Risk factors for Hodgkin lymphoma include infection with Epstein–Barr virus
and a history of the disease in the family.
Risk factors for common types of non-Hodgkin lymphomas include autoimmune diseases
, infection with human T-lymphotropic virus
, immunosuppressant medications
, and some pesticides
Eating large amounts of red meat and tobacco smoking
may also increase the risk.
Diagnosis, if enlarged lymph nodes are present, is usually by lymph node biopsy
Blood, urine, and bone marrow testing
may also be useful in the diagnosis. Medical imaging
may then be done to determine if and where the cancer has spread.
Lymphoma most often spreads to the lungs, liver, and brain.
Treatment may involve one or more of the following: chemotherapy
, radiation therapy
, proton therapy
, targeted therapy
, and surgery.
In some non-Hodgkin lymphomas, an increased amount of protein produced by the lymphoma cells causes the blood to become so thick that plasmapheresis
is performed to remove the protein. Watchful waiting
may be appropriate for certain types.
The outcome depends on the subtype with some being curable and treatment prolonging survival in most.
The five-year survival rate
in the United States for all Hodgkin lymphoma subtypes is 85%,
while that for non-Hodgkin lymphomas is 69%.
Worldwide, lymphomas developed in 566,000 people in 2012 and caused 305,000 deaths.
They make up 3–4% of all cancers, making them as a group the seventh-most common form.
In children, they are the third-most common cancer.
They occur more often in the developed world
than the developing world
Signs and symptoms
The lymph nodes where lymphoma most commonly develops
Lymphoma and lymphatic system
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 or swelling of lymph nodes, is the primary presentation in lymphoma. It is generally painless.
- B symptoms (systemic symptoms) – can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. They consist of:
- Other symptoms:
Asymptomatic soft swelling, which may or may not be ulcerated, is primarily seen on the tonsils, buccal mucosa, palate, gums, salivary glands, tongue, floor of the mouth, and retromolar region.
Lymphoma is definitively diagnosed by a lymph-node biopsy
, meaning a partial or total excision of a lymph node
examined under the microscope.
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:
Lymph node with mantle cell lymphoma (low-power view, H&E)
According to the World Health Organization (WHO), lymphoma classification should reflect in which lymphocyte population the neoplasm arises.
Thus, neoplasms that arise from precursor lymphoid cells are distinguished from those that arise from mature lymphoid cells.
Most mature lymphoid neoplasms comprise the non-Hodgkin lymphomas.
Historically, mature histiocytic and dendritic cell (HDC) neoplasms have been considered mature lymphoid neoplasms, since these often involve lymphoid tissue.
Hodgkin lymphoma accounts for about 15% of lymphomas.
It differs from other forms of lymphomas in its prognosis
and several pathological
characteristics. A division into Hodgkin and non-Hodgkin 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
, 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 prognoses vary by type. The number of cases per year of non-Hodgkin lymphoma increases with age. It is further divided into several subtypes.
Epstein-Barr virus-associated lymphoproliferative diseases
Epstein-Barr virus-associated lymphoproliferative diseases
are a group of benign, premalignant
, and malignant diseases of lymphoid cells
, i.e. B cells
, T cells
, NK cells
, and histiocytic-dendritic cells
in which one or more of these cell types is infected with the Epstein-Barr virus
(EBV). The virus may be responsible for the development and/or progression of these diseases. In addition to EBV-positive Hodgkin lymphomas
, the World Health Organization (2016) includes the following lymphomas, when associated with EBV infection, in this group of diseases: Burkitt lymphoma
; large B cell lymphoma, not otherwise specified
; diffuse large B cell lymphoma associated with chronic inflammation
; fibrin-associated diffuse large B cell lymphoma
; primary effusion lymphoma
; plasmablastic lymphoma
; extranodal NK/T cell lymphoma, nasal type
; peripheral T cell lymphoma, not otherwise specified
; angioimmunoblastic T cell lymphoma
; follicular T cell lymphoma
; and systemic T cell lymphoma of childhood
The WHO classification, published in 2001 and updated in 2008,
is based upon the foundations laid within the "revised European-American lymphoma classification" (REAL). This system groups lymphomas by cell type (i.e. the normal cell type that most resembles the tumor) and defining phenotypic
, 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, albeit markedly abnormal, of 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 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
Lymphoma subtypes (WHO 2008)
DNA-microarray analysis of Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) showing differences in gene expression patterns. Colors indicate levels of expression; green indicates genes that are underexpressed in lymphoma cells (as compared to normal cells), whereas red indicates genes that are overexpressed in lymphoma cells.
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
5-year survival rate 50%.
Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, most patients have peripheral blood involvement, indolent
About 5% of lymphomas in adults
Variable cell size and differentiation, 40% show plasma cell
of B cells to epithelium creates lymphoepithelial lesions.
, surface Ig
Frequently occurs outside lymph nodes, very indolent, may be cured by local excision
About 40% of lymphomas in adults
Small "cleaved" [cleft] cells (centrocytes
) mixed with large activated cells (centroblasts
), usually nodular ("follicular") growth patternCD10
, surface Ig
Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, associated with t(14;18) translocation
About 3 to 4% of lymphomas in adults
Lymphocytes of small to intermediate size growing in diffuse patternCD5
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
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 IgFive-year survival rate
Occurs in all ages, but most commonly in older adults, may occur outside lymph nodes, aggressive
< 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
Five-year survival rate 50%
Endemic in Africa, sporadic elsewhere, more common in immunocompromised and children, often visceral involvement, highly aggressive
Most common T cell lymphoma
Variable, usually a mix small to large lymphoid cells with irregular nuclear contoursCD3
Probably consists of several rare tumor types, often disseminated and generally aggressive
Precursor lymphoid neoplasms
Most common type of Hodgkin lymphoma
Reed-Sternberg cell variants and inflammation, usually broad sclerotic bands that consist of collagenCD15
Most common in young adults, often arises in the mediastinum
or cervical lymph nodes
Mixed cellularity Hodgkin lymphoma
Second-most common form of Hodgkin lymphoma
Many classic Reed-Sternberg cells and inflammation
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
Immunodeficiency-associated lymphoproliferative disorders
- Associated with a primary immune disorder
- Associated with the human immunodeficiency virus (HIV)
- Associated with methotrexate therapy
- 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.
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 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
and B-cell lymphomas
. It was widely accepted at the time of its publication, but is now obsolete.
In 1994, the Revised European-American Lymphoma (REAL) classification applied immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin lymphoma.
For coding purposes, the ICD-O
Diagram showing common sites where lymphoma spreads
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). The stage of a lymphoma helps predict a patient's prognosis and is used to help select the appropriate therapy.
The Ann Arbor staging system
is routinely used for staging of both HL and NHL. In this staging system, I represents localized disease contained within a lymph node group, II represents the presence of lymphoma in two or more lymph nodes groups, III represents spread of the lymphoma to lymph nodes groups on both sides of the diaphragm
, and IV indicates spread to tissue outside the lymphatic system. Different suffixes imply involvement of different organs, for example S for the spleen and H for the liver. Extra-lymphatic involvement is expressed with the letter E. In addition, the presence of B symptoms (one or more of the following: unintentional loss of 10% body weight in the last 6 months, night sweats, or persistent fever of 38 °C or more) or their absence is expressed with B or A, respectively.
or PET scan
imaging modalities are used to stage a cancer. PET scanning is advised for fluorodeoxyglucose
-avid lymphomas, such as Hodgkin lymphoma, as a staging tool that can even replace bone marrow biopsy. For other lymphomas, CT scanning is recommended for staging.
Age and poor performance status
are other established poor prognostic factors.
This means that people who are elderly or too sick to take care of themselves are more likely to die from lymphoma than others.
Mantle cell lymphoma: Notice the irregular nuclear contours of the medium-sized lymphoma cells and the presence of a pink histiocyte. By immunohistochemistry, the lymphoma cells expressed CD20, CD5, and Cyclin D1 (high-power view, H&E)
Hodgkin lymphoma, nodular lymphocyte predominant (low-power view): Notice the nodular architecture and the areas of "mottling".(H&E)
Hodgkin lymphoma, nodular lymphocyte predominant (high-power view): Notice the presence of L&H cells, also known as "popcorn cells". (H&E)
Certain lymphomas (extranodal NK/T-cell lymphoma, nasal type
and type II enteropathy-associated T-cell lymphoma
) can be mimicked by two benign diseases which involve the excessive proliferation of non-malignant NK cells in the GI tract, natural killer cell enteropathy
, a disease wherein NK cell infiltrative lesions occur in the intestine, colon, stomach, or esophagus, and lymphomatoid gastropathy
, a disease wherein these cells' infiltrative lesions are limited to the stomach. These diseases do not progress to cancer, may regress spontaneously and do not respond to, and do not require, chemotherapy or other lymphoma treatments.
Prognoses and treatments are different for HL and between all the different forms of NHL,
and also depend on the grade
of tumour, referring to how quickly a cancer replicates. Paradoxically, high-grade lymphomas are more readily treated and have better prognoses: Burkitt lymphoma
, for example, is a high-grade tumour known to double within days, and is highly responsive to treatment. Lymphomas may be curable if detected in early stages with modern treatment.
Many low-grade lymphomas remain indolent
(growing slowly or not at all) for many years – sometimes, for the rest of the person's life. With an indolent lymphoma, such as follicular lymphoma, watchful waiting
is often the initial course of action, because monitoring is less risky and less harmful than early treatment.
If a low-grade lymphoma becomes symptomatic, radiotherapy or chemotherapy are the treatments of choice. Although these treatments do not permanently cure the lymphoma, they can alleviate the symptoms, particularly painful lymphadenopathy
. People with these types of lymphoma can live near-normal lifespans, even though the disease is technically 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 desirable strategy for everyone, as it leads to significant distress and anxiety
in some people. It has been called "watch and worry".
Treatment of some other, more aggressive, forms of lymphoma[which?]
can result in a cure in the majority of cases, but the prognosis for people with a poor response to therapy is worse.
Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or R-CHOP
regimen. A number of people are cured with first-line chemotherapy. Most relapses occur within the first two years, and the relapse risk drops significantly thereafter.
For people who relapse, high-dose chemotherapy followed by autologous stem cell transplantation is a proven approach.
The treatment of side effects is also important as they can occur due to the chemotherapy or the stem cell transplantation
. It was evaluated whether mesenchymal stromal cells can be used for the treatment and prophylaxis of graft-versus-host diseases
. The evidence is very uncertain about the therapeutic effect of mesenchymal stromal cells to treat graft-versus-host diseases on the all-cause mortality and complete disappear of chronic acute graft-versus-host diseases. Mesenchymal stromal cells may result in little to no difference in the all-cause mortality, relapse of malignant disease and incidence of acute and chronic graft-versus-host diseases if they are used for prophylactic reason.
Moreover, it was seen that platelet transfusions
for people undergoing a chemotherapy or a stem cell transplantation for the prevention of bleeding events had different effects on the number of participants with a bleeding event, the number of days on which a bleeding occurred, the mortality secondary to bleeding and the number of platelet transfusions depending on the way they were used (therapeutic, depending on a threshold, different dose schedules or prophylactic).
Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized.
Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy.
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.
Scientists evaluated whether positron-emission-tomography
scans between the chemotherapy cycles can be used to make assumptions about the survival. The evidence is very uncertain about the effect of negative (= good prognosis) or positive (= bad prognosis) interim PET scan results on the progression-free survival. Negative interim PET scan results may result in an increase in progression-free survival compared if the adjusted result was measured. Negative interim PET scan results probably result in a large increase in the overall survival compared to those with a positive interim PET scan result.
Current research evaluated whether Nivolumab
can be used for the treatment of a Hodgkin's lymphoma. The evidence is very uncertain about the effect of Nivolumab for patients with a Hodgkin's lymphoma on the overall survival, the quality of life, the survival without a progression, the response rate (=complete disappear) and grade 3 or 4 serious adverse events.
, 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.
It is used to address both the direct symptoms of lymphoma and many unwanted side effects that arise from treatments.
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.
For these reasons, palliative care is especially important for people requiring bone marrow transplants.
Adding physical exercises to the standard treatment for adult patients with haematologicl malignancies like lymphomas may result in little to no difference in the mortality, the quality of life and the physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect on anxiety and serious adverse events.
Deaths from lymphomas and multiple myeloma per million persons in 2012
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 5%, and Hodgkin lymphoma in particular accounts for less than 1% of all cases of cancer in the United States.
Because the whole system is part of the body's immune system, people with a weakened immune system such as from HIV infection or from certain drugs or medication also have a higher number of cases of lymphoma.
published the first description of lymphoma in 1832, specifically of the form named after him.
Since then, many other forms of lymphoma have been described.
The term "lymphoma" is from Latin lympha ("water") and from Greek -oma ("morbid growth, tumor").
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 applicable way, such as testing a new drug in people. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for people, or appropriate care in remission or after cures. Hundreds of clinical trials
are being planned or conducted at any given time.
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 people with the disease,
but can improve scientists' understanding of lymphoma and form the foundation for future, more effective treatments.
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