Lymphoma
Lymphoma
Lymphoma
Lymphoma
From Wikipedia, the free encyclopedia
Lymphoma is a group of blood cell tumors that develop from
lymphocytes (a type of white blood cell). The name often refers Lymphoma
to just the cancerous ones rather than all such tumors.[1] Signs
and symptoms may include enlarged lymph nodes, fever,
drenching sweats, unintended weight loss, itching, and
constantly feeling tired.[2][3] The enlarged lymph nodes are
usually painless.[2] The sweats are most common at night.[2][3]
There are dozens of subtypes of lymphomas.[4] The two main
categories of lymphomas are Hodgkin's lymphomas (HL) and
the nonHodgkin lymphomas (NHL).[5] The World Health
Organization (WHO) includes two other categories as types of
lymphoma: multiple myeloma and immunoproliferative
diseases.[6] About 90% of lymphomas are nonHodgkin Follicular lymphoma replacing a lymph node
lymphomas.[5][7] Lymphomas and leukemias are a part of the Classification and external resources
broader group of tumors of the hematopoietic and lymphoid
Specialty Hematology and oncology
tissues.[8]
ICD10 C81 (http://apps.who.int/classification
Risk factors for Hodgkin lymphoma include infection with s/icd10/browse/2016/en#/C81)–C96 (h
Epstein–Barr virus and a history of the disease in the family.[2] ttp://apps.who.int/classifications/icd10/
Risk factors for common types of nonHodgkin lymphomas browse/2016/en#/C96)
include autoimmune diseases, HIV/AIDS, infection with human
ICD9CM 202.8
Tlymphotropic virus, immunosuppressant medications, and
some pesticides.[3] Eating large amounts of red meat and ICDO 9590–9999
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Contents
1 Signs and symptoms
2 Diagnosis
2.1 Classification
2.2 Staging
3 Treatment
3.1 Lowgrade lymphomas
3.2 Highgrade lymphomas
3.3 Palliative care
4 Prognosis
5 Epidemiology
6 History
7 Research
8 Other animals
9 References
10 External links
Signs and symptoms
Lymphoma may present with certain nonspecific symptoms; if the
symptoms are persistent, an evaluation to determine their cause, including
possible lymphoma, should be undertaken.
Lymphadenopathy[16][17] or swelling of lymph nodes, is the primary
presentation in lymphoma.
B symptoms (systemic symptoms) – can be associated with both
Hodgkin lymphoma and nonHodgkin lymphoma. They consist of:
Fever[16][17]
Night sweats[16][17]
Weight loss[16][17]
Other symptoms:
Loss of appetite or anorexia[17]
Fatigue[16][17]
Respiratory distress or dyspnea[17] The lymph nodes where lymphoma
Itching[16][17] most commonly develops
Diagnosis
Lymphoma is definitively diagnosed by a lymph node biopsy, meaning a
partial or total excision of a lymph node examined under the
microscope.[18] This examination reveals histopathological features that
may indicate lymphoma. After lymphoma is diagnosed, a variety of tests
may be carried out to look for specific features characteristic of different
types of lymphoma. These include:
Immunophenotyping Lymphoma and lymphatic system
Flow cytometry
Fluorescence in situ hybridization testing
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Classification
Lymphomas sensu stricto are any neoplasms of the lymphatic tissues
(lympho + oma) .[19] The main classes are malignant neoplasms (that is,
cancers) of the lymphocytes, a type of white blood cell that belongs to both
the lymph and the blood and pervades both. Thus, lymphomas and
leukemias are both tumors of the hematopoietic and lymphoid tissues, and
as lymphoproliferative disorders, lymphomas and lymphoid leukemias are
closely related, to the point that some of them are unitary disease entities
that can be called by either name (for example, adult Tcell
leukemia/lymphoma).
Lymph node with mantle cell
Several classification systems have existed for lymphoma, which use
lymphoma (lowpower view, H&E)
histological and other findings to divide lymphoma into different
categories. The classification of a lymphoma can affect treatment and
prognosis. Classification systems generally classify lymphoma according to:
Whether or not it is a Hodgkin lymphoma
Whether the cell that is replicating is a T cell or B cell
The site from which the cell arises
Lymphoma can also spread to the central nervous system, often around the brain in the meninges, known as
lymphomatous meningitis (LM).[20]
Hodgkin lymphoma
Hodgkin lymphoma is one of the most commonly known types of lymphoma, and differs from other forms of
lymphoma in its prognosis and several pathological characteristics. A division into Hodgkin and nonHodgkin
lymphomas is used in several of the older classification systems. A Hodgkin lymphoma is marked by the presence
of a type of cell called the Reed–Sternberg cell.[21][22]
NonHodgkin lymphomas
NonHodgkin lymphomas, which are defined as being all lymphomas except Hodgkin lymphoma, are more
common than Hodgkin lymphoma. A wide variety of lymphomas are in this class, and the causes, the types of cells
involved, and the prognosis vary by type. The incidence of nonHodgkin lymphoma increases with age. It is
further divided into several subtypes.
WHO classification
The WHO classification, published in 2001 and updated in 2008,[23][24] is based upon the foundations laid within
the "revised EuropeanAmerican lymphoma classification" (REAL). This system groups lymphomas by cell type
(i.e. the normal cell type that most resembles the tumor) and defining phenotypic, molecular, or cytogenetic
characteristics. The five groups are shown in the table. Hodgkin lymphoma is considered separately within the
WHO and preceding classifications, although it is recognized as being a tumor of, albeit markedly abnormal,
lymphocytes of mature B cell lineage.
Of the many forms of lymphoma, some 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
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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).[25]
Lymphoma subtypes (WHO 2008)
Mature B cell neoplasms
Bcell chronic lymphocytic leukemia/small cell lymphoma
3 to 4% of lymphomas in adults
Small resting lymphocytes mixed with variable numbers of
large activated cells, lymph nodes diffusely effaced
CD5, surface immunoglobulin
50%.[26]
Occurs in older adults, usually involves lymph nodes, bone
marrow and spleen, most patients have peripheral blood
involvement, indolent
DNAmicroarray analysis of Burkitt's
Bcell prolymphocytic leukemia lymphoma and diffuse large Bcell
Lymphoplasmacytic lymphoma (such as Waldenström lymphoma (DLBCL) showing
macroglobulinemia) differences in gene expression patterns.
Splenic marginal zone lymphoma Colors indicate levels of expression;
Hairy cell leukemia green indicates genes that are
Plasma cell neoplasms: underexpressed in lymphoma cells (as
Plasma cell myeloma (also known as multiple myeloma) compared to normal cells), whereas red
Plasmacytoma indicates genes that are overexpressed
Monoclonal immunoglobulin deposition diseases in lymphoma cells.
Heavy chain diseases
Extranodal marginal zone B cell lymphoma, also called MALT
lymphoma
About 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
Nodal marginal zone B cell lymphoma
Follicular lymphoma
About 40% of lymphomas in adults
Small "cleaved" cells (centrocytes) mixed with large activated cells (centroblasts), usually nodular
("follicular") growth pattern
CD10, surface Ig
72–77%[27]
Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, associated with
t(14;18) translocation overexpressing Bcl2, indolent
Primary cutaneous follicle center lymphoma
Mantle cell lymphoma
3 to 4% of lymphomas in adults
Lymphocytes of small to intermediate size growing in diffuse pattern
CD5
50%[28] to 70%[28]
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Occurs mainly in adult males, usually involves lymph nodes, bone marrow, spleen and GI tract,
associated with t(11;14) translocation overexpressing cyclin D1, moderately aggressive
Diffuse large B cell lymphoma, not otherwise specified
About 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
5year survival 60%[29]
Occurs in all ages, but most commonly in older adults, may occur outside lymph nodes, aggressive
Diffuse large Bcell lymphoma associated with chronic inflammation
Epstein–Barr viruspositive DLBCL of the elderly
Lymphomatoid granulomatosis
Primary mediastinal (thymic) large Bcell lymphoma
Intravascular large Bcell lymphoma
ALK+ large Bcell lymphoma
Plasmablastic lymphoma
Primary effusion lymphoma
Large Bcell lymphoma arising in HHV8associated multicentric Castleman's disease
Burkitt lymphoma/leukemia
< 1% of lymphomas in the United States
Round lymphoid cells of intermediate size with several nucleoli, starrysky appearance by diffuse
spread with interspersed apoptosis
CD10, surface Ig
5year
survival 50%[30]
Endemic in Africa, sporadic elsewhere, more common in immunocompromised and children, often
visceral involvement, highly aggressive
Mature T cell and natural killer (NK) cell neoplasms
Tcell prolymphocytic leukemia
Tcell large granular lymphocyte leukemia
Aggressive NK cell leukemia
Adult Tcell leukemia/lymphoma
Extranodal NK/Tcell lymphoma, nasal type
Enteropathyassociated Tcell lymphoma
Hepatosplenic Tcell lymphoma
Blastic NK cell lymphoma
Mycosis fungoides / Sezary syndrome
Most common cutaneous lymphoid malignancy
Usually small lymphoid cells with convoluted nuclei that often infiltrate the epidermis, creating Pautrier
microabscesseses
CD4
5year
survival 75%[31]
Localized or more generalized skin symptoms, generally indolent, in a more aggressive variant,
Sézary's disease, skin erythema and peripheral blood involvement
Primary cutaneous CD30positive T cell lymphoproliferative disorders
Primary cutaneous anaplastic large cell lymphoma
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Lymphomatoid papulosis
Peripheral Tcell 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, often disseminated and generally aggressive
Angioimmunoblastic T cell lymphoma
Anaplastic large cell lymphoma
Precursor lymphoid neoplasms
Blymphoblastic leukemia/lymphoma not otherwise specified
Blymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
Tlymphoblastic leukemia/lymphoma
15% of childhood acute lymphoblastic leukemia and 90% of lymphoblastic lymphoma.[23]:635
Lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli and scant
cytoplasm without granules
TdT, CD2, CD7
It often presents as a mediastinal mass because of involvement of the thymus. It is highly associated
with NOTCH1 mutations, and is most common in adolescent males.
Hodgkin lymphoma
Classical Hodgkin lymphomas:
Nodular sclerosis form of Hodgkin lymphoma
Most common type of Hodgkin lymphoma
ReedSternberg cell variants and inflammation, usually broad sclerotic bands that consist of collagen
CD15, CD30
Most common in young adults, often arises in the mediastinum or cervical lymph nodes
Mixed cellularity Hodgkin lymphoma
Secondmost common form of Hodgkin lymphoma
Many classic ReedSternberg cells and inflammation
CD15, CD30
Most common in men, more likely to be diagnosed at advanced stages than the nodular sclerosis form
EpsteinBarr virus involved in 70% of cases
Lymphocyterich
Lymphocyte depleted or not depleted
Nodular lymphocytepredominant Hodgkin lymphoma
Immunodeficiencyassociated lymphoproliferative disorders
Associated with a primary immune disorder
Associated with the human immunodeficiency virus (HIV)
Posttransplant
Associated with methotrexate therapy
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Primary central nervous system lymphoma occurs most often in immunocompromised 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.
Previous classifications
Several previous classifications have been used, including Rappaport 1956, Lennert / Kiel 1974, BNLI, Working
formulation (1982), and REAL (1994).
The Working formulation of 1982 was a classification of nonHodgkin 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 Tcell lymphomas and Bcell lymphomas. It was widely accepted at the time of its publication,
but is now obsolete.[32] It is still used by some cancer agencies for compilation of lymphoma statistics and
historical rate comparisons.
In 1994, the Revised EuropeanAmerican Lymphoma (REAL) classification applied immunophenotypic and
genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin
lymphoma.[33] For coding purposes, the ICDO (codes 9590–9999)[34] and ICD10 (codes C81C96)[35] are
available.
Staging
After a diagnosis and before treatment, a cancer is staged. This refers to
determining if the cancer has spread, and if so, whether locally or to distant
sites. Staging is reported as a grade between I (confined) and IV (spread).
Staging is carried out because the stage of a cancer impacts its prognosis
and treatment.
The Ann Arbor staging system is routinely used for staging of both HL and
NHL. In this staging system, I represents a localized disease contained
within a lymph node, II represents the presence of lymphoma in two or
more lymph nodes, III represents spread of the lymphoma to both sides of
the diaphragm, and IV indicates tissue outside a lymph node.
CT scan or PET scan imaging modalities are used to stage a cancer.
Age and poor performance status are established poor prognostic factors, as
well.[36] Diagram showing common sites
where lymphoma spreads
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Treatment
Prognoses and treatments are different for HL and between all the different forms of NHL,[37] and also depend on
the grade of tumour, referring to how quickly a cancer replicates. Paradoxically, highgrade lymphomas are more
readily treated and have better prognoses: Burkitt lymphoma, for example, is a highgrade tumour known to double
within days, and is highly responsive to treatment. Lymphomas may be curable if detected in early stages with
modern treatment.
Lowgrade lymphomas
Many lowgrade lymphomas remain indolent for many years. Treatment of the nonsymptomatic patient is often
avoided. In these forms of lymphoma, such as follicular lymphoma, watchful waiting is often the initial course of
action. This is carried out because the harms and risks of treatment outweigh the benefits.[38] If a lowgrade
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 nearnormal lifespans, but the disease is incurable. Some centers advocate the use of
single agent rituximab in the treatment of follicular lymphoma rather than the wait and watch approach. Watchful
waiting is not a good strategy for all patients, as it leads to significant distress and anxiety in some patients. It has
been equated with watch and worry.[39]
Highgrade lymphomas
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.[40] Treatment for these types of lymphoma
typically consists of aggressive chemotherapy, including the CHOP or RCHOP regimen. A number of people are
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cured with firstline chemotherapy. Most relapses occur within the first two years, and the relapse risk drops
significantly thereafter.[41] For people who relapse, highdose chemotherapy followed by autologous stem cell
transplantation is a proven approach.[42]
Hodgkin lymphoma
Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized.[43]
Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy.[44]
Chemotherapy used includes the ABVD regimen, which is commonly used in the United States. Other regimens
used in the management of Hodgkin lymphoma include BEACOPP and Stanford V. Considerable controversy
exists regarding the use of ABVD or BEACOPP. Briefly, both regimens are effective, but BEACOPP is associated
with more toxicity. Encouragingly, a significant number of people who relapse after ABVD can still be salvaged by
stem cell transplant.[45]
Palliative care
Palliative care, a specialized medical care focused on the symptoms, pain, and stress of a serious illness, is
recommended by multiple national cancer treatment guidelines as an accompaniment to curative treatments for
people suffering from lymphoma.[46][47] It is used to address both the direct symptoms of lymphoma and many
unwanted side effects that arise from treatments.[48][49] Palliative care can be especially helpful for children who
develop lymphoma, helping both children and their families deal with the physical and emotional symptoms of the
disease.[48][50][51][52] For these reasons, palliative care is especially important for patients requiring bone marrow
transplants.[53][54]
Prognosis
Fiveyear relative survival by stage at diagnosis[55]
Fiveyear relative Percentage
Stage at diagnosis
survival (%) of cases (%)
Localized (confined to primary site) 82.3 26
Regional (spread to regional lymph nodes) 78.3 19
Distant (cancer has metastasized) 62.7 47
Unknown (unstaged) 68.6 8
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.[56]
According to the U.S. National Institutes of Health, lymphomas account for about 5%, and Hodgkin lymphoma in
particular accounts for less than 1% of all cases of cancer in the United States.
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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.[57]
History
Thomas Hodgkin published the first description of lymphoma in Deaths from lymphomas and multiple myeloma
1832, specifically of the form named after him.[58] Since then, per million persons in 2012
many other forms of lymphoma have been described. 013 2934 89121
1418 3542 122184
Research 1922 4357
2328 5888
The two types of lymphoma research are clinical or translational
research and basic research. Clinical/translational research
focuses on studying the disease in a defined and generally immediately patientapplicable way, such as testing a
new drug in patients. Studies may focus on effective means of treatment, better ways of treating the disease,
improving the quality of life for patients, or appropriate care in remission or after cures. Hundreds of clinical trials
are being planned or conducted at any given time.[59]
Basic science research studies the disease process at a distance, such as seeing whether a suspected carcinogen can
cause healthy cells to turn into lymphoma cells in the laboratory or how the DNA changes inside lymphoma cells
as the disease progresses. The results from basic research studies are generally less immediately useful to patients
with the disease,[60] but can improve scientists' understanding of lymphoma and form the foundation for future,
more effective treatments.
Other animals
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