Lymphoma

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Lymphoma
Classification and external resources
Lymphoma macro.jpg
ICD-10 C81-C96
ICD-9 202.8
ICD-O: 9590–9999
MedlinePlus 000580 000581
MeSH D008223

Lymphoma is a group of blood cell tumors that develop from lymphocytes.[1] It is sometimes used to refer to just the cancerous ones rather than all tumors.[1] Symptoms may include: enlarged lymph nodes that are not generally painful, fevers, sweats, itchiness, weight loss and feeling tired among others.[2][3] The sweats are most common at night.[2][3]

There are two main types: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL),[4] with two others, multiple myeloma and immunoproliferative diseases, also included by the World Health Organization within the category.[5] Non-Hodgkin lymphoma makes up about 90% of cases and includes a large number of sub-types.[4][6] Lymphomas are part of the broader group of neoplasms called tumors of the hematopoietic and lymphoid tissues.[7]

Risk factors for HL include: infection with Epstein-Barr virus and having other in the family with the disease.[2] Risk factors for NHL include: autoimmune diseases, HIV/AIDS, infection with human T-lymphotropic virus, eating a large amount of meat and fat, as well as immunosuppressant medications and some pesticides.[3] They are usually diagnosed by blood, urine, or bone marrow testing.[3] A biopsy of a lymph node may also be useful.[2][3] Medical imaging then may be done to determine if and where the cancer has spread.[2][3] This spread can occur to many other organs including: lungs, liver, and brain.[2][3]

Treatment may involve some combination of chemotherapy, radiation therapy, targeted therapy and surgery.[2][3] In NHL the blood may become so thick with protein that a procedure called plasmapheresis is needed.[3] Watchful waiting may be appropriate for certain types.[3] Some types are curable.[4] The overall five-year survival rate in the United States for HL is 85%[8] while that for NHL is 69%.[9] Worldwide, lymphomas developed in 566,000 people in 2012 and caused 305,000 deaths.[5] They make up 3-4% of all cancers, making them as a group the 7th most common form.[5][10] In children they are the third most common cancer.[11] They occur more often in the developed world than the developing world.[5]

Signs and symptoms[edit]

Lymphoma and lymphatic system

Lymphoma presents with certain non-specific symptoms. If symptoms are persistent, lymphoma needs to be excluded medically.

Diagnosis[edit]

Lymph node with mantle cell lymphoma (low power view, H&E)

Lymphoma is definitively diagnosed by a lymph node biopsy, meaning a partial or total excision of a lymph node that is then examined under the microscope.[14] 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:

Several classification systems have existed for lymphoma. These systems use histological findings and other findings to divide lymphoma into different categories. The classification of 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 that the cell arises from.

Hodgkin lymphoma[edit]

Main article: Hodgkin lymphoma

Hodgkin lymphoma is one of the best-known types of lymphoma,[citation needed] and differs from other forms of lymphoma in its prognosis and several pathological characteristics. A division into Hodgkin and non-Hodgkin lymphomas is used in several formal classification systems. A Hodgkin lymphoma is marked by the presence of a type of cell called the Reed-Sternberg cell.[15][16]

WHO classification[edit]

The current accepted definition is the WHO classification, published in 2001 and updated in 2008,[17][18] 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 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.

Subtypes[edit]

Working Formulation[edit]

Main article: Working Formulation

First proposed in 1982, the Working Formulation 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 or B-cell lymphomas. It was widely accepted at the time of its publication but is now obsolete.[19] It is still used by some cancer agencies for compilation of lymphoma statistics and historical rate comparisons.[citation needed]

Other[edit]

  • 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.[20]
  • ICD-O (codes 9590–9999, details at Archived June 27, 2004 at the Wayback Machine)
  • ICD-10 (codes C81-C96, details at who.int)

Subtypes[edit]

There are many forms of lymphoma. 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).[21]

Lymphoma subtypes.[22]
Lymphoma type Relative incidence[22] Histopathology[22] Immunophenotype Overall
5-year
survival
Other comments[22]
Precursor T-cell leukemia/lymphoma 40% of lymphomas in childhood. 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. Most common in adolescent males.
Follicular lymphoma 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%[23] Occurs in older adults. Usually involves lymph nodes, bone marrow and spleen. Associated with t(14;18) translocation overexpressing Bcl-2. Indolent
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%[24] 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 intermediate size growing in diffuse pattern CD5 50%[25] to 70%[25] 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.
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 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.
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%[27] 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 Pautrier microabscesseses. CD4 75%[28] Localized or more generalized skin symptoms. Generally indolent. In a more aggressive variant, Sézary's disease, there is skin erythema and peripheral blood involvement.
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.

Staging[edit]

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)
Diagram showing common sites where lymphoma spreads

After a diagnosis and before treatment, a cancer is staged. This refers to deducing how far the cancer has spread, in local tissue and to other 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.[citation needed]

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 the presence of lymphoma in two or more lymph nodes, III spread of the lymphoma to both sides of the diaphragm, and IV to tissue outside a lymph node.[citation needed]

A CT scan or PET scan are imaging modalities used to stage a cancer.[citation needed]

Treatment[edit]

Prognosis and treatment is different for HL and between all the different forms of NHL,[29] and also depends on the grade of tumour, referring to how quickly a cancer replicates. Paradoxically, high-grade lymphomas are more readily treated and have better prognoses .[citation needed] A well-known example of a high-grade tumour is that of Burkitt's lymphoma, which is a high-grade tumour that has been known to double within days, but is readily treated.

Low-grade lymphomas[edit]

Many low-grade lymphomas remain indolent for many years. Treatment of the non-symptomatic patient is often avoided. In these forms of lymphoma,[which?] watchful waiting is often the initial course of action. This is carried out because the harms and risks of treatment outweigh the benefits.[30] 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.

High-grade lymphomas[edit]

Treatment of some other, more aggressive, forms of lymphoma[which?] can result in a cure in the majority of cases, but the prognosis for patients with a poor response to therapy is worse.[31] Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or R-CHOP regimen.

Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized.[32] Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy.[33] Chemotherapy used includes the ABVD regimen.

Palliative care[edit]

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.[34][35] It is used to address both the direct symptoms of lymphoma and many unwanted side-effects that arise from treatments.[36][37] 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.[36][38][39][40] For these reasons, palliative care is especially important for patients requiring bone marrow transplants.[41][42]

Prognosis[edit]

The lymph nodes where lymphoma most commonly develops
5-year relative survival by stage at diagnosis[43]
Stage at diagnosis 5-year relative
survival (%)
Percentage
of cases (%)
Localized (confined to primary site) 82.1 27
Regional (spread to regional lymph nodes) 77.5 19
Distant (cancer has metastasized) 59.9 45
Unknown (unstaged) 67.5 9

Epidemiology[edit]

Age-standardized death from lymphomas and multiple myeloma per 100,000 inhabitants in 2004.[44]
  no data
  less than 1.8
  1.8–3.6
  3.6–5.4
  5.4–7.2
  7.2–9
  9–10.8
  10.8–12.6
  12.6–14.4
  14.4–16.2
  16.2–18
  18–19.8
  more than 19.8

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.[45]

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.[46]

History[edit]

Thomas Hodgkin published the first description of lymphoma in 1832, specifically of the form named after him, Hodgkin's lymphoma.[47] Since then, many other forms of lymphoma have been described, grouped under several proposed classifications. The 1982 Working formulation became very popular. It introduced the category non-Hodgkin lymphoma, divided into 16 diseases. However, because these 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 forms of lymphoma divided into four broad groups.[17]

As an alternative to the American Lakes-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.[48]

Research directions[edit]

Significant research into the causes, prevalence, diagnosis, treatment, and prognosis of lymphoma is being performed. Hundreds of clinical trials are being planned or conducted at any given time.[49] 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.

In general, there are two types of lymphoma research: clinical or translational research and basic research. Clinical/translational research focuses on studying the disease in a defined and generally immediately patient-applicable way, such as testing a new drug in patients. By contrast, 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[50] but can improve scientists' understanding of lymphoma and form the foundation for future, more effective treatments.

Other animals[edit]

Main article: Lymphoma in animals

For a discussion of lymphoma in animals other than humans see the above link.

References[edit]

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External links[edit]