Lymphoma is a group of blood and lymph tumors that develop from

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

s (a type of

white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

). The name typically refers to just the

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

ous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes,

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

, drenching sweats, unintended weight loss,

itching An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night. Many subtypes of lymphomas are known. The two main categories of lymphomas are the

non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredn ...

(NHL) (90% of cases) and

Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...

(HL) (10%). Lymphomas,

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

s and myelomas are a part of the broader group of

tumors of the hematopoietic and lymphoid tissues Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...

. Risk factors for Hodgkin lymphoma include infection with

Epstein–Barr virus The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...

and a history of the disease in the family. Risk factors for common types of non-Hodgkin lymphomas include

autoimmune disease An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

, infection with

human T-lymphotropic virus The primate T-lymphotropic viruses (PTLVs) are a group of retroviruses that infect primates, using their lymphocytes to reproduce. The ones that infect humans are known as human T-lymphotropic virus (HTLV), and the ones that infect Old World monk ...

immunosuppressant medication Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

s, and some

pesticide Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for approximately 50% of all p ...

s. Eating large amounts of red meat and

tobacco smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...

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 Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...

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 Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

proton therapy In medicine, proton therapy, or proton radiotherapy, is a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often to treat cancer. The chief advantage of proton therapy over other types of external beam ...

targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy (oncology), hormonal therapy and cytotoxic chemotherapy. As a form of molecular medici ...

, 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 Plasmapheresis (from the Greek language, Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the ...

is performed to remove the protein.

Watchful waiting Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed. Related terms include ''expe ...

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 The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surv ...

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 A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...

than in the

developing world A developing country is a sovereign state with a less-developed industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. There is also no clear agreeme ...

Signs and symptoms

Diagram showing the lymph nodes lymphoma most commonly develops in CRUK 311

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 Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In c ...

or swelling of lymph nodes, is the primary presentation in lymphoma. It is generally painless. *

B symptoms B symptoms are a set of symptoms, namely fever, night sweats, and unintentional weight loss, that can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. These symptoms are not specific to lymphomas, especially each one considered ...

(systemic symptoms) – can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. They consist of: **

Fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

Night sweats Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the horm ...

Weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

* Other symptoms: **

Anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

, bleeding, increased susceptibility to infections ** Loss of appetite or anorexia **

Fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

** Respiratory distress or dyspnea **

Itching An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

Diagnosis

Lymphoma is definitively diagnosed by a lymph-node biopsy, meaning a partial or total excision of a

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

examined under the microscope. This examination reveals

histopathological Histopathology (compound of three Greek language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...

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 Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose. This can be done on tissue section (fresh or fixed tissue), cell suspensio ...

Flow cytometry Flow cytometry (FC) is a technique used to detect and measure the physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the ...

* Fluorescence ''in situ'' hybridization testing

Classification

According to the World Health Organization (WHO), lymphoma classification should reflect in which lymphocyte population the neoplasm arises.Manli Jiang, N. Nora Bennani, and Andrew L. Feldman. Lymphoma classification update: T-cell lymphomas, Hodgkin lymphoma, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol. 2017 Mar; 10(3): 239–249. Author Manuscript. 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. Lymphoma can also spread to the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

, often around the brain in the

meninges In anatomy, the meninges (; meninx ; ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in the subarachnoid spac ...

, known as lymphomatous meningitis (LM).

Hodgkin lymphoma

Hodgkin lymphoma accounts for about 15% of lymphomas. It differs from other forms of lymphomas in its

prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...

and several

pathological Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

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 Reed–Sternberg cells (also known as lacunar histiocytes for certain types) are distinctive, giant cells found with light microscopy in biopsies from individuals with Hodgkin lymphoma. They are usually derived from B lymphocytes, classicall ...

Non-Hodgkin lymphomas

Non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredn ...

s, 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 A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and i ...

(i.e.,

B cells B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...

, NK cells, and histiocytic-dendritic cells) in which one or more of these cell types is infected with the

(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 Burkitt's lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa ...

; 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.

WHO classification

The WHO classification, published in 2001 and updated in 2008, 2017, and 2022, 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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

molecular A molecule is a group of two or more atoms that are held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemistry, ...

, or

cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

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 Burkitt's lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa ...

), causing rapid deterioration and death. However, most of the aggressive lymphomas respond well to treatment and are curable. The

, therefore, depends on the correct diagnosis and classification of the disease, which is established after examination of a biopsy by a

pathologist Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

(usually a hematopathologist).

Lymphoma subtypes (WHO 2008)

* B-cell chronic lymphocytic leukemia/small cell lymphoma :: 3–4% of lymphomas in adults :: Small resting lymphocytes mixed with variable numbers of large activated cells, lymph nodes diffusely effaced :: CD5, surface

immunoglobulin An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

:: 5-year survival rate 50%. :: Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, most patients have peripheral blood involvement, indolent *

B-cell prolymphocytic leukemia B-cell prolymphocytic leukemia, referred to as B-PLL, is a rare blood cancer. It is a more aggressive, but still treatable, form of leukemia. Specifically, B-PLL is a prolymphocytic leukemia (PLL) that affects prolymphocytes – immature forms ...

* Lymphoplasmacytic lymphoma (such as

Waldenström macroglobulinemia Waldenström macroglobulinemia ( , ) is a type of cancer affecting two types of white blood cells: lymphoplasmacytoid cells and plasma cells (both B cells). It is characterized by having high levels of a circulating antibody, immunoglobulin M (I ...

) * Splenic marginal zone lymphoma *

Hairy cell leukemia Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. The incidence of hairy cell leukemia (HCL) is 0.28-0.30 cases per 100,000 people in Europe and the United States and the pre ...

Plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances ca ...

neoplasms: ** Plasma cell myeloma (also known as multiple myeloma) **

Plasmacytoma Plasmacytoma is a plasma cell dyscrasia in which a plasma cell tumour grows within soft tissue or within the axial skeleton. The International Myeloma Working Group lists three types: Plasma cell dyscrasia#Solitary plasmacytoma, solitary plasma ...

** Monoclonal immunoglobulin deposition diseases ** Heavy chain diseases * Extranodal marginal zone B cell lymphoma, also called

MALT lymphoma MALT lymphoma (also called MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zon ...

:: About 5% of lymphomas in adults :: Variable cell size and differentiation, 40% show

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances ca ...

differentiation, homing of B cells to epithelium creates lymphoepithelial lesions. :: CD5,

CD10 Neprilysin (; also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10) and common acute lymphoblastic leukemia antigen (CALLA)) is an enzyme that in humans is encoded by the ''MME'' ge ...

, surface Ig :: Frequently occurs outside lymph nodes, very indolent, may be cured by local excision *

Nodal marginal zone B cell lymphoma Nodal marginal zone B cell lymphoma (NMZL) is an uncommon form of marginal-zone lymphoma that can produce colonization of the follicles in the lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the ad ...

Follicular lymphoma Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. This cancer is a form of Non-Hodgkin Lymphoma and it originates from the uncontrolled division of specific types of B-cells ( centrocytes ...

:: About 40% of lymphomas in adults :: Small "cleaved"

left Left may refer to: Music * ''Left'' (Hope of the States album), 2006 * ''Left'' (Monkey House album), 2016 * ''Left'' (Helmet album), 2023 * "Left", a song by Nickelback from the album ''Curb'', 1996 Direction * Left (direction), the relativ ...

cells ( centrocytes) mixed with large activated cells ( centroblasts), usually nodular ("follicular") growth pattern ::

, surface Ig :: About 72–77% :: Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, associated with t(14;18) translocation overexpressing

Bcl-2 Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first a ...

, indolent * Primary cutaneous follicle center lymphoma *

Mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of Non-Hodgkin lymphoma, non-Hodgkin's lymphoma, comprising about 6% of cases. It is named for the mantle zone of the lymph nodes where it develops. The term 'mantle cell lymphoma' was first adopted by Raffe ...

:: About 3–4% of lymphomas in adults :: Lymphocytes of small to intermediate size growing in diffuse pattern :: CD5 :: About 50 to 70% :::: 50% for limited stage: :::: 70% for advanced stage: :: Occurs mainly in adult males, usually involves lymph nodes, bone marrow, spleen and

GI tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

, associated with t(11;14) translocation overexpressing cyclin D1, moderately aggressive *

Diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 ...

, not otherwise specified :: About 40–50% of lymphomas in adults :: Variable, most resemble B cells of large germinal centers, diffuse growth pattern :: Variable expression of

and surface Ig ::

Five-year survival rate The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surv ...

60% :: Occurs in all ages, but most commonly in older adults, may occur outside lymph nodes, aggressive * Diffuse large B-cell lymphoma associated with chronic inflammation * Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified * Lymphomatoid granulomatosis *

Primary mediastinal (thymic) large B-cell lymphoma Primary mediastinal B-cell lymphoma, abbreviated PMBL or PMBCL, is a rare type of lymphoma that forms in the mediastinum (the space in between the lungs) and predominantly affects young adults. While it had previously been considered a subtype of ...

Intravascular large B-cell lymphoma Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other types of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, o ...

* ALK+ large B-cell lymphoma * Plasmablastic lymphoma * Primary effusion lymphoma *

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease 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 ...

* Burkitt lymphoma/leukemia :: < 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 Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

:: CD10, surface Ig :: Five-year survival rate 50% :: Endemic in Africa, sporadic elsewhere, more common in immunocompromised and children, often visceral involvement, highly aggressive * T-cell prolymphocytic leukemia * T-cell large granular lymphocyte leukemia * Aggressive NK cell leukemia * Adult T-cell leukemia/lymphoma * Extranodal NK/T-cell lymphoma, nasal type * Enteropathy-associated T-cell lymphoma * Hepatosplenic T-cell lymphoma *

Blastic NK cell lymphoma Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic disease#Hematological malignancies, hematologic malignancy. It was initially regarded as a form of lymphocyte-derived cutaneous lymphoma and alternatively named CD4+CD56+ h ...

* Mycosis fungoides/ Sézary syndrome :: Most common cutaneous lymphoid malignancy :: Usually small lymphoid cells with convoluted nuclei that often infiltrate the epidermis, creating Pautrier microabscesseses ::

CD4 In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...

5-year survival The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...

75% :: Localized or more generalized skin symptoms, generally indolent, in a more aggressive variant, Sézary's disease, skin

erythema Erythema (, ) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology inc ...

and peripheral blood involvement * Primary cutaneous CD30-positive T-cell lymphoproliferative disorders ** Primary cutaneous anaplastic large cell lymphoma ** Lymphomatoid papulosis * 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, often disseminated and generally aggressive * Angioimmunoblastic T-cell lymphoma *

Anaplastic large cell lymphoma Anaplastic large-cell lymphoma (ALCL) refers to a group of non-Hodgkin lymphomas in which aberrant T cells proliferate uncontrollably. Considered as a single entity, ALCL is the most common type of peripheral lymphoma and represents ~10% of all per ...

: ALK-positive and ALK-negative types * Breast plant-associated anaplastic large cell lymphoma * B-lymphoblastic leukemia/lymphoma not otherwise specified * B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities * T-lymphoblastic leukemia/lymphoma :: 15% of childhood

acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...

and 90% of lymphoblastic lymphoma. ::

Lymphoblast __NOTOC__ A lymphoblast is a modified naive lymphocyte with altered cell morphology. It occurs when the lymphocyte is activated by an antigen and increased in volume by nucleus and cytoplasm growth as well as new mRNA and protein synthesis. The ly ...

s 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 The thymus (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...

. It is highly associated with '' NOTCH1'' mutations, and is most common in

adolescent Adolescence () is a transitional stage of human physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated w ...

males. * Classical

s: ** Nodular sclerosis form of Hodgkin lymphoma :: Most common type of Hodgkin lymphoma :: Reed–Sternberg cell variants and inflammation, usually broad sclerotic bands that consist of collagen :: CD15,

CD30 CD30, also known as TNFRSF8 ( TNF receptor superfamily member 8), is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker for anaplastic large cell lymphoma. Function This receptor is expressed by activate ...

:: Most common in young adults, often arises in the

mediastinum The mediastinum (from ;: mediastina) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is a region that contains vital organs and structures within the thorax, mainly the heart and its vessels, the eso ...

or cervical lymph nodes ** Mixed cellularity Hodgkin lymphoma :: Second-most common form of Hodgkin 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

involved in 70% of cases ** Lymphocyte-rich ** Lymphocyte depleted or not depleted *

Nodular lymphocyte-predominant Hodgkin lymphoma Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a slow-growing CD20 positive form of Hodgkin lymphoma, a cancer of the immune system's B cells. NLPHL is an uncommon sub-type of Hodgkin lymphoma, making up 5-10% of Hodgkin lymphomas. It ...

* Associated with a primary immune disorder * Associated with the human immunodeficiency virus (

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

) * Post-transplant * Associated with

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

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 Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

, and

, 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 The Working Formulation is a classification of non-Hodgkin lymphomas, first proposed in 1982. It has become outdated in light of modern shifts in the understanding and classification of non-Hodgkin lymphomas, leading to the rise of new systems such ...

of 1982 was a classification of

. 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 made no distinction between

T-cell lymphoma T-cell lymphoma is a rare form of cancerous lymphoma affecting T cell, T-cells. Lymphoma arises mainly from the uncontrolled proliferation of lymphocytes, such as T-cells, and can become cancerous. T-cell lymphoma is categorized under Non-Hodgkin ...

s and

B-cell lymphoma The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are Tumors of the hematopoietic and lymphoid tissues, "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. ...

s. It was widely accepted at the time of its publication but by 2004 was 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 (codes 9590–9999) and

ICD-10 ICD-10 is the 10th revision of the International Classification of Diseases (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social cir ...

(codes C81-C96) are available.

Staging

DIagram showing where lymphoma can spread in the body CRUK 382

After a diagnosis and before treatment, 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, stage 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 the 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.

CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bloo ...

imaging modalities are used to stage 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 be killed by lymphoma than others. File:Nodular Mantle Cell Lymphoma - high power view - by Gabriel Caponetti.jpg, 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) File:Hodgkin lymphoma, nodular lymphocyte predominant - low power view - H&E - by Gabriel Caponetti.jpg, Hodgkin lymphoma, nodular lymphocyte predominant (low-power view): Notice the nodular architecture and the areas of "mottling". (H&E) File:Hodgkin lymphoma, nodular lymphocyte predominant - high power view - H&E - by Gabriel Caponetti.jpg, Hodgkin lymphoma, nodular lymphocyte predominant (high-power view): Notice the presence of L&H cells, also known as "popcorn cells". (H&E)

Differential diagnosis

Certain lymphomas ( extranodal NK/T-cell lymphoma, nasal type and type II enteropathy-associated T-cell lymphoma) can be mimicked by two benign diseases that involve the excessive proliferation of nonmalignant 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.

Treatment

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:

, for example, is a high-grade tumour known to double within days, and is highly responsive to treatment.

Low-grade

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 Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed. Related terms include ''expe ...

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 Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In c ...

. 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 Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in children and ad ...

in the treatment of follicular lymphoma rather than the wait-and-watch approach.

is not a desirable strategy for everyone, as it leads to significant distress and

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

in some people. It has been called "watch and worry".

High-grade

Treatment of some other, more aggressive, forms of lymphoma 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 Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...

. It was evaluated whether mesenchymal stromal cells can be used for the treatment and prophylaxis of

graft-versus-host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which rema ...

s. 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 transfusion Platelet transfusion, is the process of infusing platelet concentrate into the body via vein, to prevent or treat the bleeding in people with either a thrombocytopenia, low platelet count or poor platelet function. Often this occurs in people ...

s 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). Four chimeric antigen receptor T cell therapies are FDA-approved for non-Hodgkin lymphoma, including lisocabtagene maraleucel (for relapsed or refractory large B-cell lymphoma with two failed systemic treatments), axicabtagene ciloleucel,

tisagenlecleucel Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer (adoptive cell transfer). The most common serious ...

(for large B-cell lymphoma), and brexucabtagene autoleucel (for

mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of Non-Hodgkin lymphoma, non-Hodgkin's lymphoma, comprising about 6% of cases. It is named for the mantle zone of the lymph nodes where it develops. The term 'mantle cell lymphoma' was first adopted by Raffe ...

). These therapies come with certification and other restrictions.

Hodgkin lymphoma

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 Leland Stanford Junior University, commonly referred to as Stanford University, is a Private university, private research university in Stanford, California, United States. It was founded in 1885 by railroad magnate Leland Stanford (the eighth ...

. 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 Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

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 Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication in the class of immune checkpoint inhibitors. It selectively binds and blocks the programmed death-1 (PD-1) receptor on T cells, thereby facilitating their activation ...

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.

Palliative care

Palliative care Palliative care (from Latin root "to cloak") is an interdisciplinary medical care-giving approach aimed at optimizing quality of life and mitigating or reducing suffering among people with serious, complex, and often terminal illnesses. Man ...

, 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 with 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.

Supportive treatment

Adding physical exercises to the standard treatment for adult patients with haematological 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.

Prognosis

Epidemiology

Lymphoma is the most common form of

hematological malignancy Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...

, 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 5%, and Hodgkin lymphoma in particular accounts for less than 1% of all cases of cancer in the United States. Because the whole lymphatic 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.

History

Thomas Hodgkin 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 ("water") and from Greek ''-oma'' ("morbid growth, tumor").

Research

The two types of lymphoma research are clinical or

translational research Translational research (also called translation research, translational science, or, when the context is clear, simply translation) is research aimed at translating (converting) results in basic research into results that directly benefit humans ...

and

basic research Basic research, also called pure research, fundamental research, basic science, or pure science, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenome ...

. 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 Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

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. A study from

Lund University Lund University () is a Public university, public research university in Sweden and one of Northern Europe's oldest universities. The university is located in the city of Lund in the Swedish province of Scania. The university was officially foun ...

revealed that people with

tattoos A tattoo is a form of body modification made by inserting tattoo ink, dyes, or pigments, either indelible or temporary, into the dermis layer of the Human skin, skin to form a design. Tattoo artists create these designs using several Process of ...

are a high risk group for lymphoma, especially diffuse large B-cell non-Hodgkin lymphoma and follicular non-Hodgkin lymphoma. The risk of lymphoma was highest among those who had their first tattoo after 2021, regardless of the tattoo's size.

Other animals

References

External links

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