Non-Hodgkin Lymphoma

About 56,390 new cases of non-Hodgkin lymphoma (NHL) will occur this year in the United States.

Lymphomas are cancers that begin by the malignant transformation of a lymphocyte in the lymphatic system. The prefix "lymph" indicates their origin in the malignant change of a lymphocyte and the suffix "oma" is derived from the Greek word meaning "tumor".

Lymphomas, including Hodgkin lymphoma, result from an acquired injury to the DNA of a lymphocyte. Scientists know that the damage to the DNA occurs after birth and, therefore, is acquired rather than inherited. The change or mutation of DNA in one lymphocyte produces a malignant transformation. This mutation results in the uncontrolled and excessive growth of the lymphocyte, and confers a survival advantage on the malignant lymphocyte and the cells that are formed from its multiplication. The accumulation of these dividing cells results in the tumor masses in lymph nodes and other sites.

Lymphomas generally start in lymph nodes or collections of lymphatic tissue in organs like the stomach or intestines. Lymphomas may involve the marrow and the blood in some cases. Spread from a lymphoma site is not unexpected. Lymphocytic leukemias originate and are most prominent in the marrow and spill over into the blood. They occasionally spread to involve the lymph nodes.

Non-Hodgkin lymphoma is the sixth most common cancer in males and the fifth most common cancer in females in the United States. The age-adjusted incidence of non-Hodgkin lymphoma rose by 74 percent from 1975 to 2002, annual percentage increase of nearly 2.7 percent.

Age-specific incidence rates are 3.0/100,000 at ages 20-24 for males and 1.9/100,000 for females. By ages 60-64, they are 51.5/100,000 for males and 37.5/100,000 for females.

Symptoms and Signs
In most cases, patients seek attention because of the appearance of swollen glands in the neck, armpits or groin. These swollen lymph nodes are mostly painless. They are present for several weeks before attention is directed toward them. They are unresponsive to treatment with antibiotics.

Patients may experience loss of appetite and weight loss, along with nausea, vomiting, indigestion and abdominal pain or bloating. Sometimes a feeling of fullness may be present, the result of an enlarged liver, spleen or abdominal lymph nodes. Pressure or pain in the lower back, often extending down one or both legs, is another fairly common symptom. Other symptoms include itching, bone pain, headaches, constant coughing and abnormal pressure and congestion in the face, neck and upper chest.

General symptoms may include feeling tired, having a flu-like syndrome or aching all over. Fatigue may be the result of anemia. Others experience night sweats and some may have recurring high-grade or constant low-grade fevers. Since all these symptoms are common to many illnesses, from minor ailments to serious disorders, the correct diagnostic procedures must be performed in order to confirm or rule out the diagnosis of lymphoma.

Staging (determining the extent of disease)
After the diagnosis is confirmed, the extent of the disease is determined. This is called "staging." The blood and the marrow are examined. Blood cell counts assess if anemia or low white cells or platelets are present or if lymphoma cells are in the blood. Examination of the bone marrow can detect the presence of lymphoma cells, as well. Other tests include: imaging studies of the chest and abdomen using CT or MR imaging to detect en-larged lymph nodes, liver, spleen, or kidneys.

Measurements of blood chemicals and other constituents look for chemical evidence of other organ involvement, such as liver or kidney dysfunction, and indicate whether immune globulins made by lymphocytes are deficient or abnormal.

A spinal tap (lumbar puncture) and/or imaging of the brain or spinal column may be required in cases in which the type of lymphoma or the patient's symptoms suggest the central nervous system (brain or spinal cord) might be affected. When all of the tests are completed, the physician determines the areas involved using the evidence at hand.

Factors Influencing Treatment
Six major factors are used to determine whether treatment should be initiated immediately after diagnosis. Some of the sub-types of NHL progress at a more rapid pace. The selection of treatment may differ from one treatment facility to another.

Type of Lymphoma
The first factor is the class of lymphoma. Thirty or more subtypes of specific lymphomas or closely related lymphocytic leukemias have been categorized. Table 3 gives examples of these subtypes. To simplify this classification, many oncologists group the various subtypes into whether, on average, the lymphoma is growing very slowly (low-grade) or progressing very rapidly (aggressive).


Stage of the Disease
The second consideration is the distribution of the lymphoma.

Stage I signifies the lymphoma can be detected in one lymph node area or in only one organ outside of lymph nodes.
Stage II indicates the involvement of two or more lymph node regions, which are near to each other, for example all are in the neck and chest, or in the abdomen.
Stage III represents the involvement of several lymph node regions in the neck and chest and abdomen.
Stage IV is used if there is widespread involvement of lymph node areas and organs such as lungs, liver, intestines and bone.

Cell Type
The third consideration is whether the lymphoma cells are most closely related to T cells, B cells or NK cells. This distinction is determined by the use of immunophenotyping or by molecular diagnostic techniques. These tests measure special features of the cells, which distinguish them as one or another of these three lymphocyte types. The aggressiveness or drug responsiveness of the lymphoma can be deduced, in part, from these measurements.


Extranodal involvement
The fourth consideration is whether organs outside of lymph nodes are involved as the approach to therapy is often affected. If the brain, liver or bones are involved, for example, the approach to treatment should consider these areas outside the lymph node.

Age
Advanced age of the patient (over 60) and concurrent medical conditions are also important considerations.

Body Reaction
The presence of a body reaction to lymphoma also influences the approach to treatment. Factors such as fever, exaggerated sweating and weight loss over 10 percent of body weight, referred to as B symptoms, are important findings. The designation A (as opposed to B) signifies the absence of these three findings.

Approach to Diagnosis

Medical history and physical examination
Complete blood counts
Bone marrow examination
Lymph node or tissue biopsy
Imaging studies
Immunophenotyping
Cytogenetics
The medical history provides strong clues to the diagnosis of lymphoma. In a thorough physical examination the lymphoma reveals itself by node or liver and/or spleen enlargement. Blood samples are also taken to determine overall disease composition, cell count, and how well the kidneys and liver are functioning.

The physician may suspect lymphoma by finding enlarged lymph nodes during a physical examination or in an imaging test (for example, a chest x-ray) in the absence of another explanation, such as a nearby infection. A computed tomography (CT) scan uses multiple images in the computer to create a two dimensional image of the body at several levels. This is a technique for imaging body tissues and organs. The resulting images are displayed as a cross-section of the body at any level from the head to the feet. A CT scan of the chest or abdomen permits detection of an enlarged lymph node, liver or spleen. A CT scan can be used to measure the size of these and other structures during and after treatment. Use of the CT scan for staging enables the physician to determine the extent of enlarged nodes and other organ involvement in the thorax or abdomen. CT scans are more sensitive than x-rays in finding tumors.

Magnetic resonance imaging (MRI) equipment uses large magnets and radiowaves to generate a computer image of the internal organs. It differs from a CT scan in that the patient is not exposed to x-rays. The signals generated in the tissues from the magnetic field of the instrument are converted into images of body structures. The pictures show soft tissue such as lymph nodes and, therefore, may be used effectively to diagnose or stage blood-related cancers. The size and a change in size of organs or tumor masses, such as the lymph nodes, liver and spleen or bone can be measured.

A gallium scan is an image produced by a radioactive isotope of gallium, which is injected into a vein and collects in the lymphoma tissues. The resulting image demonstrates where the tumors are located. This type of image may be used both before and after treatment to show changes or to assist in the staging process.

The diagnosis of NHL can be made with certainty by a biopsy of an involved lymph node or another involved organ, such as a bone, a lung, the liver or other sites. In some cases, the diagnosis may be made by the discovery of abnormal lymphocytes (lymphoma cells) in the marrow obtained as part of the initial diagnostic evaluation.

The node or other biopsy tissue often can be removed using a local anesthetic. Occasionally, chest or abdominal surgery may be used for diagnosis. Surgical biopsy requires general anesthesia. However, newer approaches using the laparoscope may permit biopsies within body cavities without major incisions being required.

When the tissue is obtained, it is prepared and then examined under the microscope by a pathologist to determine the pattern of the tissue abnormalities and types of cells involved. Sometimes, it is relatively easy for an experienced physician to decide that the abnormality is lymphoma and what the category or classification of the lymphoma is. Occasionally, the diagnosis may be unclear and require consultation with expert hematopathologists, who specialize in lymphoma diagnosis.

The biopsy material is appropriately fixed, stained and analyzed to define the type, structural characteristics, arrangement and pattern of growth within the organ and the immunologic features (the latter via fluorescent cell sorting). In addition, cells obtained at the time of tissue biopsy can be studied by immunophenotyping to provide additional evidence that they are lymphoma cells and to determine if they are B, T or NK lymphocyte types.

Cells can be studied by cytogenetics to see if chromosomal abnormalities are present. This type of examination is referred to as a cytogenetic analysis. Chromosome abnormalities can be important in identifying the specific type of lymphoma that is present, which may help in the choice of drugs for treatment.

If an initial examination indicates the possibility of lymphoma, treatment should be provided by an appropriate physician, usually a hematologist-oncologist specializing in the diagnosis and care of the broad spectrum of malignant blood and related diseases.

Hodgkin Lymphoma

Hodgkin (disease) lymphoma has been known as a disease that affects lymphatic tissue since Thomas Hodgkin described it in 1832. Hodgkin lymphoma has continued to receive special recognition by the World Health Organization, which influences disease classification throughout the world. The disease was called Hodgkin's disease for about 170 years and was officially changed to Hodgkin lymphoma when sufficient evidence accrued that the cancer originated in a lymphocyte.

Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell (named for the scientists who discovered it). Although they are found within the lymph nodes, Reed-Sternberg cells may not be lymphocytes.

Hodgkin lymphoma has other characteristic features that distinguish it from all other cancers of the lymph system. One of its unique features is its pattern of spread. Hodgkin lymphoma usually begins in the lymph nodes in one region of the body. As the disease progresses, it tends to spread in a fairly predictable manner, moving from one part of the lymph system to the next. Hodgkin lymphoma then moves into organs including the lungs, liver, bone and bone marrow.

There are four stages of Hodgkin lymphoma, based on the pattern of spread of the disease. Stage I represents local early-stage disease, while Stage IV means that the disease has spread to various organs distant from the original site of the disease. The histology, or pathologic interpretation under the microscope, may be nodular sclerosis, mixed cellularity, lymphocyte predominant or lymphocyte depleted. Because of the overall success of therapy, these subtypes are generally not important to the prognosis of Hodgkin lymphoma.

Symptoms and Signs
The most common early sign of Hodgkin lymphoma is a painless swelling of the lymph nodes in the neck, upper chest, interior of the chest, armpit, abdomen or groin. Involvement of lymph nodes in other locations may occur less frequently. Other symptoms include fever, sweating (especially at night), weight loss and itching. Patients may experience pain in the lymph nodes after drinking alcohol, an uncommon but distinctive finding in Hodgkin lymphoma. The spleen may be enlarged.

Approach to Diagnosis
The diagnosis of Hodgkin lymphoma requires the biopsy of an involved lymph node or other tumor site. A pathologist prepares a slide from the biopsy specimen and evaluates the cells using a microscope. Several patterns of lymph node changes are characteristic and diagnostic of Hodgkin lymphoma. The changes can be categorized into four patterns: lymphocyte predominance, nodular sclerosis, mixed cellularity or lymphocyte depletion types of Hodgkin lymphoma.

In some cases, the use of immunophenotyping can help distinguish Hodgkin lymphoma from the other types of lymphomas or other lymph node reactions that are not cancerous. The pathologist also uses the presence of special cells to confirm the diagnosis. These cells are called Reed-Sternberg cells in recognition of the pathologists who first described them. Other related cells are referred to as Hodgkin cells.

The pathological diagnosis of Hodgkin lymphoma can be difficult. Diagnosis often requires an experienced pathologist to analyze the biopsy slides.

Staging
In addition to physical examination, the physician can use imaging procedures to determine the extent of the disease. These tests help the physician to evaluate: 1) the location and distribution of lymph node enlargement; 2) whether organs other than lymph nodes are involved; and 3) whether there are very large masses of tumor in one site or another.

In most cases, these procedures will include computed tomography (CT) or magnetic resonance (MR) imaging of the abdomen. Today, it is unusual to require a procedure referred to as a staging laparotomy, which is a surgical procedure to inspect and biopsy the lymph nodes in the abdomen and the liver and remove the spleen. The information gathered from these studies permits the patient to be assigned to a "stage" of disease.

Stage I represents apparent involvement of a single lymph node region or a single organ, such as bone.

Stage II indicates the involvement of two or three lymph node regions that are close to each other, for example, all in the neck and chest, or all in the abdomen.

Stage III represents the involvement of several lymph node regions in the neck, chest and abdomen.

Stage IV means there is widespread involvement of lymph nodes and other organs, such as lungs, liver and bone.
The four stages of Hodgkin lymphoma can be divided into "A" and "B" categories. The "A" category indicates the absence of fever, exaggerated sweating and weight loss. Patients who experience these symptoms belong to the "B" category. For example, Stage IIB indicates that the patient has two nearby lymph node sites involved in the disease and has fever, exaggerated sweating, or weight loss. Examples of two nearby sites include enlarged lymph nodes in the neck and near the collar bone - or in the neck and the armpit.

Blood cell counts, bone marrow examination and performance of blood tests that can detect liver involvement and the severity of the disease also are useful in assessing the approach to treatment.

Myeloproliferative Disorders

Myeloproliferative disorders are a group of blood diseases characterized by chronic increases in some or all of the blood cells. This group of blood disorders includes

Polycythemia vera
Essential (or primary) thrombocythemia
Idiopathic myelofibrosis
All blood cells start out as hemopoietic (blood-forming) stem cells with the potential to become red cells, white cells, or platelets. Myeloproliferative disorders begin with a change to the DNA of a single stem cell in the marrow, where blood cells are made.

Polycythemia vera is a disease in which the red cells are the main cells that are increased beyond normal levels. In many patients, white blood cell and platelets counts are also elevated.

Complications result mainly from the increase in red cells and in platelets: too many red blood cells make it difficult for the blood to flow smoothly; too many platelets can lead to the formation of blood clots; and underlying vascular disease, commonly found in older people, can increase the risk of serious complications, such as strokes or heart attacks.

Essential (or primary) thrombocythemia is a disease in which the platelets are the main cells that are increased beyond normal levels.

The normal formation of platelets consists of stem cells forming a few very large cells in the marrow called megakaryocytes. Each of the megakaryocytes generates hundreds or thousands of platelets. In essential thrombocythemia, the altered stem cells produce an excessive number of megakaryocytes. The end result is abnormally high levels of platelets in the blood. When present in very large numbers, these platelets may not function normally and can cause blockages in blood vessels or bleeding problems.

Idiopathic myelofibrosis is a disease in which scar-like tissue forms in the marrow as a result of abnormal production of red cells, white cells, and platelets.

Too few red cells are made, and usually too many white cells and megakaryocytes. The excessive production of megakaryocytes leads to abnormally high levels of platelets in the blood. The overproduction of abnormal megakaryocytes also releases chemicals in the marrow that lead to the production of fibrous (scar-like) tissue in the marrow.

Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) are a group of diseases that originate in an early blood-forming cell in the marrow. In patients with this disorder, the marrow produces too few red blood cells, white blood cells and often platelets.

In the myelodysplastic syndromes, the maturing blood cells often die in the marrow before they reach full maturity and enter the blood, accounting for the low blood cell concentrations. There may also be an accumulation of very immature marrow cells, called leukemic blast cells.

The severity of the marrow cell disturbance is varied and can range from mild to very severe.

Thus, the disease may be indolent or chronic and be manifest primarily as mild anemia; it may have severe decreases in red and white blood cells and platelets and be more troublesome; or it may have severe decreases in blood cells and have leukemic blast cells in the marrow and be even more threatening to the health of the patient.

In addition, the disease can progress such that the leukemic blast cells take over the marrow and the disease evolves into acute myelogenous leukemia. The marked decrease in blood cell formation makes it difficult for patients to prevent or fight infection and it predisposes them to exaggerated bleeding.

Incidence
The annual incidence may be in the range of 4,000 to 6,000 cases per year. The age of onset closely follows that of acute myelogenous leukemia, increasing dramatically after age 50. The disorder affects both genders but, like other leukemias, is more common in men than women.

Disease Subgroups
Although myelodysplastic syndrome covers a spectrum of neoplastic myeloid diseases, most cases can be placed into several subgroups based on the blood cell counts and the appearance of blood cells under the microscope. The two principal subgroups are:

Chronic and Nonprogressive Anemia
Blood cell count deficiencies without evidence of leukemic blast cells make up about one third of the myelodysplastic disorders. The disorder may cause principally a deficiency 1) of red cells, 2) of red cells and white cells or 3) of red cells, white cells and platelets. These situations are often referred to as refractory anemia (even though white cell and platelet counts may be low as well as red cell counts).

These situations may be nonprogressive for years or decades. If the blood-cell count deficiencies are mild, the circumstance may have little effect on the patient's ability to conduct his or her usual activities. About 10 to 15 percent of patients in this subgroup may later develop acute myelogenous leukemia.

Progressive and Symptomatic Blood Cell Deficiencies
The second principal subgroup of myelodysplastic disease shows evidence of leukemic blast cells in the marrow. This finding is associated often with low red cell, white cell and platelet counts, and other changes of blood cell shape and structure under the microscope that is characteristic of these leukemic syndromes. This category of disease has been variously designated as low blast count myelogenous leukemia, refractory anemia with excess blasts, smoldering leukemia and other designations. Like the other category of myelodysplastic syndrome, it may have a wide range of severity and a difference in the rate of worsening.

If the leukemic blast count was high the designation "refractory anemia with excess blasts in transition" (to acute myelogenous leukemia) was used but the designation is not useful and it has been recommended that it be dropped. (Table 1). Such patients are considered to have acute myelogenous leukemia. In fact, these disorders are each gradations of severity of myelogenous leukemia. The proportion of leukemic blasts cells in the marrow and the degree of the abnormalities in blood cell counts correlates with the rate of progression of the disease.

Causes and Risk Factors
In most cases the disease has no external cause. The use of certain drugs that are designed to damage DNA and are used to treat lymphoma, myeloma or other cancers, such as breast or ovarian cancer, increase the risk of developing acute myelogenous leukemia or a myelodysplastic disorder.

The same sequence of events can follow the use of therapeutic radiation for lymphoma. Benzene exposure above threshold levels for protracted periods of time, usually in an industrial setting, may increase the incidence of acute myelogenous leukemia and may precede the onset of myelodysplasia. The increasingly stringent regulation of benzene use in the workplace has diminished this sequence of events.

Signs and Symptoms
In the chronic or nonprogressive form of the disorder, the diagnosis may first be suspected from a finding of anemia during a medical evaluation. If the anemia is moderate or severe, exaggerated fatigue, shortness of breath on exertion (such as during climbing stairs), pale skin or weakness may be present. In this form of the disease, abnormalities in white cells or platelets, which may be present, are usually insufficient to contribute to signs or symptoms.

In the more advanced and progressive form of the disease, which is a low blast cell count myelogenous leukemia, the patient often comes to medical attention because of loss of sense of well being, fatigue, weakness or loss of appetite.

Approaches to Diagnosis

Complete blood count
Bone marrow examination
Cytogenetics
A diagnosis can only be made by measuring the blood cell counts and examining the appearance of blood cells through the microscope, usually supplemented by a microscopic examination of marrow cells. Evaluation of chromosome structure using techniques applicable to blood and marrow cells can be performed on the samples obtained. This cytogenetic evaluation can be helpful in reaching a conclusion about the diagnosis.

Myeloma part 2

Marrow

In normal marrow, plasma cells are relatively sparse. In patients with myeloma, plasma cells are often present in abnormally large numbers. The myeloma cells accumulate in an uncontrolled manner (a sign of cancer), forming a tumor in the marrow. Sometimes, the myeloma cells collect in tissue and form a single mass (tumor) called a plasmacytoma. In most cases, however, this tumor spreads, usually in the marrow of many bones, including the ribs, backbone, pelvis, shoulder bones, breastbone, skull and others.

M Proteins (Monoclonal Immunoglobulins)

In myeloma, large amounts of a single type of protein, called M protein or monoclonal immunoglobulin, is made and secreted into the blood. The term monoclonal indicates the protein is derived from one cell population, the malignant plasma cells.

The body's normal process is for plasma cells to produce many types of proteins, called polyclonal immunoglobulins (antibodies), to protect the body against infection caused by invading viruses, bacteria, or other agents. By contrast, the production of M protein does not take place in response to an antigen, such as an infectious agent.

M protein can be measured in the blood. Changes in the amount of this protein usually parallel myeloma progression (increasing M protein concentration in the blood) or regression (decreasing M protein concentration in the blood).

Normal immunoglobulin is made up of of two heavy (larger) chains and two light (smaller) chains that are attached to each other. The normal immunoglobulin is too large to pass through the kidney, and so it is present in the blood, but not the urine.

The M protein in myeloma, like the normal immunoglobulin, is also made up of two heavy chains and two light chains attached to each other. However, in many cases of myeloma, the coordination of making and attaching light chains and heavy chains in the malignant plasma cells is lost and light chains (also called Bence Jones protein) leave the cell unattached. This fragment of immunoglobulin, the light chain, enters the blood, but is excreted rapidly in the urine (see Figure 2).



Figure 2. The Bence Jones protein (light chains) made by M protein are small enough to pass through the kidney and enter the urine, where they can be detected. When excreted in large amounts, Bence Jones protein can cause renal injury and kidney failure

Bone Destruction

Another special feature of malignant plasma (myeloma) cells is that they secrete chemicals (cytokines) that stimulate other cells that dissolve bone:

Bone is remodeled continuously. This remodeling is a coordinated effect of cells that dissolve bone (osteoclasts) and cells that lay down new bone (osteoblasts).
The chemicals secreted by plasma cells stimulate the bone-dissolving cells into marked overactivity. The bone-forming cells cannot keep up.
Holes (lytic spots) develop in the bone.
Bone is thinned (osteoporosis), and can be weakened sufficiently to break (fracture) with normal stresses of walking or lifting.
Slightly increased stresses of coughing and minor falls or injuries can also break the bones.

Symptoms and Signs

Bone pain is the most common early symptom of myeloma.
Most patients feel pain in the back or the ribs, but it can occur in any bone.
The pain is usually made worse by movement.
Patients fatigue more easily and often feel weak.
They may have a pale complexion from anemia, which is a common medical problem for patients with myeloma. Anemia may contribute to fatigue.
Patients may have repeated infections because antibodies to invading viruses, bacteria or other disease agents are not made efficiently or in adequate amounts.
A urinary tract, bronchial, lung, skin or other site of infection are often the first sign of the disease. In addition, recurrent infections may complicate the course of the disease.

Diagnosis

Myeloma may be discovered during a routine medical examination, before patients have symptoms of the disease. Approaches to diagnosis consist of:

Medical history and physical examination
Complete blood counts
Bone marrow examination
Bone imaging
M protein analysis
The diagnosis of myeloma depends on three principal findings. Taken together, these findings make it possible to for physicians to diagnose myeloma in a patient:
Increased numbers of malignant plasma cells (myeloma cells) are found when a bone marrow aspiration and biopsy are performed (usually from the hip bone).
Monoclonal immunoglobulin and Bence Jones (light chain) proteins are found in the blood or urine, respectively. In most patients with myeloma at least small amounts of light chains can be detected in the urine. In some myeloma patients blood tests do not show the characteristic increase or "spike" of M protein but the urine will have large amounts of light chains.
Thinning, holes or fractures of the bones that characterize myeloma are identified by imaging studies. Imaging studies include:
X-rays (skeletal surveys) and computerized tomography (CT) scans to identify any holes, breaks or thinning of the bones.
Magnetic resonance imaging studies (MRIs) and positron emission tomography (PET) scans to look for marrow changes and myeloma cell masses.
Physicians also order blood tests to obtain red cell, white cell and platelet counts (CBC or complete blood count) to measure the degree to which myeloma cells in marrow are affecting normal blood cell production.

Blood calcium is measured because the bone destruction causes calcium to leave bone and raise the blood levels.

The concentration of three proteins in the blood, lactic dehydrogenase, beta-2 microblobulin, and C-reactive protein, are obtained. These proteins are each an indirect measure of the size and growth rate of the myeloma tumors.

Tests that reflect kidney function (urea nitrogen and creatinine) and a urine examination (urinalysis) are usually performed.

Myeloma

An estimated 15,980 new cases of myeloma will be diagnosed in the United States in 2005. Myeloma may be called by several names, including plasma cell dyscrasia, plasma cell myeloma, myelomatosis and multiple myeloma.

The major forms of myeloma are divided into categories, which allows the physician to decide what treatment works best for the particular type of disease.

The most common form of myeloma (about 90 percent of cases) involves many sites in the body. It is sometimes called multiple myeloma.

Some people have a single clump of myeloma cells outside the marrow. This is called an extramedullary plasmacytoma.

Plasmacytomas can form in the skin, muscle, lungs or almost any other part of the body.

Some people diagnosed with myleoma have solitary myeloma. This means they have one area of myeloma in the body.

Some cases of myeloma progress slowly. These cases are called smoldering or indolent myeloma. Sometimes patients with smoldering or indolent myeloma are not treated right away. In most cases treatment is needed at some point.

Myeloma results from an acquired injury to the DNA of a single cell in the lymphocyte development sequence that leads to the formation of plasma cells. Myeloma occurs in lymphocytes developing into B cells, as opposed to T cells. B lymphocytes transform into plasma cells, which produce proteins called antibodies (see Figure 1).



Figure 1. Early lymphocyte development in adults takes place mainly in the lymph nodes. The lymphocyte then migrates to the marrow (a major site of plasma cell development and function), where further development takes place. The malignant transformation in myeloma may occur in a more developed B lymphocyte. The affected lymphocytes are induced to complete step three and transform into malignant cells that have the appearance of plasma cells.