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Non-Hodgkin's Lymphoma
Classification and external resources
ICD-10 C82.-C85.
ICD-9 200, 202
ICD-O: 9591/3
OMIM 605027
DiseasesDB 9065
MedlinePlus 000581
eMedicine med/1363  ped/1343
MeSH D008228

Non-Hodgkin lymphomas (NHL) are a diverse group of cancers which arise from lymphocytes, a type of white blood cell. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The International Classification of Diseases for Oncology (ICD-O is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled A lymphocyte is a type of White blood cell in the Vertebrate Immune system. NHL is distinct from Hodgkin lymphoma in its pathologic features, epidemiology, common sites of involvement, clinical behavior, and treatment. Hodgkin's lymphoma, also known as Hodgkin's disease is a type of Lymphoma first described by Thomas Hodgkin in 1832 Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and Epidemiology is the study of factors affecting the Health and Illness of populations and serves as the foundation and Logic of interventions made in the The broad category of non-Hodgkin lymphoma encompasses diseases with varying courses, treatments, and prognoses. Prognosis (older Greek πρόγνωσις modern Greek πρόγνωση - literally fore-knowing foreseeing) is a medical term denoting the

Non-Hodgkin lymphoma is medically classified as a hematological malignancy, meaning that it is a cancer which arises from the blood. Hematological malignancies are the types of Cancer that affect Blood, Bone marrow, and Lymph nodes As the three are intimately connected through Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Non-Hodgkin lymphoma may develop in any organ associated with the lymphatic system, such as the spleen, lymph nodes, or tonsils. The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. For the structure in the Cerebellum, see Cerebellar tonsil. The tonsils are areas The diagnosis of non-Hodgkin lymphoma requires a biopsy of involved tissue. A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues The numerous subtypes of non-Hodgkin lymphoma are typically grouped into three distinct categories based on their aggressiveness. These categories are indolent (or low-grade), aggressive (or intermediate-grade), and highly aggressive (or high-grade). The treatment of indolent or low-grade lymphoma may initially involve a period of observation, while aggressive or highly aggressive non-Hodgkin lymphoma is typically treated with chemotherapy and/or radiation therapy. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Some forms of non-Hodgkin lymphoma can be cured with chemotherapy, radiation, or hematopoietic stem cell transplantation.

Contents

Symptoms

The most common symptom of non-Hodgkin's lymphoma is a painless, enlarged, rubbery swelling of the lymph nodes in the neck, underarm (axilla), or groin. Lymphadenopathy is a term meaning "disease of the Lymph nodes. However, unlike Hodgkin's disease, which is localized to cervical and supraclavicular nodes 80-90% times, NHL is localized at diagnosis only 10-20% of the time.

Other symptoms may include the following:

Organ-specific symptoms

Symptoms such as shortness of breath, chest pain, cough, abdominal pain and distention, or bone pain, may lead to the identification of specific sites of involvement. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid Sleep hyperhidrosis, more commonly known as the night sweats, is the occurrence of excessive sweating ( Hyperhidrosis) during Sleep. Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Careful evaluation for neurologic symptoms is necessary in order to rule out central nervous system (CNS) involvement, which may occur with aggressive histologies

Such symptoms are non-specific and may be caused by other, less serious conditions.

Diagnosis

If non-Hodgkin's lymphoma is suspected, the doctor asks about the person's medical history and performs a physical exam. The exam includes feeling to see if the lymph nodes in the neck, underarm, or groin are enlarged. Lymphadenopathy is a term meaning "disease of the Lymph nodes. In addition to checking general signs of health, the doctor may perform blood tests.

Excisional biopsy NHL specimen
Excisional biopsy NHL specimen

Biopsy: A biopsy is needed to make a diagnosis. A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues A surgeon removes a sample of tissue, which a pathologist can examine under a microscope to check for cancer cells. Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and A biopsy for non-Hodgkin's lymphoma is usually taken from lymph nodes that are enlarged, but other tissues may be sampled as well. Biopsies in internal lymph nodes can also be taken as needle biopsies under the guidance of CT scans. Rarely, an operation called a laparotomy may be performed. A laparotomy is a surgical procedure involving an incision through the Abdominal wall to gain access into the Abdominal cavity. During this operation, a surgeon cuts into the abdomen and removes samples of tissue to be checked under a microscope.

Common tests:

The doctor may also order tests that produce pictures of the inside of the body. Medical imaging refers to the techniques and processes used to create Images of the human body (or parts thereof for clinical purposes ( Medical procedures seeking to These may include:

Less common tests: These tests are only used under certain circumstances.

Types of non-Hodgkin's lymphoma

Over the years, doctors have used a variety of terms to classify the many different types of non-Hodgkin's lymphoma. Most often, they are grouped by how the cancer cells look under a microscope and how quickly they are likely to grow and spread. A microscope ( Greek: ( micron) = small + ( skopein) = to look or see is an instrument for viewing objects that are Current lymphoma classification is complex.

MeSH includes four different criteria for classifying NHL. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books (It is possible to be classified under more than one. )

Details of the most popular classifications of lymphoma can be found in the lymphoma page. Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system)

Causes

The etiology, or cause, of most lymphomas is not known. Etiology (alternatively aetiology, aitiology) is the study of causation. Some types of lymphomas are associated with viruses. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable Burkitt's lymphoma, extranodal NK/T cell lymphoma, classical Hodgkin's disease and most AIDS-related lymphoma are associated with Epstein-Barr virus. Burkitt lymphoma (or "Burkitt's tumor" or "Malignant lymphoma Burkitt's type" is a cancer of the lymphatic system (in particular B lymphocytes Hodgkin's lymphoma, also known as Hodgkin's disease is a type of Lymphoma first described by Thomas Hodgkin in 1832 AIDS-related lymphoma describes Lymphomas occurring in Patients with acquired immunodeficiency syndrome ( AIDS) The Epstein-Barr Virus ( EBV) also called Human herpesvirus 4 (HHV-4 is a Virus of the herpes family (which includes Herpes Adult T-cell lymphoma/leukemia, endemic in parts of Japan and the Caribbean, is caused by the HTLV-1 virus. Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood For a topic outline on this subject see List of basic Japan topics. The Caribbean (ˌkærəˡbiən kæ'rəbiən Cariben|Caraïben or Caraïben; Caraïbe or more commonly Antilles; Caribe is a Region consisting Human T-lymphotropic virus (HTLV is a Human, single-stranded RNA Retrovirus that causes T-cell Leukemia and T-cell Lymphoma Lymphoma of the stomach (extranodal marginal zone B-cell lymphoma) is often caused by the Helicobacter bacteria. Helicobacter is a Genus of Gram-negative bacteria possessing a characteristic Helix shape

The incidence of non-Hodgkin lymphoma has increased dramatically over the last couple of decades. This disease has gone from being relatively rare to being the fifth most common cancer in the United States. At this time, little is known about the reasons for this increase or about exactly what causes non-Hodgkin lymphoma.

Doctors can seldom explain why one person gets non-Hodgkin's lymphoma and another does not. It is clear, however, that cancer is not caused by an injury, and is not contagious; no one can "catch" non-Hodgkin's lymphoma from another person.

By studying patterns of cancer in the population, researchers have found certain risk factors that are more common in people who get non-Hodgkin's lymphoma than in those who do not. However, most people with these risk factors do not get non-Hodgkin lymphoma, and many who do get this disease have none of the known risk factors.

The following are some of the risk factors associated with this disease:

There is no clear connection between alcohol consumption and NHL. For further information, see the alcohol and cancer article. "Considerable evidence suggests a connection between heavy alcohol consumption and increased risk for cancer with an estimated 2 to 4 percent of all cancer cases thought to be caused either

Staging

If non-Hodgkin's lymphoma is diagnosed, the doctor needs to learn the stage, or extent, of the disease. Staging is a careful attempt to find out whether the cancer has spread and, if so, what parts of the body are affected. The stage of a cancer is a descriptor (usually numbers I to IV of how much the Cancer has spread Treatment decisions depend on these findings. [1]

The doctor considers the following to determine the stage of non-Hodgkin's lymphoma:

In staging, the doctor may use some of the same tests used for the diagnosis of non-Hodgkin's lymphoma. Other staging procedures may include additional biopsies of lymph nodes, the liver, bone marrow, or other tissue. A bone marrow biopsy involves removing a sample of bone marrow through a needle inserted into the hip or another large bone. A pathologist examines the sample under a microscope to check for cancer cells.

Stages of NHL

The various stages of NHL (the Ann Arbor staging classification, developed for Hodgkin's lymphoma) are based on how far the cancer has spread throughout and beyond the lymphatic system, and whether constitutional symptoms (fever, night sweats, or weight loss) are present. Ann Arbor staging is the staging system for Lymphomas both in Hodgkin's lymphoma (previously called Hodgkin's Disease and Non-Hodgkin lymphoma

Stage I
"Stage I" indicates that the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.
Stage II
"Stage II" indicates that the cancer is located in two separate regions, an affected lymph node or organ within the lymphatic system and a second affected area, and that both affected areas are confined to one side of the diaphragm - that is, both are above the diaphragm, or both are below the diaphragm.
Stage III
"Stage III" indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.
Stage IV
"Stage IV" indicates that the cancer has spread beyond the lymphatic system and involves one or more major organs, possibly including the bone marrow or skin.

The absence of constitutional symptoms is denoted by adding an "A" to the stage; the presence is denoted by adding a "B" to the stage (hence the name B symptoms). B symptoms refer to Systemic symptoms of Fever, Night sweats and Weight loss which can be associated with both Hodgkin's lymphoma

Staging in non-Hodgkin's lymphomas is far less significant in determining therapy than it is in Hodgkin's lymphoma

Prognosis

See also: International Prognostic Index

The most significant factor in overall prognosis is the grade, or aggressiveness, of the lymphoma. The International Prognostic Index (IPI is a clinical tool developed by oncologists to aid in predicting the Prognosis of patients with aggressive Non-Hodgkin's lymphoma Prognosis (older Greek πρόγνωσις modern Greek πρόγνωση - literally fore-knowing foreseeing) is a medical term denoting the Indolent (low-grade) non-Hodgkin's lymphoma is generally not curable, but is typically slowly progressive and responds temporarily to therapy. Aggressive and highly aggressive (intermediate- and high-grade) NHL's are potentially curable with combination chemotherapy. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Long-term survival or cure rates for these diseases vary with a number of prognostic factors.

International Prognostic Index

The International Prognostic Index, or IPI, is the most widely used prognostic system for non-Hodgkin's lymphoma. The International Prognostic Index (IPI is a clinical tool developed by oncologists to aid in predicting the Prognosis of patients with aggressive Non-Hodgkin's lymphoma This system uses 5 factors:

  • Age
  • Lactate dehydrogenase level (a blood test)
  • Performance status
  • Clinical stage
  • Sites of extranodal disease

However, it should be noted that the IPI was developed prior to the introduction of rituximab. Lactate dehydrogenase ( LDH) is an Enzyme ( present in a wide variety of organisms including plants and animals Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20 As rituximab has become a standard part of therapy for B-cell NHL's, the impact on the prognostic value of the IPI is unclear. Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20 B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by

FLIPI

For the subtype of NHL known as follicular lymphoma, a modified version of the IPI called the FLIPI (follicular lymphoma international prognostic index) has been developed. Follicular lymphoma is the most common of the indolent Non-Hodgkin's lymphomas It is defined as a Lymphoma of follicle center B-cells ( Centrocytes The International Prognostic Index (IPI is a clinical tool developed by oncologists to aid in predicting the Prognosis of patients with aggressive Non-Hodgkin's lymphoma The factors which figure into the FLIPI are age, clinical stage, lactate dehydrogenase level, hemoglobin level, and number of nodal sites involved. Lactate dehydrogenase ( LDH) is an Enzyme ( present in a wide variety of organisms including plants and animals Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein As with the IPI, the FLIPI was developed and validated prior to the widespread use of rituximab, so the same caveats apply as were mentioned with the IPI above. Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20

Treatment

The doctor develops a treatment plan to fit each patient's needs. Treatment for non-Hodgkin's lymphoma depends on the stage of the disease, the type of cells involved, whether they are indolent or aggressive, and the age and general health of the patient.

Non-Hodgkin's lymphoma is often treated by a team of specialists that may include a hematologist, medical oncologist, and/or radiation oncologist. Hematology ( American English) or haematology ( British English) is the branch of biology (physiology Pathology, Clinical laboratory Non-Hodgkin's lymphoma is usually treated with chemotherapy, radiation therapy, or a combination of these treatments. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant In some cases, bone marrow transplantation, biological therapies, or surgery may be options. For indolent lymphomas, the doctor may decide to wait until the disease causes symptoms before starting treatment. Often, this approach is called "watchful waiting. "

Taking part in a clinical trial (research study) to evaluate promising new ways to treat non-Hodgkin's lymphoma is an important option for many people with this disease.

Chemotherapy and radiation therapy

Chemotherapy and radiation therapy are the most common treatments for non-Hodgkin's lymphoma, although bone marrow transplantation, biological therapies, or surgery are sometimes used. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant CHOP, with rituximab added in certain circumstances, is the most commonly used combination of chemotherapy. CHOP is the acronym for a Chemotherapy regimen used in the treatment of Non-Hodgkin lymphoma. Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20

Rituximab is an antibody-based therapy. Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20 Ibritumomab tiuxetan (commonly known as Zevalin) and Tositumomab (Bexxar) are FDA-approved options, requiring a Nuclear Medicine facility, but only two short infusions one week apart. Ibritumomab tiuxetan, also sold under the trade name Zevalin, is a monoclonal antibody Radioimmunotherapy treatment for some forms of B cell Tositumomab is a Monoclonal antibody derived from immortalized mouse cells There is mounting evidence that more patients have long-term remission if they use radioimmunotherapy first.

Radiation therapy (also called radiotherapy) is the use of high-energy rays to kill cancer cells. Treatment with radiation may be given alone or with chemotherapy. Radiation therapy is local treatment; it affects cancer cells only in the treated area. Radiation therapy for Non Hodgkin's lymphoma comes from a machine that aims the high-energy rays at a specific area of the body. There is no radioactivity in the body when the treatment is over.

Sometimes patients are given chemotherapy and/or radiation therapy to kill undetected cancer cells that may be present in the central nervous system (CNS). In this treatment, called central nervous system prophylaxis, the doctor injects anticancer drugs directly into the cerebrospinal fluid.

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT), or Bone marrow transplantation (BMT) may also be a treatment option, especially for patients whose non-Hodgkin's lymphoma has recurred (come back). BMT provides the patient with healthy stem cells (very immature cells, found in the marrow, that produce blood cells), the function of which is to replace white blood cells that are damaged or destroyed by treatment with very high doses of chemotherapy and/or radiation therapy. The healthy bone marrow may come from a donor, or it may be "autologous" (marrow that was removed from the patient, stored, and then given back to the person following the high-dose treatment). Autologous transplants are preferred, as the recipient is less likely to reject the cells, the origins of which were the same entity. However, in order for an autologous transplant to be performed, certain physiological conditions must be optimal within the patient. If these conditions are not present, transplanted stem cells can come from other donors. Until the transplanted bone marrow begins to produce enough white blood cells, patients have to be carefully protected from infection due to the virtual elimination of the immune system resulting from the high-intensity treatment. Without the introduction of the stem cells following the high dose treatment, the patient will not survive as the body will be unable to produce infection-fighting white blood cells. Patients usually stay in the hospital for several weeks and will be monitored for transplant rejection and overall health.

Immunotherapy

Biological therapy (also called immunotherapy) is a form of treatment that uses the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that can be caused by some cancer treatments. Immunotherapy in medicine refers to an array of treatment strategies based upon the concept of modulating the Immune system to achieve a prophylactic and/or It uses materials made by the body or made in a laboratory to boost, direct, or restore the body's natural defenses against disease. This approach is under close investigation. Biological therapy is sometimes also called biological response modifier therapy.

Measuring response to treatment

After treatment for non-Hodgkin's lymphoma, the response is classified as follows:

  • Complete Response (CR). This indicates the disappearance of all detectable disease.
  • Partial Response (PR). A reduction in the bulk of disease by at least 50%, but with some remaining disease.
  • Stable Disease. Less than a partial remission, but no progression of disease and no new sites of disease.
  • Progressive Disease. Growth in bulk of disease by >50%, or the appearance of new sites of disease.

If a complete remission is achieved, the patient is watched closely for any evidence of recurrent disease. Standard guidelines dictate that a patient be monitored for relapse every three months in the first year following a complete remission, every six months in the second year, and finally once annually in the third and later years. Diffuse large b-cell lymphoma is the most common type of lymphoma that is considered curable. Currently, if a patient maintains a complete remission for 3 years, the patient is considered cured. Generally most relapses of diffuse large b-cell lymphoma occur within the first year after a complete remission is obtained. Reoccurrences after 3 years are rare but they do occur. The effect of Rituximab on relapse rates for diffuse large b-cell lymphoma is still largely unknown, though initial relapse rates since 2003 have been much lower than expected.

Patients with follicular lymphoma are generally not considered cured. Instead, they are categorized as in ongoing complete remission. Relapses occur steadily over time. Relapse rates are estimated to be 33%, 66%, and 100% for follicular lymphoma's Grades I, II, and III respectively.

Research has indicated that relapse rates can be lowered on patients with follicular lymphoma by giving supplemental radiation therapy, however, it is known that this additional therapy increases the chances of a second malignancy of unknown type later in life.

If the response to treatment falls short of a complete response, more treatment may be administered (using a different chemotherapy regimen), or watchful waiting may be utilized, depending on the goals of treatment. Chemotherapy regimens are often identified with acronyms identifying the agents used in combination

Nutrition during treatment

Eating well during cancer treatment means getting enough food energy and protein to help prevent weight loss and regain strength. Food energy is the amount of Energy in food that is available through Digestion. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Good nutrition often helps people feel better and have more energy.

Some people with cancer find it hard to eat a balanced diet because they may lose their appetite. In addition, common side effects of treatment, such as nausea, vomiting, or mouth sores, can make eating difficult. Often, foods may taste or smell different. Also, people being treated for cancer may not feel like eating when they are uncomfortable or tired.

Doctors, nurses, and dietitians can offer advice on how to get enough food energy and protein during cancer treatment. Patients and their families also may want to read the National Cancer Institute (USA) booklet Eating Hints for Cancer Patients, which contains many useful suggestions. The National Cancer Institute (NCI is part of the United States Federal government's National Institutes of Health. [2]

Followup care

People who have had non-Hodgkin's lymphoma should have regular followup examinations after their treatment is over. Followup care is an important part of the overall treatment plan, and people should not hesitate to discuss it with their health care provider. Regular followup care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between followup appointments, people who have had Non Hodgkin's lymphoma should report any health problems as soon as they appear.

Notable patients

Notable persons treated for non-Hodgkin's lymphoma include:

References

  1. ^ Staging NHL. Cancer Research UK 2002. Retrieved on April 25, 2005.
  2. ^ Eating Hints for Cancer Patients: Before, During, and After Treatment. National Cancer Institute. Retrieved on 2007-07-15. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1099 - First Crusade: Christian soldiers take the Church of the Holy Sepulchre in Jerusalem after the final

External links

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