Human body is made up of trillions of living cells. Normal human body cells are growing, dividing into new cell and dying in an orderly fashion. Cancer begins when cells in a part of the body start to grow out of control. 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. Growing out of control and invading other tissues are what makes a cell a cancer cell.
When cancer cells get into the bloodstream or lymph vessel, the process called metastasis can happen. It is a process where the cancer cells travel to the other parts of the body, where they begin to grow and form new tumors. No matter where a cancer may spread, it is always named for the place where it started. Different types of cancer can behave very differently. They grow at different rates 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.
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According to â€¦â€¦.yg pdf tueâ€¦â€¦â€¦â€¦.., multiple myeloma is a type of cancer that affects certain white blood cells called plasma cells. Plasma cells and other white blood cells are part of the immune system, which helps protect the body from infection and disease. All white blood cells begin their development in bone marrow, the soft, spongy tissue that fills the center of most bone. Certain white blood cells leave the bone marrow and finish growing in other parts of the body. Some develop into plasma cells when the immune systems need to fight infection and disease.
Plasma cells produce antibodies, which are special chemicals that move through the bloodstream to help the body get rid of harmful substances. Each type of plasma cell responds to only one specific substance by making large amount of antibodies that find and fight that one substance. Since the body has many types of plasma cells, it can defend the body against many types of bacteria and diseases. When cancer involves plasma cells, the body keeps producing more and more of these cells. The unneeded plasma cells, all abnormal and exactly alike, are called myeloma cells.
Myeloma cells tend to collect in bone marrow and in the hard, outer part of bones. Sometimes they collect in only one bone and form a single mass or tumor, called a plasmacytoma. In most cases, myeloma cells collect in many bones, often forming many tumors and causing other problems. When this happens, the disease is called multiple myeloma. Since people with multiple myeloma have an abnormally large number of identical plasma cells, they also have too much of one type of antibody. These myeloma cells and antibodies can cause a number of serious medical problems. Each year, nearly 15000 people in the United States find out that they have multiple myeloma.
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.
Figure 1 showed a photomicrograph of bone marrow from patient with multiple myeloma.(Tobias 2012)
The immune system works to recognize and eliminate foreign material and pathogens. Multiple myeloma is a cancer of B lymphocytes,a type of immune cell (Immune cells and multiple myeloma 2013). In adults, B cells form and mature in the bone marrow. When activated, B cells produce Y-shaped proteins (antibodies) that are part of the immune response. Antibodies bind to their target leading to the destruction of the target and clearance from the body. The many different B cells in our bodies each make only one type of antibody. B cells that have become activated to produce antibodies are called 'plasma cells'.
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In multiple myeloma a plasma B cell becomes genetically damaged and proliferates uncontrollably (Immune cells and multiple myeloma 2013). The cancerous cells over-produce antibodies that may accumulate in the bone marrow. The altered plasma cells also stimulate bone cells called osteoclasts. Osteoclasts produce enzymes that dissolve the bone structure and cause some of the symptoms associated with the disease, including pain and disfigurement (Immune cells and multiple myeloma 2013). Because B cell normally move around the body, the cancerous cells are able to get in the blood stream and metastasis is very common. Frequently, multiple tumors are present in different bones (Immune cells and multiple myeloma 2013).
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 role of radiological imaging in multiple myeloma is important in the initial staging of disease, in detection and characterization of complication and in the evaluation of patient's response to treatment.
A full skeletal survey includes 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) almost 80% of multiple myeloma patients will have radiological evidence of skeletal involvement on skeletal survey. The multiple myeloma are most commonly effecting the 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 detecting cortical bone lesions. It also has the advantage of being universally available and relatively inexpensive compare to the other imaging modalities (Healy et al. 2011).
One of the disadvantages of plain radiography is diffuse bone marrow involvement, which may or may not be associated with cortical bone destruction, is not evaluable using conventional radiography (Healy et al. 2011). Furthermore, the lytic lesions become apparent on plain radiography only when 30-50% of the bone mineral density is already lost (Healy et al. 2011). In addition, diffuse osteopenia as a result of multiple myeloma cannot be distinguished on plain radiographs from more common cause of osteopenia like osteoporosis (Healy et al. 2011). Another drawback of plain radiography is that varied positions required for radiography film are painful for patients who are usually elderly and disabled due to previous pathological fractures (Healy et al. 2011).
Figures 2: Example of plain radiograph of multiple myeloma patients (Healy et al. 2011).
According to (Healy et al. 2011) CT is a sensitive imaging modality in detecting the osteolytic effects of multiple myeloma and has a higher sensitivity than plain radiography at detecting small lytic lesions. CT findings in myeloma consist of punched out lytic lesions, expansile lesions with soft tissue masses, diffuse osteopenia, fractures and rarely osteosclerosis (Healy et al. 2011).
If the CT, MRI and conventional radiography is being compared in patient with newly diagnosed multiple myeloma, then CT was superior to 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 evaluation of areas at risk of fracture. According to (Healy et al. 2011) CT is of use in identifying bone destruction in case where MRI is negative, hence may provide complementary imaging information. One of the advantages of CT is it accurately demonstrating the presence and the extent of extraosseous lesions and is the tool of choice utilized in image guided spinal or pelvic bone biopsy of MRI defined focal lesions (Healy et al. 2011). Furthermore, CT also has advantage of being quick and patient just lying comfortable.
According to (Healy et al. 2011) a disadvantage of CT is that it typically shows persistent bone lesions throughout the course of the disease and unlike MRI and PET/CT, it cannot assess continued activity of myeloma in areas of prior bone destruction.
figure 3: examples of low dose whole body ct (Healy et al. 2011).
WHOLE BODY MRI
According to (Healy et al. 2011) whole body MRI has emerged as the most sensitive imaging modality at detecting diffuse and focal multiple myeloma in the spine as well as the extra axial skeleton. It is important to know that MRI predominately reflects marrow infiltration, which may or may not be associated with bone destruction (Healy et al. 2011).
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MRI has ability to visualize large volumes of bone marrow without inducing radiation exposure and in an acceptable amount of time, its suitable and favorable method to evaluate disease within bone marrow (Healy et al. 2011). In addition it's also has prognostic significance, the number and pattern of lesions detected on MRI correlates very well with treatment outcome and overall survival (Healy et al. 2011). In patient with extraosseous lesions, MRI is the study of choice to define the degree of involvement and to evaluate for cord compression.
Figure 4: example of whole body MRI (Healy et al. 2011).
According to (Michael 2011) MRI, although sensitive to the presence of disease, is not disease specific because, almost any musculoskeletal tumor has the same signal intensity profile and enhancement pattern as myeloma. So, additional test must be employed to diagnose myeloma, such as measurement of gamma globulin levels and direct aspiration of bone marrow to asses for plasmacytosis (Michael 2011). That is why, MRI may understage or overstage patients with myeloma (Michael 2011).
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 rely on osteoblastic activity for diagnosis. As such, standard tecnetium -99m (99m Tc) bone scans have underestimated the extend and severity of disease and should not be used routinely.
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 alternative to MRI in cases in which MRI is not readily available or when its use is limited.
According to (Michael 2011) the fast- negative rate of standard 99m Tc bone scintigraphy in diagnosing multiple myeloma is high. Scans may be positive with normal radiographs, requiring another test for confirmation (Michael 2011).
PET/CT is a tomographoc nuclear imaging tecnique that uses a labelled radiopharmaceutical such as flouro-deoxy-glucose (FDG) injected inti the patient followed by tomographic scanning approximately 10-40 minutes later. Tumor cell can be imaging with this tecnique due to their high metabolic rate and the resulting high glucose demand, allowing tumour cells to be distinguished from normal cells. PET/CT is used to the patient with multiple myeloma to detect early bone marrow involvement with apparenr solitary plasmacytoma, to assess the extent of active disease, detect extramedullary involvement or evaluate treatment response (Michael 2011).
According to (Michael 2011) one of the most significant advantages of PET/CT imaging is its ability to distinguish between active myeloma and monoclonal gammopathy of undetermine significance (MGUS) smouldering disease.
According to (Michael 2011) the main limitation of PET is limited spatial resolution, which may result in limitation in detecting subcentumetre lytic lesions seen on plain radiography
CAUSES OF MULTIPLE MYELOMA
The etiology of the multiple myeloma is poorly known to the physician. According to (Multiple myeloma 2011) although the exact cause is not known, doctors do know that multiple myeloma begins with one abnormal plasma cell in bone marrow. This abnormal cell then starts to multiply (Multiple myeloma 2011).
SIGN AND SYMPTOM
Usually, the symptoms of multiple myeloma depend on how advanced the disease has become (What is multiple myeloma 2013). In the earliest stages, a person may be assystomatic (What is multiple myeloma 2013). When present, its may be vague and similar to those of other conditions. Sometimes not all patient have all these symptoms (What is multiple myeloma 2013).
According to (What is multiple myeloma 2013) excess protein in the blood, which is filtered through the kidneys, can cause kidney damage and lead to renal failure. Hypercalcemia overworks the kidneys and can cause a variety of symptoms including loss of appetite, fatigue, muscle weakness, restlessness, diffficulty in thinking or confusing, constipation, increased thirst, increased urine production and nausea and vomiting (What is multiple myeloma 2013) .
It is a common early symptom of multiple myeloma is pain in the lower back pain or in he ribs (What is multiple myeloma 2013). This is caused by tiny fractures in the bones caused by accumulation of plasma cells and weakened bone structures (What is multiple myeloma 2013).
According to (What is multiple myeloma 2013) as the number of malignant plasma cells increases in the bone marrow, the growth and development of red blood cells in the bone marrow may be supressed, leading to anemia. Anemia can result in unusual tiredness and abnormal paleness.
According to (What is multiple myeloma 2013) myeloma patient have as much as a 15 fold increase in risk of infections, particularly pneumonia. As the number of myeloma cells increases, the blood often produces fewer white cells to fight infection, leading to an overall reduction in immunity from infections such as bacterial pneumonia, urinary tract infection and shingles (What is multiple myeloma 2013) .
Nervous system dysfunction.
Weakening and collapsing bone structures may impinge on nerves, producing severe pain, tingling or numbnes (What is multiple myeloma 2013). Myeloma cells often produce abnormal proteins which contribute to the symptoms and in large amounts, cause hyperviscosity (What is multiple myeloma 2013).
Risk factors of multiple myeloma.
The exact causes of multiple myeloma is stil unknown. Doctors seldom know why one person develops this disease and another doesn't. 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.
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).
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 monoclonal gammopathy of undetermined significance (MGUS)
MGUS is a benign condition in which abnormal plasma cell make M proteins. Usually, its assystomatic and the abnormal level of M protein is found with a blood test (Multiple myeloma 2013). Sometimes people who have MGUS can develop certain cancers, like multiple myeloma(Multiple myeloma 2013).
The risk of getting multiple myeloma is increased if a close relative had the disease(Multiple myeloma 2013) .
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). The peaks incidences are in the 50s, 60s and 70s (Multiple myeloma quick statistics 2012). According to (Multiple myeloma quick statistics 2012) multiple myelomas are most common among people over 65 years old, 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.
MORTALITY OF MULTIPLE MYELOMA
One of the fastest growing types of cancer in the western world is multiple myeloma (Multiple myeloma quick statistics 2012). Patient with multiple myeloma have a high mortality rate because there is no known cure for this disease (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.
PROGNOSIS OF MULTIPLE MYELOMA
Prognosis is a medical term to describe the possible outcome of a disease. 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 35% of people in coma will be paralyzed within one year, but it's hard to accurately state that a specific patient with multiple myeloma will die within a specific eriod as this might involve a lot of patient specific research.
According to (Multiple myeloma prognosis 2011) in multiple myeloma cases, the prognosis can be done using the international staging system. With the helps of this system, the survival of the myeloma patient can be predicted by depending on stages. The system predicts 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 (Multiple myeloma prognosis 2011).
Just like any other disease, the prognosis for multiple myeloma may be different between one patient to others. In this disease, the average age of onset is about 70 years old (Multiple myeloma prognosis 2011). Furthermore, it has also been found that younger patients have more change of survival than the older ones as the older ones could be having many other diseases that complicate the situation (Multiple myeloma prognosis 2011).
IMAGE FEATURES OF MULTIPLE MYELOMA
FIGURE 5: showed osteolytic lesions that are characteristic areas of damage caused by myeloma (Karen 2010). Lesions with a specific " punched out"appearance (Karen 2010).
Pepper pot skull appearance
Figure 6: showed a lateral radiograph of skull that show numerous diffuse lytic lesions giving classical "pepper pot skull" appearance (Healy et al. 2011).
Figure 7 showed a plain radiograph of humerus (Healy et al. 2011). The above arrow shows the diffuse lytic lesions while the below arrow shows old phathological fracture (Healy et al. 2011).
Figure 8 showed a coronal T1- weighted magnetic resonance image through a myeloma lesion of the humerus (Michael 2011). This image shows that the lesion has a low intensity (Michael 2011). The outer cortical margin is eroded but intact (Michael 2011).
Axial computed tomography (CT) scan of the glenoid
Figure 9 showed an axial computed tomography (CT) scan of the glenoid (Michael 2011). This image shows a well define lesion, with the typical CT scan appearance of myeloma (Michael 2011). The cortex is intact (Michael 2011).
TREATMENT FOR MULTIPLE MYELOMA
Though multiple myeloma is incurable, but with the good treatment the patient can return to near normal activity. According to (Multiple myeloma 2012) standard treatment options include:
Bortezomib (Velcade) (Multiple myeloma 2012)
It is administered intravenously. This drug causes the cancer cells to die by blocking the action of proteasomes (Multiple myeloma 2012). It is approved for people with newly diagnosed and previously treated myeloma (Multiple myeloma 2012).
Thalidomide (thalomid) (Multiple myeloma 2012)
This drug is approved for he treatment of newly diagnosed multiple myeloma (Multiple myeloma 2012). This drug is given 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 is approved for patient with previously treated myeloma, but is also often used in people with newly diagnosed disease (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 often given in cycles over a period of months, followed by a rest period (Multiple myeloma 2012). Common chemotherapy drugs used to treat myeloma are melphalan, cyclophosphamide, vincristine, doxorubicin and liposomal dexoribicin (Multiple myeloma 2012).
Corticosteroids (Multiple myeloma 2012)
Corticosteroids, such as prednisone and dexamethasone, have been used for decade to treat multiple myeloma (Multiple myeloma 2012). They are typically given in pill form.
Stem cell plantation (Multiple myeloma 2012)
This treatment involves using high doses of melphalan, along with transfusion of previously collected immature blood cells to replace diseased or damaged marrow (Multiple myeloma 2012). The stem cell can come from the patient or donor (Multiple myeloma 2012).
Radiation therapy (Multiple myeloma 2012)
This treatment uses high energy penetration waves to destroy myeloma cell and stop their growth (Multiple myeloma 2012). Radiation therapy may used to quickly shrink myeloma cells in a specific area (Multiple myeloma 2012) .
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.