Multiple Myeloma

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Multiple Myeloma
Abstract
Multiple Myeloma is a plasma cell cancer that causes an overproduction of plasma cells.
Multiple Myeloma is a difficult disease to diagnosis because symptoms might not be present for
some patients until the advanced stages of the cancer. There are certain tests like blood and urine
tests, bone marrow biopsies and medical imaging that can be used to confirm and diagnosis this
disease. Medical imaging also plays an important role in the evaluation and diagnosis of this
disease. X-rays, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and
Positron Emission Tomography (PET) scans are each used to benefit the patient. Though this
cancer isn’t curable there are treatment options like chemotherapy, radiation therapy, and stem
cell transplant that can help manage the disease.
Introduction
Multiple Myeloma is a cancer of the plasma cells. Plasma cells are a type of white blood
cell. Multiple Myeloma is known by a few different names: Myelomatosis, plasma cell myeloma
and also Kahler’s disease.1 Plasma cells are a part of the body’s immune system. They play the
part of making antibodies to fight off infections. This cancer makes the plasma cells start
growing out of control. When this happens it alters the production of other cells like white and
red blood cells. Plasma cells are made in your bone marrow and when they start growing out of
control they start moving out of the bone marrow to other parts of the body. They damage the
kidneys as well as make bone legions. Multiple Myeloma is the “second most common
hematological malignancies and represents 1% of all malignant diseases.” 1(p.2) Multiple Myeloma
is difficult to detect early. Many patients don’t show any symptoms of the disease until it is in an
advanced or late stage. There are many test that can be performed to diagnosis multiple
myeloma. Tests include urine and blood tests, bone marrow biopsies and medical imaging
exams. Some of the medical imaging tests that can be used in diagnosis are x-rays, MRI, CT and
PET scans. Each of these tests can be used to help detect the cancer. Medical imaging is starting
to be one of the most common tools to diagnosis this disease.1,
1
Diagnosis
About 30% of patients are diagnosis with Multiple Myeloma because of routine blood or
urine tests done in the doctor’s office. These patients don’t show any symptoms or signs of
cancer. Another 30% of patients suffer from symptoms like bone pain of pathological fractures.4
“Additionally, many patients present with one or more nonspecific clinical complaints. These
include low back pain, generalized skeletal pain, fractures, fatigue, anemia, and sinus or upper
respiratory infections-symptoms often overlooked as being normal manifestation of aging.” 4(p.8)
For a true diagnosis of Multiple Myeloma, blood, urine, bone marrow biopsy and imaging exams
need to be done to rule out any other diseases. 3
Signs and Symptoms
Like many other diseases physicians usually will look for signs and symptoms before
trying to diagnose Multiple Myeloma. Some common signs and symptoms of Multiple Myeloma
cancer are listed below:
 Anemia
 Fatigue
 Bone pain
 Kidney damage failure
 Weight loss
 Hypercalcemia
 Fever and infections
 Blood clots 2
There are some patients with Multiple Myeloma that do not present with any signs or symptoms
until the later stages of the disease. This can make diagnosing the patient very difficult. In these
cases diagnosis of the disease is accomplished through other means like blood and urine tests. 2, 34
Risk Factors
Multiple Myeloma is a fairly common disease; According to the American Cancer
Society “In the United States, the lifetime risk of getting multiple myeloma is 1 in 143
2
(0.7%).”3(p.2) There are many risk factors that can increase someone’s chance of having Multiple
Myeloma, age is just one example of a risk factor that can increase your chances for getting the
cancer. For people 65 years of age or older the risk goes up significantly. Other risk factors
include:
 Gender; men slightly more than women
 Race; African Americans are more at risk than Caucasians

Radiation

Family history

Obesity

Having other plasma cell disease 3
Because the disease is difficult to diagnose, physicians will look at these risk factors to assist in
the diagnosis process. For example a Caucasian woman in her twenties with some of the signs
and symptoms of Multiple Myeloma is in a very low risk category. Medical staff can use this
information to rule out Multiple Myeloma and look at other diseases that have some of the same
symptoms.2, 3
Presentation of Multiple Myeloma
Multiple Myeloma affects 3 main systems: the skeletal, hematological and the renal
system.
Skeletal
In Multiple Myeloma there is the overproduction of plasma cells that infiltrates into the
bone marrow. This weakens the structure of the bone, and then there is a release of Osteoclast
Activating Factor (OAF). OAF is a type of protein that damages the bone and produces lytic
lesion and causes pathological fractures. 4
Hematological
Hematological normochromic and normocytic anemia are a common occurrence in
patient diagnosis with Multiple Myeloma. With the increase of plasma cell there is a decreased
amount of erythropoietin. 4
3
Renal
There is an occurrence of getting a myeloma kidney with this cancer. With the increase of
plasma cells, they are “filtered, catabolized, and excreted by the kidney, causes obstruction
dilation, inflammation and fibrosis of the epithelial cells lining the renal tubules” 4(p. 8). The
kidneys function then becomes severely impaired ultimately leading to kidney failure.4
Staging of Multiple Myeloma
There are 3 stages of Multiple Myeloma that physicians use to describe how far the
cancer has progressed. It is also used to show where the cancer is located and where it has spread
throughout the body. Learning what stage the cancer will assist the physician in knowing what
type of treatment would most benefit the patient. The Durie-Salmon system is used to stage the 3
different stages of Multiple Myeloma. 2
Stage I
In this stage of this disease there are typically no symptoms for the patient to experience .
This is sometimes known as smoldering myeloma. There are a small number of cancer cells in
the body. The red blood cells and calcium in the blood are in normal ranges. There is no
evidence of bone damage on conventional x-rays.
Stage II
At this stage more cancer cells are within the body. Kidney function begins to be
affected.
Stage III
There begins to be a great amount of cancer cells present in the body. At this point the
patient is suffering from anemia, hypocalcemia, and bone pain from the advanced bone lesions
and damage. 2, 3
X-ray
X-rays are a part of imaging Multiple Myeloma in patients. Skeletal surveys are used to
detect the cancer. A skeletal survey is x-rays of multiple bones in the body. Usually a skeletal
survey comprises x-rays of the skull, spine, ribs, pelvis, humerus and femur. Myeloma patients
have bones legions that can be seen form the x-rays of these body parts (see Figure 1).1, 3
4
Computed tomography
CT is also used as an imaging procedure for Multiple Myeloma. It is preferred that it is a
low dose CT scan to limit the radiation dose to the patient. CT is also used for the evaluation of
the disease progression.
There are some advantages to CT over conventional x-ray imaging. CT is a faster
alternative to imaging the bony structure than regular x-ray. Also, CT is more sensitive to seeing
bone legions and fractures on the image. Overall, CT is used in imaging the disease, but it is not
used as frequently as MRI. 1, 3
Magnetic Resonance Imaging
There has been an increase in the use of MRI for imaging Multiple Myeloma. MRI is an
imaging procedure that uses radio waves and very strong magnets instead of x-rays to make
images of the body. MRI’s can be very time consuming, but the images they produce are
incredibly detailed. Compared to a conventional x-ray, a MRI is able to “offer improved
detection of lesions in the spine, pelvis, sternum, skull and scapula” 1(p.10) in Multiple Myeloma
patients. MRI’s are used to look at bones, but also can be helpful in looking at soft tissues like
the brain and the spinal cord.5
One of the drawbacks to MRI is the time it takes to complete. Some MRI’s can take an
hour or longer. They can also be very noisy during the procedure. Possibly the biggest
drawback is that some patients can’t undergo the procedure due to medical devices. One
example would be a patient that has a pacemaker. Because the MRI machine uses a large
magnets to complete the procedure anything metal in the body has the risk of being pulled out by
the magnet.
MRI plays a role in imaging bone legions of patients with this cancer but it has a more
important role of imaging bone marrows. There are different manifestations or patterns of
infiltration in the bone marrow of myeloma patients. There are “salt and pepper”, focal or
multifocal, diffuse, and diffuse plus focal patterns.5 Each pattern is tied to the staging of the
disease. It is recommended that myeloma patients have a whole-body MRI to exclude additional
disease and evaluate and monitor the disease.1, 5
5
Positron Emission Tomography
The imaging procedure known as a PET scan stands for Positron Emission Tomography.
Before a PET scan procedure, there are radioactive tracers that are injected into the patient’s
vein. They are then scanned in a CT scanner. The radioactive tracers are absorbed into the body
and show how well the tissues and organs are working. The PET scan evaluates the blood flow,
metabolism, and oxygen intake of the organs and tissues. When the patient is scanned in the CT
scanner the radioactive tracers will show where any abnormalities within the body are located
(see Figure 2). It is the best way to monitor the patient’s response to treatment. CT and MRI will
show the bone legions even if the patient is in remission of the disease. PET scan is able to show
only the area on the body where the disease is active. This is an effective diagnostic tool for
physician to see the presence of a Multiple Myeloma and monitor it.6
Case Report
A 55 year old woman was going to a rheumatology clinic for joint pain and swelling. She
also noticed she had been losing weight and increasingly fatigued. She had a number of joints
affected with joint stiffness and swelling. The joints affected were the knees, shoulders, wrist,
and hand joints. At the clinic her physician found “generalized soft tissue swelling of her hands,
with markedly reduced wrist movements. Tinel’s and Phalen’s test were strongly positive
bilaterally consistent with carpel tunnel syndrome. No synovitis was present elsewhere and the
rest of her systemic examination was normal” 7(p.1)
Further testing was done. The results showed that she had normochromic anemia and
leucopoenia. She also had elevated calcium in her blood making her hypercalcaemic.
Through the blood testing it was also shown that she had decreased liver function and also
kidney disease. Hand x-rays were performed that showed narrowing of the wrist joints. Along
with these blood tests synovial fluid was execrated from her left knee and analyzed. The results
from the analyses show abnormal cells that resembled plasmablast. There was also evidence of
bone and cartilage damage.
The diagnosis for this 55 year old woman was aggressive Multiple Myeloma with the
presence of polyarthritis due to the plasmablast infiltration in the joints. There has been research
done that shows patients diagnosed with myeloma are susceptible to arthritis as shown in this
case. The prognosis was poor and she was in the advanced stages. She had advance bone
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legions, impaired kidney function, and the blood test showing hypercalcaemia along with
anemia. She was diagnosed with stage 3 Multiple Myeloma and died about 7 weeks later.
This case report shows that signs and symptoms of this cancer can be perceived as
something else, as in this case polyarthritis. This demonstrates the importance of being able to
diagnose the disease correctly and as early on as possible. Better diagnosis will lead to saving
more lives.7
Treatments
In the case of cancer the treatment highly depends on the stage or how advanced the
cancer is. In Multiple Myeloma it depends on what symptoms the patient is experiencing and the
total health of the patient. The overall goal of treatment is to kill the cancer cells and have
patients get back to their lives. In the case of Multiple Myeloma there is unfortunately no cure to
this cancer, but it can be managed. There are few common options for treatment listed below.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells growing in the body. Chemotherapy
is a combination of drugs that can be given by IV or orally. These drugs are given to stop the
cancer cells from spreading, but there can also be damage to healthy cells in the body. Having
chemotherapy can have side effects. Some common side effects are hair loss, decreased appetite,
nausea with vomiting, mouth sores and low blood counts. 8
Radiation Therapy
Radiation therapy is a common treatment for cancer. This type of therapy uses high
energy x-rays the go into the body and kills the cancer cells. Radiation therapy can also be used
to manage pain in myeloma patients. In certain advance stages of myeloma there is great
weakening of the spinal bones. This can cause pressure on the spinal cord along with leg
weakness, problems with urinary and bowel movements. Radiation therapy is the answer for
treatment for these conditions.
The type of radiation therapy used in this cancer is called external beam radiation
therapy. Where a certain body part is targeted and radiation is applied to the spot of cancer in the
body. Just like other treatments there are side effects of radiation therapy. They include,
reddening of the skin, nausea, vomiting, and fatigue. 8
Stem cell transplant
7
Stem cell transplant is another form of treatment for Multiple Myeloma. Before the stem
cell transplant is preformed the patient goes through chemotherapy and radiation therapy to
eliminate the cancer cells in the body. Then healthy stems cells either from another bone marrow
from the patient or from a donor is transplanted into the patient’s bone marrow.8
Prognosis
The prognosis for Multiple Myeloma is dependent on a few things. It depends on what
stage of the cancer the patient is at and how effectively they respond to the treatment. Survival
rates are lower for those who are older and higher for younger patients. The American cancer
society reports that about 33 % of patients with this cancer die within five years of diagnosis.
There is still no cure for Multiple Myeloma. 1-2
Conclusion
Multiple Myeloma is a common bone cancer in U.S. adults and the incidence of this
disease is increasing. The treatment of this cancer has come a long way but Multiple Myeloma is
still a challenging disease to diagnose and treat. Many medical imaging exams play a very
important role in the treatment and diagnoses of this cancer. Imaging exams like, conventional xray, MRI, CT, and PET have made it easier to see the legions on the bones and detect other
symptoms. Each of the different imaging techniques provides both benefits, and drawbacks. It is
important that there be several different options available to patients that might have better
results from one of the imaging types. Multiple Myeloma today is still an incurable disease and
the prognosis for it can vary depending on the stage of the cancer. Early detection is key in
saving lives.
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References
1. Derlin T, Bannas P. Imaging of multiple myeloma: Current concepts. World journal of
orthopedic. 2014; 5(3): 272-82. doi:10.5312/wjo.v5.i3.272.
2. Cancer.Net. Multiple Myeloma: Symptoms and Signs. http://www.cancer.net/cancertypes/multiple-myeloma/symptoms-and-signs. Accessed October 21.2014.
3. American Cancer Society. Learn About Multiple Myeloma. http://www.cancer.org/
cancer/multiplemyeloma/detailedguide/index. Accessed October 25, 2014.
4. Barrick MC, Mitchell SA. Multiple Myeloma: Recent advances for this common plasma
cell disorder. American Journal of Nursing. 2001; 101(1); 6-12.
http://journals.lww.com/ajnonline/Fulltext/2001/04001/Multiple_Myeloma__Recent_adv
ances_for_this_common.2.aspx#P9. Accessed October 22, 2014.
5. Koppula B, Kaptuch J, Hanrahan CJ. Imaging of Multiple Myeloma: Usefulness of MRI
and PET/CT. Seminars in Ultrasound, CT and MRI. 2013; 34(6); 566-577.doi:
10.1053/j.sult.2013.05.006.
6. Agarwal A, Chirindel A, Shah BA, Subramaniam RM, Evolving role of FDG PET/CT in
multiple myeloma imaging and management. American Journal of Roentgenlolgy.2013;
200(4):884-90. doi 10.2214/AJR.12.9653.
7. Molloy CB, Peck RA, Bonny SJ, et al. An unusual presentation of multiple myeloma: a
case report. Journal of Medical Case Reports.2007; 84(1):1-3. doi: 10.1186/1752-19471-84.
8. Watanabe R, Tokuhira M, Kizaki M. Current approaches for the treatment of multiple
myeloma. International journal of hematology. 2013; 97(3): 333-344.doi
10.1007/s12185-013-1294-z.
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Figures and Captions
Figure 1. This is a single radiographic image of the skull in a skeletal survey that demonstrates
bone legions in a Multiple Myeloma patient. Image courtesy of: American Cancer Society. Learn
About Multiple Myeloma. http://www.cancer.org/cancer/multiplemyeloma/detailedguide/index.
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Figure 2. The picture on the left shows many bone lesions in a Multiple Myeloma patient. The
picture on the right is the same patient after a course of chemotherapy and radiation therapy.
Image courtesy of : Agarwal A, Chirindel A, Shah BA, Subramaniam RM, Evolving role of
FDG PET/CT in multiple myeloma imaging and management. American Journal of
Roentgenlolgy.2013; 200(4):884-90. doi 10.2214/AJR.12.9653.
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