Lymphomas are cancers of the lymphatic system - the body's blood-filtering tissues that help to fight infection and disease. Like other cancers, lymphomas, occur when cells divide too much and too fast. Growth control is lost, and the lymphatic cells may overcrowd, invade, and destroy lymphoid tissues and metastasize (spread) to other organs.
There are two general types of lymphomas: "Hodgkin's Disease" (named after Dr. Thomas Hodgkin, who first recognized it in 1832) and non-Hodgkin's lymphoma. The lymphatic tissue in Hodgkin's disease contains specific cells - Reed-Sternberg cells - that are not found in any other cancerous lymphomas or cancers. These cells distinguish Hodgkin's disease (HD) from non-Hodgkin's lymphomas (NHLs).
The lymphatic system - the target of lymphomas - includes the lymph nodes and other organs that make up the immune and blood-forming (hematopoietic) elements of the body.
The lymph nodes are oval, pea-sized organs. They are found beneath the skin along the route of large blood vessels, and they are grouped in areas such as the neck, underarms, groin, abdomen (trunk), and pelvis (hips). The lymph nodes are linked throughout the body by narrow tubes known as lymphatic vessels. These vessels carry lymph, a colorless liquid that is collected from the body's tissues; chyle, a milky fluid taken from food in the intestine during digestion; lymphocytes, specialized white blood cells; and other blood cells. The lymphatic fluids and lymphocytes ultimately are funneled back into the bloodstream through a connection in the left upper chest.
Other organs that contain lymphatic tissue and so are affected by lymphoma include the:
- Spleen, a "ductless gland" that is located on the left side of the body under the lower rib cage; it makes lymphocytes and other infection-fighting cells, stores healthy blood cells, and filters the blood;
- Thymus gland, a gland located in front of the heart; it produces immature T-cells that, when mature, are involved in immune system responses;
- Bone marrow, the inner region of the bones;
- Adenoids, the lymphatic tissue in the post-nasal area; and
- Tonsils, the rounded mass of lymphatic tissue at the back of the throat
Both Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHLs) begin in lymphatic tissues and can invade other organs. But NHLs are much less predictable than HD, and they are more likely to spread to areas beyond the lymph nodes.
Anatomically, lymphomas are composed of malignant lymphocytes. Lymphocytes are a normally occurring part of the white blood cell series. The lymphocyte population can be simplistically divided into B-cells, T-cells and null cells. The job of B-cell lymphocytes is to participate in the immune system by producing antibodies. The job of the T-cell lymphocytes is to direct the participation of B-cells and other cell types in an overall immune response; they are the conductors of the immune system. Lymphomas are the malignant counterpart of these normal cells.
Non-Hodgkin's lymphoma (NHL) is a heterogeneous disease. Each year, there are approximately 50,000 new cases and almost 25,000 deaths from the disease in the United States. Unlike Hodgkin's disease, NHL is comprised of approximately 10 different subtypes (in the Working Formulation) and 20 different disease entities in the Revised European-American Lymphoma Classification (REAL) system.
These subtypes are grouped into 3 biologic states- low grade, intermediate grade, and high grade lymphomas. Therapy is determined by several factors, including the biologic state of the lymphoma, the stage of lymphoma, the presence or absence of symptoms (e.g., weight loss, night sweats, organ dysfunction), and the overall general health of the patient.
A number of factors, including congenital and acquired immunodeficiency states, and infectious, physical, and chemical agents, have been associated with an increased risk for NHL. Infectious agents, such as viral infections (e.g., Epstein barr virus, HIV, human T-cell leukemia virus), and bacterial infections (e.g., helicobacter pylori) may be associated with the development of NHL. Additionally, physical and chemical agents such as pesticides, solvents, arsenate, and lead, as well as hair dyes, radiation exposure (high dose), and paint thinners may also increase the risk.
Non-Hodgkin's lymphoma occurs more often in patients between the ages of 40 and 70.) Risk for disease recurrence and overall survival rate can be predicted by using an international prognostic index (IPI) which takes into account age, stage of disease, general health (also known as performance status), number of extra nodal sites, and presence or absence of an elevated serum enzyme named LDH (lactate dehydrogenase).
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 is, 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 non-cancerous 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 a 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.
After reviewing 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.
In addition, the physician may request a lymph angiogram, 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 is now typical to perform the procedure on only one side.
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.
Once the physician has diagnosed lymphoma, he or she will want to perform studies to establish the patient's stage - that is, to find out how far the patient's cancer has spread. Staging helps the physician to select appropriate treatment options and helps him/her to arrive at a prognosis, or estimate of disease outlook and survival. Clinical information is reviewed, including findings from the physical examination, blood tests, and imaging studies. The imaging studies most often employed are chest X-ray and computed tomographic (CT) scan of the chest, abdomen, and pelvis.
If the patient has non-Hodgkin's lymphoma (NHL), the physician may order additional tests such as blood tests that reflect kidney and liver function which are important factors in the choice of chemotherapeutic drugs, bone marrow aspiration/ biopsy, and lumbar puncture.
Lumbar puncture, otherwise known as a "spinal tap," is performed if the physician suspects that NHL has spread to the central nervous system (CNS) or bone marrow. In addition, lumbar puncture is performed routinely for certain aggressive lymphomas (e.g., primary central nervous system lymphoma, or PCNSL, in AIDS patients).
The Ann Arbor Staging
As with many other cancers, NHL is categorized on the basis of tumor burden. The Ann Arbor Staging System is the most popular system for classifying NHL. The Ann Arbor Staging groups are as follows:
NHL is limited to one lymph node group (e.g., neck, underarm, groin, etc.) above or below the diaphragm, or NHL is in an organ or site other than the lymph nodes (extranodal) but has not spread to other organs or lymph nodes.
NHL is limited to two lymph node groups on the same side of the diaphragm, or NHL is limited to one extranodal organ and has spread to one or more lymph node groups on the same side of the diaphragm.
NHL is in two lymph node groups, with/without partial involvement of an extranodal organ or site above and below the diaphragm.
NHL is extensive (diffuse) in one organ or site, with/without NHL in distant lymph nodes.
After an NHL patient has been assigned a stage, this categorization may be refined by adding the biologic grade of the disease, that is, "low," "intermediate," or "high" grade. Other descriptive terms - such as "bulky" versus "non-bulky" disease and the presence or absence of B symptoms - may be used to fully describe a particular case of lymphoma.