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The T-cell lymphomas are four types of lymphoma that affect T cells. These account for about one in ten cases of non-Hodgkin lymphoma.
They can be associated with Epstein Barr virus and Human T-cell leukemia virus-1.
Peripheral T-cell lymphoma refers to a group of T-cell lymphomas that develop away from the thymus.
Examples include:
- Cutaneous T-cell lymphomas
- Angioimmunoblastic T-cell lymphoma
- Extranodal natural killer/T-cell lymphoma, nasal type
- Enteropathy type T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
- Anaplastic large cell lymphoma
- Peripheral T-cell lymphoma-Not-Otherwise-Specified
In ICD-10, cutaneous T-cell lymphomas are classified separately.
One classification system for lymphomas divides the diseases according to the size of the white blood cells that has turned cancerous. The large-cell lymphomas have large cells. A large cell, in this context, has a diameter of 17 to 20 µm. Other groups of lymphomas in this system are the small-cell lymphomas and mixed-cell lymphomas.
The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.
B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.
Prognosis and treatment depends on the specific type of lymphoma as well as the stage and grade. Treatment includes radiation and chemotherapy. Early-stage indolent B-cell lymphomas can often be treated with radiation alone, with long-term non-recurrence. Early-stage aggressive disease is treated with chemotherapy and often radiation, with a 70-90% cure rate. Late-stage indolent lymphomas are sometimes left untreated and monitored until they progress. Late-stage aggressive disease is treated with chemotherapy, with cure rates of over 70%.
The symptoms of AIDS-related lymphoma can include: weight loss, fever, and night sweats.
Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure.
The median age of diagnosis is approximately fourth and fifth decades. The disease often arises in the oral cavity, particularly in HIV disease, but other sites include nasal cavity, gastrointestinal tract, skin, bone soft tissue, and lung. There is usually immunodeficiency, such as HIV, organ transplants, autoimmune diseases
Like Burkitt's lymphoma, the morphology has a "starry sky". However, the immunophenotype resembles plasma cells: CD45-, CD20-, CD79a+/-, PAX5-, CD38+, CD38+ and MUM1+. Ki67 is over 90%. EBV is positive in 75%; HHV-8 is negative.
There are numerous kinds of lymphomas involving B cells. The most commonly used classification system is the WHO classification, a convergence of more than one, older classification systems.
Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.
The four classes are:
- Extranodal T cell lymphoma
- Cutaneous T cell lymphomas: Sézary syndrome and Mycosis fungoides
- Anaplastic large cell lymphoma
- Angioimmunoblastic T cell lymphoma
More information on various classification schemes is in the main lymphoma article.
Plasmablastic lymphoma is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is CD20 negative, and has an immunophenotype that resembles plasma cells. In formal use, lymphomas with plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease and extracavitary HHV–8-positive lymphoma are not part of this category, although sometimes the literature has confused this point.
"MALT lymphoma" is an often multifocal disease in the organ of origin and is frequently macroscopically indistinguishable from other disease processes in the GI tract. Endoscopy is key to diagnosing "MALT lymphoma", with multiple biopsies of the visible lesions required, as well as samples of macroscopically normal tissue, termed gastric mapping. Histologically, there is expansion of the marginal zone compartment with development of sheets of neoplastic small lymphoid cells. The morphology of the neoplastic cells is variable with small mature lymphocytes, cells resembling centrocytes (centrocyte like cells), or marginal zone/monocytoid B cells. Plasmacytoid or plasmacytic differentiation is frequent. Lymphoid follicles are ubiquitous to "MALT lymphoma" but may be indistinct as they are often overrun or colonized by the neoplastic cells. Large transformed B cells are present scattered among the small cell population. If these large cells are present in clusters or sheets, a diagnosis of associated large B-cell lymphoma should be considered. A characteristic feature of MALT lymphoma is the presence of neoplastic cells within epithelial structures with associated destruction of the glandular architecture to form lymphoepithelial lesions.
"MALT lymphoma" may be difficult to distinguish from reactive infiltrates, and in some cases, multiple endoscopies are required before a confident diagnosis is reached. The Wotherspoon score, which grades the presence of histological features associated with "MALT lymphoma", is useful in expressing confidence in diagnosis at presentation.
Immunohistochemistry can be used to help distinguish "MALT lymphoma" from other small B-cell NHLs. B-cell-associated antigens such as CD19, CD20, CD22, and CD79a are usually expressed. In contrast to small lymphocytic lymphoma and MCL, staining for CD5 is usually negative, and these lymphomas can be further distinguished with CD23 (positive in small lymphocytic lymphoma) and CyclinD1 (positive in MCL).
Follicular lymphoma is a type of blood cancer. It is the most common of the indolent (slow-growing) non-Hodgkin's lymphomas, and the second-most-common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern. It is positive for the B-cell markers CD10, CD19, CD22, and usually CD20, but almost always negative for CD5.
There are several synonymous and obsolete terms for this disease, such as CB/CC lymphoma (Centroblastic and Centrocytic lymphoma), nodular lymphoma and Brill-Symmers Disease.
This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.
Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.
Diffuse large B-cell lymphoma encompasses a biologically and clinically diverse set of diseases, many of which cannot be separated from one another by well-defined and widely accepted criteria. The World Health Organization (WHO) classification system defines more than a dozen subtypes, each of which can be differentiated based on the location of the tumor, the presence of other cells within the tumor (such as T cells), and whether the patient has certain other illnesses related to DLBCL. One of these well-defined groupings of particular note is "primary mediastinal (thymic) large B cell lymphoma", which arises within the thymus or mediastinal lymph nodes.
In some cases, a tumor may share many features with both DLBCL and Burkitt's lymphoma. In these situations, the tumor is classified as simply “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma”. A similar situation can arise between DLBCL and Hodgkin's lymphoma; the tumor is then classified as “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin’s lymphoma”.
When a case of DLBCL does not conform to any of these subtypes, and is also not considered unclassifiable, then it is classified as “diffuse large B-cell lymphoma, not otherwise specified” (DLBCL, NOS). The majority of DLBCL cases fall into this category. Much research has been devoted to separating this still-heterogeneous group; such distinctions are usually made along lines of cellular morphology, gene expression, and immunohistochemical properties.
Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:
- Acute lymphoblastic leukemia
- Chronic lymphocytic leukemia
However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:
- B-cell leukemia
- T-cell leukemia
- NK-cell leukemia
The most common type of lymphoid leukemia is B-cell chronic lymphocytic leukemia.
Castleman disease (CD) is a lymphoproliferative disorder of unknown cause. CD is associated with an increased risk of B-cell lymphoma.
Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV) has been found in some cases of multicentric Castleman disease (MCD). The HHV8 can give rise to an increased number of plasmablast cells within the mantle zone of B-cell follicles. These plasmablasts express IgM-immunoglobulin light chains, most often of lambda subtype. These plasmablasts can give rise to a spectrum of abnormalities including progression to microlymphoma (microscopic clusters of plasmablast cells) or clinical lymphoma.
This type of lymphoma is predominantly seen in acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) but it can also occur in immunosuppression such as with organ transplantation or the elderly. The plasmablasts do not show rearranged immunoglobulin genes, and typically lack EBV infection.
The disease predominantly affects lymph nodes and the spleen, a pattern dissimilar to plasmablastic lymphoma of the oral cavity of AIDS which is not associated with HHV-8 infection. Despite traditional chemotherapy with CHOP (cyclophosphamide, doxorubicin, prednisone, vincristine), and the possible addition of antiviral therapy and inhibition of specific cellular targets including the use of rituximab, the prognosis in this lymphoma has been poor.
This lymphoma subtype has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. Similarly, this subtype is considered distinct from other lymphomas which have a plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, and extracavitary HHV–8-positive lymphoma.
HHV8 is also associated with Kaposi's sarcoma and with another subtype of lymphoma, primary effusion lymphoma, previously called body cavity-based lymphoma.
As other thyroid lesions, thyroid lymphoma affects predominantly females over 70 years of age with a history of Hashimoto's thyroiditis. Thus, Hashimoto's thyroiditis is considering as risk factor for thyroid lymphoma development.
The thyroid lymphoma manifests as rapidly enlarging neck mass causing respiratory difficulty. On physical examination, patients usually exhibit a firm thyroid and lymphadenopathy.
This disease is typically found and diagnosed in peripheral blood, and while it can involve any organ, it is usually found in the spleen, liver, and bone marrow.
Patients with Hodgkin's lymphoma may present with the following symptoms:
- Lymph nodes: the most common symptom of Hodgkin's is the painless enlargement of one or more lymph nodes, or lymphadenopathy. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph.
- Itchy skin
- Night sweats
- Unexplained weight loss
- Splenomegaly: enlargement of the spleen occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive, and the size of the spleen may fluctuate during the course of treatment.
- Hepatomegaly: enlargement of the liver, due to liver involvement, is present in about 5% of cases.
- Hepatosplenomegaly: the enlargement of both the liver and spleen caused by the same disease.
- Pain following alcohol consumption: classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon, occurring in only two to three percent of people with Hodgkin's lymphoma, thus having a low sensitivity. On the other hand, its positive predictive value is high enough for it to be regarded as a pathognomonic sign of Hodgkin lymphoma. The pain typically has an onset within minutes after ingesting alcohol, and is usually felt as coming from the vicinity where there is an involved lymph node. The pain has been described as either sharp and stabbing or dull and aching.
- Back pain: nonspecific back pain (pain that cannot be localised or its cause determined by examination or scanning techniques) has been reported in some cases of Hodgkin's lymphoma. The lower back is most often affected.
- Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count (as a result of bone marrow infiltration, increased trapping in the spleen etc.—i.e. decreased production, increased removal)
- Systemic symptoms: about one-third of patients with Hodgkin's disease may also present with systemic symptoms, including low-grade fever; night sweats; unexplained weight loss of at least 10% of the patient's total body mass in six months or less, itchy skin (pruritus) due to increased levels of eosinophils in the bloodstream; or fatigue (lassitude). Systemic symptoms such as fever, night sweats, and weight loss are known as B symptoms; thus, presence of fever, weight loss, and night sweats indicate that the patient's stage is, for example, 2B instead of 2A.
- Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein fever, or more simply "P-E fever". However, there is debate as to whether the P-E fever truly exists.
- Nephrotic syndrome can occur in individuals with Hodgkin's lymphoma and is most commonly caused by minimal change disease.
Diffuse large B-cell lymphoma is the most common of the large-cell lymphomas. MeSH now classifies the phrase "large-cell lymphoma" under "Diffuse large B cell lymphoma".
Many other B-cell lymphomas feature large cells:
- Angiocentric lymphoma
- Burkitt’s lymphoma
- Follicular large-cell lymphoma
- Immunoblastic lymphoma
- Intravascular large-cell lymphoma
- Primary mediastinal B-cell lymphoma
- T-cell–rich B-cell lymphoma
- Primary splenic lymphoma (rare)
- Primary central nervous system lymphomas, which are often diffuse large-B-cell lymphomas
Activated B-Cell Diffuse Large B-Cell Lymphoma, or ABC-DLBCL, is believed to be caused by aberrant activation of a critical intracellular pathway.
This intracellular signaling pathway involved in B-cell activation and proliferation stays constantly activated, driving lymphocytes to proliferate continuously.
The inhibition of this pathway can be induced by a drug known as NEMO Binding Domain, or NBD, a peptide causing increased cell death of malignant lymphocytes.
T-cell leukemia describes several different types of lymphoid leukemia which affect T cells.
Types include:
- Large granular lymphocytic leukemia
- Adult T-cell leukemia/lymphoma
- T-cell prolymphocytic leukemia
In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.
AIDS-related lymphoma describes lymphomas occurring in patients with acquired immunodeficiency syndrome (AIDS).
A lymphoma is a type of cancer arising from lymphoid cells. In AIDS, the incidences of non-Hodgkin's lymphoma, primary cerebral lymphoma and Hodgkin's disease are all increased. There are three different varieties of AIDS-related lymphoma: Diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, and Burkitt's lymphoma (small non-cleaved cell lymphoma).
Lymphoid leukemias — also called lymphocytic, lymphogenous, or lymphoblastic leukemias — are a group of leukemias affecting circulating lymphocytes, a type of white blood cells. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma). Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.
The majority of thyroid lymphomas are non–Hodgkin's B-cell lymphomas; the rest exhibit properties of T-cell lymphomas .
- Diffuse large B-cell lymphoma with marginal zone
- Diffuse large B-cell lymphoma without marginal zone
- Marginal zone В-cell lymphoma of mucosa-associated lymphoid tissue (MALT)
- Follicular lymphoma