lymphoma - Basic Medical Terms

Lymphoma is a cancer in the lymphatic of the immune system and presents as a solid tumor of lymphoid cells. It is treatable with 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. 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 (2001) lists 43 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.

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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 classification of the disease, established by a pathologist after examination of a biopsy.

Working Formulation and Non-Hodgkin lymphoma

The 1982 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.

The Working Formulation 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.

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 Waldenstr??m 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 immunocomprimised 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 )

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Symptoms

Anorexia

Dyspnea

Fatigue

Fever of unknown origin

Lymphadenopathy

Night sweats

Pruritus

Weight loss

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Diagnosis, etiology, staging, prognosis, and treatment

colspan=3|5-year relative survival by stage at diagnosis
! 5-year relative
survival (%) !! Percentage
of cases (%)
Distant (cancer has metastasized) 59.9 45
Localized (confined to primary site) 82.1 28
Regional (spread to regional lymphnodes) 77.5 19
Unknown (unstaged) 67.5 8

These depend on the specific form of lymphoma. See the articles on the corresponding form of lymphoma for further information.

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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.

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Comparison

Following is a comparison of the most common types of lymphoma:
! Relative incidence !! Histopathology !! Cell surface marker|Cell markers !! Overall
Five-year survival rate|5-year
survival !! Other comments
Precursor T-cell leukemia/lymphoma 40% of lymphomas in childhood. Lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli and scant cytoplasm without granules. Terminal deoxynucleotidyl transferase|TdT, CD2, CD7 | It often presents as a mediastinal mass because of involvement of the thymus.
Follicular lymphoma 40% of lymphomas in adults Small "cleaved" cells (centrocytes) mixed with large activated cells (centroblasts). Usually nodular ("follicular") growth pattern CD10, surface immunoglobulin|Ig 72-77% Occurs in older adults. Usually involves lymph nodes, bone marrow and spleen.
Diffuse large B cell lymphoma 40 to 50% of lymphomas in adults Variable. Most resemble B cells of large germinal centers. Diffuse growth pattern. Variable expression of CD10 and surface Ig 60% Occurs in all ages, but most commonly in older adults. Often occurs outside lymph nodes. Aggressive.
Mantle cell lymphoma 3 to 4% of lymphomas in adults Lymphocytes of small to internediate size growing in diffuse pattern CD5 50% to 70%
50% for limited stage, according to:
70% for advanced stage, according to most recent values in:
Occurs mainly in adult males. Usually involves lymph nodes, bone marrow, spleen and gastrointestinal tract|GI tract. Associated with t(11;14) translocation overexpressing cyclin D1. Moderately aggressive.
B-cell chronic lymphocytic leukemia/lymphoma 3 to 4 % of lymphomas in adults Small resting lymphocytes mixed with variable number of large activated cells. Lymph nodes are diffusely effacement|effaced CD5, surface immunoglobulin 50%. Occurs in older adults. Usually involves lymph nodes, bone marrow and spleen. Most patients have peripheral blood involvement. Indolent.
MALT lymphoma ~5% of lymphomas in adults Variable cell size and differentiation. 40% show plasma cell differentiation. Homing of B cells to epithelium creates lymphoepithelial lesions. CD5, CD10, surface Ig | |Frequently occurs outside lymph nodes. Very indolent. May be cured by local excision.
Burkitt's lymphoma < 1% of lymphomas in the United States Round lymphoid cells of intermediate size with several nucleoli. Starry-sky appearance by diffuse spread with interspersed apoptosis. CD10, surface Ig 50% Endemic in Africa, sporadic elsewhere. More common in immunocompromised and in children. Often visceral involvement. Highly aggressive.
Mycosis fungoides Most common cutaneous lymphoid malignancy Usually small lymphoid cells with convoluted nuclei that often infiltrate the epidermis, creating Pautier microabscesses CD4 75% Localized or more generalized skin symptoms. Generally indolent. In a more aggressive variant,
Peripheral T-cell lymphoma-Not-Otherwise-Specified Most common T cell lymphoma Variable. Usually a mix small to large lymphoid cells with irregular nuclear contours. CD3 | Probably consists of several rare tumor types. It is often disseminated and generally aggressive.
Nodular sclerosis form of Hodgkin lymphoma Most common type of Hodgkin's lymphoma Reed-Sternberg cell variants and inflammation. usually broad sclerotic bands that consists of collagen. CD15, CD30 | Most common in young adults. It often arises in the mediastinum or cervical lymph nodes.
''Mixed-cellularity subtype of Hodgkin lymphoma Second most common form of Hodgkin's lymphoma Many classic Reed-Sternberg cells and inflammation CD15, CD30 | Most common in men. More likely to be diagnosed at advanced stages than the nodular sclerosis form. Epstein-Barr virus involved in 70% of cases.

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