Cancer Treatment & Information

If a person has swelling or symptoms described in the Symptoms section, his or her health care provider will ask many questions about the symptoms (when they began, recent illnesses, past or current medical problems, any medications, workplace, health history, family history, and habits and lifestyle). These questions are followed by a thorough examination.

If, after an initial interview and examination, the health care provider suspects that a patient may have lymphoma, the patient will undergo a series of tests designed to provide further clarification. At some point in this workup, the patient will likely be referred to a specialist in cancer (oncologist).

Blood tests

Blood is drawn for various tests.

• Some of these tests evaluate the function and performance of blood cells and important organs, such as the liver and kidneys.
• Certain blood chemicals or enzymes (lactate dehydrogenase [LDH]) may be determined. High levels of LDH in cases in which NHL is suspected may indicate a more aggressive form of the disorder.
• Other tests may be done to learn more about lymphoma subtypes.

Biopsy

If there is a swelling (also called lump or mass), a sample of tissue from the swelling will be removed for examination. This is called a biopsy. Any of several methods can be used to obtain a biopsy of a mass.

• Masses that can be seen and felt under the skin are relatively easy to biopsy. A hollow needle can be inserted into the mass and a small sample removed with the needle (called a core-needle biopsy). This is usually done in the health care provider’s office with a local anesthetic.
• Core-needle biopsy does not always obtain a good-quality sample. For that reason, many health care providers prefer a surgical biopsy. This involves removal of the entire swollen lymph node through a small incision in the skin. This procedure often is done with a local anesthetic, but it sometimes requires a general anesthetic.
• If the mass is not immediately under the skin but is instead deep inside the body, access is somewhat more complicated. The specimen is usually obtained via laparoscopy. This means making a tiny incision in the skin and inserting a thin tube with a light and a camera on the end (a laparoscope). The camera sends pictures of the inside of the body to a video monitor, and the surgeon can see the mass. A small cutting tool on the end of the laparoscope can remove all or part of the mass. This tissue is withdrawn from the body with the laparoscope.
• A pathologist (a physician who specializes in diagnosing diseases by looking at cells and tissues) examines the tissue sample with a microscope. The pathologist’s report will specify whether the tissue is lymphoma and, with the use of appropriate biologic tools, the type and subset of lymphoma.

Imaging studies

If there is no palpable mass in the presence of persistent symptoms, imaging studies will likely be carried out in order to determine whether a mass is present and, if so, how then to direct a biopsy.

• X-rays: In certain parts of the body, such as the chest, a simple x-ray can sometimes detect lymphoma.
• CT scan: This test provides a 3-dimensional view and much greater detail and may detect enlarged lymph nodes and other masses anywhere in the body.
• MRI scan: This test uses differences in magnetic fields among different types of tissue to create pictures of the inside of the body. Similar to the CT scan, MRI gives 3-dimensional images with excellent detail. MRI provides better definition than CT scan in certain parts of the body, especially the brain and the spinal cord.
• Lymphangiogram: This approach, which provides an image of the lymphatic system by tracing a dye that moves though the system, has essentially been replaced by either CT scan, MRI, or PET (see below).
• Gallium scan: Lymphomas tend to collect a substance called gallium. For this test, a tiny amount of radioactive gallium is injected into the body. A scan is then done to find areas where the gallium has collected. Collections of gallium suggest a tumor.
• Positron-emission tomographic (PET) scan: PET scan is a newer alternative to lymphangiogram and gallium scan for detecting areas in the body that are affected by lymphoma. A tiny amount of a radioactive substance is injected into the body and then traced on the PET scan. Sites of radioactivity on the scan indicate areas of increased metabolic activity, which implies a tumor.

Bone marrow examination

Most of the time, an examination of the bone marrow is necessary to see if the marrow is affected by the lymphoma. This is done by collecting a biopsy of the bone marrow.

• Samples of both liquid (aspirate) and solid bone marrow (biopsy) are taken, usually from a hip bone.
• A pathologist examines the bone marrow under a microscope.
• Bone marrow containing certain types of abnormal B or T lymphocytes confirms lymphoma.
• Bone marrow biopsy can be an uncomfortable procedure, but it can usually be performed in a medical office. Most people receive pain medication prior to the procedure to make them more comfortable.

Other tests

• Lumbar puncture: This test, sometimes called a spinal tap, is a method for collecting a sample of the fluid surrounding the brain and spinal cord. This fluid is called cerebrospinal fluid. If the lymphoma has affected the central nervous system, the cerebrospinal fluid will likely contain lymphoma cells.
• Organ function tests: These tests are usually done before starting treatment to make sure that one’s organs are healthy enough to withstand the side effects of therapy. Examples include an echocardiogram or MUGA scan for the heart and pulmonary function tests for the lungs.

Staging

Staging is the classification of a cancer type by its size and whether and how much it has spread around the body. Determining a cancer’s stage is very important because it tells the oncologist which treatment is most likely to work and what are the chances of remission or a cure (prognosis).

Staging of lymphomas, as in all cancers, is based on the microscopic examination and on the results of imaging studies and related tests that reveal the extent of the cancer involvement. HL is often described as being “bulky” or “nonbulky.” Nonbulky means the tumor is small; bulky means the tumor is large. Nonbulky disease has a better prognosis than bulky disease.

NHL is a complicated set of diseases with a complex classification system. In fact, the classification system is continuously evolving as we learn more about these cancers. The newest classification system takes into account not only the microscopic appearance of the lymphoma but also its location in the body and genetic and molecular features.

Grade is also an important component of the NHL classification.

• Low grade: These are often called “indolent” lymphomas because they grow slowly. Low-grade lymphomas are often widespread when discovered, but because they grow slowly, they usually do not require immediate treatment unless organ function is compromised. They are rarely cured and can transform over time to a combination of indolent and aggressive types.
• Intermediate grade: These are rapidly growing (aggressive) lymphomas that usually require immediate treatment, but they are often curable.
• High grade: These are very rapidly growing and aggressive lymphomas that require immediate, intensive treatment and are much less often curable.

The “staging,” or evaluation of extent of disease, for both HL and NHL, are similar.

• Stage I (early disease) - Lymphoma located in a single lymph node region or in one area or organ outside the lymph node
• Stage II (locally advanced disease) - Lymphoma located in two or more lymph node regions all located on the same side of the diaphragm or in one lymph node region and a nearby tissue or organ. (The diaphragm is a flat muscle that separates the chest from the abdomen.)
• Stage III (advanced disease) - Lymphoma affecting two or more lymph node regions, or one lymph node region and one organ, on opposite sides of the diaphragm
• Stage IV (widespread or disseminated disease) - Lymphoma outside the lymph nodes and spleen that has spread to another area or organ such as the bone marrow, bone, or central nervous system

Both HL and NHL are further classified with letters.

• An “A” or “B” designation indicates whether the person with lymphoma had symptoms such as fevers and/or weight loss at the time of diagnosis. “A” indicates no such symptoms, and “B” indicates symptoms.
• An “E” designation indicates that the tumor spread directly from a lymph node into an organ or that a single organ outside the lymphatic system is affected with no apparent lymphatic involvement.

Prognostic factors

Several risk factors have been extensively evaluated and shown to play a role in treatment outcome. For HL, the International Prognostic Index includes the following 7 risk factors:

1. Male sex
2. Age 45 years or older
3. Stage IV disease
4. Albumin (blood test) less then 4.0 g/dL
5. Hemoglobin (red blood cell level) less than 10.5 g/dL
6. Elevated white blood cell (WBC) count of 15,000/mL
7. Low lymphocyte count less than 600/mL or less than 8% of total WBC

The absence of any of the above risk factors is associated with an 84% rate of control of Hodgkin disease, whereas the presence of a risk factor is associated with a 77% rate of disease control. The presence of 5 or more risk factors was associated with a disease control rate of only 42%.The outcomes for these patients were also determined by the treatment they received, which occurred primarily in the 1980s. Newer treatments for Hodgkin lymphoma may improve these predicted outcomes. Furthermore, new treatments are being developed for patients with greater risk factors. The International Prognostic Index for NHL includes 5 risk factors:

1. Age older than 60 years
2. Stage III or IV disease
3. High LDH
4. More than one extranodal site
5. Poor performance status (as a measure of general health) - From these factors, the following risk groups were identified: 
   • Low risk: 0-1 risk factor, 5-year lymphoma-free survival (LFS) of 70%
   • Intermediate risk: 2-3 risk factors, 5-year LFS of 49-50%
   • Poor risk: 4-5 risk factors, 5-year LFS of 26%

A T-cell NHL subtype is usually considered an additional risk factor. However, a T-cell anaplastic large cell NHL has a lower risk than B-cell NHL. The prognostic models were developed to evaluate groups of patients and are useful in developing therapeutic strategies.

What are the symptoms of Lymphoma Cancer?

The most common sign of both Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL) is a painless swelling in one or more of the lymph nodes of the neck, collarbone region, armpits, or groin. But it is important to remember that most lymph node swelling - especially in children - is caused by an infection, not by lymphoma. Affected lymph nodes usually return to normal size within a few weeks or months after an infection has cleared. Physicians often observe swollen lymph nodes during this time to see if they change in size following antibiotic treatment. However, if a lymph node(s) is larger than one inch in size (>1 in), and if there are other suspicious symptoms, the physician may choose to perform an immediate biopsy to rule out or confirm a diagnosis of cancer.

If HD or NHL involves lymphatic tissue within the abdomen the belly may become swollen, and even resemble pregnancy in some female patients. Fluid may build up within the abdominal cavity, and swelling near the intestines may block the normal passage of feces. Such blockage may cause sensations of abdominal pressure or pain.

Other symptoms include:

• Chest Pain
• Trachea
• General Symptoms
• B Symptoms

Chest Pain
If lymphoma involves the lymphatic tissue of the thymus, the gland located in front of the heart, it may cause chest pain. In addition, an enlarged thymus may press on nearby structures such as the trachea (windpipe) or superior vena cava (SVC), the large vein that carries blood from the head and arms back to the heart.

Trachea
Pressure on the trachea can lead to coughing, fatigue, shortness of breath, and other respiratory difficulties. Pressure on the superior vena cava may produce SVC syndrome, a swelling of the head and arms. SVC syndrome involving the brain can be fatal and must be treated immediately. But enlarged lymphatic tissue in the chest cavity generally tends to displace - rather than press upon or encase- adjacent structures. Therefore, compromised breathing and SVC syndrome are relatively uncommon signs of lymphoma.

General Symptoms
As lymphomas progress and cancerous lymphocytes spread beyond the lymphatic system, the body loses its ability to fight infections. The generalized symptoms that develop may be confused with influenza, other infections, such as infectious mononucleosis (”mono”), tuberculosis (TB), or other cancers. In particular, people with HD or NHL may experience:

• fever
• drenching night sweats
• weight loss
• fatigue
• appetite loss
• red patches on the skin
• severely itchy skin, often affecting the legs/feet

The itching associated with Hodgkin’s disease is much more severe than that caused by dry skin. In some cases, patients may actually scratch through the skin with their fingernails in attempts to get some relief. The night sweats caused by HD or NHL may be so extreme that they completely soak the individual’s sheets and blankets.

Some oncologists refer to these generalized symptoms as B symptoms. Unfortunately, B symptoms are related to an increased cancer “burden” - more cancerous tissue - in many patients and, therefore, indicate a worse prognosis, or outcome.

How is Lymphoma Cancer diagnosed?

The fact is that most people with lymphoma (e.g., up to 75% of HD patients) experience no classic symptoms. Often, lymphomas are diagnosed because of abnormalities found on chest x-rays or other imaging studies that are performed for nonspecific complaints.

If lymphoma is suspected, the physician will want to obtain a full medical history to uncover any relevant symptoms or risk factors. A complete physical examination will supply other clues about possible infection, health problems, or signs of lymphoma. The physician will pay particular attention to the size, location, tenderness, and consistency (firmness) of swollen lymph nodes, and will examine other lymphatic sites for possible disease.

Once the physician suspects that a patient has Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL), he or she will want to perform a biopsy of an enlarged lymph node, that us, remove a small amount of tissue for examination. A pathologist (disease diagnosis specialist) will evaluate the size and shape of the sampled tissue under a microscope. In particular, the pathologist will look for Reed-Sternberg (R-S) cells, which confirm a diagnosis of Hodgkin’s disease.

Types of Biopsy

Several types of biopsy are available:

• Fine Needle Aspiration (FNA) biopsy uses a very thin, hollow needle that is attached to a syringe. If the enlarged lymph node is palpable (can be felt) and near the skin’s surface, the needle is inserted into the swollen lump. It is then pushed back and forth to free some cells, which are aspirated (drawn up) into the syringe and are smeared on a glass slide for analysis.If the suspicious nodes or tissues are deep within the body (e.g., abdominal nodes, thymus), the needle may be guided while it is viewed on a CT (computed tomography) scan.FNA can distinguish noncancerous conditions, like infections, from NHLs or other cancers. FNA also is useful for staging, or determining the extent, of disease, and for monitoring recurrence, or return of cancer. But, because of small sample sizes and lack of information about lymph node structure, FNA often is inadequate for the initial diagnosis of HD or NHL. In such cases, larger tissue samples are obtained by surgical biopsy.
• Large Needle/Core Biopsy uses a large-bore needle to obtain a small tissue sample for analysis. Core biopsy has limited role in the diagnosis of lymphoma and is reserved for those patients who are unable to tolerate an invasive surgical procedure. Both FNA and core biopsy procedures may be guided by CT, ultrasound, or other imaging techniques.
• Surgical Biopsy refers to both incisional (cutting into) and excisional (cutting away) procedures. If a tumor mass is large and only a tiny piece of it is removed for examination, the procedure is called an incisional biopsy. Incisional biopsy has, in large part, been replaced by needle biopsy; needle biopsy is less time-consuming and less prone to infection and it produces less scarring.If the tumor mass is small and it is completely removed by biopsy, the procedure is called an excisional biopsy. Excisional biopsy usually is performed if a physician suspects that a lump is not cancerous (benign). Local anesthesia is used if the node is located near the skin’s surface and the child or adult is cooperative; however, deeper nodes (e.g., in the chest or abdomen) require general anesthesia.

Biopsy samples usually are sent to a laboratory for a number of additional tests, such as immunocytochemistry, flow cytometry, and cytogenetic studies. These tests, which also are used in diagnosing leukemia, rely on changes in cell-specific antibodies, the immune system chemicals that are directed against foreign substances, and genetic material to help identify specific types of lymphoma.

Imaging Studies

After reviewed the findings from preliminary x-rays, the physician may want to conduct additional imaging studies. Computed tomography (CT or CAT scan), a computer-assisted x-ray that produces cross-sectional images of the body, and magnetic resonance imaging (MRI scan), a technique that uses electromagnets and radio waves to create computer-generated pictures of the internal organs, are particularly useful for detecting enlarged lymph nodes or lymphoma-related abnormalities of the spleen or other organs.

A newer imaging test, called CT/PET fusion imaging, combines the technology of CT scan with the technology of PET (positive emission tomography) scan. PET scans involve injecting a sugar-based radiopharmaceutical, which travels through the body and collects in organs and tissues. The PET scan is used to detect cancer cells in the body and the CT scan provides detailed images that can determine the location and size of the cancer. When the results of these tests are “fused” (brought together), the images provide more complete diagnostic information.

In addition, the physician may request a lymphangiogram, a form of x-ray in which pictures are made of the lymphatic system. The patient is injected with a special dye that helps to highlight the lymph nodes and their vessels. Imaging studies also are significant tools for the staging of HD and NHL.

Bone Marrow Tests

If lymphoma has been diagnosed, the physician may want to sample the bone marrow to assist with cancer staging, that is, determining the extent of disease. The bone marrow is sampled by a technique known as bone marrow aspiration. During this procedure, a thin, hollow needle with a syringe attachment is used to aspirate (suction up) a teaspoon-sized sample of liquid bone marrow from the back of the hip bone. A larger needle then is employed to obtain a bone marrow biopsy (core biopsy), which removes roughly a 1/16 inch cylindrical piece of bone marrow from the hip site.

After the bone marrow samples are obtained, they are examined by many physician specialists, including a pathologist (disease diagnosis specialist), hematologist (blood specialist), and oncologist (cancer specialist). In the past, biopsy of both hip bones was standard procedure, but it now typical to perform the procedure on only one side.

Lumbar Puncture

Lumbar puncture, also known as a spinal tap, is a procedure in which a thin needle is inserted through the lumbar (lower) backbone, below the level of the spinal cord. Cerebrospinal fluid (CSF) is withdrawn through the needle, and is then analyzed for the presence of lymphoma cells. This test is performed to see whether lymphoma has spread to the central nervous system.

What is Lymphoma Cancer?

Lymphoma is a type of cancer involving cells of the immune system, called lymphocytes. Just as cancer represents many different diseases, lymphoma represents many different cancers of lymphocytes—about 35 different subtypes, in fact.

Lymphoma is a group of cancers that affect the cells that play a role in the immune system, and primarily represents cells involved in the lymphatic system of the body. The lymphatic system is part of the immune system. It consists of a network of vessels that carry a fluid called lymph, similar to the way that the network of blood vessels carry blood throughout the body. Lymph contains white blood cells called lymphocytes. Lymphocytes attack a variety of infectious agents as well as many cells in the precancerous stages of development.

Lymph nodes are small collections of lymph tissue that occur throughout the body. The lymphatic system involves lymphatic channels that connect thousands of lymph nodes scattered throughout the body. Lymph flows through the lymph nodes, as well as through other lymphatic tissues including the spleen, the tonsils, the bone marrow, and the thymus gland.

These lymph nodes filter the lymph, which may carry bacteria, viruses, or other microbes. The lymph nodes, or glands as they may be called, filter the lymph, which may on various occasions carry different microbial organisms. At infection sites, large numbers of these microbial organisms collect in the regional nodes and produce the swelling and tenderness typical of a localized infection. These enlarged and occasionally confluent collections of lymph nodes (so-called lymphadenopathy) are often referred to as “swollen glands.”

Lymphocytes recognize pathogens (infections and abnormal cells) and destroy them. There are 2 major subtypes of lymphocytes: B lymphocytes and T lymphocytes, also referred to as B cells and T cells.

• B lymphocytes produce antibodies (proteins that circulate through the blood and lymph and attach to infectious organisms and abnormal cells). The combination attachment cell or antibody microbial organism essentially alerts other cells of the immune system recognize and destroy these intruders, also known as pathogens.
• T cells, when activated, can kill pathogens directly. T cells also play a part in the mechanisms of immune system control, to prevent the system from inappropriate overactivity or underactivity.
• After fighting off an invader, some of the B and T lymphocytes “remember” the invader and are prepared to fight it off if it returns.

Cancer occurs when normal cells undergo a transformation whereby they grow and multiply uncontrollably. Lymphoma is a malignant transformation of either lymphocytes B or T cells or their subtypes. As the abnormal cells multiply, they may collect in 1 or more lymph nodes or in other lymph tissues such as the spleen. As the cells continue to multiply, they form a mass often referred to as a tumor. Tumors often overwhelm surrounding tissues by invading their space, thereby depriving them of the necessary oxygen and nutrients needed to survive and function normally.

Because of their uncontrolled growth, lymphomas can encroach on and/or invade neighboring tissues or distant organs. In lymphoma, abnormal lymphocytes travel from one lymph node to the next, and sometimes to remote organs, via the lymphatic system. While lymphomas are often confined to lymph nodes and other lymphatic tissue, they can spread to other types of tissue almost anywhere in the body. Lymphoma development outside of lymphatic tissue is called extranodal disease.

Lymphomas fall into 1 of 2 major categories. Hodgkin lymphoma (HL, previously called Hodgkin’s disease) and all other lymphomas (non-Hodgkin lymphomas or NHLs). These 2 types occur in the same places, may be associated with the same symptoms, and often have similar gross physical characteristics. However, they are readily distinguishable via microscopic examination.

Hodgkin disease develops from a specific abnormal B lymphocyte lineage. NHL may derive from either abnormal B or T cells and are distinguished by unique genetic markers. There are 5 subtypes of Hodgkin disease and about 30 subtypes of non-Hodgkin lymphoma. Because there are so many different subtypes of lymphoma, the classification of lymphomas is complicated and includes both the microscopic appearance and well-defined genetic and molecular rearrangements.

Many of the NHL subtypes look similar, but they are functionally quite different and respond to different therapies with different probabilities of cure. HL subtypes are microscopically distinct, and typing is based upon the microscopic differences as well as extent of disease. Lymphoma is the most common type of blood cancer in the United States. It is the sixth most common cancer in adults and the third most common in children. Non-Hodgkin lymphoma is far more common than Hodgkin disease. In the United States, about 54,000 new cases of NHL and 7000 new cases of HL were diagnosed in 2004, and the overall incidence is increasing.

About 24,000 people die of NHL and 1400 of HL each year, with the survival rate of all but the most advanced cases of HL greater than that of other lymphomas. Lymphoma can occur at any age, including childhood. Hodgkin disease is most common in 2 age groups: young adults aged 16-34 years and in older people aged 55 years and older. Non-Hodgkin lymphoma is more likely to occur in older people.

What Causes Lymphoma Cancer?

The exact causes of lymphoma are not known. Several factors have been linked to an increased risk of developing lymphoma, but it is unclear what role they play in the actual development of lymphoma. These risk factors include the following:

• Age: Generally the risk of NHL increases with advancing age. HL in the elderly is associated with a poorer prognosis than that observed in younger patients.
• Infections
  • Infection with HIV
  • Infection with human T-lymphocytic virus type 1 (HTLV-1)
  • Infection with Epstein-Barr virus (EBV), one of the etiologic factors in mononucleosis
  • Infection with Helicobacter pylori, a bacterium that lives in the digestive tract
  • Infection with hepatitis B or hepatitis C virus
• Medical conditions that compromise the immune system
  • HIV
  • Autoimmune disease
  • Diseases requiring immune suppressive therapy, often used following organ transplant
  • Inherited immunodeficiency diseases (severe combined immunodeficiency, ataxia telangiectasia, among a host of others)
• Exposure to toxic chemicals
  • Farm work or an occupation with exposure to certain toxic chemicals such as pesticides, herbicides, or benzene and/or other solvents 
  • Black hair dye, which for more than 20 years has been linked to higher rates of NHL
• Genetics: Family history of lymphoma

The presence of these risk factors does not mean a person will actually develop lymphoma. In fact, most people with one or several of these risk factors do not develop lymphoma.