INTRODUCTION — Lymphoma is a cancer of lymphocytes, a type of white blood cell. Lymphocytes circulate in the body through a network referred to as the lymphatic system, which includes the bone marrow, spleen, thymus, and lymph nodes. The organs and vessels of the lymphatic system work together to produce and store cells that fight infection (show figure 1).
There are two main types of lymphoma: Hodgkin's lymphoma (also called Hodgkin's disease) Non-Hodgkin's lymphoma (NHL).
NHL is the most common type of lymphoma. Follicular lymphoma is one form of NHL. In contrast to some of the other forms of NHL, follicular lymphoma usually grows slowly and thus may not require treatment for many years. Because of its slow growth characteristics, follicular lymphoma is referred to as being an indolent (rather than aggressive or highly aggressive) lymphoma.
The following discussion will review the risk factors, classification, and clinical symptoms of follicular lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing follicular lymphoma, although most persons have no known risk factors. Follicular lymphoma is slightly more likely to be diagnosed in women than men, and is less commonly found in persons of Asian and black ethnicity. Nearly all persons diagnosed with follicular lymphoma are adults, with the average age at diagnosis being 60 years.
SYMPTOMS — The initial symptoms of follicular lymphoma include painless swelling in one or more of the body's lymph nodes, particularly in the neck, armpit, or groin areas; this is called adenopathy. Often, patients with follicular lymphoma complain that their lymph nodes have been swollen for a long time; the size may increase and decrease several times before the patient seeks medical attention.
Some persons with follicular lymphoma develop large tumors in the abdomen. These may cause no symptoms, but can cause obstruction of the gastrointestinal, vascular, or urinary tract.
In the early stages, only one or two lymph nodes may be involved with the lymphoma. However, staging studies typically show that follicular lymphoma affects lymph node sites throughout the body:
DIAGNOSIS — The diagnosis of follicular lymphoma is confirmed by removing all or part of an enlarged lymph node to examine its cells under a microscope, a procedure known as a biopsy. Additional diagnostic tests are used to obtain more information about the type of lymphoma and the extent to which the disease has spread in the body. This process is called staging. The results of these tests will help determine the most effective course of treatment.
History and physical exam — A careful history and physical examination will help determine the extent of the disease. The physical exam may reveal swollen lymph nodes in various locations (show figure 1).
Diagnostic tests — A number of diagnostic tests are available to help determine which areas of the body have been affected. Tests that may be done include: CT scan of the chest, abdomen, and pelvis Blood tests Bone marrow biopsy: Removal of tissue from the bone marrow, the spongy area in the middle of large bones, for analysis. PET scan: This test uses a small amount of a radioactive substance, which is injected into a vein; the radioactive substance is absorbed by the cancer cells and can be viewed with a special camera.
STAGING — Staging involves dividing patients into groups (stages) based upon how much of the lymphatic system is involved at the time of diagnosis. Staging helps determine a person's prognosis and whether treatment is required (show table 1).
The following are terms used in the staging criteria: Lymph node regions: An area of lymph nodes and the surrounding tissue. Examples include the cervical nodes in the neck (show figure 2), the axillary nodes in the armpit, the inguinal nodes in the groin, or the mediastinal nodes in the chest (show figure 3). Lymph structures: Organs or structures that are part of the lymphatic system, such as the lymph nodes, spleen, and thymus gland. Diaphragm: A large muscle that separates the chest cavity from the abdominal cavity.
Stage I — Only one lymph node region is involved, or only one lymph structure is involved.
Stage II — Two or more lymph node regions or lymph node structures on the same side of the diaphragm are involved.
Stage III — Lymph node regions or structures on both sides of the diaphragm are involved.
Stage IV — There is widespread involvement of a number of organs or tissues other than lymph node regions or structures, such as the liver, lung, or bone marrow.
Subclassifications — Additional criteria help clinicians further identify subgroups within each stage, as follows: A or B — The letter "A," as in stage IIA, means that symptoms of unexplained fever, night sweats, or weight loss (at least 10 percent of the body weight) were NOT present during the six months prior to diagnosis. The letter "B," as in stage IIIB, means that these symptoms were present. These symptoms are therefore referred to as "B symptoms". About one in five patients with follicular lymphoma experiences systemic "B" symptoms E — The presence of local spread of the disease from one nodal area or structure to surrounding tissue in the same area of the body is indicated by the letter "e," as in stage IIe.
For example, a patient with follicular lymphoma involving lymph nodes in the neck, mediastinum, and groin (ie, involvement above and below the diaphragm) who also has symptoms of fever, night sweats, and weight loss (ie, systemic symptoms), would be in stage IIIB.
CLASSIFICATION — The World Health Organization (WHO) classifies follicular lymphoma into three different grades, according to the number of large cells they contain. This is determined by a pathologist, who looks at tumor sections under a microscope. A high-power field refers to what the pathologist sees in one area of the tissue using high-power magnification. Grade I: Fewer than five large cells are seen per high power field. Grade I is the most common type of follicular lymphoma. Generally, physicians consider grades I and II to be indolent or slow growing. Grade II: Between 6 and 15 large cells are seen per high power field. Grade III: More than 15 large cells are seen per high power field. This is also referred to as follicular large cell lymphoma. Unlike other grades of follicular lymphoma, this variant is less likely to invade the bone marrow and more likely to occur as large masses in the lymph tissues. Although this is similar to the lower grades of lymphoma, the symptoms and growth pattern of follicular large cell lymphoma is similar to that seen in patients with diffuse large B-cell lymphoma. (See "Patient information: Diffuse large B-cell lymphoma").
DISEASE PROGRESSION — The disease progression of follicular lymphoma varies from one person to another, depending upon the speed of the tumor's growth and the involvement of other organs. Sometimes patients with the disease have no symptoms for many years and do not need treatment. In other patients, treatment may be required for symptoms such as fever, night sweats, weight loss, pain, obstruction of organs, or the development of anemia and other changes in blood counts.
Treatment for follicular lymphoma depends on the patient's symptoms, tumor grade, age and general health. Early treatment does not always improve overall survival if a patient has no symptoms and the disease is not affecting their organs. Thus, close observation (a "watch and wait" approach) is often recommended.
Because of follicular lymphoma's ability to change into a more aggressive, widespread form of lymphoma (an aggressive B-cell lymphoma that occurs in 10 to 70 percent of patients), continued follow-up is required. (See "Patient information: Diffuse large B-cell lymphoma").
TREATMENT — The majority of patients with follicular lymphoma have widespread, advanced-stage disease when first diagnosed. However, because follicular lymphoma is slow-growing, it may take many years for the disease to progress, during which time patients may not need any form of treatment. Furthermore, the slow-growth characteristics make the tumors relatively less responsive to standard forms of cancer treatment (compared to the more aggressive lymphomas). As a result, a cure is not usually possible; the main reason to treat is to improve symptoms.
Features that may warrant treatment include one or more of the following: Progressively enlarging lymph nodes Fever, weight loss, or night sweats Low blood counts
Patients without these features are usually monitored with frequent physical examination and blood testing. For older patients who have symptoms but have no evidence of organ obstruction, monoclonal antibody therapy with rituximab (Rituxan®) may be recommended (see "Monoclonal antibody treatment" below).
Early stage disease — Patients with early stage disease (stage I or II) who develop symptoms may be treated with radiation therapy alone.
Radiation therapy — Radiation therapy uses high-energy beams (gamma rays) to slow or stop the growth of cancer cells, and is administered to the region of affected lymph nodes (called involved field radiation) or to the affected and surrounding lymph nodes (called extended field radiation). Radiation therapy must be given in small daily doses over a period of weeks to minimize the side effects; the number of weeks depends upon the amount of radiation to be administered.
Advanced stage disease — Advanced stage disease includes persons with stage II, III and IV disease. There are many treatment options for patients with advanced stage disease. The choice of treatment depends upon the patient's preference and the need for the treatment to act quickly (if organ function is threatened by the follicular lymphoma). Most advanced stage disease is treated with either a single chemotherapy drug or combination of chemotherapy drugs.
Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or multiply. Because most of an adult's normal cells are not actively dividing or multiplying, they are not affected by chemotherapy. However, the bone marrow (where the blood cells are produced), the hair follicles, and the lining of the gastrointestinal (GI) tract are all growing. The side effects of chemotherapy drugs are related to effects on these and other normal tissues.
A chemotherapy drug or combination of drugs is referred to as a regimen. Regimens used for the treatment of follicular lymphoma may include a single agent taken by mouth on a daily basis, while other regimens are given intravenously in treatment cycles. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover. For example, a typical chemotherapy regimen is a one-hour IV infusion of two or more different chemotherapy medications given once every three to four weeks. This three- or four-week period is one cycle of therapy. If this regimen were repeated for a total of three or four cycles, it would take up to four months to complete.
Monoclonal antibody treatment — A monoclonal antibody is a purified protein that targets a specific group of cells (usually cancer cells). This has advantages over other cancer treatments such as chemotherapy, which targets all rapidly growing cells. There are usually fewer side effects and long-term risks of monoclonal antibody therapies as compared to traditional chemotherapy.
Rituximab (Rituxan®) is a monoclonal antibody treatment that may be used for patients with follicular lymphoma who have relapsed or not responded to other treatments. Rituximab is frequently combined with chemotherapy treatments, and is being tested as a long-term maintenance treatment after chemotherapy. It has also been tested as an initial treatment for follicular lymphoma; follow-up trials are needed to determine if this treatment can prolong overall survival.
Radioimmunotherapy — Radioimmunotherapy (RIT) uses radioactive isotopes that are linked to monoclonal antibodies. As a result, radiation therapy can be delivered directly to proteins on cancer cells, which reduces the exposure of healthy tissues to radiation. The radioimmunotherapy treatments used for follicular lymphoma includes 90 Y-ibritumomab tiuxetan (Zevalin®) or 131I-tositumomab (Bexxar®), both of which are administered through a vein. The patient is usually given treatment in a hospital-based setting, but may go home after treatment is completed.
RIT is currently reserved for patients who have relapsed or failed to respond to other treatments. Administering RIT requires specialized equipment and additional training of physicians, nurses, and other involved personnel. The cost of RIT is quite high, and there are potentially serious short and long-term side effects of the treatment.
Bone marrow transplantation — Hematopoietic cell (bone marrow) transplantation is generally reserved for patients whose lymphoma has recurred after treatment. (See "Patient information: Overview of bone marrow transplantation").
Summary — For patients with advanced stage follicular lymphoma that has never been treated, the following table summarizes treatment recommendations (show table 2). For patients who have received treatment and relapsed, the following table summarizes treatment recommendations (show table 3).
Clinical trials — A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Clinical trials are especially important for persons with follicular lymphoma since there is no treatment currently available to cure this disease. Ask a healthcare provider for more information, or read about clinical trials at: National Cancer Institute
(www.cancer.gov/clinicaltrials/)
National Library of Medicine
(http: clinicaltrials.gov/)
PROGNOSIS — For patients with advanced forms of follicular lymphoma (ie, stages III and IV disease, show table 1), the average survival is approximately 10 years. Despite its slow-growing nature, most cases of follicular lymphoma are not curable with currently available therapies.
The Follicular Lymphoma International Prognostic Index (FLIPI) has identified five factors that are useful for predicting survival (prognosis). In addition, physicians can use these data to predict which patients benefit from specific chemotherapy treatments. Age >60 years Advanced clinical stages (ie, stages III or IV, show table 1) Low hemoglobin level More than 4 involved lymph node areas (show figure 1) Serum lactate dehydrogenase level greater than the upper limit of normal
Persons with zero to one of these factors are considered to have a low risk of dying; on average, 91 percent of this group is alive at 5 years after diagnosis, and 71 percent are alive 10 years after diagnosis.
Persons with 2 of these factors are considered to have an intermediate risk of dying; on average, 78 percent of this group is alive at 5 years after diagnosis, and 51 percent are alive 10 years after diagnosis.
Persons with 3 or more of these factors are considered to have a higher risk of dying; on average, 52 percent of this group is alive at 5 years after diagnosis, and 36 percent are alive 10 years after diagnosis.
It is important to remember that these numbers represent averages, and do not necessarily predict which persons with follicular lymphoma will live or die.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
OncoLink
(www.oncolink.com/index.cfm)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. The Non-Hodgkin's Classification Project. Blood 1997; 89:3909.
2. Glass, A, Karnell, L, Menck, H. The National Cancer Data Base report on non-Hodgkin's lymphoma. Cancer 1997; 80:2311.
3. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp. (Accessed 3/7/05).
Saturday, October 13, 2007
Follicular lymphoma
INTRODUCTION — Lymphoma is a cancer of lymphocytes, a type of white blood cell. Lymphocytes circulate in the body through a network referred to as the lymphatic system, which includes the bone marrow, spleen, thymus, and lymph nodes. The organs and vessels of the lymphatic system work together to produce and store cells that fight infection (show figure 1).
There are two main types of lymphoma: Hodgkin's lymphoma (also called Hodgkin's disease) Non-Hodgkin's lymphoma (NHL).
NHL is the most common type of lymphoma. Follicular lymphoma is one form of NHL. In contrast to some of the other forms of NHL, follicular lymphoma usually grows slowly and thus may not require treatment for many years. Because of its slow growth characteristics, follicular lymphoma is referred to as being an indolent (rather than aggressive or highly aggressive) lymphoma.
The following discussion will review the risk factors, classification, and clinical symptoms of follicular lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing follicular lymphoma, although most persons have no known risk factors. Follicular lymphoma is slightly more likely to be diagnosed in women than men, and is less commonly found in persons of Asian and black ethnicity. Nearly all persons diagnosed with follicular lymphoma are adults, with the average age at diagnosis being 60 years.
SYMPTOMS — The initial symptoms of follicular lymphoma include painless swelling in one or more of the body's lymph nodes, particularly in the neck, armpit, or groin areas; this is called adenopathy. Often, patients with follicular lymphoma complain that their lymph nodes have been swollen for a long time; the size may increase and decrease several times before the patient seeks medical attention.
Some persons with follicular lymphoma develop large tumors in the abdomen. These may cause no symptoms, but can cause obstruction of the gastrointestinal, vascular, or urinary tract.
In the early stages, only one or two lymph nodes may be involved with the lymphoma. However, staging studies typically show that follicular lymphoma affects lymph node sites throughout the body:
DIAGNOSIS — The diagnosis of follicular lymphoma is confirmed by removing all or part of an enlarged lymph node to examine its cells under a microscope, a procedure known as a biopsy. Additional diagnostic tests are used to obtain more information about the type of lymphoma and the extent to which the disease has spread in the body. This process is called staging. The results of these tests will help determine the most effective course of treatment.
History and physical exam — A careful history and physical examination will help determine the extent of the disease. The physical exam may reveal swollen lymph nodes in various locations (show figure 1).
Diagnostic tests — A number of diagnostic tests are available to help determine which areas of the body have been affected. Tests that may be done include: CT scan of the chest, abdomen, and pelvis Blood tests Bone marrow biopsy: Removal of tissue from the bone marrow, the spongy area in the middle of large bones, for analysis. PET scan: This test uses a small amount of a radioactive substance, which is injected into a vein; the radioactive substance is absorbed by the cancer cells and can be viewed with a special camera.
STAGING — Staging involves dividing patients into groups (stages) based upon how much of the lymphatic system is involved at the time of diagnosis. Staging helps determine a person's prognosis and whether treatment is required (show table 1).
The following are terms used in the staging criteria: Lymph node regions: An area of lymph nodes and the surrounding tissue. Examples include the cervical nodes in the neck (show figure 2), the axillary nodes in the armpit, the inguinal nodes in the groin, or the mediastinal nodes in the chest (show figure 3). Lymph structures: Organs or structures that are part of the lymphatic system, such as the lymph nodes, spleen, and thymus gland. Diaphragm: A large muscle that separates the chest cavity from the abdominal cavity.
Stage I — Only one lymph node region is involved, or only one lymph structure is involved.
Stage II — Two or more lymph node regions or lymph node structures on the same side of the diaphragm are involved.
Stage III — Lymph node regions or structures on both sides of the diaphragm are involved.
Stage IV — There is widespread involvement of a number of organs or tissues other than lymph node regions or structures, such as the liver, lung, or bone marrow.
Subclassifications — Additional criteria help clinicians further identify subgroups within each stage, as follows: A or B — The letter "A," as in stage IIA, means that symptoms of unexplained fever, night sweats, or weight loss (at least 10 percent of the body weight) were NOT present during the six months prior to diagnosis. The letter "B," as in stage IIIB, means that these symptoms were present. These symptoms are therefore referred to as "B symptoms". About one in five patients with follicular lymphoma experiences systemic "B" symptoms E — The presence of local spread of the disease from one nodal area or structure to surrounding tissue in the same area of the body is indicated by the letter "e," as in stage IIe.
For example, a patient with follicular lymphoma involving lymph nodes in the neck, mediastinum, and groin (ie, involvement above and below the diaphragm) who also has symptoms of fever, night sweats, and weight loss (ie, systemic symptoms), would be in stage IIIB.
CLASSIFICATION — The World Health Organization (WHO) classifies follicular lymphoma into three different grades, according to the number of large cells they contain. This is determined by a pathologist, who looks at tumor sections under a microscope. A high-power field refers to what the pathologist sees in one area of the tissue using high-power magnification. Grade I: Fewer than five large cells are seen per high power field. Grade I is the most common type of follicular lymphoma. Generally, physicians consider grades I and II to be indolent or slow growing. Grade II: Between 6 and 15 large cells are seen per high power field. Grade III: More than 15 large cells are seen per high power field. This is also referred to as follicular large cell lymphoma. Unlike other grades of follicular lymphoma, this variant is less likely to invade the bone marrow and more likely to occur as large masses in the lymph tissues. Although this is similar to the lower grades of lymphoma, the symptoms and growth pattern of follicular large cell lymphoma is similar to that seen in patients with diffuse large B-cell lymphoma. (See "Patient information: Diffuse large B-cell lymphoma").
DISEASE PROGRESSION — The disease progression of follicular lymphoma varies from one person to another, depending upon the speed of the tumor's growth and the involvement of other organs. Sometimes patients with the disease have no symptoms for many years and do not need treatment. In other patients, treatment may be required for symptoms such as fever, night sweats, weight loss, pain, obstruction of organs, or the development of anemia and other changes in blood counts.
Treatment for follicular lymphoma depends on the patient's symptoms, tumor grade, age and general health. Early treatment does not always improve overall survival if a patient has no symptoms and the disease is not affecting their organs. Thus, close observation (a "watch and wait" approach) is often recommended.
Because of follicular lymphoma's ability to change into a more aggressive, widespread form of lymphoma (an aggressive B-cell lymphoma that occurs in 10 to 70 percent of patients), continued follow-up is required. (See "Patient information: Diffuse large B-cell lymphoma").
TREATMENT — The majority of patients with follicular lymphoma have widespread, advanced-stage disease when first diagnosed. However, because follicular lymphoma is slow-growing, it may take many years for the disease to progress, during which time patients may not need any form of treatment. Furthermore, the slow-growth characteristics make the tumors relatively less responsive to standard forms of cancer treatment (compared to the more aggressive lymphomas). As a result, a cure is not usually possible; the main reason to treat is to improve symptoms.
Features that may warrant treatment include one or more of the following: Progressively enlarging lymph nodes Fever, weight loss, or night sweats Low blood counts
Patients without these features are usually monitored with frequent physical examination and blood testing. For older patients who have symptoms but have no evidence of organ obstruction, monoclonal antibody therapy with rituximab (Rituxan®) may be recommended (see "Monoclonal antibody treatment" below).
Early stage disease — Patients with early stage disease (stage I or II) who develop symptoms may be treated with radiation therapy alone.
Radiation therapy — Radiation therapy uses high-energy beams (gamma rays) to slow or stop the growth of cancer cells, and is administered to the region of affected lymph nodes (called involved field radiation) or to the affected and surrounding lymph nodes (called extended field radiation). Radiation therapy must be given in small daily doses over a period of weeks to minimize the side effects; the number of weeks depends upon the amount of radiation to be administered.
Advanced stage disease — Advanced stage disease includes persons with stage II, III and IV disease. There are many treatment options for patients with advanced stage disease. The choice of treatment depends upon the patient's preference and the need for the treatment to act quickly (if organ function is threatened by the follicular lymphoma). Most advanced stage disease is treated with either a single chemotherapy drug or combination of chemotherapy drugs.
Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or multiply. Because most of an adult's normal cells are not actively dividing or multiplying, they are not affected by chemotherapy. However, the bone marrow (where the blood cells are produced), the hair follicles, and the lining of the gastrointestinal (GI) tract are all growing. The side effects of chemotherapy drugs are related to effects on these and other normal tissues.
A chemotherapy drug or combination of drugs is referred to as a regimen. Regimens used for the treatment of follicular lymphoma may include a single agent taken by mouth on a daily basis, while other regimens are given intravenously in treatment cycles. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover. For example, a typical chemotherapy regimen is a one-hour IV infusion of two or more different chemotherapy medications given once every three to four weeks. This three- or four-week period is one cycle of therapy. If this regimen were repeated for a total of three or four cycles, it would take up to four months to complete.
Monoclonal antibody treatment — A monoclonal antibody is a purified protein that targets a specific group of cells (usually cancer cells). This has advantages over other cancer treatments such as chemotherapy, which targets all rapidly growing cells. There are usually fewer side effects and long-term risks of monoclonal antibody therapies as compared to traditional chemotherapy.
Rituximab (Rituxan®) is a monoclonal antibody treatment that may be used for patients with follicular lymphoma who have relapsed or not responded to other treatments. Rituximab is frequently combined with chemotherapy treatments, and is being tested as a long-term maintenance treatment after chemotherapy. It has also been tested as an initial treatment for follicular lymphoma; follow-up trials are needed to determine if this treatment can prolong overall survival.
Radioimmunotherapy — Radioimmunotherapy (RIT) uses radioactive isotopes that are linked to monoclonal antibodies. As a result, radiation therapy can be delivered directly to proteins on cancer cells, which reduces the exposure of healthy tissues to radiation. The radioimmunotherapy treatments used for follicular lymphoma includes 90 Y-ibritumomab tiuxetan (Zevalin®) or 131I-tositumomab (Bexxar®), both of which are administered through a vein. The patient is usually given treatment in a hospital-based setting, but may go home after treatment is completed.
RIT is currently reserved for patients who have relapsed or failed to respond to other treatments. Administering RIT requires specialized equipment and additional training of physicians, nurses, and other involved personnel. The cost of RIT is quite high, and there are potentially serious short and long-term side effects of the treatment.
Bone marrow transplantation — Hematopoietic cell (bone marrow) transplantation is generally reserved for patients whose lymphoma has recurred after treatment. (See "Patient information: Overview of bone marrow transplantation").
Summary — For patients with advanced stage follicular lymphoma that has never been treated, the following table summarizes treatment recommendations (show table 2). For patients who have received treatment and relapsed, the following table summarizes treatment recommendations (show table 3).
Clinical trials — A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Clinical trials are especially important for persons with follicular lymphoma since there is no treatment currently available to cure this disease. Ask a healthcare provider for more information, or read about clinical trials at: National Cancer Institute
(www.cancer.gov/clinicaltrials/)
National Library of Medicine
(http: clinicaltrials.gov/)
PROGNOSIS — For patients with advanced forms of follicular lymphoma (ie, stages III and IV disease, show table 1), the average survival is approximately 10 years. Despite its slow-growing nature, most cases of follicular lymphoma are not curable with currently available therapies.
The Follicular Lymphoma International Prognostic Index (FLIPI) has identified five factors that are useful for predicting survival (prognosis). In addition, physicians can use these data to predict which patients benefit from specific chemotherapy treatments. Age >60 years Advanced clinical stages (ie, stages III or IV, show table 1) Low hemoglobin level More than 4 involved lymph node areas (show figure 1) Serum lactate dehydrogenase level greater than the upper limit of normal
Persons with zero to one of these factors are considered to have a low risk of dying; on average, 91 percent of this group is alive at 5 years after diagnosis, and 71 percent are alive 10 years after diagnosis.
Persons with 2 of these factors are considered to have an intermediate risk of dying; on average, 78 percent of this group is alive at 5 years after diagnosis, and 51 percent are alive 10 years after diagnosis.
Persons with 3 or more of these factors are considered to have a higher risk of dying; on average, 52 percent of this group is alive at 5 years after diagnosis, and 36 percent are alive 10 years after diagnosis.
It is important to remember that these numbers represent averages, and do not necessarily predict which persons with follicular lymphoma will live or die.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
OncoLink
(www.oncolink.com/index.cfm)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. The Non-Hodgkin's Classification Project. Blood 1997; 89:3909.
2. Glass, A, Karnell, L, Menck, H. The National Cancer Data Base report on non-Hodgkin's lymphoma. Cancer 1997; 80:2311.
3. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp. (Accessed 3/7/05).
There are two main types of lymphoma: Hodgkin's lymphoma (also called Hodgkin's disease) Non-Hodgkin's lymphoma (NHL).
NHL is the most common type of lymphoma. Follicular lymphoma is one form of NHL. In contrast to some of the other forms of NHL, follicular lymphoma usually grows slowly and thus may not require treatment for many years. Because of its slow growth characteristics, follicular lymphoma is referred to as being an indolent (rather than aggressive or highly aggressive) lymphoma.
The following discussion will review the risk factors, classification, and clinical symptoms of follicular lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing follicular lymphoma, although most persons have no known risk factors. Follicular lymphoma is slightly more likely to be diagnosed in women than men, and is less commonly found in persons of Asian and black ethnicity. Nearly all persons diagnosed with follicular lymphoma are adults, with the average age at diagnosis being 60 years.
SYMPTOMS — The initial symptoms of follicular lymphoma include painless swelling in one or more of the body's lymph nodes, particularly in the neck, armpit, or groin areas; this is called adenopathy. Often, patients with follicular lymphoma complain that their lymph nodes have been swollen for a long time; the size may increase and decrease several times before the patient seeks medical attention.
Some persons with follicular lymphoma develop large tumors in the abdomen. These may cause no symptoms, but can cause obstruction of the gastrointestinal, vascular, or urinary tract.
In the early stages, only one or two lymph nodes may be involved with the lymphoma. However, staging studies typically show that follicular lymphoma affects lymph node sites throughout the body:
DIAGNOSIS — The diagnosis of follicular lymphoma is confirmed by removing all or part of an enlarged lymph node to examine its cells under a microscope, a procedure known as a biopsy. Additional diagnostic tests are used to obtain more information about the type of lymphoma and the extent to which the disease has spread in the body. This process is called staging. The results of these tests will help determine the most effective course of treatment.
History and physical exam — A careful history and physical examination will help determine the extent of the disease. The physical exam may reveal swollen lymph nodes in various locations (show figure 1).
Diagnostic tests — A number of diagnostic tests are available to help determine which areas of the body have been affected. Tests that may be done include: CT scan of the chest, abdomen, and pelvis Blood tests Bone marrow biopsy: Removal of tissue from the bone marrow, the spongy area in the middle of large bones, for analysis. PET scan: This test uses a small amount of a radioactive substance, which is injected into a vein; the radioactive substance is absorbed by the cancer cells and can be viewed with a special camera.
STAGING — Staging involves dividing patients into groups (stages) based upon how much of the lymphatic system is involved at the time of diagnosis. Staging helps determine a person's prognosis and whether treatment is required (show table 1).
The following are terms used in the staging criteria: Lymph node regions: An area of lymph nodes and the surrounding tissue. Examples include the cervical nodes in the neck (show figure 2), the axillary nodes in the armpit, the inguinal nodes in the groin, or the mediastinal nodes in the chest (show figure 3). Lymph structures: Organs or structures that are part of the lymphatic system, such as the lymph nodes, spleen, and thymus gland. Diaphragm: A large muscle that separates the chest cavity from the abdominal cavity.
Stage I — Only one lymph node region is involved, or only one lymph structure is involved.
Stage II — Two or more lymph node regions or lymph node structures on the same side of the diaphragm are involved.
Stage III — Lymph node regions or structures on both sides of the diaphragm are involved.
Stage IV — There is widespread involvement of a number of organs or tissues other than lymph node regions or structures, such as the liver, lung, or bone marrow.
Subclassifications — Additional criteria help clinicians further identify subgroups within each stage, as follows: A or B — The letter "A," as in stage IIA, means that symptoms of unexplained fever, night sweats, or weight loss (at least 10 percent of the body weight) were NOT present during the six months prior to diagnosis. The letter "B," as in stage IIIB, means that these symptoms were present. These symptoms are therefore referred to as "B symptoms". About one in five patients with follicular lymphoma experiences systemic "B" symptoms E — The presence of local spread of the disease from one nodal area or structure to surrounding tissue in the same area of the body is indicated by the letter "e," as in stage IIe.
For example, a patient with follicular lymphoma involving lymph nodes in the neck, mediastinum, and groin (ie, involvement above and below the diaphragm) who also has symptoms of fever, night sweats, and weight loss (ie, systemic symptoms), would be in stage IIIB.
CLASSIFICATION — The World Health Organization (WHO) classifies follicular lymphoma into three different grades, according to the number of large cells they contain. This is determined by a pathologist, who looks at tumor sections under a microscope. A high-power field refers to what the pathologist sees in one area of the tissue using high-power magnification. Grade I: Fewer than five large cells are seen per high power field. Grade I is the most common type of follicular lymphoma. Generally, physicians consider grades I and II to be indolent or slow growing. Grade II: Between 6 and 15 large cells are seen per high power field. Grade III: More than 15 large cells are seen per high power field. This is also referred to as follicular large cell lymphoma. Unlike other grades of follicular lymphoma, this variant is less likely to invade the bone marrow and more likely to occur as large masses in the lymph tissues. Although this is similar to the lower grades of lymphoma, the symptoms and growth pattern of follicular large cell lymphoma is similar to that seen in patients with diffuse large B-cell lymphoma. (See "Patient information: Diffuse large B-cell lymphoma").
DISEASE PROGRESSION — The disease progression of follicular lymphoma varies from one person to another, depending upon the speed of the tumor's growth and the involvement of other organs. Sometimes patients with the disease have no symptoms for many years and do not need treatment. In other patients, treatment may be required for symptoms such as fever, night sweats, weight loss, pain, obstruction of organs, or the development of anemia and other changes in blood counts.
Treatment for follicular lymphoma depends on the patient's symptoms, tumor grade, age and general health. Early treatment does not always improve overall survival if a patient has no symptoms and the disease is not affecting their organs. Thus, close observation (a "watch and wait" approach) is often recommended.
Because of follicular lymphoma's ability to change into a more aggressive, widespread form of lymphoma (an aggressive B-cell lymphoma that occurs in 10 to 70 percent of patients), continued follow-up is required. (See "Patient information: Diffuse large B-cell lymphoma").
TREATMENT — The majority of patients with follicular lymphoma have widespread, advanced-stage disease when first diagnosed. However, because follicular lymphoma is slow-growing, it may take many years for the disease to progress, during which time patients may not need any form of treatment. Furthermore, the slow-growth characteristics make the tumors relatively less responsive to standard forms of cancer treatment (compared to the more aggressive lymphomas). As a result, a cure is not usually possible; the main reason to treat is to improve symptoms.
Features that may warrant treatment include one or more of the following: Progressively enlarging lymph nodes Fever, weight loss, or night sweats Low blood counts
Patients without these features are usually monitored with frequent physical examination and blood testing. For older patients who have symptoms but have no evidence of organ obstruction, monoclonal antibody therapy with rituximab (Rituxan®) may be recommended (see "Monoclonal antibody treatment" below).
Early stage disease — Patients with early stage disease (stage I or II) who develop symptoms may be treated with radiation therapy alone.
Radiation therapy — Radiation therapy uses high-energy beams (gamma rays) to slow or stop the growth of cancer cells, and is administered to the region of affected lymph nodes (called involved field radiation) or to the affected and surrounding lymph nodes (called extended field radiation). Radiation therapy must be given in small daily doses over a period of weeks to minimize the side effects; the number of weeks depends upon the amount of radiation to be administered.
Advanced stage disease — Advanced stage disease includes persons with stage II, III and IV disease. There are many treatment options for patients with advanced stage disease. The choice of treatment depends upon the patient's preference and the need for the treatment to act quickly (if organ function is threatened by the follicular lymphoma). Most advanced stage disease is treated with either a single chemotherapy drug or combination of chemotherapy drugs.
Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or multiply. Because most of an adult's normal cells are not actively dividing or multiplying, they are not affected by chemotherapy. However, the bone marrow (where the blood cells are produced), the hair follicles, and the lining of the gastrointestinal (GI) tract are all growing. The side effects of chemotherapy drugs are related to effects on these and other normal tissues.
A chemotherapy drug or combination of drugs is referred to as a regimen. Regimens used for the treatment of follicular lymphoma may include a single agent taken by mouth on a daily basis, while other regimens are given intravenously in treatment cycles. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover. For example, a typical chemotherapy regimen is a one-hour IV infusion of two or more different chemotherapy medications given once every three to four weeks. This three- or four-week period is one cycle of therapy. If this regimen were repeated for a total of three or four cycles, it would take up to four months to complete.
Monoclonal antibody treatment — A monoclonal antibody is a purified protein that targets a specific group of cells (usually cancer cells). This has advantages over other cancer treatments such as chemotherapy, which targets all rapidly growing cells. There are usually fewer side effects and long-term risks of monoclonal antibody therapies as compared to traditional chemotherapy.
Rituximab (Rituxan®) is a monoclonal antibody treatment that may be used for patients with follicular lymphoma who have relapsed or not responded to other treatments. Rituximab is frequently combined with chemotherapy treatments, and is being tested as a long-term maintenance treatment after chemotherapy. It has also been tested as an initial treatment for follicular lymphoma; follow-up trials are needed to determine if this treatment can prolong overall survival.
Radioimmunotherapy — Radioimmunotherapy (RIT) uses radioactive isotopes that are linked to monoclonal antibodies. As a result, radiation therapy can be delivered directly to proteins on cancer cells, which reduces the exposure of healthy tissues to radiation. The radioimmunotherapy treatments used for follicular lymphoma includes 90 Y-ibritumomab tiuxetan (Zevalin®) or 131I-tositumomab (Bexxar®), both of which are administered through a vein. The patient is usually given treatment in a hospital-based setting, but may go home after treatment is completed.
RIT is currently reserved for patients who have relapsed or failed to respond to other treatments. Administering RIT requires specialized equipment and additional training of physicians, nurses, and other involved personnel. The cost of RIT is quite high, and there are potentially serious short and long-term side effects of the treatment.
Bone marrow transplantation — Hematopoietic cell (bone marrow) transplantation is generally reserved for patients whose lymphoma has recurred after treatment. (See "Patient information: Overview of bone marrow transplantation").
Summary — For patients with advanced stage follicular lymphoma that has never been treated, the following table summarizes treatment recommendations (show table 2). For patients who have received treatment and relapsed, the following table summarizes treatment recommendations (show table 3).
Clinical trials — A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Clinical trials are especially important for persons with follicular lymphoma since there is no treatment currently available to cure this disease. Ask a healthcare provider for more information, or read about clinical trials at: National Cancer Institute
(www.cancer.gov/clinicaltrials/)
National Library of Medicine
(http: clinicaltrials.gov/)
PROGNOSIS — For patients with advanced forms of follicular lymphoma (ie, stages III and IV disease, show table 1), the average survival is approximately 10 years. Despite its slow-growing nature, most cases of follicular lymphoma are not curable with currently available therapies.
The Follicular Lymphoma International Prognostic Index (FLIPI) has identified five factors that are useful for predicting survival (prognosis). In addition, physicians can use these data to predict which patients benefit from specific chemotherapy treatments. Age >60 years Advanced clinical stages (ie, stages III or IV, show table 1) Low hemoglobin level More than 4 involved lymph node areas (show figure 1) Serum lactate dehydrogenase level greater than the upper limit of normal
Persons with zero to one of these factors are considered to have a low risk of dying; on average, 91 percent of this group is alive at 5 years after diagnosis, and 71 percent are alive 10 years after diagnosis.
Persons with 2 of these factors are considered to have an intermediate risk of dying; on average, 78 percent of this group is alive at 5 years after diagnosis, and 51 percent are alive 10 years after diagnosis.
Persons with 3 or more of these factors are considered to have a higher risk of dying; on average, 52 percent of this group is alive at 5 years after diagnosis, and 36 percent are alive 10 years after diagnosis.
It is important to remember that these numbers represent averages, and do not necessarily predict which persons with follicular lymphoma will live or die.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
OncoLink
(www.oncolink.com/index.cfm)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. The Non-Hodgkin's Classification Project. Blood 1997; 89:3909.
2. Glass, A, Karnell, L, Menck, H. The National Cancer Data Base report on non-Hodgkin's lymphoma. Cancer 1997; 80:2311.
3. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp. (Accessed 3/7/05).
Features and diagnosis of Hodgkin's disease
INTRODUCTION — Hodgkin's disease, also known as Hodgkin's lymphoma, is one of several types of cancer of the body's lymphatic system. It is named after the British physician who first described the disease in 1832.
The lymphatic system is a network of lymph nodes and interconnecting lymph vessels (show figure 1). Lymph nodes are small, pea-shaped organs that make and store lymphocytes, a type of white blood cell that fights infection. Lymph vessels are similar to blood vessels, and carry a watery fluid (lymphatic fluid) that contains lymphocytes. The thymus, spleen, and bone marrow are other organs in the lymphatic system.
In Hodgkin's lympoma, a cancerous tumor develops in a lymph node, usually in the neck or chest. If the disease spreads, it spreads first to adjacent lymph nodes, and then to the spleen, liver, or bone marrow. As it progresses, Hodgkin's lympoma affects the body's ability to fight infection.
The following discussion will review the risk factors for Hodgkin's disease and how it is diagnosed. Issues regarding the staging and treatment of the disease are discussed in a separate topic review. (See "Patient Information: Staging and treatment for Hodgkin's disease").
RISK FACTORS — There are several characteristics that are known to be associated with an increased risk of developing Hodgkin's lymphoma. However, these factors account for only a small number of the total number of people who develop it.
Age — Hodgkin's disease is more common in persons between ages 20 to 30, and also in those over age 50 (show figure 2). Approximately 7800 new cases of Hodgkin's lympoma are diagnosed in the United States annually. This compares to the other common cancer of the lymphatic system, non-Hodgkin's lymphoma, which is diagnosed in approximately 54,000 persons per year.
Epstein-Barr virus history — A number of studies have suggested that the Epstein-Barr virus (EBV), which causes infectious mononucleosis ("mono"), may play a role in the development of Hodgkin's lympoma.
Family history — Close relatives of younger patients with Hodgkin's lympoma have a three to five times higher risk of developing Hodgkin's lympoma, probably due to genetic and environmental exposures. There is no increased risk for the families of older adults with Hodgkin's lympoma. Men are at slightly higher risk for Hodgkin's lympoma than women.
Persons with immune deficiencies — Persons who have a weakened immune system due to disease (such as infection due to the virus causing AIDS), medications (such as chemotherapy or immunosuppressant drugs), or from immune deficiencies (such as autoimmune disease) have an increased risk of developing Hodgkin's lympoma.
CAUSES — The exact cause of Hodgkin's lympoma is not known. The cancer cells in Hodgkin's lympoma are known as Reed-Sternberg cells (named after the physicians who discovered them). Reed-Sternberg cells are believed to be a cancerous type of B lymphocyte. B cell lymphocytes normally function to make antibodies (proteins) that help fight infection. Instead of following the normal pattern of production of B cells and eventual cell death, Reed-Sternberg cells produce more abnormal B cells and do not die.
There are two main types of Hodgkin's lympoma: classical Hodgkin's lympoma (which includes the subtypes nodular sclerosis, mixed cellularity, lymphocyte depleted, and unclassified) and nodular lymphocyte predominant Hodgkin's lympoma. Nodular sclerosis is the most common type of Hodgkin's lympoma in developed countries.
DIAGNOSIS — The diagnosis of Hodgkin's lympoma is based upon a patient's history and physical examination, a tissue biopsy, laboratory studies, and imaging studies. The initial evaluation provides important information about prognosis, staging, and appropriate treatment.
History and physical examination — Most patients with Hodgkin's lympoma are diagnosed after the patient or clinician notices a painless, enlarged lymph node in the neck. Enlarged nodes may also be found above the clavicle, in the armpit (axilla), or the inguinal (groin) area. Some patients are diagnosed after a mass is seen with a chest x-ray, often done for other reasons. Patients may also have symptoms such as fever, night sweats, and weight loss.
Patients who are suspected of having Hodgkin's disease should be seen by a physician who specializes in cancer treatment (called a hematologist/oncologist) for further evaluation and diagnosis.
Tissue biopsy — If the history and physical exam suggests Hodgkin's lympoma, the enlarged lymph node will be surgically removed, usually from the neck. This is usually done as a day surgery procedure with general (the patient is completely asleep) or local (numbing medicine is injected in the area to be biopsied) anesthesia.
If the lymph node to be removed is in an easily accessible area, it may be removed as an outpatient procedure, under local anesthesia. If it is not easily accessible, it may have to be removed as an inpatient procedure, under general anesthesia. The lymph node, after it has been sectioned and treated with specific stains, is then examined under a microscope by a specifically trained pathologist (called a hematopathologist) for evidence of lymphoma.
Bone marrow biopsy — A bone marrow biopsy may be recommended if the clinician suspects that Hodgkin's lympoma is advanced, if the patient has fever, weight loss, and night sweats, or if the patient has an abnormal blood count. This test determines if there are cancerous cells in the bone marrow, which is, by definition, associated with an advanced stage of Hodgkin's lympoma.
A bone marrow biopsy involves removal of a sample of bone marrow fluid, usually from the pelvic or hip bones. Patients are given local anesthesia, which prevents pain during the procedure. The bone marrow fluid is then examined under a microscope to determine if it is involved with Hodgkin's lympoma.
Laboratory studies — Once the diagnosis of Hodgkin's disease is established by biopsy, other blood tests are recommended, including a complete blood count, erythrocyte sedimentation rate (ESR) (a measure of inflammation), and tests of liver, bone, and kidney function.
Imaging studies — Following the diagnosis of Hodgkin's lympoma, additional imaging studies are done, including a chest X-ray and computed tomography (CT scan) of the chest, abdomen, and pelvis. Some patients may undergo PET scanning, which can detect biochemical changes due to the presence of actively growing cancer cells.
STAGING AND TREATMENT — After a person is diagnosed with Hodgkin's lympoma, he/she is grouped according to the number of lymph nodes and other organs found to contain cancer. The recommended treatment of Hodgkin's lympoma depends upon this grouping (called staging). A full discussion of this is available in a separate topic review. (See "Patient information: Staging and treatment for Hodgkin's disease").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.cancer.gov)
American Cancer Society
(www.cancer.org)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
Cure for Lymphoma Foundation
(www.cfl.org)
Lymphoma Research Foundation of America
(www.lymphoma.org)
National Marrow Donor Program
(www.marrow.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lister, TA, Crowther, D, Sutcliffe, SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630.
2. Mauch, PM, Kalish, LA, Kadin, M, et al. Patterns of presentation of Hodgkin disease. Implication for etiology and pathogenesis. Cancer 1993; 71:2062.
3. Alexander, FE, Jarrett, RF, Lawrence, D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer 2000; 82:1117.
4. Hjalgrim, H, Askling, J, Sorensen, P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000; 92:1522.
5. Mauch, PM, Armitage, JO, Diehl, V, et al (editors). Hodgkin's Disease. Lipincott, Philadelphia, 1999.
The lymphatic system is a network of lymph nodes and interconnecting lymph vessels (show figure 1). Lymph nodes are small, pea-shaped organs that make and store lymphocytes, a type of white blood cell that fights infection. Lymph vessels are similar to blood vessels, and carry a watery fluid (lymphatic fluid) that contains lymphocytes. The thymus, spleen, and bone marrow are other organs in the lymphatic system.
In Hodgkin's lympoma, a cancerous tumor develops in a lymph node, usually in the neck or chest. If the disease spreads, it spreads first to adjacent lymph nodes, and then to the spleen, liver, or bone marrow. As it progresses, Hodgkin's lympoma affects the body's ability to fight infection.
The following discussion will review the risk factors for Hodgkin's disease and how it is diagnosed. Issues regarding the staging and treatment of the disease are discussed in a separate topic review. (See "Patient Information: Staging and treatment for Hodgkin's disease").
RISK FACTORS — There are several characteristics that are known to be associated with an increased risk of developing Hodgkin's lymphoma. However, these factors account for only a small number of the total number of people who develop it.
Age — Hodgkin's disease is more common in persons between ages 20 to 30, and also in those over age 50 (show figure 2). Approximately 7800 new cases of Hodgkin's lympoma are diagnosed in the United States annually. This compares to the other common cancer of the lymphatic system, non-Hodgkin's lymphoma, which is diagnosed in approximately 54,000 persons per year.
Epstein-Barr virus history — A number of studies have suggested that the Epstein-Barr virus (EBV), which causes infectious mononucleosis ("mono"), may play a role in the development of Hodgkin's lympoma.
Family history — Close relatives of younger patients with Hodgkin's lympoma have a three to five times higher risk of developing Hodgkin's lympoma, probably due to genetic and environmental exposures. There is no increased risk for the families of older adults with Hodgkin's lympoma. Men are at slightly higher risk for Hodgkin's lympoma than women.
Persons with immune deficiencies — Persons who have a weakened immune system due to disease (such as infection due to the virus causing AIDS), medications (such as chemotherapy or immunosuppressant drugs), or from immune deficiencies (such as autoimmune disease) have an increased risk of developing Hodgkin's lympoma.
CAUSES — The exact cause of Hodgkin's lympoma is not known. The cancer cells in Hodgkin's lympoma are known as Reed-Sternberg cells (named after the physicians who discovered them). Reed-Sternberg cells are believed to be a cancerous type of B lymphocyte. B cell lymphocytes normally function to make antibodies (proteins) that help fight infection. Instead of following the normal pattern of production of B cells and eventual cell death, Reed-Sternberg cells produce more abnormal B cells and do not die.
There are two main types of Hodgkin's lympoma: classical Hodgkin's lympoma (which includes the subtypes nodular sclerosis, mixed cellularity, lymphocyte depleted, and unclassified) and nodular lymphocyte predominant Hodgkin's lympoma. Nodular sclerosis is the most common type of Hodgkin's lympoma in developed countries.
DIAGNOSIS — The diagnosis of Hodgkin's lympoma is based upon a patient's history and physical examination, a tissue biopsy, laboratory studies, and imaging studies. The initial evaluation provides important information about prognosis, staging, and appropriate treatment.
History and physical examination — Most patients with Hodgkin's lympoma are diagnosed after the patient or clinician notices a painless, enlarged lymph node in the neck. Enlarged nodes may also be found above the clavicle, in the armpit (axilla), or the inguinal (groin) area. Some patients are diagnosed after a mass is seen with a chest x-ray, often done for other reasons. Patients may also have symptoms such as fever, night sweats, and weight loss.
Patients who are suspected of having Hodgkin's disease should be seen by a physician who specializes in cancer treatment (called a hematologist/oncologist) for further evaluation and diagnosis.
Tissue biopsy — If the history and physical exam suggests Hodgkin's lympoma, the enlarged lymph node will be surgically removed, usually from the neck. This is usually done as a day surgery procedure with general (the patient is completely asleep) or local (numbing medicine is injected in the area to be biopsied) anesthesia.
If the lymph node to be removed is in an easily accessible area, it may be removed as an outpatient procedure, under local anesthesia. If it is not easily accessible, it may have to be removed as an inpatient procedure, under general anesthesia. The lymph node, after it has been sectioned and treated with specific stains, is then examined under a microscope by a specifically trained pathologist (called a hematopathologist) for evidence of lymphoma.
Bone marrow biopsy — A bone marrow biopsy may be recommended if the clinician suspects that Hodgkin's lympoma is advanced, if the patient has fever, weight loss, and night sweats, or if the patient has an abnormal blood count. This test determines if there are cancerous cells in the bone marrow, which is, by definition, associated with an advanced stage of Hodgkin's lympoma.
A bone marrow biopsy involves removal of a sample of bone marrow fluid, usually from the pelvic or hip bones. Patients are given local anesthesia, which prevents pain during the procedure. The bone marrow fluid is then examined under a microscope to determine if it is involved with Hodgkin's lympoma.
Laboratory studies — Once the diagnosis of Hodgkin's disease is established by biopsy, other blood tests are recommended, including a complete blood count, erythrocyte sedimentation rate (ESR) (a measure of inflammation), and tests of liver, bone, and kidney function.
Imaging studies — Following the diagnosis of Hodgkin's lympoma, additional imaging studies are done, including a chest X-ray and computed tomography (CT scan) of the chest, abdomen, and pelvis. Some patients may undergo PET scanning, which can detect biochemical changes due to the presence of actively growing cancer cells.
STAGING AND TREATMENT — After a person is diagnosed with Hodgkin's lympoma, he/she is grouped according to the number of lymph nodes and other organs found to contain cancer. The recommended treatment of Hodgkin's lympoma depends upon this grouping (called staging). A full discussion of this is available in a separate topic review. (See "Patient information: Staging and treatment for Hodgkin's disease").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.cancer.gov)
American Cancer Society
(www.cancer.org)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
Cure for Lymphoma Foundation
(www.cfl.org)
Lymphoma Research Foundation of America
(www.lymphoma.org)
National Marrow Donor Program
(www.marrow.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lister, TA, Crowther, D, Sutcliffe, SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630.
2. Mauch, PM, Kalish, LA, Kadin, M, et al. Patterns of presentation of Hodgkin disease. Implication for etiology and pathogenesis. Cancer 1993; 71:2062.
3. Alexander, FE, Jarrett, RF, Lawrence, D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer 2000; 82:1117.
4. Hjalgrim, H, Askling, J, Sorensen, P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000; 92:1522.
5. Mauch, PM, Armitage, JO, Diehl, V, et al (editors). Hodgkin's Disease. Lipincott, Philadelphia, 1999.
Features and diagnosis of Hodgkin's disease
INTRODUCTION — Hodgkin's disease, also known as Hodgkin's lymphoma, is one of several types of cancer of the body's lymphatic system. It is named after the British physician who first described the disease in 1832.
The lymphatic system is a network of lymph nodes and interconnecting lymph vessels (show figure 1). Lymph nodes are small, pea-shaped organs that make and store lymphocytes, a type of white blood cell that fights infection. Lymph vessels are similar to blood vessels, and carry a watery fluid (lymphatic fluid) that contains lymphocytes. The thymus, spleen, and bone marrow are other organs in the lymphatic system.
In Hodgkin's lympoma, a cancerous tumor develops in a lymph node, usually in the neck or chest. If the disease spreads, it spreads first to adjacent lymph nodes, and then to the spleen, liver, or bone marrow. As it progresses, Hodgkin's lympoma affects the body's ability to fight infection.
The following discussion will review the risk factors for Hodgkin's disease and how it is diagnosed. Issues regarding the staging and treatment of the disease are discussed in a separate topic review. (See "Patient Information: Staging and treatment for Hodgkin's disease").
RISK FACTORS — There are several characteristics that are known to be associated with an increased risk of developing Hodgkin's lymphoma. However, these factors account for only a small number of the total number of people who develop it.
Age — Hodgkin's disease is more common in persons between ages 20 to 30, and also in those over age 50 (show figure 2). Approximately 7800 new cases of Hodgkin's lympoma are diagnosed in the United States annually. This compares to the other common cancer of the lymphatic system, non-Hodgkin's lymphoma, which is diagnosed in approximately 54,000 persons per year.
Epstein-Barr virus history — A number of studies have suggested that the Epstein-Barr virus (EBV), which causes infectious mononucleosis ("mono"), may play a role in the development of Hodgkin's lympoma.
Family history — Close relatives of younger patients with Hodgkin's lympoma have a three to five times higher risk of developing Hodgkin's lympoma, probably due to genetic and environmental exposures. There is no increased risk for the families of older adults with Hodgkin's lympoma. Men are at slightly higher risk for Hodgkin's lympoma than women.
Persons with immune deficiencies — Persons who have a weakened immune system due to disease (such as infection due to the virus causing AIDS), medications (such as chemotherapy or immunosuppressant drugs), or from immune deficiencies (such as autoimmune disease) have an increased risk of developing Hodgkin's lympoma.
CAUSES — The exact cause of Hodgkin's lympoma is not known. The cancer cells in Hodgkin's lympoma are known as Reed-Sternberg cells (named after the physicians who discovered them). Reed-Sternberg cells are believed to be a cancerous type of B lymphocyte. B cell lymphocytes normally function to make antibodies (proteins) that help fight infection. Instead of following the normal pattern of production of B cells and eventual cell death, Reed-Sternberg cells produce more abnormal B cells and do not die.
There are two main types of Hodgkin's lympoma: classical Hodgkin's lympoma (which includes the subtypes nodular sclerosis, mixed cellularity, lymphocyte depleted, and unclassified) and nodular lymphocyte predominant Hodgkin's lympoma. Nodular sclerosis is the most common type of Hodgkin's lympoma in developed countries.
DIAGNOSIS — The diagnosis of Hodgkin's lympoma is based upon a patient's history and physical examination, a tissue biopsy, laboratory studies, and imaging studies. The initial evaluation provides important information about prognosis, staging, and appropriate treatment.
History and physical examination — Most patients with Hodgkin's lympoma are diagnosed after the patient or clinician notices a painless, enlarged lymph node in the neck. Enlarged nodes may also be found above the clavicle, in the armpit (axilla), or the inguinal (groin) area. Some patients are diagnosed after a mass is seen with a chest x-ray, often done for other reasons. Patients may also have symptoms such as fever, night sweats, and weight loss.
Patients who are suspected of having Hodgkin's disease should be seen by a physician who specializes in cancer treatment (called a hematologist/oncologist) for further evaluation and diagnosis.
Tissue biopsy — If the history and physical exam suggests Hodgkin's lympoma, the enlarged lymph node will be surgically removed, usually from the neck. This is usually done as a day surgery procedure with general (the patient is completely asleep) or local (numbing medicine is injected in the area to be biopsied) anesthesia.
If the lymph node to be removed is in an easily accessible area, it may be removed as an outpatient procedure, under local anesthesia. If it is not easily accessible, it may have to be removed as an inpatient procedure, under general anesthesia. The lymph node, after it has been sectioned and treated with specific stains, is then examined under a microscope by a specifically trained pathologist (called a hematopathologist) for evidence of lymphoma.
Bone marrow biopsy — A bone marrow biopsy may be recommended if the clinician suspects that Hodgkin's lympoma is advanced, if the patient has fever, weight loss, and night sweats, or if the patient has an abnormal blood count. This test determines if there are cancerous cells in the bone marrow, which is, by definition, associated with an advanced stage of Hodgkin's lympoma.
A bone marrow biopsy involves removal of a sample of bone marrow fluid, usually from the pelvic or hip bones. Patients are given local anesthesia, which prevents pain during the procedure. The bone marrow fluid is then examined under a microscope to determine if it is involved with Hodgkin's lympoma.
Laboratory studies — Once the diagnosis of Hodgkin's disease is established by biopsy, other blood tests are recommended, including a complete blood count, erythrocyte sedimentation rate (ESR) (a measure of inflammation), and tests of liver, bone, and kidney function.
Imaging studies — Following the diagnosis of Hodgkin's lympoma, additional imaging studies are done, including a chest X-ray and computed tomography (CT scan) of the chest, abdomen, and pelvis. Some patients may undergo PET scanning, which can detect biochemical changes due to the presence of actively growing cancer cells.
STAGING AND TREATMENT — After a person is diagnosed with Hodgkin's lympoma, he/she is grouped according to the number of lymph nodes and other organs found to contain cancer. The recommended treatment of Hodgkin's lympoma depends upon this grouping (called staging). A full discussion of this is available in a separate topic review. (See "Patient information: Staging and treatment for Hodgkin's disease").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.cancer.gov)
American Cancer Society
(www.cancer.org)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
Cure for Lymphoma Foundation
(www.cfl.org)
Lymphoma Research Foundation of America
(www.lymphoma.org)
National Marrow Donor Program
(www.marrow.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lister, TA, Crowther, D, Sutcliffe, SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630.
2. Mauch, PM, Kalish, LA, Kadin, M, et al. Patterns of presentation of Hodgkin disease. Implication for etiology and pathogenesis. Cancer 1993; 71:2062.
3. Alexander, FE, Jarrett, RF, Lawrence, D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer 2000; 82:1117.
4. Hjalgrim, H, Askling, J, Sorensen, P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000; 92:1522.
5. Mauch, PM, Armitage, JO, Diehl, V, et al (editors). Hodgkin's Disease. Lipincott, Philadelphia, 1999.
The lymphatic system is a network of lymph nodes and interconnecting lymph vessels (show figure 1). Lymph nodes are small, pea-shaped organs that make and store lymphocytes, a type of white blood cell that fights infection. Lymph vessels are similar to blood vessels, and carry a watery fluid (lymphatic fluid) that contains lymphocytes. The thymus, spleen, and bone marrow are other organs in the lymphatic system.
In Hodgkin's lympoma, a cancerous tumor develops in a lymph node, usually in the neck or chest. If the disease spreads, it spreads first to adjacent lymph nodes, and then to the spleen, liver, or bone marrow. As it progresses, Hodgkin's lympoma affects the body's ability to fight infection.
The following discussion will review the risk factors for Hodgkin's disease and how it is diagnosed. Issues regarding the staging and treatment of the disease are discussed in a separate topic review. (See "Patient Information: Staging and treatment for Hodgkin's disease").
RISK FACTORS — There are several characteristics that are known to be associated with an increased risk of developing Hodgkin's lymphoma. However, these factors account for only a small number of the total number of people who develop it.
Age — Hodgkin's disease is more common in persons between ages 20 to 30, and also in those over age 50 (show figure 2). Approximately 7800 new cases of Hodgkin's lympoma are diagnosed in the United States annually. This compares to the other common cancer of the lymphatic system, non-Hodgkin's lymphoma, which is diagnosed in approximately 54,000 persons per year.
Epstein-Barr virus history — A number of studies have suggested that the Epstein-Barr virus (EBV), which causes infectious mononucleosis ("mono"), may play a role in the development of Hodgkin's lympoma.
Family history — Close relatives of younger patients with Hodgkin's lympoma have a three to five times higher risk of developing Hodgkin's lympoma, probably due to genetic and environmental exposures. There is no increased risk for the families of older adults with Hodgkin's lympoma. Men are at slightly higher risk for Hodgkin's lympoma than women.
Persons with immune deficiencies — Persons who have a weakened immune system due to disease (such as infection due to the virus causing AIDS), medications (such as chemotherapy or immunosuppressant drugs), or from immune deficiencies (such as autoimmune disease) have an increased risk of developing Hodgkin's lympoma.
CAUSES — The exact cause of Hodgkin's lympoma is not known. The cancer cells in Hodgkin's lympoma are known as Reed-Sternberg cells (named after the physicians who discovered them). Reed-Sternberg cells are believed to be a cancerous type of B lymphocyte. B cell lymphocytes normally function to make antibodies (proteins) that help fight infection. Instead of following the normal pattern of production of B cells and eventual cell death, Reed-Sternberg cells produce more abnormal B cells and do not die.
There are two main types of Hodgkin's lympoma: classical Hodgkin's lympoma (which includes the subtypes nodular sclerosis, mixed cellularity, lymphocyte depleted, and unclassified) and nodular lymphocyte predominant Hodgkin's lympoma. Nodular sclerosis is the most common type of Hodgkin's lympoma in developed countries.
DIAGNOSIS — The diagnosis of Hodgkin's lympoma is based upon a patient's history and physical examination, a tissue biopsy, laboratory studies, and imaging studies. The initial evaluation provides important information about prognosis, staging, and appropriate treatment.
History and physical examination — Most patients with Hodgkin's lympoma are diagnosed after the patient or clinician notices a painless, enlarged lymph node in the neck. Enlarged nodes may also be found above the clavicle, in the armpit (axilla), or the inguinal (groin) area. Some patients are diagnosed after a mass is seen with a chest x-ray, often done for other reasons. Patients may also have symptoms such as fever, night sweats, and weight loss.
Patients who are suspected of having Hodgkin's disease should be seen by a physician who specializes in cancer treatment (called a hematologist/oncologist) for further evaluation and diagnosis.
Tissue biopsy — If the history and physical exam suggests Hodgkin's lympoma, the enlarged lymph node will be surgically removed, usually from the neck. This is usually done as a day surgery procedure with general (the patient is completely asleep) or local (numbing medicine is injected in the area to be biopsied) anesthesia.
If the lymph node to be removed is in an easily accessible area, it may be removed as an outpatient procedure, under local anesthesia. If it is not easily accessible, it may have to be removed as an inpatient procedure, under general anesthesia. The lymph node, after it has been sectioned and treated with specific stains, is then examined under a microscope by a specifically trained pathologist (called a hematopathologist) for evidence of lymphoma.
Bone marrow biopsy — A bone marrow biopsy may be recommended if the clinician suspects that Hodgkin's lympoma is advanced, if the patient has fever, weight loss, and night sweats, or if the patient has an abnormal blood count. This test determines if there are cancerous cells in the bone marrow, which is, by definition, associated with an advanced stage of Hodgkin's lympoma.
A bone marrow biopsy involves removal of a sample of bone marrow fluid, usually from the pelvic or hip bones. Patients are given local anesthesia, which prevents pain during the procedure. The bone marrow fluid is then examined under a microscope to determine if it is involved with Hodgkin's lympoma.
Laboratory studies — Once the diagnosis of Hodgkin's disease is established by biopsy, other blood tests are recommended, including a complete blood count, erythrocyte sedimentation rate (ESR) (a measure of inflammation), and tests of liver, bone, and kidney function.
Imaging studies — Following the diagnosis of Hodgkin's lympoma, additional imaging studies are done, including a chest X-ray and computed tomography (CT scan) of the chest, abdomen, and pelvis. Some patients may undergo PET scanning, which can detect biochemical changes due to the presence of actively growing cancer cells.
STAGING AND TREATMENT — After a person is diagnosed with Hodgkin's lympoma, he/she is grouped according to the number of lymph nodes and other organs found to contain cancer. The recommended treatment of Hodgkin's lympoma depends upon this grouping (called staging). A full discussion of this is available in a separate topic review. (See "Patient information: Staging and treatment for Hodgkin's disease").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.cancer.gov)
American Cancer Society
(www.cancer.org)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
Cure for Lymphoma Foundation
(www.cfl.org)
Lymphoma Research Foundation of America
(www.lymphoma.org)
National Marrow Donor Program
(www.marrow.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lister, TA, Crowther, D, Sutcliffe, SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630.
2. Mauch, PM, Kalish, LA, Kadin, M, et al. Patterns of presentation of Hodgkin disease. Implication for etiology and pathogenesis. Cancer 1993; 71:2062.
3. Alexander, FE, Jarrett, RF, Lawrence, D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer 2000; 82:1117.
4. Hjalgrim, H, Askling, J, Sorensen, P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000; 92:1522.
5. Mauch, PM, Armitage, JO, Diehl, V, et al (editors). Hodgkin's Disease. Lipincott, Philadelphia, 1999.
Diffuse large B-cell lymphoma
INTRODUCTION — Diffuse large B-cell lymphoma (DLBCL) is a fast-growing, aggressive form of non-Hodgkin's lymphoma (NHL), a cancer of the body's lymphatic system. The lymphatic system includes the tissues and organs (including the bone marrow, spleen, thymus and lymph nodes) that produce and store cells that fight infection. Although there are more than 20 types of NHL, DLBCL is the most common type, making up about 30 percent of all lymphomas [1]. In the United States, DLBCL affects about 5 people out of 100,000 each year [2].
Diffuse large B-cell lymphoma can be fatal if left untreated, but with timely and appropriate treatment, up to half of all patients are curable. The following discussion will review the risk factors, classification, clinical symptoms, and prognosis of this type of non-Hodgkin's lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing diffuse large B-cell lymphoma. Although DLBCL has been found in people of all age groups, it is found most commonly in people who are middle-aged or elderly. The average age at the time of diagnosis is 64 years. Men are slightly more likely to develop DLBCL than women. People who are white are more likely to develop this type of lymphoma than people of African or Asian race/ethnicity.
CLASSIFICATION — Diffuse large B-cell lymphoma is a cancer of B lymphocytes. The lymph organs include the bone marrow, thymus, spleen, and lymph nodes. These help to fight infection throughout the body. The organs of the lymphatic systems are connected by a network of lymphatic and blood vessels, through which lymphatic fluid flows. Lymphatic fluid contains white blood cells called lymphocytes (show figure 1).
There are two primary types of lymphocytes: B-cells and T-cells. Almost all lymphocytes begin growing in the bone marrow or lymph nodes. T-cells leave the bone marrow before they are completely matured, and finish maturing in the thymus gland. However, B-cells continue to develop and mature in the bone marrow and lymph nodes.
In DLBCL, the abnormal B-cell lymphocytes are larger than normal. The presence of these large cells characterizes DLBCL; typically, the large cells present in DLBCL have nuclei at least twice the size of small lymphocytes. Researchers have identified several variants of DLBCL, including a centroblastic variant, immunoblastic variant, anaplastic variant, T-cell histiocyte rich large B-cell lymphoma, and T-cell infiltration. It is not clear whether understanding the differences between these variants can improve patients' symptoms or overall prognosis.
Genetic events and chromosomal abnormalities are suspected to be related to the development of DLBCL. In 30 percent of cases of diffuse large B-cell lymphoma, an abnormal transfer (translocation) of part of a chromosome occurs (the t(3;14) gene translocation). This translocation causes a rearrangement in a gene called BCL-6. As a result, the abnormal gene signals the body to produce a protein that alters the growth and development of these cells [3].
PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA — Patients with this subtype of DLBCL have tumors within the chest cavity that usually involve the thymus, the gland of the immune system that is located in the front upper middle of the chest and extends from the base of the throat to the front of the heart.
Primary mediastinal large B-cell lymphoma comprises 7 percent of all diffuse large B-cell lymphomas and accounts for 2.4 percent of all non-Hodgkin's lymphomas. Women are slightly more likely to develop this disorder, and the median age of diagnosis occurs in the fourth decade of life.
People who have this form of DLBCL usually present to their physicians with a malignant tumor in the chest cavity that causes difficulty breathing and a condition known as superior vena cava syndrome. If this subtype of diffuse large B-cell lymphoma recurs, it can cause problems with other organs, including the liver, gastrointestinal tract, kidneys, ovaries, and central nervous system.
This type of tumor is aggressive, but it is treatable with programs that combine chemotherapy and radiation.
SYMPTOMS — The first noticeable symptom that patients with diffuse large B-cell lymphoma experience is a quickly growing mass, which may be found either in the neck, groin, or abdomen.
In about one in five patients, tumors caused by DLBCL are confined to one part of the body. However, in about 40 percent of people diagnosed with this type of NHL, the cancer spreads from the lymph system into adjacent organs, a condition known as extranodal infiltration. In some patients, DLBCL spreads to the bone marrow.
As DLBCL spreads from the original site of the tumor throughout the body, it may involve other organs, such as the liver, kidney, and lungs, and cause the following complications: Superior vena cava syndrome (SVCS), in which the blood vessels of the upper half of the body become compressed and partially blocked by the growing tumor, making it difficult for the body's circulatory system to transport blood from the head, neck, chest, and arms back to the heart. A person with SVCS may experience respiratory problems, coughing, and swelling in the upper half of the body. Tracheobronchial compression, in which the airways in the lung become compressed by the tumor, making it difficult to breathe Nerve damage Destruction of bone in the spinal column leading to compression of the spinal cord, with resulting back pain, leg weakness, or paralysis
Patients may also experience fever, weight loss, and drenching night sweats. These symptoms are called "B" symptoms and may alert the physician to the possible diagnosis of lymphoma.
In addition to occurring on its own (de novo DLBCL), DLBCL may occur as other indolent or low-grade forms of B-cell lymphoma change and progress during the disease process (transformed diffuse large B-cell lymphoma). DLBCL may develop from the following types of low-grade lymphomas: B-cell chronic lymphocytic leukemia (Richter's transformation) Lymphoplasmacytic lymphoma Follicular lymphoma Mucosa-associated lymphoid tissue (MALT) lymphoma Splenic marginal zone lymphoma
DIAGNOSIS — Physicians confirm a diagnosis of DLBCL by removing an enlarged lymph node or a portion of an involved organ in a procedure known as a biopsy. This procedure may be performed under a local anesthetic if the involved tissue is relatively close to the surface. In other cases, a sample of tissue must be obtained under a general anesthetic. The cells from the removed tissue are then examined in detail, using a number of different techniques to determine the nature of the abnormal cell.
Physicians also order blood tests, x-rays, imaging scans, and bone marrow samples to obtain more information about the type of lymphoma and the extent to which it has spread in the body, a process termed "staging" (show table 1). The results of these tests will help physicians decide on the most effective course of treatment. As an example of the importance of staging, treatment of diffuse large B-cell lymphoma is generally more likely to provide a cure when the lymphoma is localized than when it has spread to other parts of the body.
Gene studies, such as the use of gene expression profiling, may allow clinicians to determine which patients have a reduced chance of remission after standard treatments and could suggest which patients would be candidates for more aggressive treatment [4]. These studies are investigational and are not yet part of standard practice.
TREATMENT — The standard of treatment of DLBCL is combination chemotherapy, occasionally with the addition of radiation to areas of large, bulky disease. The most common chemotherapeutic program for patients with advanced disease consists of 5 medicines (called CHOP-rituximab or CHOP-R) given every three weeks for 6 to 8 cycles. Patients with only localized disease may be treated with fewer cycles of chemotherapy in combination with radiation therapy to the involved area.
PROGNOSIS — The five-year survival rate of patients with DLBCL is between 26 and 73 percent, meaning that between one quarter and three quarters of patients with DLBCL will be disease-free for five years after diagnosis. Relapses tend to occur within the first two to three years after the diagnosis of DLBCL; the disease rarely recurs if the patient has been disease-free for four or more years.
The following factors were found to correlate with significantly shorter overall or relapse-free survival and have been incorporated into an International Prognostic index: Age >60 Serum lactate dehydrogenase (LDH, a protein in the blood) concentration greater than normal Poor performance status (ECOG performance status 2) (show table 2) Advanced Ann Arbor clinical stage (III or IV) (show table 1) Number of involved extranodal disease sites >1
In this system, one point is given for each of the above characteristics present in the patient, for a total score ranging from zero to five, representing increasing degrees of risk: Low risk — IPI score of zero or one Low intermediate risk — IPI score of two High intermediate risk — IPI score of three High risk — IPI score of four or five
When applied to patients with aggressive NHL, such as diffuse large B-cell lymphoma, five-year overall survivals for patients with scores of 0 to 1, 2, 3, and 4 to 5 were 73, 51, 43, and 26 percent, respectively (show table 3).
CLINICAL TRIALS — A clinical trial is an approved research study which seeks to determine the best treatment for a particular disease. This is especially important in diffuse large B-cell lymphoma, since there is no currently approved treatment program capable of curing all patients with this disorder.
Therefore, for all patients with diffuse large B-cell lymphoma, enrollment in a clinical trial, if available, is always recommended. Ask your doctor for more information, or read about clinical trials at: www.cancer.gov/clinical_trials/ and at http://clinicaltrials.gov/
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Armitage, J, Weisenburger, D. New approach to classifying Non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. J Clin Oncol 1998; 16:2780.
2. Kallab, AM. Diffuse large cell lymphoma. January 31, 2002. Available online at www.emedicine.com/med/topic1360.htm (Accessed 3/7/05).
3. Huang, JZ, Sanger, WG, Greiner, TC, et al. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 2002; 99:2285.
4. Lossos, IS, Czerwinski, DK, Alizadeh, AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004; 350:1828.
5. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp (Accessed 3/7/05).
Diffuse large B-cell lymphoma can be fatal if left untreated, but with timely and appropriate treatment, up to half of all patients are curable. The following discussion will review the risk factors, classification, clinical symptoms, and prognosis of this type of non-Hodgkin's lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing diffuse large B-cell lymphoma. Although DLBCL has been found in people of all age groups, it is found most commonly in people who are middle-aged or elderly. The average age at the time of diagnosis is 64 years. Men are slightly more likely to develop DLBCL than women. People who are white are more likely to develop this type of lymphoma than people of African or Asian race/ethnicity.
CLASSIFICATION — Diffuse large B-cell lymphoma is a cancer of B lymphocytes. The lymph organs include the bone marrow, thymus, spleen, and lymph nodes. These help to fight infection throughout the body. The organs of the lymphatic systems are connected by a network of lymphatic and blood vessels, through which lymphatic fluid flows. Lymphatic fluid contains white blood cells called lymphocytes (show figure 1).
There are two primary types of lymphocytes: B-cells and T-cells. Almost all lymphocytes begin growing in the bone marrow or lymph nodes. T-cells leave the bone marrow before they are completely matured, and finish maturing in the thymus gland. However, B-cells continue to develop and mature in the bone marrow and lymph nodes.
In DLBCL, the abnormal B-cell lymphocytes are larger than normal. The presence of these large cells characterizes DLBCL; typically, the large cells present in DLBCL have nuclei at least twice the size of small lymphocytes. Researchers have identified several variants of DLBCL, including a centroblastic variant, immunoblastic variant, anaplastic variant, T-cell histiocyte rich large B-cell lymphoma, and T-cell infiltration. It is not clear whether understanding the differences between these variants can improve patients' symptoms or overall prognosis.
Genetic events and chromosomal abnormalities are suspected to be related to the development of DLBCL. In 30 percent of cases of diffuse large B-cell lymphoma, an abnormal transfer (translocation) of part of a chromosome occurs (the t(3;14) gene translocation). This translocation causes a rearrangement in a gene called BCL-6. As a result, the abnormal gene signals the body to produce a protein that alters the growth and development of these cells [3].
PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA — Patients with this subtype of DLBCL have tumors within the chest cavity that usually involve the thymus, the gland of the immune system that is located in the front upper middle of the chest and extends from the base of the throat to the front of the heart.
Primary mediastinal large B-cell lymphoma comprises 7 percent of all diffuse large B-cell lymphomas and accounts for 2.4 percent of all non-Hodgkin's lymphomas. Women are slightly more likely to develop this disorder, and the median age of diagnosis occurs in the fourth decade of life.
People who have this form of DLBCL usually present to their physicians with a malignant tumor in the chest cavity that causes difficulty breathing and a condition known as superior vena cava syndrome. If this subtype of diffuse large B-cell lymphoma recurs, it can cause problems with other organs, including the liver, gastrointestinal tract, kidneys, ovaries, and central nervous system.
This type of tumor is aggressive, but it is treatable with programs that combine chemotherapy and radiation.
SYMPTOMS — The first noticeable symptom that patients with diffuse large B-cell lymphoma experience is a quickly growing mass, which may be found either in the neck, groin, or abdomen.
In about one in five patients, tumors caused by DLBCL are confined to one part of the body. However, in about 40 percent of people diagnosed with this type of NHL, the cancer spreads from the lymph system into adjacent organs, a condition known as extranodal infiltration. In some patients, DLBCL spreads to the bone marrow.
As DLBCL spreads from the original site of the tumor throughout the body, it may involve other organs, such as the liver, kidney, and lungs, and cause the following complications: Superior vena cava syndrome (SVCS), in which the blood vessels of the upper half of the body become compressed and partially blocked by the growing tumor, making it difficult for the body's circulatory system to transport blood from the head, neck, chest, and arms back to the heart. A person with SVCS may experience respiratory problems, coughing, and swelling in the upper half of the body. Tracheobronchial compression, in which the airways in the lung become compressed by the tumor, making it difficult to breathe Nerve damage Destruction of bone in the spinal column leading to compression of the spinal cord, with resulting back pain, leg weakness, or paralysis
Patients may also experience fever, weight loss, and drenching night sweats. These symptoms are called "B" symptoms and may alert the physician to the possible diagnosis of lymphoma.
In addition to occurring on its own (de novo DLBCL), DLBCL may occur as other indolent or low-grade forms of B-cell lymphoma change and progress during the disease process (transformed diffuse large B-cell lymphoma). DLBCL may develop from the following types of low-grade lymphomas: B-cell chronic lymphocytic leukemia (Richter's transformation) Lymphoplasmacytic lymphoma Follicular lymphoma Mucosa-associated lymphoid tissue (MALT) lymphoma Splenic marginal zone lymphoma
DIAGNOSIS — Physicians confirm a diagnosis of DLBCL by removing an enlarged lymph node or a portion of an involved organ in a procedure known as a biopsy. This procedure may be performed under a local anesthetic if the involved tissue is relatively close to the surface. In other cases, a sample of tissue must be obtained under a general anesthetic. The cells from the removed tissue are then examined in detail, using a number of different techniques to determine the nature of the abnormal cell.
Physicians also order blood tests, x-rays, imaging scans, and bone marrow samples to obtain more information about the type of lymphoma and the extent to which it has spread in the body, a process termed "staging" (show table 1). The results of these tests will help physicians decide on the most effective course of treatment. As an example of the importance of staging, treatment of diffuse large B-cell lymphoma is generally more likely to provide a cure when the lymphoma is localized than when it has spread to other parts of the body.
Gene studies, such as the use of gene expression profiling, may allow clinicians to determine which patients have a reduced chance of remission after standard treatments and could suggest which patients would be candidates for more aggressive treatment [4]. These studies are investigational and are not yet part of standard practice.
TREATMENT — The standard of treatment of DLBCL is combination chemotherapy, occasionally with the addition of radiation to areas of large, bulky disease. The most common chemotherapeutic program for patients with advanced disease consists of 5 medicines (called CHOP-rituximab or CHOP-R) given every three weeks for 6 to 8 cycles. Patients with only localized disease may be treated with fewer cycles of chemotherapy in combination with radiation therapy to the involved area.
PROGNOSIS — The five-year survival rate of patients with DLBCL is between 26 and 73 percent, meaning that between one quarter and three quarters of patients with DLBCL will be disease-free for five years after diagnosis. Relapses tend to occur within the first two to three years after the diagnosis of DLBCL; the disease rarely recurs if the patient has been disease-free for four or more years.
The following factors were found to correlate with significantly shorter overall or relapse-free survival and have been incorporated into an International Prognostic index: Age >60 Serum lactate dehydrogenase (LDH, a protein in the blood) concentration greater than normal Poor performance status (ECOG performance status 2) (show table 2) Advanced Ann Arbor clinical stage (III or IV) (show table 1) Number of involved extranodal disease sites >1
In this system, one point is given for each of the above characteristics present in the patient, for a total score ranging from zero to five, representing increasing degrees of risk: Low risk — IPI score of zero or one Low intermediate risk — IPI score of two High intermediate risk — IPI score of three High risk — IPI score of four or five
When applied to patients with aggressive NHL, such as diffuse large B-cell lymphoma, five-year overall survivals for patients with scores of 0 to 1, 2, 3, and 4 to 5 were 73, 51, 43, and 26 percent, respectively (show table 3).
CLINICAL TRIALS — A clinical trial is an approved research study which seeks to determine the best treatment for a particular disease. This is especially important in diffuse large B-cell lymphoma, since there is no currently approved treatment program capable of curing all patients with this disorder.
Therefore, for all patients with diffuse large B-cell lymphoma, enrollment in a clinical trial, if available, is always recommended. Ask your doctor for more information, or read about clinical trials at: www.cancer.gov/clinical_trials/ and at http://clinicaltrials.gov/
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Armitage, J, Weisenburger, D. New approach to classifying Non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. J Clin Oncol 1998; 16:2780.
2. Kallab, AM. Diffuse large cell lymphoma. January 31, 2002. Available online at www.emedicine.com/med/topic1360.htm (Accessed 3/7/05).
3. Huang, JZ, Sanger, WG, Greiner, TC, et al. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 2002; 99:2285.
4. Lossos, IS, Czerwinski, DK, Alizadeh, AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004; 350:1828.
5. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp (Accessed 3/7/05).
Diffuse large B-cell lymphoma
INTRODUCTION — Diffuse large B-cell lymphoma (DLBCL) is a fast-growing, aggressive form of non-Hodgkin's lymphoma (NHL), a cancer of the body's lymphatic system. The lymphatic system includes the tissues and organs (including the bone marrow, spleen, thymus and lymph nodes) that produce and store cells that fight infection. Although there are more than 20 types of NHL, DLBCL is the most common type, making up about 30 percent of all lymphomas [1]. In the United States, DLBCL affects about 5 people out of 100,000 each year [2].
Diffuse large B-cell lymphoma can be fatal if left untreated, but with timely and appropriate treatment, up to half of all patients are curable. The following discussion will review the risk factors, classification, clinical symptoms, and prognosis of this type of non-Hodgkin's lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing diffuse large B-cell lymphoma. Although DLBCL has been found in people of all age groups, it is found most commonly in people who are middle-aged or elderly. The average age at the time of diagnosis is 64 years. Men are slightly more likely to develop DLBCL than women. People who are white are more likely to develop this type of lymphoma than people of African or Asian race/ethnicity.
CLASSIFICATION — Diffuse large B-cell lymphoma is a cancer of B lymphocytes. The lymph organs include the bone marrow, thymus, spleen, and lymph nodes. These help to fight infection throughout the body. The organs of the lymphatic systems are connected by a network of lymphatic and blood vessels, through which lymphatic fluid flows. Lymphatic fluid contains white blood cells called lymphocytes (show figure 1).
There are two primary types of lymphocytes: B-cells and T-cells. Almost all lymphocytes begin growing in the bone marrow or lymph nodes. T-cells leave the bone marrow before they are completely matured, and finish maturing in the thymus gland. However, B-cells continue to develop and mature in the bone marrow and lymph nodes.
In DLBCL, the abnormal B-cell lymphocytes are larger than normal. The presence of these large cells characterizes DLBCL; typically, the large cells present in DLBCL have nuclei at least twice the size of small lymphocytes. Researchers have identified several variants of DLBCL, including a centroblastic variant, immunoblastic variant, anaplastic variant, T-cell histiocyte rich large B-cell lymphoma, and T-cell infiltration. It is not clear whether understanding the differences between these variants can improve patients' symptoms or overall prognosis.
Genetic events and chromosomal abnormalities are suspected to be related to the development of DLBCL. In 30 percent of cases of diffuse large B-cell lymphoma, an abnormal transfer (translocation) of part of a chromosome occurs (the t(3;14) gene translocation). This translocation causes a rearrangement in a gene called BCL-6. As a result, the abnormal gene signals the body to produce a protein that alters the growth and development of these cells [3].
PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA — Patients with this subtype of DLBCL have tumors within the chest cavity that usually involve the thymus, the gland of the immune system that is located in the front upper middle of the chest and extends from the base of the throat to the front of the heart.
Primary mediastinal large B-cell lymphoma comprises 7 percent of all diffuse large B-cell lymphomas and accounts for 2.4 percent of all non-Hodgkin's lymphomas. Women are slightly more likely to develop this disorder, and the median age of diagnosis occurs in the fourth decade of life.
People who have this form of DLBCL usually present to their physicians with a malignant tumor in the chest cavity that causes difficulty breathing and a condition known as superior vena cava syndrome. If this subtype of diffuse large B-cell lymphoma recurs, it can cause problems with other organs, including the liver, gastrointestinal tract, kidneys, ovaries, and central nervous system.
This type of tumor is aggressive, but it is treatable with programs that combine chemotherapy and radiation.
SYMPTOMS — The first noticeable symptom that patients with diffuse large B-cell lymphoma experience is a quickly growing mass, which may be found either in the neck, groin, or abdomen.
In about one in five patients, tumors caused by DLBCL are confined to one part of the body. However, in about 40 percent of people diagnosed with this type of NHL, the cancer spreads from the lymph system into adjacent organs, a condition known as extranodal infiltration. In some patients, DLBCL spreads to the bone marrow.
As DLBCL spreads from the original site of the tumor throughout the body, it may involve other organs, such as the liver, kidney, and lungs, and cause the following complications: Superior vena cava syndrome (SVCS), in which the blood vessels of the upper half of the body become compressed and partially blocked by the growing tumor, making it difficult for the body's circulatory system to transport blood from the head, neck, chest, and arms back to the heart. A person with SVCS may experience respiratory problems, coughing, and swelling in the upper half of the body. Tracheobronchial compression, in which the airways in the lung become compressed by the tumor, making it difficult to breathe Nerve damage Destruction of bone in the spinal column leading to compression of the spinal cord, with resulting back pain, leg weakness, or paralysis
Patients may also experience fever, weight loss, and drenching night sweats. These symptoms are called "B" symptoms and may alert the physician to the possible diagnosis of lymphoma.
In addition to occurring on its own (de novo DLBCL), DLBCL may occur as other indolent or low-grade forms of B-cell lymphoma change and progress during the disease process (transformed diffuse large B-cell lymphoma). DLBCL may develop from the following types of low-grade lymphomas: B-cell chronic lymphocytic leukemia (Richter's transformation) Lymphoplasmacytic lymphoma Follicular lymphoma Mucosa-associated lymphoid tissue (MALT) lymphoma Splenic marginal zone lymphoma
DIAGNOSIS — Physicians confirm a diagnosis of DLBCL by removing an enlarged lymph node or a portion of an involved organ in a procedure known as a biopsy. This procedure may be performed under a local anesthetic if the involved tissue is relatively close to the surface. In other cases, a sample of tissue must be obtained under a general anesthetic. The cells from the removed tissue are then examined in detail, using a number of different techniques to determine the nature of the abnormal cell.
Physicians also order blood tests, x-rays, imaging scans, and bone marrow samples to obtain more information about the type of lymphoma and the extent to which it has spread in the body, a process termed "staging" (show table 1). The results of these tests will help physicians decide on the most effective course of treatment. As an example of the importance of staging, treatment of diffuse large B-cell lymphoma is generally more likely to provide a cure when the lymphoma is localized than when it has spread to other parts of the body.
Gene studies, such as the use of gene expression profiling, may allow clinicians to determine which patients have a reduced chance of remission after standard treatments and could suggest which patients would be candidates for more aggressive treatment [4]. These studies are investigational and are not yet part of standard practice.
TREATMENT — The standard of treatment of DLBCL is combination chemotherapy, occasionally with the addition of radiation to areas of large, bulky disease. The most common chemotherapeutic program for patients with advanced disease consists of 5 medicines (called CHOP-rituximab or CHOP-R) given every three weeks for 6 to 8 cycles. Patients with only localized disease may be treated with fewer cycles of chemotherapy in combination with radiation therapy to the involved area.
PROGNOSIS — The five-year survival rate of patients with DLBCL is between 26 and 73 percent, meaning that between one quarter and three quarters of patients with DLBCL will be disease-free for five years after diagnosis. Relapses tend to occur within the first two to three years after the diagnosis of DLBCL; the disease rarely recurs if the patient has been disease-free for four or more years.
The following factors were found to correlate with significantly shorter overall or relapse-free survival and have been incorporated into an International Prognostic index: Age >60 Serum lactate dehydrogenase (LDH, a protein in the blood) concentration greater than normal Poor performance status (ECOG performance status 2) (show table 2) Advanced Ann Arbor clinical stage (III or IV) (show table 1) Number of involved extranodal disease sites >1
In this system, one point is given for each of the above characteristics present in the patient, for a total score ranging from zero to five, representing increasing degrees of risk: Low risk — IPI score of zero or one Low intermediate risk — IPI score of two High intermediate risk — IPI score of three High risk — IPI score of four or five
When applied to patients with aggressive NHL, such as diffuse large B-cell lymphoma, five-year overall survivals for patients with scores of 0 to 1, 2, 3, and 4 to 5 were 73, 51, 43, and 26 percent, respectively (show table 3).
CLINICAL TRIALS — A clinical trial is an approved research study which seeks to determine the best treatment for a particular disease. This is especially important in diffuse large B-cell lymphoma, since there is no currently approved treatment program capable of curing all patients with this disorder.
Therefore, for all patients with diffuse large B-cell lymphoma, enrollment in a clinical trial, if available, is always recommended. Ask your doctor for more information, or read about clinical trials at: www.cancer.gov/clinical_trials/ and at http://clinicaltrials.gov/
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Armitage, J, Weisenburger, D. New approach to classifying Non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. J Clin Oncol 1998; 16:2780.
2. Kallab, AM. Diffuse large cell lymphoma. January 31, 2002. Available online at www.emedicine.com/med/topic1360.htm (Accessed 3/7/05).
3. Huang, JZ, Sanger, WG, Greiner, TC, et al. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 2002; 99:2285.
4. Lossos, IS, Czerwinski, DK, Alizadeh, AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004; 350:1828.
5. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp (Accessed 3/7/05).
Diffuse large B-cell lymphoma can be fatal if left untreated, but with timely and appropriate treatment, up to half of all patients are curable. The following discussion will review the risk factors, classification, clinical symptoms, and prognosis of this type of non-Hodgkin's lymphoma.
RISK FACTORS — Age, gender, and race/ethnicity affect a person's likelihood of developing diffuse large B-cell lymphoma. Although DLBCL has been found in people of all age groups, it is found most commonly in people who are middle-aged or elderly. The average age at the time of diagnosis is 64 years. Men are slightly more likely to develop DLBCL than women. People who are white are more likely to develop this type of lymphoma than people of African or Asian race/ethnicity.
CLASSIFICATION — Diffuse large B-cell lymphoma is a cancer of B lymphocytes. The lymph organs include the bone marrow, thymus, spleen, and lymph nodes. These help to fight infection throughout the body. The organs of the lymphatic systems are connected by a network of lymphatic and blood vessels, through which lymphatic fluid flows. Lymphatic fluid contains white blood cells called lymphocytes (show figure 1).
There are two primary types of lymphocytes: B-cells and T-cells. Almost all lymphocytes begin growing in the bone marrow or lymph nodes. T-cells leave the bone marrow before they are completely matured, and finish maturing in the thymus gland. However, B-cells continue to develop and mature in the bone marrow and lymph nodes.
In DLBCL, the abnormal B-cell lymphocytes are larger than normal. The presence of these large cells characterizes DLBCL; typically, the large cells present in DLBCL have nuclei at least twice the size of small lymphocytes. Researchers have identified several variants of DLBCL, including a centroblastic variant, immunoblastic variant, anaplastic variant, T-cell histiocyte rich large B-cell lymphoma, and T-cell infiltration. It is not clear whether understanding the differences between these variants can improve patients' symptoms or overall prognosis.
Genetic events and chromosomal abnormalities are suspected to be related to the development of DLBCL. In 30 percent of cases of diffuse large B-cell lymphoma, an abnormal transfer (translocation) of part of a chromosome occurs (the t(3;14) gene translocation). This translocation causes a rearrangement in a gene called BCL-6. As a result, the abnormal gene signals the body to produce a protein that alters the growth and development of these cells [3].
PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA — Patients with this subtype of DLBCL have tumors within the chest cavity that usually involve the thymus, the gland of the immune system that is located in the front upper middle of the chest and extends from the base of the throat to the front of the heart.
Primary mediastinal large B-cell lymphoma comprises 7 percent of all diffuse large B-cell lymphomas and accounts for 2.4 percent of all non-Hodgkin's lymphomas. Women are slightly more likely to develop this disorder, and the median age of diagnosis occurs in the fourth decade of life.
People who have this form of DLBCL usually present to their physicians with a malignant tumor in the chest cavity that causes difficulty breathing and a condition known as superior vena cava syndrome. If this subtype of diffuse large B-cell lymphoma recurs, it can cause problems with other organs, including the liver, gastrointestinal tract, kidneys, ovaries, and central nervous system.
This type of tumor is aggressive, but it is treatable with programs that combine chemotherapy and radiation.
SYMPTOMS — The first noticeable symptom that patients with diffuse large B-cell lymphoma experience is a quickly growing mass, which may be found either in the neck, groin, or abdomen.
In about one in five patients, tumors caused by DLBCL are confined to one part of the body. However, in about 40 percent of people diagnosed with this type of NHL, the cancer spreads from the lymph system into adjacent organs, a condition known as extranodal infiltration. In some patients, DLBCL spreads to the bone marrow.
As DLBCL spreads from the original site of the tumor throughout the body, it may involve other organs, such as the liver, kidney, and lungs, and cause the following complications: Superior vena cava syndrome (SVCS), in which the blood vessels of the upper half of the body become compressed and partially blocked by the growing tumor, making it difficult for the body's circulatory system to transport blood from the head, neck, chest, and arms back to the heart. A person with SVCS may experience respiratory problems, coughing, and swelling in the upper half of the body. Tracheobronchial compression, in which the airways in the lung become compressed by the tumor, making it difficult to breathe Nerve damage Destruction of bone in the spinal column leading to compression of the spinal cord, with resulting back pain, leg weakness, or paralysis
Patients may also experience fever, weight loss, and drenching night sweats. These symptoms are called "B" symptoms and may alert the physician to the possible diagnosis of lymphoma.
In addition to occurring on its own (de novo DLBCL), DLBCL may occur as other indolent or low-grade forms of B-cell lymphoma change and progress during the disease process (transformed diffuse large B-cell lymphoma). DLBCL may develop from the following types of low-grade lymphomas: B-cell chronic lymphocytic leukemia (Richter's transformation) Lymphoplasmacytic lymphoma Follicular lymphoma Mucosa-associated lymphoid tissue (MALT) lymphoma Splenic marginal zone lymphoma
DIAGNOSIS — Physicians confirm a diagnosis of DLBCL by removing an enlarged lymph node or a portion of an involved organ in a procedure known as a biopsy. This procedure may be performed under a local anesthetic if the involved tissue is relatively close to the surface. In other cases, a sample of tissue must be obtained under a general anesthetic. The cells from the removed tissue are then examined in detail, using a number of different techniques to determine the nature of the abnormal cell.
Physicians also order blood tests, x-rays, imaging scans, and bone marrow samples to obtain more information about the type of lymphoma and the extent to which it has spread in the body, a process termed "staging" (show table 1). The results of these tests will help physicians decide on the most effective course of treatment. As an example of the importance of staging, treatment of diffuse large B-cell lymphoma is generally more likely to provide a cure when the lymphoma is localized than when it has spread to other parts of the body.
Gene studies, such as the use of gene expression profiling, may allow clinicians to determine which patients have a reduced chance of remission after standard treatments and could suggest which patients would be candidates for more aggressive treatment [4]. These studies are investigational and are not yet part of standard practice.
TREATMENT — The standard of treatment of DLBCL is combination chemotherapy, occasionally with the addition of radiation to areas of large, bulky disease. The most common chemotherapeutic program for patients with advanced disease consists of 5 medicines (called CHOP-rituximab or CHOP-R) given every three weeks for 6 to 8 cycles. Patients with only localized disease may be treated with fewer cycles of chemotherapy in combination with radiation therapy to the involved area.
PROGNOSIS — The five-year survival rate of patients with DLBCL is between 26 and 73 percent, meaning that between one quarter and three quarters of patients with DLBCL will be disease-free for five years after diagnosis. Relapses tend to occur within the first two to three years after the diagnosis of DLBCL; the disease rarely recurs if the patient has been disease-free for four or more years.
The following factors were found to correlate with significantly shorter overall or relapse-free survival and have been incorporated into an International Prognostic index: Age >60 Serum lactate dehydrogenase (LDH, a protein in the blood) concentration greater than normal Poor performance status (ECOG performance status 2) (show table 2) Advanced Ann Arbor clinical stage (III or IV) (show table 1) Number of involved extranodal disease sites >1
In this system, one point is given for each of the above characteristics present in the patient, for a total score ranging from zero to five, representing increasing degrees of risk: Low risk — IPI score of zero or one Low intermediate risk — IPI score of two High intermediate risk — IPI score of three High risk — IPI score of four or five
When applied to patients with aggressive NHL, such as diffuse large B-cell lymphoma, five-year overall survivals for patients with scores of 0 to 1, 2, 3, and 4 to 5 were 73, 51, 43, and 26 percent, respectively (show table 3).
CLINICAL TRIALS — A clinical trial is an approved research study which seeks to determine the best treatment for a particular disease. This is especially important in diffuse large B-cell lymphoma, since there is no currently approved treatment program capable of curing all patients with this disorder.
Therefore, for all patients with diffuse large B-cell lymphoma, enrollment in a clinical trial, if available, is always recommended. Ask your doctor for more information, or read about clinical trials at: www.cancer.gov/clinical_trials/ and at http://clinicaltrials.gov/
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society
(www.cancer.org)
National Cancer Institute
(www.cancer.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Armitage, J, Weisenburger, D. New approach to classifying Non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. J Clin Oncol 1998; 16:2780.
2. Kallab, AM. Diffuse large cell lymphoma. January 31, 2002. Available online at www.emedicine.com/med/topic1360.htm (Accessed 3/7/05).
3. Huang, JZ, Sanger, WG, Greiner, TC, et al. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 2002; 99:2285.
4. Lossos, IS, Czerwinski, DK, Alizadeh, AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004; 350:1828.
5. American Cancer Society. What is non-Hodgkin's lymphoma? www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_Lymphoma_32.asp (Accessed 3/7/05).
Daily regime for healthier skin
Most women don`t bother looking after their skin until it is too late. When will you start when you notice the wringles, by that time you will have no chance of slowing the aging process. You should start looking after your skin from your late teens, early twentys right up until your hands are too shakey to pick up any thing. Start now with a daily regime of cleansing, toning, exfoliating and moisturising. Once you get use to doing it daily you will feel and look a lot healthier and good about yourself.
Step one -- Cleanse. Cleansing you skin and removing dirt, makeup and other impurities that clog your skin is essential. You should cleanse your skin at least twice a day with a mild, non-irritating cleanser. Your cleanser should not strip your skin of its natural oils and it should easily rinse away.
Always consider your skin type first when choosing a cleanser. A good cleanser will remove impurities without leaving residue. You should avoid cleansing with soap. This is because skin is slightly acidic and soap is alkaline. This disrupts the skins naturally acidic protective film.
Oil based cleansers are suitable for all skin types.
Cream cleansers will suit a dry skin.
Smooth on the cleanser and leave it for a few seconds to dissolve impurities. Then very gently wipe it off with cotton wool or damp tissue. When using a wash off cleanser you should apply it to damp skin and then remove with warm water
Step two -- Tone. Using a toner rehydrates, cools, nourishes and refreshes your skin. Toners remove any remaining traces of dirt, makeup or oil you cleanser may have not removed. It's good to use a toner that is alcohol-free, as alcohol may dry your skin.
Step three -- Exfoliate. Exfoliating gives the skin a healthy glow and gets rid of the spots that tend to make you look sallow and your skin blotchy.
Exfoliants help remove dead cells that accumulate on the surface of your skin. Make sure the exfoliant is not granular so you do not damage new skin. An exfoliant can be as simple as a face cloth or as high-tech as the latest serums containing AHAs.
Step four -- Moisturise. Just as the rest of you body requires hydration and nutrients, so does your skin. Your skin should be treated with a daytime moisturiser that provides a broad spectrum sunscreen daily. At night, using a more intense moisturiser helps to rebalance and normalize your skin as you sleep.
There's no rule that says you have to use moisturiser all over your face; you may just need a light eye cream and a bit of moisturiser on your drier cheek area.
All skin has its own natural moiturising factor that regulates water flow from the dermis to the surface. Sebum also helps by forming a barrier on the skin that prevents moisture loss. As we grow older both of these however decrease in activity and therefore we need a water regulating moisturiser. All skin types really need moisturising twice a day.
You should be carefull to choose a moisturiser to suit your skin type. For oily skins oil free formulas and oil in emulsions. Water in oil formulations suit dry normal skin. You should always spritz your skin with water before applying moisturiser. Water plumps up the skin cells creating an even surface making lines less apparent.
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