system and the International staging system, which was revised in 2015.