Multiple Myeloma: Causes, Signs and Treatments

1.0 Introduction
Human body is consisting of so many of cells, almost uncountable. Normal human body cells are growing, dividing into new cell and dying in an orderly fashion. There are different how the body cell is growing between normal cells and cancer cells. Instead of dying, cancer cell continue to grow and form news and abnormal cells. Differ from normal cells; cancer cells can invade other tissue. The cancer cells are the cell that is growing out of control and invading the other cell.

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When cancer cells diffuse the blood vessel or lymph vessel, the process called metastasis can happen. It is a process where the cancer cells travel, grow out and form new tumors at the other part of the body but it is always named from its origin. Different types of cancer can act very differently like they growing at different speed and respond to different treatments. Not all tumors are cancerous. They are called benign tumor. This type of tumors cannot invade others tissues and cannot metastasize. This kind of tumors are almost never life threatening.
Multiple myeloma is a cancer of plasma cells. It is malignant cancer cells. The other names for multiple myeloma are plasma cell myeloma or Kahler’s disease. Plasma cell is a type of white blood cells that functioning as producer of antibodies. In the human body, the interference of the production of normal blood cells happened because of multiple myeloma, when the collection of abnormal plasma cells is accumulating in the bone marrow.
The multiple myeloma usually started at the bone marrow. Bone marrow is the soft, spongy tissue that can be found inside the most bone in the human body. The breastbone, spine, ribs, skull, pelvic bones, and femur are rich with marrow. The myeloma cells that accumulate in the bone marrow can destroy the solid part of the bone. It is called multiple myeloma when more than on of the bone have the collection of myeloma cells. Besides that other tissue and organ like, kidneys can be affected and damaged by this disease. This is because the myeloma cells can produce antibodies that called M protein and other protein. They can be found and collected in the blood, urine and organs.
2.0 LITERATURE REVIEW
2.1 CAUSES
The etiology of the multiple myeloma is poorly known to the physician. According to (Multiple myeloma 2011) although the exact cause is unknown, the one thing for sure is multiple myeloma is begin with one abnormal plasma cell and its started to multiple in bone marrow (Multiple myeloma 2011).
2.2 CLINICAL FINDING
Usually the multiple myeloma is found out accidently when the patients do the routine blood test for another reason. The blood test result will indicate that patients have anemia, abnormal red blood cells, high serum protein level and how levels of normal antibody. In addition, when patients do the urine test, the results will show that the calcium levels is high and same to go to blood urea nitrogen levels and creatinine levels. If the kidneys are not functioning properly, then there is high level of urea and creatinines exist in urine because the kidneys cannot eliminate these substances properly. When the protein electrophoresis is carried out, the result will shows a large M protein spike, high concentration of monoclonal lg and the Bence – Jones protein also detected. The marrow is examined by using bone marrow aspiration techniques. The multiple myeloma usually shows 10%-30% of the cells are plasma cells.
2.3 INCIDENCE OF MULTIPLE MYELOMA
Incidence of multiple myeloma means the annual diagnosing rate, or the number of new multiple myeloma case being diagnosed each year. According to (Multiple myeloma quick statistics 2012) multiple myelomas are seldom affected children, teenagers and young adults. The incidences of multiple myeloma are increased with age (Multiple myeloma quick statistics 2012). In 50s, 60s and 70s the incidences of the multiple myeloma is the highest (Multiple myeloma quick statistics 2012). According to (Multiple myeloma quick statistics 2012) 65 years old and above is the onset age for this disease, with an incidence rate of 28.6 per 100000 versus 1.8 per 100000 people under 65 years old. In addition, multiple myeloma is common in men and in individuals of African descent (Multiple myeloma quick statistics 2012). In Asian, about 1/100000 population/year will get multiple myeloma, while in Caucasian, 4/100000 population/ year will get multiple myeloma but, for African descent, 8-10/100000 population/year will get multiple myeloma (Multiple myeloma quick statistics 2012). According to (General information about plasma cell neoplasm 2012) the incidence of multiple myeloma in United States in 2012 is 21700. While in Canada, according to (Canadian statistics for multiple myeloma 2013) about 2300 new case of multiple myeloma is recorded in 2011.
2.4 MORTALITY OF MULTIPLE MYELOMA
The mortality rate for patients with multiple myeloma is high because the cure for this disease is still unknown to the people and physicians (Multiple myeloma quick statistics 2012). The median survival rate is approximately 3 or 5 years following a diagnosis of systematic multiple myeloma (Multiple myeloma quick statistics 2012). However, there are some patients that live 10 or 20 years following their diagnosing (Multiple myeloma quick statistics 2012). It is making things so unpredictable. According to (General information about plasma cell neoplasm 2012) 10710 of people have die from multiple myeloma in the United Stated. While in Canada, according to (Canadian statistics for multiple myeloma 2013) about 1370 people had die from multiple myeloma in 2011.
2.5 Risk factors
The real causes of multiple myeloma is stil unknown. physicians hardly aware why someone get the multiple myeloma and why others do not but, one thing for sure is multiple myeloma is not contangious disease. There are several risk factors that can contribute to the multiple myeloma.
Age over 65 years old
As the age increase, the change of developing multiple myeloma also increasing (Multiple myeloma 2013). According to (Multiple myeloma 2013) most people are diagnosed with myeloma after the age of 65 years old.
Race
According to (Multiple myeloma 2013) the african americans have the highest risk to get multiple myeloma while the asian americanshave the lowest risk. The reason of why this happen is unknown (Multiple myeloma 2013).
Gender
According to (Multiple myeloma 2013) in the United Stated, the numbers of men that are diagnosed with multiple myeloma is higher compared to women. The reason of why this happen is unknown (Multiple myeloma 2013).
Personal history of (MGUS) monoclonal gammopathy of undetermined significance
MGUS is a benign condition in which abnormal plasma cell make M proteins. Usually, its assystomatic and by running the blood test to the pateint, the abnormal M protein level can be found out (Multiple myeloma 2013). Sometimes people who have MGUS can develop certain cancers, like multiple myeloma(Multiple myeloma 2013).
Family history
The risk of getting multiple myeloma is increased if a close relative had the disease(Multiple myeloma 2013) .
2.6 SIGN AND SYMPTOMS
Usually, depending on how advanced the disease, the symptoms of multiple myeloma may be varies (What is multiple myeloma 2013). In the earliest stages, a person may be assystomatic (What is multiple myeloma 2013). When these symptoms present, its may be obscure and similar to those of other conditions also,it is kindly hard to diffrentiate whether it is multiple myeloma or other diseases. Sometimes not all patient have all these symptoms (What is multiple myeloma 2013).
Kidney problem
According to (What is multiple myeloma 2013) kidney damage can happen when the kidney filtering excess protein the blood and this may lead to renal failure. The symptoms like loss of appetite, fatigue, muscle weakness,conctipation, nausea and vomiting will appear when hypercalcemia overworks the kidneys (What is multiple myeloma 2013) .
Pain
One of the most common early symptom of the multiple myeloma is lower back pain or pain at the ribs area (What is multiple myeloma 2013). Because of accumulation of plasma cells and weakened bone structures, there is tiny fracture in the bone and it can leads to the lower back pain ot pain in the area of the fractures(What is multiple myeloma 2013).
Fatigue
According to (What is multiple myeloma 2013) the number of malignant plasma cells is increases in the bone marrow caused the growth and development of red blood cells in the bone marrow lessen it can lead to anemia. unusual tiredness and abnormal paleness is the common symptoms of anemia.
Recurent infection
According to (What is multiple myeloma 2013) myeloma patient have higher risk, about 15 fold than a healthy person to get infection, espeacially pneumonia. the immunity of patient is reduced from infections such as bacterial pneumonia, urinary tract infection and shingles and it is happened when the blood produces fewer white blood cell that functional to fight the infection , as the number of myeloma cell increases.(What is multiple myeloma 2013) .
Nervous system disfunction
Because of the bone structure is weakened and collapsed, it may encroach on thenerves, produce severe pain, tingling or numbnes (What is multiple myeloma 2013). Accoding to (What is multiple myeloma 2013) the abnormal proteins that have been produce by the myeloma cellswill contribute to the appearant of the symptoms and if it is produce in the large amounts, it will cause hyperviscosity.
2.7 PATHOPHYSIOLOGY
B-lymphocytes are developed from the stem cell in the bone marrow, and from them the plasma cells is being produces. The antibodies that can recognize antigen are carries by the B-cells. Antibodies are responsible in recognizing and destroying material and organisms such as bacteria. As his antibodies recognize and want to destroy the antigen, they will proliferate rapidly and become mature plasma cells. These plasma cells are monoclonal.
If there is damaged to the genetic materials when stem cell is develop to B cell, multiple myeloma will begin. This is because; it will lead to the development of plasmablast. The plasmablast will bond together inside the bone marrow because of production of adhesive molecule that allows them to do so. These myeloma cells are growing out uncontrollable and did not die naturally because of interference of a growth factor that called interleukin-6. Multiple myeloma patient have higher contain of plasma cells in their bone marrow compared to normal individual.
In this disease, a plasma B cell is genetically damaged and proliferated uncontrollably (Immune cells and multiple myeloma 2013). The antibodies are overproduced by cancerous cell and accumulated in bone marrow. The bone cells named osteoclasts are stimulated by altered plasma cell. The bone structure is dissolved by the enzymes that be produced by the Osteoclasts, caused some of the symptoms associated with the disease, including pain and disfigurement (Immune cells and multiple myeloma 2013). Normally, B cell is move freely around the body, that is why the cancerous cells are available in the blood stream and metastasis is a common thing. Usually, multiple tumors are available in different bones (Immune cells and multiple myeloma 2013).
The malignant myeloma cell will produce identical lg (immunoglobulin). The dysfunctional immunoglobulin’s that produce from myeloma cell are called paraprotein. They are called monoclonal because the myeloma cells are identical clones of a single plasma cell. Multiple myeloma will depress immune system because of action of paraprotein that destroy the functional lgs and other components of immune system. The malignant plasma cells also produce monoclonal light chain or incomplete lgs that call Bence – Jones protein and secreted in the urine.
2.8 HISTOPATHOLOGY OF THE MULTIPLE MYELOMA
According to (Tobias 2012), plasma cells from patients with myeloma are usually immature in appearance with centrally located nuclei, distinct nucleoli and perinuclear vacuolization. There are also often multinucleated plasma cells. Immunohistochemical analysis can verify monoclonality. The plasma cells produce monoclonal lgG or lgA that can be detected through a characteristic serum protein electrophoresis pattern. Eighty percent of the patients have a complete monoclonal lg in the serum and most of them simultaneously produce light chain in the urine (bence jones protein). The light chain concentration in the urine is often so low that Hellers urinary test is negative.
 
3.0 IMAGING MODALITIES OF MULTIPLE MYELOMA
There are several imaging modalities that can be used to rule out multiple myeloma. According to (Healy et al. 2011) the function of medical imaging in multiple myeloma is crucial in the initial staging of disease, in detection and characterization of complication and to asses’ patient response toward the treatment.
CONVENTIONAL RADIOGRAPHY
A full skeletal survey is done in order to rule out the multiple myeloma. This skeletal survey is included a frontal and lateral view of the skull, the cervical, thoracic and lumbar spine, a coned down frontal view of the dens axis, as well as frontal view of ribs cage, humeri, knees and pelvis (Healy et al. 2011).

According to (Healy et al. 2011) the evidence of multiple myeloma can be seen on the radiograph of skeletal survey in 80% of patient. The radiological evidence of multiple myeloma can been seen on vertebrae in 66%, ribs in 45%, skull in 40%, shoulder in 40%, and pelvis in 30% and long bones in 25% (Healy et al. 2011). The advantage of plain radiography compare to MRI is in discovering the cortical bone lesions in the radiograph. It also has the advantage of being easily available and inexpensive compare to the other imaging modalities (Healy et al. 2011).

One of the disfavor of conventional radiography is diffusion of bone marrow, which may or may not be associated with cortical bone destruction, is cannot be evaluated by the conventional radiography (Healy et al. 2011). Furthermore, the lytic lesions become clear and appear on plain radiography if only when 30-50% of the bone mineral density is already loss (Healy et al. 2011). In addition, the causes of the diffuse osteopenia that shown on the radiograph cannot be differentiate whether it is because of multiple myeloma or because of other reason such as osteoporosis (Healy et al. 2011). According to (Healy et al. 2011)because of plain radiograph required patient to be in varied positioning that is sometimes painful for the patients who are usually elderly and disable because of pathological fracture then this plain radiograph become disfavor for the multiple myeloma patients.
 
COMPUTED TOMOGRAPHY
According to (Healy et al. 2011) CT is a sensitive imaging modality in evaluating the osteolytic effects of multiple myeloma and has a higher sensitivity than conventional radiography at detecting small lytic lesions. The characteristic of myeloma disease like punched out lytic lesions, expansile lesions with soft tissue masses, diffuse osteopenia, fractures and rarely osteosclerosis can be detected by the CT scan (Healy et al. 2011).

If the CT, MRI and conventional radiography is being compared in patient with newly diagnosed multiple myeloma, then CT was advance than conventional radiography at defining lytic lesion and in combination with MRI, aiding in staging the extent of the disease(Healy et al. 2011). CT is more accurate than MRI in the assessing of fracture areas. According to (Healy et al. 2011) in case where MRI is negative, CT is used in identifying bone destruction, hence complementary imaging information may be provided. Furthermore, the presence and extend of extraosseous lesions is demonstrated accurately by CT scan. In image guided spinal or pelvic bone biopsy of MRI defined focal lesions; CT is preferred (Healy et al. 2011). Furthermore, CT can be done quickly and comfortable for the patient as they just need to be lying stilly.

According to (Healy et al. 2011) a disadvantage of CT is that it typically shows persistent bone lesions throughout the trend of the disease and unlike MRI and PET/CT, it cannot evaluate continued activity of myeloma in areas of anterior to bone destruction.
 
WHOLE BODY MRI
According to (Healy et al. 2011) in detecting diffuse and focal multiple myeloma in the spine as well as the extra axial skeleton, the whole body MRI is proven to be the most sensitive imaging modalities to do it. It is crucial to know that MRI preponderantly showing bone marrow infiltration, which may or may not be related with bone destruction (Healy et al. 2011).

MRI has capability to visualize large volumes of bone marrow without producing radiation exposure and in shorten time, its suitable and favorable method to evaluate disease within bone marrow (Healy et al. 2011). In addition as the number and pattern of lesions detected on MRI is mutual related very well with treatment outcome and overall survival, which is means MRI has prognostic significance (Healy et al. 2011). In patient with extraosseous lesions, it is important to define the degree of involvement and to asses for cord compression so MRI can be the best choice to do it.
 

According to (Michael 2011) ,although MRI is sensitive to the existance of disease, but it it not disease particular, that is why extra test such as direct aspiration of bone marrow and measurement of gamma globulin level to asses for plasmacytosis need to be taken. It is because the signal intensity profile and enhancement pattern produce by MRI is almost the same between any muscoskeletal tumor and myeloma.(Michael 2011). That is why, MRI may give worse or better result about the disease to the patients with myeloma, in the other word it may understage the disease or overstage the disease. (Michael 2011).
NUCLEAR IMAGING
Myeloma is a disease that is caused by overactivity of osteoclasts, with resultant liberation of bone and suppression of osteoblasts (Michael 2011). According to (Michael 2011) nuclear medicine bone scans are depended on osteoblastic activity for diagnosing. In addition, the extend and severity of the disease is underestimated by standard tecnetium -99m (99m Tc) bone scans. So, this bone scan should not be used mundanely.

According to (Michael 2011) 99m TC-MIBI can demonstrated the extend and intensity of bone marrow infiltration equally as well as MRI and it’s may serve as subtituition to MRI in cases in which MRI is not convenient.

According to (Michael 2011) the fast- negative rate of standard 99m Tc bone scintigraphy is high in diagnosing multiple myeloma. Additional test is required for the confirmation if the scan is positive with normal radiograph(Michael 2011).
PET/CT
PET/CT is a tomographic nuclear imaging tecnique that injected labelled radiopharmaceutical such as flouro-deoxy-glucose (FDG) into the patient then, followed by tomographic scanning 10-40 minutes later. Because of tumor cell have high metabolic rate and high glucose demand, then it can be differentiate from the normal cell by using thic tecnique. in detecting early bone marrow involvement with apparent of solitary plasmacytoma, PET/CT is used. Besides that, PET/CT also used in assessing the extent of active disease, detecting extramedullary involvement or evaluating treatment response given by the doctors to the multiple myeloma patient. (Michael 2011).

According to (Michael 2011) the most substantial benefits of PET/CT imaging is it has ability to differentiate between active myeloma and monoclonal gammopathy of undetermine significance (MGUS) smouldering disease.

According to (Michael 2011) the primary drawback of PET is it have limited spatial resolution, that can cause restriction in detecting subcentumetre lytic lesions seen on conventional radiography.
4.0 DISCUSSION
Multiple myeloma is known as the disease that is incurable but treaterable,. This disease is also progression slowly and can be repeated again. If this disease is in stage 1, it is very hard to diagnose this disease by the imaging modalities. Usually, in stage 1, this disease have normal bone structure or only isolated plasmacytoma. Most patient are diagnosed at stage 3. As there is no clear cause of these disease, so there is no method for preventing multiple myeloma.
5.0 TREATMENT FOR MULTIPLE MYELOMA
Though multiple myeloma is incurable, but with the good treatment the patient can be as normal as healthy person. According to (Multiple myeloma 2012) standard intervention options include:
Bortezomib (Velcade) (Multiple myeloma 2012)
It is administered intravenously. This drug will blocking the action of proteasomes and can lead to the death of cancers cell (Multiple myeloma 2012). For the people who are newly diagnosed and previously treated myeloma, this drugs can be useful and approvable.
5.2 Thalidomide (thalomid) (Multiple myeloma 2012)
This drug is suitable for the treatment of newly diagnosed multiple myeloma (Multiple myeloma 2012). This drug is admitted orally.
Lenalidomine (revlimid) (Multiple myeloma 2012)
This drug is more potent and causes fewer side effects than thalidomide (Multiple myeloma 2012). It is given orally. This drug can be used for the patient who has previously treated with myeloma and the patient with newly diagnosed myeloma (Multiple myeloma 2012).
Chemotherapy (Multiple myeloma 2012)
It is involves using medicines that need to be taken orally as a pill or through intravenous injection to kill myeloma cells (Multiple myeloma 2012). Chemotherapy is carry out in a cycles over a period of months,and then followed by a rest period (Multiple myeloma 2012). melphalan, cyclophosphamide, vincristine, doxorubicin and liposomal dexoribicin are the most common chemothreaphy drugs that has veen used in treating myeloma (Multiple myeloma 2012).
Corticosteroids (Multiple myeloma 2012)
For decade the treatment of the multiple myeloma is using corticosteroids, like prednisone and dexamethasone (Multiple myeloma 2012). The corticosteroids are come in pill form.
Stem cell plantation (Multiple myeloma 2012)
This treatment is done by using high doses of melphalan, and the immature blood cells that have been collected are transfused to subtitute diseased or damaged marrow (Multiple myeloma 2012). The stem cell is derived from the patient or donor (Multiple myeloma 2012).
Radiation therapy (Multiple myeloma 2012)
This treatment applies high energy penetration waves to destroy myeloma cell and restrain their growth (Multiple myeloma 2012). In the purpose of to shrinking myeloma cells in a specific area quickly, radiation therapy may be the best choice (Multiple myeloma 2012).
6.0 PROGNOSIS OF MULTIPLE MYELOMA
To see the posible outcome of a disease, prognosis is the right medical term for it. It is easy to apply the prognosis to a larger population of patients rather than to a single of patient. For example, it is easy to state that within one year, almost 35% of people in coma will be paralyzed, but it’s hard to accurately state when will a patient with multiple myeloma die or free from this disease because it is required a lot of patient research specifically.
According to (Multiple myeloma prognosis 2011) in multiple myeloma cases by using the international staging system, the prognosis can be done. With the helps of this system, the survival of the myeloma patient can be predicted by depending on stages. The average survival of 62 months for stage one, 42 months for stage 2 and 29 months for a disease that have entered the stage 3 of the disease prognosis ranking is predicted by the international staging system (Multiple myeloma prognosis 2011).
The differences of prognosis for multiple myeloma between one patient and others is the common thing. In this disease, 70 years old is the average age that people ussually get the multiple myeloma (Multiple myeloma prognosis 2011). Furthermore, based on the research, the older patient have low change of survival to be compared with younger patients as the older patient may have many other disease that can complicate the situation (Multiple myeloma prognosis 2011).
7.0 CONCLUSION
As the conclusion, we can say that imaging modalities have played a big role in diagnosing and treating multiple myeloma patient. Without imaging modalities like plain xray, ct scan , MRI, and others it is hard to diagnose for sure that a patient have multiple myeloma. In addition, it is also hard for physicians to see the progression of the disease or the progression of the treatment without imaging modalities. So, we should be grateful to have so many efficient imaging modalities that can be useful to patients and physicians. By having many imaging modalities, that is mean the doctors will have several choice of use according the type of disease. Different imaging modalities is the best for different types of disease. In this assigment, I can know which imaging modalities is the best for multiple myeloma. Besides that, by doing this assigment, I can learn and differenciate between normal and abnormal appearance of anatomical structures on the radiological images.