Lymphoma

Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage of the disease. These malignant cells often originate in lymph nodes, presenting as an enlargement of the node (a tumor). It can also affect other organs in which case it is referred to as extranodal lymphoma. Extranodal sites include the skin, brain, bowels and bone. Lymphomas are closely related to lymphoid leukemias, which also originate in lymphocytes but typically involve only circulating blood and the bone marrow (where blood cells are generated in a process termed haematopoesis) and do not usually form static tumors. There are many types of lymphomas, and in turn, lymphomas are a part of the broad group of diseases called hematological neoplasms.

Thomas Hodgkin published the first description of lymphoma in 1832, specifically of the form named after him, Hodgkin's lymphoma. Since then, many other forms of lymphoma have been described, grouped under several proposed classifications. The 1982 Working formulation classification became very popular. It introduced the category non-Hodgkin lymphoma (NHL), divided into 16 different diseases. However, because these different lymphomas have little in common with each other, the NHL label is of limited usefulness for doctors or patients and is slowly being abandoned. The latest classification by the WHO (2008) lists 70 different forms of lymphoma divided in four broad groups.

Although older classifications referred to histiocytic lymphomas, these are recognized in newer classifications as of B, T or NK cell lineage. True histiocytic malignancies are rare and are classified as sarcomas.

Classification
A number of various different classification systems exist for lymphoma. As an alternative to the American Lukes-Butler classification, in the early 1970s, Karl Lennert of Kiel, Germany, proposed a new system of classifying lymphomas based on cellular morphology and their relationship to cells of the normal peripheral lymphoid system.

Some forms of lymphoma are categorized as indolent (e.g. small lymphocytic lymphoma), compatible with a long life even without treatment, whereas other forms are aggressive (e.g. Burkitt's lymphoma), causing rapid deterioration and death. However, most of the aggressive lymphomas respond well to treatment and are curable. The prognosis therefore depends on the correct diagnosis and classification of the disease, which is established after examination of a biopsy by a pathologist (usually a hematopathologist).

Working Formulation and non-Hodgkin lymphoma
The 1996 Working Formulation is a classification of non-Hodgkin lymphoma. It excluded the Hodgkin lymphomas and divided the remaining lymphomas into four grades (Low, Intermediate, High, and Miscellaneous) related to prognosis, with some further subdivisions based on the size and shape of affected cells. This purely histological classification included no information about cell surface markers, or genetics, and it made no distinction between T-cell lymphomas or B-cell lymphomas.See here

It was widely accepted at the time of its publication but is now obsolete. It was superseded by subsequent classifications (see below) but it is still used by cancer agencies for compilation of lymphoma statistics and historical rare comparisons.

REAL
In the mid 1990s,the Revised European-American Lymphoma (REAL) Classification attempted to apply immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin's lymphoma. REAL has been superseded by the WHO classification. REAL & WHO •B-cell neoplasms –precursor –mature •T-cell neoplasms –precursor –mature •Hodgkin lymphomaNon-HodgkinLymphomas

World Health Organization (WHO)
The WHO Classification, published in 2001 and updated in 2008, is the latest classification of lymphoma and is based upon the foundations laid within the "Revised European-American Lymphoma classification" (REAL). This system attempts to group lymphomas by cell type (i.e. the normal cell type that most resembles the tumor) and defining phenotypic, molecular or cytogenetic characteristics. There are three large groups: the B cell, T cell, and natural killer cell tumors. Other less common groups, are also recognized. Hodgkin's lymphoma, although considered separately within the World Health Organization (and preceding) classifications, is now recognized as being a tumor of, albeit markedly abnormal, lymphocytes of mature B cell lineage.

Mature B cell neoplasms



 * Chronic lymphocytic leukemia/Small lymphocytic lymphoma
 * B-cell prolymphocytic leukemia
 * Lymphoplasmacytic lymphoma (such as Waldenström macroglobulinemia)
 * Splenic marginal zone lymphoma
 * Plasma cell neoplasms:
 * Plasma cell myeloma
 * Plasmacytoma
 * Monoclonal immunoglobulin deposition diseases
 * Heavy chain diseases
 * Extranodal marginal zone B cell lymphoma, also called MALT lymphoma
 * Nodal marginal zone B cell lymphoma (NMZL)
 * Follicular lymphoma
 * Mantle cell lymphoma
 * Diffuse large B cell lymphoma
 * Mediastinal (thymic) large B cell lymphoma
 * Intravascular large B cell lymphoma
 * Primary effusion lymphoma
 * Burkitt lymphoma/leukemia

Mature T cell and natural killer (NK) cell neoplasms

 * T cell prolymphocytic leukemia
 * T cell large granular lymphocytic leukemia
 * Aggressive NK cell leukemia
 * Adult T cell leukemia/lymphoma
 * Extranodal NK/T cell lymphoma, nasal type
 * Enteropathy-type T cell lymphoma
 * Hepatosplenic T cell lymphoma
 * Blastic NK cell lymphoma
 * Mycosis fungoides / Sezary syndrome
 * Primary cutaneous CD30-positive T cell lymphoproliferative disorders
 * Primary cutaneous anaplastic large cell lymphoma
 * Lymphomatoid papulosis
 * Angioimmunoblastic T cell lymphoma
 * Peripheral T cell lymphoma, unspecified
 * Anaplastic large cell lymphoma

Hodgkin lymphoma

 * Classical Hodgkin lymphomas:
 * Nodular sclerosis
 * Mixed cellularity
 * Lymphocyte-rich
 * Lymphocyte depleted or not depleted
 * Nodular lymphocyte-predominant Hodgkin lymphoma

Immunodeficiency-associated lymphoproliferative disorders

 * Associated with a primary immune disorder
 * Associated with the Human Immunodeficiency Virus (HIV)
 * Post-transplant
 * Associated with methotrexate therapy
 * Primary central nervous system lymphoma occurs most often in immuno-compromised patients, in particular those with AIDS, but it can occur in the immunocompetent as well. It has a poor prognosis, particularly in those with AIDS. Treatment can consist of corticosteroids, radiotherapy, and chemotherapy, often with methotrexate.

Other classification systems

 * ICD-O (codes 9590-9999, details at )
 * ICD-10 (codes C81-C96, details at )

Symptoms

 * Anorexia
 * Dyspnea
 * Fatigue
 * Fever of unknown origin
 * Lymphadenopathy
 * Night sweats
 * Pruritus
 * Weight loss

Diagnosis, etiology, staging, prognosis, and treatment
These depend on the specific form of lymphoma. For some forms of lymphoma, watchful waiting is often the initial course of action. If a low-grade lymphoma is becoming symptomatic, radiotherapy or chemotherapy are the treatments of choice; although they do not cure the lymphoma, they can alleviate the symptoms, particularly painful lymphadenopathy. Patients with these types of lymphoma can live near-normal lifespans, but the disease is incurable. Treatment of some other, more aggressive, forms of lymphoma can result in a cure in the majority of cases, but the prognosis for patients with a poor response to therapy is worse. Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or RCHOP regimen. Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized. Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy. See the articles on the corresponding form of lymphoma for further information.

Epidemiology
Lymphoma is the most common form of hematological malignancy, or "blood cancer", in the developed world.

Taken together, lymphomas represent 5.3% of all cancers (excluding simple basal cell and squamous cell skin cancers) in the United States and 55.6% of all blood cancers.

According to the U.S. National Institutes of Health, lymphomas account for about five percent of all cases of cancer in the United States, and Hodgkin's lymphoma in particular accounts for less than one percent of all cases of cancer in the United States.

Because the whole system is part of the body's immune system, patients with a weakened immune system such as from HIV infection or from certain drugs or medication also have a higher incidence of lymphoma.

Comparison
Following is a comparison of the most common types of lymphoma: