View source for Medicine:Lymphoma

{{Short description|Hematologic cancer that affects lymphocytes}}
{{Infobox medical condition (new)
| name            = Lymphoma
| image           = Lymphoma macro.jpg
| caption         = Follicular lymphoma replacing a [[Biology:Lymph node|lymph node]]
| field           = [[Medicine:Hematology|Hematology]] and [[Medicine:Oncology|oncology]]
| symptoms        = [[Medicine:Lymphadenopathy|Enlarged lymph node]]s, [[Medicine:Fever|fever]], sweats, unintended weight loss, itching, feeling tired<ref name=HL2014/><ref name=NHL2014/>
| complications   =
| onset           =
| duration        =
| causes          =
| risks           = [[Biology:Epstein–Barr virus|Epstein–Barr virus]], [[Medicine:Autoimmune disease|autoimmune disease]]s, HIV/AIDS, [[Chemistry:Tobacco smoking|tobacco smoking]]<ref name=NHL2014/><ref name=Kam2013/>
| diagnosis       = Lymph node biopsy<ref name=HL2014/><ref name=NHL2014/>
| differential    =
| prevention      =
| treatment       = [[Medicine:Chemotherapy|Chemotherapy]], [[Physics:Radiation therapy|radiation therapy]], [[Physics:Proton therapy|proton therapy]], targeted therapy, [[Medicine:Surgery|surgery]]<ref name=HL2014/><ref name=NHL2014/>
| medication      =
| prognosis       = Average five year survival 85% (USA)<ref name=seer/>
| frequency       = 4.9 million (2015)<ref name=GBD2015Pre>{{cite journal | vauthors = Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, etal | collaboration = GBD 2015 Disease and Injury Incidence and Prevalence Collaborators | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 }}</ref>
| deaths          = 204,700 (2015)<ref name=GBD2015De>{{cite journal | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 | last1 = Wang | first1 = Haidong | last2 = Naghavi | first2 = Mohsen | last3 = Allen | first3 = Christine | last4 = Barber | first4 = Ryan M. | last5 = Bhutta | first5 = Zulfiqar A. | last6 = Carter | first6 = Austin | last7 = Casey | first7 = Daniel C. | last8 = Charlson | first8 = Fiona J. | last9 = Chen | first9 = Alan Zian | last10 = Coates | first10 = Matthew M. | last11 = Coggeshall | first11 = Megan | last12 = Dandona | first12 = Lalit | last13 = Dicker | first13 = Daniel J. | last14 = Erskine | first14 = Holly E. | last15 = Ferrari | first15 = Alize J. | last16 = Fitzmaurice | first16 = Christina | last17 = Foreman | first17 = Kyle | last18 = Forouzanfar | first18 = Mohammad H. | last19 = Fraser | first19 = Maya S. | last20 = Fullman | first20 = Nancy | last21 = Gething | first21 = Peter W. | last22 = Goldberg | first22 = Ellen M. | last23 = Graetz | first23 = Nicholas | last24 = Haagsma | first24 = Juanita A. | last25 = Hay | first25 = Simon I. | last26 = Huynh | first26 = Chantal | last27 = Johnson | first27 = Catherine O. | last28 = Kassebaum | first28 = Nicholas J. | last29 = Kinfu | first29 = Yohannes | last30 = Kulikoff | first30 = Xie Rachel | display-authors = 1 }}</ref>
}}
<!-- Definition and Symptoms -->
'''Lymphoma''' is a group of blood and lymph tumors that develop from [[Biology:Lymphocyte|lymphocyte]]s (a type of [[Biology:White blood cell|white blood cell]]).<ref name=D2000/> The name typically refers to just the [[Medicine:Cancer|cancer]]ous versions rather than all such tumours.<ref name=D2000>{{cite book|last1=Taylor|first1=Elizabeth J.|title=Dorland's Illustrated medical dictionary.|date=2000|publisher=Saunders|location=Philadelphia|isbn=0721662544|page=[https://archive.org/details/trent_0116404640520/page/1038 1038]|edition=29th|url=https://archive.org/details/trent_0116404640520/page/1038}}</ref> Signs and symptoms may include [[Medicine:Lymphadenopathy|enlarged lymph node]]s, [[Medicine:Fever|fever]], drenching sweats, unintended weight loss, itching, and constantly feeling tired.<ref name=HL2014/><ref name=NHL2014/> The enlarged lymph nodes are usually painless.<ref name=HL2014/> The sweats are most common at night.<ref name=HL2014>{{cite web|title=General Information About Adult Hodgkin Lymphoma|url=http://www.cancer.gov/cancertopics/pdq/treatment/adulthodgkins/Patient/page1/AllPages|website=National Cancer Institute|access-date=20 June 2014|date=2014-04-23|url-status=live|archive-url=https://web.archive.org/web/20140705231802/http://www.cancer.gov/cancertopics/pdq/treatment/adulthodgkins/Patient/page1/AllPages|archive-date=5 July 2014}}</ref><ref name=NHL2014>{{cite web|title=General Information About Adult Non-Hodgkin Lymphoma|url=http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/Patient/page1/AllPages|website=National Cancer Institute|access-date=20 June 2014|date=2014-04-25|url-status=live|archive-url=https://web.archive.org/web/20140705115658/http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/Patient/page1/AllPages|archive-date=5 July 2014}}</ref>

<!-- Classification -->
Many subtypes of lymphomas are known.<ref>{{cite book|author1=Aditya Bardia|title=Johns Hopkins Patients' Guide to Lymphoma|date=2010|publisher=Jones & Bartlett Learning|isbn=9781449631413|page=6|url=https://books.google.com/books?id=IG05tEhKGq4C&pg=PA6|url-status=live|archive-url=https://web.archive.org/web/20170910174453/https://books.google.com/books?id=IG05tEhKGq4C&pg=PA6|archive-date=2017-09-10}}</ref> The two main categories of lymphomas are the [[Medicine:Non-Hodgkin lymphoma|non-Hodgkin lymphoma]] (NHL) (90% of cases)<ref name="Society2013" /><ref>{{cite web|date=2011-02-02|title=Lymphoma|url=http://www.cancer.gov/dictionary?cdrid=45368|url-status=live|archive-url=https://web.archive.org/web/20140705001350/http://www.cancer.gov/dictionary?CdrID=45368|archive-date=5 July 2014|access-date=13 June 2014|website=NCI}}</ref> and [[Medicine:Hodgkin lymphoma|Hodgkin lymphoma]] (HL) (10%).<ref name=Society2013>{{cite book|title=The Lymphoma Guide Information for Patients and Caregivers|date=2013|website=Leukemia and Lymphoma Society|url=http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/lymphoma/pdf/lymphomaguide.pdf|access-date=20 June 2014|url-status=live|archive-url=https://web.archive.org/web/20140714194242/http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/lymphoma/pdf/lymphomaguide.pdf|archive-date=14 July 2014}}</ref>  Lymphomas, [[Medicine:Leukemia|leukemia]]s and myelomas are a part of the broader group of tumors of the hematopoietic and lymphoid tissues.<ref>{{cite journal | vauthors = Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD | display-authors = 6 | title = The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes | journal = Blood | volume = 114 | issue = 5 | pages = 937–951 | date = July 2009 | pmid = 19357394 | doi = 10.1182/blood-2009-03-209262 | s2cid = 3101472 | doi-access = free }}</ref>

<!-- Cause and Diagnosis -->
Risk factors for Hodgkin lymphoma include infection with [[Biology:Epstein–Barr virus|Epstein–Barr virus]] and a history of the disease in the family.<ref name=HL2014/> Risk factors for common types of non-Hodgkin lymphomas include [[Medicine:Autoimmune disease|autoimmune disease]]s, HIV/AIDS, infection with [[Biology:Human T-lymphotropic virus|human T-lymphotropic virus]], immunosuppressant medications, and some [[Biology:Pesticide|pesticide]]s.<ref name=NHL2014/><ref>{{cite journal | vauthors = Hu L, Luo D, Zhou T, Tao Y, Feng J, Mei S | title = The association between non-Hodgkin lymphoma and organophosphate pesticides exposure: A meta-analysis | journal = Environmental Pollution | volume = 231 | issue = Pt 1 | pages = 319–328 | date = December 2017 | pmid = 28810201 | doi = 10.1016/j.envpol.2017.08.028 }}</ref> In 2014, the [[Organization:International Agency for Research on Cancer|International Agency for Research on Cancer]] updated its classification of [[Chemistry:Trichloroethylene|trichloroethylene]] to Group 1, indicating that sufficient evidence exists that it causes cancer of the kidney in humans as well as some evidence of cancer of the liver and non-Hodgkin's lymphoma.<ref>{{cite book|url=http://monographs.iarc.fr/ENG/Monographs/vol106/mono106-001.pdf |title=Trichloroethylene (IARC Summary & Evaluation, Volume 106, 2014) |publisher=iarc.fr |access-date=2016-03-08}}</ref> Eating large amounts of red meat and [[Chemistry:Tobacco smoking|tobacco smoking]] may also increase the risk.<ref name=Kam2013>{{cite journal | vauthors = Kamper-Jørgensen M, Rostgaard K, Glaser SL, Zahm SH, Cozen W, Smedby KE, Sanjosé S, Chang ET, Zheng T, La Vecchia C, Serraino D, Monnereau A, Kane EV, Miligi L, Vineis P, Spinelli JJ, McLaughlin JR, Pahwa P, Dosman JA, Vornanen M, Foretova L, Maynadie M, Staines A, Becker N, Nieters A, Brennan P, Boffetta P, Cocco P, Hjalgrim H | display-authors = 6 | title = Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph) | journal = Annals of Oncology | volume = 24 | issue = 9 | pages = 2245–2255 | date = September 2013 | pmid = 23788758 | pmc = 3755332 | doi = 10.1093/annonc/mdt218 }}</ref><ref>{{cite journal | vauthors = Yang L, Dong J, Jiang S, Shi W, Xu X, Huang H, You X, Liu H | display-authors = 6 | title = Red and Processed Meat Consumption Increases Risk for Non-Hodgkin Lymphoma: A PRISMA-Compliant Meta-Analysis of Observational Studies | journal = Medicine | volume = 94 | issue = 45 | pages = e1729 | date = November 2015 | pmid = 26559248 | pmc = 4912242 | doi = 10.1097/MD.0000000000001729 }}</ref><ref>{{cite journal | vauthors = Solimini AG, Lombardi AM, Palazzo C, De Giusti M | title = Meat intake and non-Hodgkin lymphoma: a meta-analysis of observational studies | journal = Cancer Causes & Control | volume = 27 | issue = 5 | pages = 595–606 | date = May 2016 | pmid = 27076059 | doi = 10.1007/s10552-016-0745-2 | hdl = 11573/865541 | s2cid = 17430078 | hdl-access = free }}</ref> Diagnosis, if enlarged lymph nodes are present, is usually by lymph node biopsy.<ref name=HL2014/><ref name=NHL2014/> Blood, urine, and bone marrow testing may also be useful in the diagnosis.<ref name=NHL2014/> [[Medicine:Medical imaging|Medical imaging]] may then be done to determine if and where the cancer has spread.<ref name=HL2014/><ref name=NHL2014/> Lymphoma most often spreads to the lungs, liver, and brain.<ref name=HL2014/><ref name=NHL2014/>

<!-- Treatment, prognosis, and epidemiology -->
Treatment may involve one or more of the following: [[Medicine:Chemotherapy|chemotherapy]], [[Physics:Radiation therapy|radiation therapy]], [[Physics:Proton therapy|proton therapy]], targeted therapy, and surgery.<ref name=HL2014/><ref name=NHL2014/> In some non-Hodgkin lymphomas, an increased amount of protein produced by the lymphoma cells causes the blood to become so thick that [[Medicine:Plasmapheresis|plasmapheresis]] is performed to remove the protein.<ref name=NHL2014/> [[Social:Watchful waiting|Watchful waiting]] may be appropriate for certain types.<ref name=NHL2014/> The outcome depends on the subtype with some being curable and treatment prolonging survival in most.<ref name=Society2013/> The [[Medicine:Five-year survival rate|five-year survival rate]] in the United States for all Hodgkin lymphoma subtypes is 85%,<ref name="seer">{{cite web |url=http://seer.cancer.gov/statfacts/html/hodg.html |title=Hodgkin Lymphoma—SEER Stat Fact Sheets |publisher=Seer.cancer.gov |access-date=2012-08-26 |url-status=live |archive-url=https://web.archive.org/web/20121017064937/http://seer.cancer.gov/statfacts/html/hodg.html |archive-date=2012-10-17 }}</ref> while that for non-Hodgkin lymphomas is 69%.<ref>{{cite web|title=SEER Stat Fact Sheets: Non-Hodgkin Lymphoma|url=http://seer.cancer.gov/statfacts/html/nhl.html|website=NCI|access-date=18 June 2014|url-status=live|archive-url=https://web.archive.org/web/20140706125600/http://www.seer.cancer.gov/statfacts/html/nhl.html|archive-date=6 July 2014}}</ref> Worldwide, lymphomas developed in 566,000 people in 2012 and caused 305,000 deaths.<ref name=WCR2014>{{cite book|title=World Cancer Report 2014.|date=2014|publisher=World Health Organization|isbn=978-9283204299|pages=Chapter 5.13}}</ref> They make up 3–4% of all cancers, making them as a group the seventh-most common form.<ref name=WCR2014/><ref name=Rob2013>{{cite book|last1=Marcus|first1=Robert|title=Lymphoma : pathology, diagnosis and treatment|date=2013|isbn=9781107010598|page=1|publisher=Cambridge University Press |edition=Second|url=https://books.google.com/books?id=SX0LAgAAQBAJ&pg=PP1|url-status=live|archive-url=https://web.archive.org/web/20150906082735/https://books.google.com/books?id=SX0LAgAAQBAJ&lpg=PP1|archive-date=2015-09-06}}</ref> In children, they are the third-most common cancer.<ref>{{cite book|last1=Tepper|first1=John E. Niederhuber, James O. Armitage, James H. Doroshow, Michael B. Kastan, Joel E.|title=Abeloff's clinical oncology|date=2014|isbn=978-1455728657|page=Chapter 97|edition=Fifth|chapter=Childhood lymphoma}}</ref> They occur more often in the developed world than the developing world.<ref name=WCR2014/>

==Signs and symptoms==
[[File:Diagram showing the lymph nodes lymphoma most commonly develops in CRUK 311.svg|thumb|right|The lymph nodes where lymphoma most commonly develops]]
[[File:Blausen 0626 lymphoma.png|thumb|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.
* [[Medicine:Lymphadenopathy|Lymphadenopathy]]<ref name=lymphoma.org>{{cite web|title=About Lymphoma|url=http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6299689|publisher=Lymphoma Research Foundation|access-date=22 December 2012|url-status=live|archive-url=https://web.archive.org/web/20121202175216/http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6299689|archive-date=2 December 2012}}</ref><ref name=lymphoma.about.com/> 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:
** [[Medicine:Fever of unknown origin|Fever]]<ref name=lymphoma.org/><ref name=lymphoma.about.com/>
** [[Medicine:Night sweats|Night sweats]]<ref name=lymphoma.org/><ref name=lymphoma.about.com/>
** Weight loss<ref name=lymphoma.org/><ref name=lymphoma.about.com/>
* Other symptoms:
** [[Medicine:Anemia|Anemia]], bleeding, increased susceptibility to infections<ref>{{Cite journal|date=2019-11-09|title=Primary CNS Lymphoma: Overview, Etiology, Epidemiology|url=https://emedicine.medscape.com/article/1157638-overview}}</ref>
** Loss of appetite or anorexia<ref name=lymphoma.about.com>{{cite web |url=http://lymphoma.about.com/od/symptoms/tp/warningsigns.htm |title=Warning Signs of Lymphoma — First Signs of Lymphoma |publisher=Lymphoma.about.com |access-date=2012-12-01 |url-status=live |archive-url=https://web.archive.org/web/20121118231746/http://lymphoma.about.com/od/symptoms/tp/warningsigns.htm |archive-date=2012-11-18 }}</ref>
** Fatigue<ref name=lymphoma.org/><ref name=lymphoma.about.com/>
** Respiratory distress or dyspnea<ref name=lymphoma.about.com/>
** Itching<ref name=lymphoma.org/><ref name=lymphoma.about.com/>

=== Mouth ===
Asymptomatic soft swelling, which may or may not be ulcerated, is primarily seen on the tonsils, buccal mucosa, palate, gums, salivary glands, tongue, the floor of the mouth, and retromolar region.{{citation needed|date=November 2021}}

==Diagnosis==
[[File:Touch prep on a lymph node.jpg|thumb|An initial evaluation of a suspected lymphoma is to make a "touch prep" wherein a glass slide is lightly pressed against excised lymphoid tissue, and subsequently stained (usually H&E stain) for evaluation under light microscopy.]]
Lymphoma is definitively diagnosed by a lymph-node biopsy, meaning a partial or total excision of a [[Biology:Lymph node|lymph node]] examined under the microscope.<ref name=diag.about.com>{{cite web|last=Mallick|first=Indranil|title=How Is Lymphoma Diagnosed?|url=http://lymphoma.about.com/od/testsforlymphoma/p/diagnosis.htm|publisher=lymphoma.about.com|access-date=22 December 2012|url-status=live|archive-url=https://web.archive.org/web/20130116151305/http://lymphoma.about.com/od/testsforlymphoma/p/diagnosis.htm|archive-date=16 January 2013}}</ref> This examination reveals [[Medicine:Histopathology|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:
* [[Medicine:Immunophenotyping|Immunophenotyping]]
* [[Biology:Flow cytometry|Flow cytometry]]
* [[Biology:Fluorescence in situ hybridization|Fluorescence ''in situ'' hybridization]] testing

===Classification===
[[File:Hodgkin lymphoma, nodular lymphocyte predominant - low power view - H&E - by Gabriel Caponetti.jpg|thumb|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.<ref name=":0">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.</ref> Thus, neoplasms that arise from precursor lymphoid cells are distinguished from those that arise from mature lymphoid cells.<ref name=":0" /> Most mature lymphoid neoplasms comprise the non-Hodgkin lymphomas.<ref name=":0" /> Historically, mature histiocytic and dendritic cell (HDC) neoplasms have been considered mature lymphoid neoplasms, since these often involve lymphoid tissue.<ref name=":0" />

Lymphoma can also spread to the [[Biology:Central nervous system|central nervous system]], often around the brain in the [[Medicine:Meninges|meninges]], known as lymphomatous meningitis (LM).<ref>{{cite journal | vauthors = Canova F, Marino D, Trentin C, Soldà C, Ghiotto C, Aversa SM | title = Intrathecal chemotherapy in lymphomatous meningitis | journal = Critical Reviews in Oncology/Hematology | volume = 79 | issue = 2 | pages = 127–134 | date = August 2011 | pmid = 20696592 | doi = 10.1016/j.critrevonc.2010.07.005 }}</ref>

====Hodgkin lymphoma====
{{Main|Medicine:Hodgkin lymphoma}}
Hodgkin lymphoma accounts for about 15% of lymphomas.<ref>{{cite web|title=Hodgkins Lymphoma Incidence|url=http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/hodgkin-lymphoma|access-date=2 October 2017|date=2015-05-14}}</ref> It differs from other forms of lymphomas in its [[Medicine:Prognosis|prognosis]] and several [[Biology:Pathology|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 [[Medicine:Reed–Sternberg cell|Reed–Sternberg cell]].<ref>National Cancer Institute, "Hodgkin Lymphoma", {{cite web |url=http://www.cancer.gov/cancertopics/types/hodgkin |title=Lymphoma—Patient Version |access-date=2013-08-05 |url-status=live |archive-url=https://web.archive.org/web/20130802123430/http://www.cancer.gov/cancertopics/types/hodgkin |archive-date=2013-08-02 }}, accessed on 2013-08-05</ref><ref>National Cancer Institute. "What You Need To Know About Hodgkin Lymphoma". U.S. Dept of Health and Human Services, (online at {{cite web |url=http://www.cancer.gov/cancertopics/wyntk/hodgkin.pdf |title=Archived copy |access-date=2013-08-05 |url-status=dead |archive-url=https://web.archive.org/web/20140124181551/http://www.cancer.gov/cancertopics/wyntk/hodgkin.pdf |archive-date=2014-01-24 }}), pg 4.</ref>

====Non-Hodgkin lymphomas====
[[Medicine:Non-Hodgkin lymphoma|Non-Hodgkin lymphoma]]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.{{citation needed|date=November 2021}}

====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 [[Biology:Histiocyte|histiocytic-dendritic cells]] in which one or more of these cell types is infected with the [[Biology:Epstein–Barr virus|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.<ref name="pmid29885408">{{cite journal | vauthors = Rezk SA, Zhao X, Weiss LM | title = Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update | journal = Human Pathology | volume = 79 | pages = 18–41 | date = September 2018 | pmid = 29885408 | doi = 10.1016/j.humpath.2018.05.020 | s2cid = 47010934 }}</ref>

====WHO classification====
The WHO classification, published in 2001 and updated in 2008,<ref name="Jaffe_2011_1"/><ref name="Swerdlow2008"/> 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, molecular, or cytogenetic characteristics. The five groups are shown in the table. Hodgkin lymphoma is considered separately within the WHO and preceding classifications, although it is recognized as being a tumor, albeit markedly abnormal, of lymphocytes of mature B cell lineage.{{citation needed|date=November 2021}}

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 [[Medicine:Prognosis|prognosis]], therefore, depends on the correct diagnosis and classification of the disease, which is established after examination of a biopsy by a [[Biology:Pathology|pathologist]] (usually a hematopathologist).<ref>{{cite book |author=Wagman LD. |chapter=Principles of Surgical Oncology |chapter-url=http://www.cancernetwork.com/cancer-management-11/chapter01/article/10165/1399286 |veditors=Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ |title=Cancer Management: A Multidisciplinary Approach |publisher=CMPMedica |year=2008 |isbn=9781891483622 |edition=11th |url=http://www.cancernetwork.com/cancer-management-11/ |url-status=live |archive-url=https://web.archive.org/web/20131004224102/http://www.cancernetwork.com/cancer-management-11/ |archive-date=2013-10-04 }}</ref>

<div style="text-align: center; background-color:#7fbfff;">Lymphoma subtypes (WHO 2008)</div>
<div style="text-align: center; background-color:#ffffec;">{{hidden begin| border=solid 1px #aaa|title=Mature [[Biology:B cell|B cell]] neoplasms}}
[[File:DNA-microarray analysis.jpg|thumb|right|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.]]
* B-cell chronic lymphocytic leukemia/small cell lymphoma
:: 3 to 4% of lymphomas in adults
:: Small resting lymphocytes mixed with variable numbers of large activated cells, lymph nodes diffusely [[Biology:Effacement (histology)|effaced]]
:: CD5, surface immunoglobulin
:: 5-year survival rate 50%.<ref>{{cite web |title=Chronic Leukemias |work=The Merck Manual of Geriatrics |url=http://www.merck.com/mkgr/mmg/sec9/ch73/ch73b.jsp |url-status=live |archive-url=https://web.archive.org/web/20100704145645/http://www.merck.com/mkgr/mmg/sec9/ch73/ch73b.jsp |archive-date=2010-07-04 }}</ref>
:: Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, most patients have peripheral blood involvement, indolent
* B-cell prolymphocytic leukemia
* Lymphoplasmacytic lymphoma (such as [[Medicine:Waldenström macroglobulinemia|Waldenström macroglobulinemia]])
* Splenic marginal zone lymphoma
* Hairy cell leukemia
* [[Biology:Plasma cell|Plasma cell]] neoplasms:
** Plasma cell myeloma (also known as multiple myeloma)
** Plasmacytoma
** Monoclonal immunoglobulin deposition diseases
** Heavy chain diseases
* Extranodal marginal zone B cell lymphoma, also called MALT lymphoma
:: About 5% of lymphomas in adults
:: Variable cell size and differentiation, 40% show [[Biology:Plasma cell|plasma cell]] differentiation, [[Medicine:Homing (hematopoietic)|homing]] of B cells to epithelium creates lymphoepithelial lesions.
:: CD5, CD10, surface Ig
:: Frequently occurs outside lymph nodes, very indolent, may be cured by local excision
* Nodal marginal zone B cell lymphoma
* Follicular lymphoma
:: About 40% of lymphomas in adults
:: Small "cleaved" [cleft] cells (centrocytes) mixed with large activated cells (centroblasts), usually nodular ("follicular") growth pattern
:: CD10, surface Ig
:: About 72–77%<ref>{{EMedicine|article|203268|Lymphoma, Follicular}}</ref>
:: Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, associated with t(14;18) [[Biology:Chromosomal translocation|translocation]] overexpressing [[Biology:Bcl-2|Bcl-2]], indolent
* Primary cutaneous follicle center lymphoma
* Mantle cell lymphoma
:: About 3 to 4% of lymphomas in adults
:: Lymphocytes of small to intermediate size growing in diffuse pattern
:: [[Biology:CD5 (protein)|CD5]]
:: About 50<ref name=Leitch&Herrmann/> to 70%<ref name=Leitch&Herrmann>
:::: 50% for limited stage: {{cite journal | vauthors = Leitch HA, Gascoyne RD, Chhanabhai M, Voss NJ, Klasa R, Connors JM | title = Limited-stage mantle-cell lymphoma | journal = Annals of Oncology | volume = 14 | issue = 10 | pages = 1555–1561 | date = October 2003 | pmid = 14504058 | doi = 10.1093/annonc/mdg414 | doi-access = free }}
:::: 70% for advanced stage: {{cite journal | vauthors = Herrmann A, Hoster E, Zwingers T, Brittinger G, Engelhard M, Meusers P, Reiser M, Forstpointner R, Metzner B, Peter N, Wörmann B, Trümper L, Pfreundschuh M, Einsele H, Hiddemann W, Unterhalt M, Dreyling M | display-authors = 6 | title = Improvement of overall survival in advanced stage mantle cell lymphoma | journal = Journal of Clinical Oncology | volume = 27 | issue = 4 | pages = 511–518 | date = February 2009 | pmid = 19075279 | doi = 10.1200/JCO.2008.16.8435 | s2cid = 32350562 | doi-access = free }}</ref>
:: Occurs mainly in adult males, usually involves lymph nodes, bone marrow, spleen and GI tract, associated with t(11;14) translocation overexpressing [[Biology:Cyclin D1|cyclin D1]], moderately aggressive
* Diffuse large B cell lymphoma, not otherwise specified
:: About 40 to 50% of lymphomas in adults
:: Variable, most resemble B cells of large germinal centers, diffuse growth pattern
:: Variable expression of CD10 and surface Ig
:: [[Medicine:Five-year survival rate|Five-year survival rate]] 60%<ref name="Turgeon">{{cite book |first=Mary Louise |last=Turgeon |title=Clinical Hematology: Theory and Procedures |url=https://books.google.com/books?id=cHAjsUgegpQC |year=2005 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-5007-3 |volume=936 |edition=4 |pages=285–6 |url-status=live |archive-url=https://web.archive.org/web/20150906095500/https://books.google.com/books?id=cHAjsUgegpQC |archive-date=2015-09-06 }}</ref>
:: 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
* Intravascular large B-cell lymphoma
* ALK+ large B-cell lymphoma
* Plasmablastic lymphoma
* Primary effusion lymphoma
* Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease
* 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 [[Biology:Apoptosis|apoptosis]]
:: CD10, surface Ig
:: Five-year survival rate 50%<ref>{{cite journal | vauthors = Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V | display-authors = 6 | title = Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol | journal = Annals of Oncology | volume = 16 | issue = 12 | pages = 1928–1935 | date = December 2005 | pmid = 16284057 | doi = 10.1093/annonc/mdi403 | doi-access = free }}</ref>
:: Endemic in Africa, sporadic elsewhere, more common in immunocompromised and children, often visceral involvement, highly aggressive
{{hidden end}}
{{hidden begin|border=solid 1px #aaa|title=
Mature [[Biology:T cell|T cell]] and [[Biology:Natural killer cell|natural killer]] (NK) cell neoplasms}}
* 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
* [[Medicine:Enteropathy-associated T-cell lymphoma|Enteropathy-associated T-cell lymphoma]]
* [[Medicine:Hepatosplenic T-cell lymphoma|Hepatosplenic T-cell lymphoma]]
* Blastic NK cell lymphoma
* [[Medicine:Mycosis fungoides|Mycosis fungoides]]/Sézary syndrome
:: Most common cutaneous lymphoid malignancy
:: Usually small lymphoid cells with convoluted nuclei that often infiltrate the epidermis, creating Pautrier microabscesseses
:: [[Biology:CD4|CD4]]
:: [[Medicine:Five-year survival rate|5-year<br>survival]] 75%<ref>{{cite journal | vauthors = Kirova YM, Piedbois Y, Haddad E, Levy E, Calitchi E, Marinello G, Le Bourgeois JP | title = Radiotherapy in the management of mycosis fungoides: indications, results, prognosis. Twenty years experience | journal = Radiotherapy and Oncology | volume = 51 | issue = 2 | pages = 147–151 | date = May 1999 | pmid = 10435806 | doi = 10.1016/S0167-8140(99)00050-X }}</ref>
:: Localized or more generalized skin symptoms, generally indolent, in a more aggressive variant, Sézary's disease, skin [[Medicine:Erythema|erythema]] and peripheral blood involvement
* Primary cutaneous CD30-positive T cell lymphoproliferative disorders
** Primary cutaneous anaplastic large cell lymphoma
** [[Medicine:Lymphomatoid papulosis|Lymphomatoid papulosis]]
* [[Medicine:Peripheral T-cell lymphoma not otherwise specified|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
:: [[Biology:CD3 (immunology)|CD3]]
:: Probably consists of several rare tumor types, often disseminated and generally aggressive
* Angioimmunoblastic T cell lymphoma
* Anaplastic large cell lymphoma: ALK-positive and ALK-negative types
* Breast plant-associated anaplastic large cell lymphoma
{{hidden end}}
{{hidden begin|border=solid 1px #aaa|title= Precursor lymphoid neoplasms}}
* B-lymphoblastic leukemia/lymphoma not otherwise specified
* B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
* T-lymphoblastic leukemia/lymphoma
:: 15% of childhood [[Medicine:Acute lymphoblastic leukemia|acute lymphoblastic leukemia]] and 90% of lymphoblastic lymphoma.<ref name="Jaffe_2011_1"/>{{rp|635}}
:: [[Biology:Lymphoblast|Lymphoblast]]s with irregular nuclear contours, condensed chromatin, small nucleoli and scant cytoplasm without granules
:: [[Biology:Terminal deoxynucleotidyl transferase|TdT]], [[Biology:CD2|CD2]], [[Biology:CD7|CD7]]
:: It often presents as a mediastinal mass because of involvement of the [[Biology:Thymus|thymus]]. It is highly associated with ''NOTCH1'' mutations, and is most common in adolescent males.{{hidden end}}
{{hidden begin|border=solid 1px #aaa|title= Hodgkin lymphoma }}
* Classical [[Medicine:Hodgkin lymphoma|Hodgkin lymphoma]]s:
** [[Medicine:Nodular sclerosis|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
:: [[Biology:CD15|CD15]], CD30
:: 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
:: CD15, CD30
:: Most common in men, more likely to be diagnosed at advanced stages than the nodular sclerosis form [[Biology:Epstein–Barr virus|Epstein–Barr virus]] involved in 70% of cases
** Lymphocyte-rich
** Lymphocyte depleted or not depleted
* Nodular lymphocyte-predominant Hodgkin lymphoma
{{hidden end}}
{{hidden begin|border=solid 1px #aaa|title=Immunodeficiency-associated lymphoproliferative disorders}}
* Associated with a primary immune disorder
* Associated with the human immunodeficiency virus ([[Biology:HIV|HIV]])
* Post-transplant
* Associated with [[Chemistry:Methotrexate|methotrexate]] therapy
* [[Medicine:Primary central nervous system lymphoma|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 [[Medicine:Chemotherapy|chemotherapy]], often with methotrexate.
{{hidden end}}</div>

====Previous classifications====

Several previous classifications have been used, including Rappaport 1956, Lennert/Kiel 1974, BNLI, Working formulation (1982), and REAL (1994).

The Working Formulation of 1982 was a classification of [[Medicine:Non-Hodgkin lymphoma|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 [[Medicine:T-cell lymphoma|T-cell lymphoma]]s and B-cell lymphomas. It was widely accepted at the time of its publication but by 2004 was obsolete.<ref>{{cite journal | vauthors = Clarke CA, Glaser SL, Dorfman RF, Bracci PM, Eberle E, Holly EA | title = Expert review of non-Hodgkin's lymphomas in a population-based cancer registry: reliability of diagnosis and subtype classifications | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 13 | issue = 1 | pages = 138–143 | date = January 2004 | pmid = 14744745 | doi = 10.1158/1055-9965.EPI-03-0250 | doi-access = free }}</ref>

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.<ref>{{EMedicine|article|203399|Non-Hodgkin Lymphoma}}</ref> For coding purposes, the ICD-O (codes 9590–9999)<ref>{{cite web|url=http://www.cog.ufl.edu/publ/apps/icdo/icdo_morph.txt |title=Archived copy |access-date=2005-11-07 |url-status=bot: unknown |archive-url=https://web.archive.org/web/20040627090029/http://www.cog.ufl.edu/publ/apps/icdo/icdo_morph.txt |archive-date=June 27, 2004 }}</ref> and ICD-10 (codes C81-C96)<ref>{{Cite web|title=2022 ICD-10-CM Codes C81-C96: Malignant neoplasms of lymphoid, hematopoietic and related tissue|url=https://www.icd10data.com/ICD10CM/Codes/C00-D49/C81-C96|access-date=2022-02-02|website=www.icd10data.com}}</ref> are available.

===Staging===
[[File:DIagram showing where lymphoma can spread in the body CRUK 382.svg|thumb|Diagram showing common sites where lymphoma spreads]]
After a diagnosis and before treatment, cancer is [[Medicine:Cancer staging|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.<ref name="Cheson">{{cite journal | vauthors = Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA | title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification | journal = Journal of Clinical Oncology | volume = 32 | issue = 27 | pages = 3059–3068 | date = September 2014 | pmid = 25113753 | pmc = 4979083 | doi = 10.1200/JCO.2013.54.8800 }}</ref>

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&nbsp;°C or more) or their absence is expressed with B or A, respectively.<ref>{{cite journal | vauthors = Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M | title = Report of the Committee on Hodgkin's Disease Staging Classification | journal = Cancer Research | volume = 31 | issue = 11 | pages = 1860–1861 | date = November 1971 | pmid = 5121694 }}</ref>

[[CT scan]] or PET scan imaging modalities are used to stage cancer. PET scanning is advised for [[Chemistry:Fludeoxyglucose (18F)|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.<ref name="Cheson"/>

Age and poor [[Medicine:Performance status|performance status]] are other established poor prognostic factors.<ref>{{cite journal | title = A predictive model for aggressive non-Hodgkin's lymphoma | journal = The New England Journal of Medicine | volume = 329 | issue = 14 | pages = 987–994 | date = September 1993 | pmid = 8141877 | doi = 10.1056/NEJM199309303291402 | author1 = International Non-Hodgkin's Lymphoma Prognostic Factors Project | doi-access =free  }}</ref>  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.

<gallery>
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)
</gallery>

=== Differential diagnosis ===
Certain lymphomas (extranodal NK/T-cell lymphoma, nasal type and [[Medicine:Enteropathy-associated T-cell lymphoma#Genetics|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.<ref name="pmid30212873">{{cite journal | vauthors = Xia D, Morgan EA, Berger D, Pinkus GS, Ferry JA, Zukerberg LR |author4-link=Geraldine Pinkus | title = NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review | journal = American Journal of Clinical Pathology | volume = 151 | issue = 1 | pages = 75–85 | date = January 2019 | pmid = 30212873 | doi = 10.1093/ajcp/aqy108 | s2cid = 52272766 | doi-access = free }}</ref>

==Treatment==
Prognoses and treatments are different for HL and between all the different forms of NHL,<ref name="pmid20017283">{{cite journal | vauthors = Sweetenham JW | title = Treatment of lymphoblastic lymphoma in adults | journal = Oncology | volume = 23 | issue = 12 | pages = 1015–1020 | date = November 2009 | pmid = 20017283 }}</ref> 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: {{Citation needed|date=July 2013}} Burkitt lymphoma, 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, [[Social:Watchful waiting|watchful waiting]] is often the initial course of action, because monitoring is less risky and less harmful than early treatment.<ref name="pmid18467294">{{cite journal | vauthors = Elphee EE | title = Understanding the concept of uncertainty in patients with indolent lymphoma | journal = Oncology Nursing Forum | volume = 35 | issue = 3 | pages = 449–454 | date = May 2008 | pmid = 18467294 | doi = 10.1188/08.ONF.449-454 | s2cid = 25207677 | doi-access = free }}</ref>

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 [[Medicine:Lymphadenopathy|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 [[Chemistry:Rituximab|rituximab]] in the treatment of follicular lymphoma rather than the wait-and-watch approach. [[Social:Watchful waiting|Watchful waiting]] is not a desirable strategy for everyone, as it leads to significant distress and [[Medicine:Anxiety|anxiety]] in some people. It has been called "watch and worry".<ref>{{cite journal | vauthors = Ansell SM | title = Follicular lymphoma: watch and wait is watch and worry | journal = The Lancet. Oncology | volume = 15 | issue = 4 | pages = 368–369 | date = April 2014 | pmid = 24602759 | doi = 10.1016/S1470-2045(14)70066-X }}</ref>

===High-grade===

Treatment of some other, more aggressive, forms of lymphoma {{which|date=July 2013}} can result in a cure in the majority of cases, but the prognosis for people with a poor response to therapy is worse.<ref name="pmid20008238">{{cite journal | vauthors = Bernstein SH, Burack WR | title = The incidence, natural history, biology, and treatment of transformed lymphomas | journal = Hematology. American Society of Hematology. Education Program | volume = 2009 | pages = 532–541 | year = 2009 | pmid = 20008238 | doi = 10.1182/asheducation-2009.1.532 | s2cid = 12185761 }}</ref> 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.<ref>{{cite journal | vauthors = Jenkins EC | title = Wire-loop application of liquid emulsion to slides for autoradiography in light microscopy | journal = Stain Technology | volume = 47 | issue = 1 | pages = 23–26 | date = January 1972 | pmid = 4550425 | doi = 10.3109/10520297209116530 }}</ref> For people who relapse, high-dose chemotherapy followed by autologous stem cell transplantation is a proven approach.<ref>{{cite journal | vauthors = Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL | display-authors = 6 | title = Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma | journal = The New England Journal of Medicine | volume = 333 | issue = 23 | pages = 1540–1545 | date = December 1995 | pmid = 7477169 | doi = 10.1056/nejm199512073332305 | doi-access = free }}</ref>

The treatment of side effects is also important as they can occur due to the chemotherapy or the [[Biology:Hematopoietic stem cell transplantation|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.<ref>{{cite journal | vauthors = Fisher SA, Cutler A, Doree C, Brunskill SJ, Stanworth SJ, Navarrete C, Girdlestone J | title = Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD009768 | date = January 2019 | pmid = 30697701 | pmc = 6353308 | doi = 10.1002/14651858.CD009768.pub2 | editor-last = Cochrane Haematological Malignancies Group }}</ref> Moreover, it was seen that [[Medicine:Platelet transfusion|platelet transfusion]]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).<ref>{{cite journal | vauthors = Estcourt L, Stanworth S, Doree C, Hopewell S, Murphy MF, Tinmouth A, Heddle N | title = Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD004269 | date = May 2012 | pmid = 22592695 | doi = 10.1002/14651858.CD004269.pub3 | editor-last = Cochrane Haematological Malignancies Group }}</ref><ref>{{cite journal | vauthors = Estcourt LJ, Stanworth SJ, Doree C, Hopewell S, Trivella M, Murphy MF | title = Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 11 | pages = CD010983 | date = November 2015 | pmid = 26576687 | pmc = 4717525 | doi = 10.1002/14651858.CD010983.pub2 | editor-last = Cochrane Haematological Malignancies Group }}</ref>

Four chimeric antigen receptor [[Biology:Chimeric antigen receptor T cell|CAR-T cell therapies]] are FDA-approved for non-Hodgkin lymphoma, including [[Biology:Lisocabtagene maraleucel|lisocabtagene maraleucel]] (for relapsed or refractory large B-cell lymphoma with two failed systemic treatments), [[Biology:Axicabtagene ciloleucel|axicabtagene ciloleucel]], [[Biology:Tisagenlecleucel|tisagenlecleucel]] (for large B-cell lymphoma), and [[Biology:Brexucabtagene autoleucel|brexucabtagene autoleucel]](for mantle cell lymphoma). These therapies come with certification and other restrictions.<ref>{{Cite web|last=Ingram|first=Ian|date=2021-02-05|title=New CAR-T for Aggressive B-Cell Lymphoma Wins FDA Nod|url=https://www.medpagetoday.com/hematologyoncology/lymphoma/91089|access-date=2021-02-09|website=www.medpagetoday.com|language=en}}</ref>

==== Hodgkin lymphoma ====
Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized.<ref name="pmid19883306">{{cite journal | vauthors = Martin NE, Ng AK | title = Good things come in small packages: low-dose radiation as palliation for indolent non-Hodgkin lymphomas | journal = Leukemia & Lymphoma | volume = 50 | issue = 11 | pages = 1765–1772 | date = November 2009 | pmid = 19883306 | doi = 10.3109/10428190903186510 | s2cid = 11004437 }}</ref>

Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy.<ref name="pmid20008235">{{cite journal | vauthors = Kuruvilla J | title = Standard therapy of advanced Hodgkin lymphoma | journal = Hematology. American Society of Hematology. Education Program | volume = 2009 | pages = 497–506 | year = 2009 | pmid = 20008235 | doi = 10.1182/asheducation-2009.1.497 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM | display-authors = 6 | title = ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned | journal = The New England Journal of Medicine | volume = 365 | issue = 3 | pages = 203–212 | date = July 2011 | pmid = 21774708 | doi = 10.1056/NEJMoa1100340 | author22 = Gruppo Italiano di Terapie Innovative nei Linfomi | s2cid = 10038896 | doi-access = free }}</ref>

Scientists evaluated whether [[Physics:Positron emission tomography|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.<ref>{{cite journal | vauthors = Aldin A, Umlauff L, Estcourt LJ, Collins G, Moons KG, Engert A, Kobe C, von Tresckow B, Haque M, Foroutan F, Kreuzberger N, Trivella M, Skoetz N | display-authors = 6 | title = Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 8 | pages = CD012643 | date = January 2020 | pmid = 31930780 | pmc = 6984446 | doi = 10.1002/14651858.CD012643.pub3 | editor-last = Cochrane Haematology Group }}</ref>

Current research evaluated whether [[Chemistry:Nivolumab|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.<ref>{{cite journal | vauthors = Goldkuhle M, Dimaki M, Gartlehner G, Monsef I, Dahm P, Glossmann JP, Engert A, von Tresckow B, Skoetz N | display-authors = 6 | title = Nivolumab for adults with Hodgkin's lymphoma (a rapid review using the software RobotReviewer) | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 7 | pages = CD012556 | date = July 2018 | pmid = 30001476 | pmc = 6513229 | doi = 10.1002/14651858.CD012556.pub2 | editor-last = Cochrane Haematological Malignancies Group }}</ref>

=== Palliative care ===
Palliative care, a specialized medical care focused on the symptoms, pain, and stress of a serious illness, is recommended by multiple national cancer treatment guidelines as an accompaniment to curative treatments for people with lymphoma.<ref name="pmid17531914">{{cite journal | vauthors = Ferrell B, Connor SR, Cordes A, Dahlin CM, Fine PG, Hutton N, Leenay M, Lentz J, Person JL, Meier DE, Zuroski K | display-authors = 6 | title = The national agenda for quality palliative care: the National Consensus Project and the National Quality Forum | journal = Journal of Pain and Symptom Management | volume = 33 | issue = 6 | pages = 737–744 | date = June 2007 | pmid = 17531914 | doi = 10.1016/j.jpainsymman.2007.02.024 | doi-access = free }}</ref><ref>*The American Society of Clinical Oncology made this recommendation based on various cancers. See {{Citation|author1=American Society of Clinical Oncology |title=Five Things Physicians and Patients Should Question |publisher=American Society of Clinical Oncology |work=Choosing Wisely: an initiative of the ABIM Foundation |url=http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Clin_Onc.pdf |access-date=August 14, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120731073425/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Clin_Onc.pdf |archive-date=July 31, 2012 }}</ref> It is used to address both the direct symptoms of lymphoma and many unwanted side effects that arise from treatments.<ref name="pmid20890138">{{cite journal | vauthors = Higginson IJ, Evans CJ | title = What is the evidence that palliative care teams improve outcomes for cancer patients and their families? | journal = Cancer Journal | volume = 16 | issue = 5 | pages = 423–435 | year = 2010 | pmid = 20890138 | doi = 10.1097/PPO.0b013e3181f684e5 | s2cid = 39881122 | doi-access = free }}</ref><ref>{{cite web |url=http://www.medscape.com/viewarticle/826011 |title=Palliative Care: It's for Caregivers Too, Says Study |access-date=2014-08-21 |url-status=live |archive-url=https://web.archive.org/web/20140601190945/http://www.medscape.com/viewarticle/826011 |archive-date=2014-06-01 }}</ref> 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.<ref name="pmid20890138"/><ref name="pmid20078405">{{cite journal | vauthors = Heath JA, Clarke NE, Donath SM, McCarthy M, Anderson VA, Wolfe J | title = Symptoms and suffering at the end of life in children with cancer: an Australian perspective | journal = The Medical Journal of Australia | volume = 192 | issue = 2 | pages = 71–75 | date = January 2010 | pmid = 20078405 | doi = 10.5694/j.1326-5377.2010.tb03420.x | s2cid = 8355159 }}</ref><ref name="pmid23901834">{{cite journal | vauthors = Schmidt P, Otto M, Hechler T, Metzing S, Wolfe J, Zernikow B | title = Did increased availability of pediatric palliative care lead to improved palliative care outcomes in children with cancer? | journal = Journal of Palliative Medicine | volume = 16 | issue = 9 | pages = 1034–1039 | date = September 2013 | pmid = 23901834 | doi = 10.1089/jpm.2013.0014 }}</ref><ref name="pmid22836818">{{cite journal | vauthors = Tang ST, Chang WC, Chen JS, Wang HM, Shen WC, Li CY, Liao YC | title = Course and predictors of depressive symptoms among family caregivers of terminally ill cancer patients until their death | journal = Psycho-Oncology | volume = 22 | issue = 6 | pages = 1312–1318 | date = June 2013 | pmid = 22836818 | doi = 10.1002/pon.3141 | s2cid = 31552330 }}</ref> For these reasons, palliative care is especially important for people requiring bone marrow transplants.<ref name="pmid19151797">{{cite journal | vauthors = Chung HM, Lyckholm LJ, Smith TJ | title = Palliative care in BMT | journal = Bone Marrow Transplantation | volume = 43 | issue = 4 | pages = 265–273 | date = February 2009 | pmid = 19151797 | doi = 10.1038/bmt.2008.436 | doi-access =  | s2cid = 20112284 }}</ref><ref>{{cite web |url=http://www.medscape.com/viewarticle/735542_4 |title=Providing Palliative Care to Family Caregivers Throughout the Bone Marrow Transplantation Trajectory |access-date=2014-08-21 |url-status=live |archive-url=https://web.archive.org/web/20130812111427/http://www.medscape.com/viewarticle/735542_4 |archive-date=2013-08-12 }}</ref>

=== 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.<ref>{{cite journal | vauthors = Knips L, Bergenthal N, Streckmann F, Monsef I, Elter T, Skoetz N | title = Aerobic physical exercise for adult patients with haematological malignancies | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD009075 | date = January 2019 | pmid = 30702150 | pmc = 6354325 | doi = 10.1002/14651858.CD009075.pub3 | editor-last = Cochrane Haematological Malignancies Group }}</ref>&nbsp; &nbsp;

==Prognosis==
{| class="wikitable"
|-
|colspan="3;" style="text-align:center;" bgcolor="#7fbfff"|Five-year relative survival by stage at diagnosis<ref>{{cite web | url = http://seer.cancer.gov/statfacts/html/lymph.html | title = SEER Stat Fact Sheets: Lymphoma | archive-url = https://web.archive.org/web/20131010130208/http://seer.cancer.gov/statfacts/html/lymph.html | archive-date = 2013-10-10 | url-status=dead }}</ref>
|-
| style=align="center;" bgcolor="#ffffec"| Stage at diagnosis
| style=align="center;" bgcolor="#ffffec"| Five-year relative<br>survival (%)
| style=align="center;" bgcolor="#ffffec"| Percentage<br>of cases (%)
|-
| style=align="center;" bgcolor="#ffffec"| Localized (confined to primary site)
| style=align="center;" bgcolor="#ffffec"| 82.3
| style=align="center;" bgcolor="#ffffec"| 26
|-
| style=align="center;" bgcolor="#ffffec"| Regional (spread to regional lymph nodes)
| style=align="center;" bgcolor="#ffffec"| 78.3
| style=align="center;" bgcolor="#ffffec"| 19
|-
| style=align="center;" bgcolor="#ffffec"| Distant (cancer has metastasized)
| style=align="center;" bgcolor="#ffffec"| 62.7
| style=align="center;" bgcolor="#ffffec"| 47
|-
| style=align="center;" bgcolor="#ffffec"| Unknown (unstaged)
| style=align="center;" bgcolor="#ffffec"| 68.6
| style=align="center;" bgcolor="#ffffec"| 8
|}

==Epidemiology==
[[File:Lymphomas, multiple myeloma world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Deaths from lymphomas and multiple myeloma per million persons in 2012 {{Div col|small=yes|colwidth=10em}}
{{legend|#ffff20|0-13}}{{legend|#ffe820|14-18}}{{legend|#ffd820|19-22}}{{legend|#ffc020|23-28}}{{legend|#ffa020|29-34}}{{legend|#ff9a20|35-42}}{{legend|#f08015|43-57}}{{legend|#e06815|58-88}}{{legend|#d85010|89-121}}{{legend|#d02010|122-184}}{{div col end}}]]

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.<ref>{{cite web |title       = SEER Cancer Statistics Review, 1975–2006 |work        = Surveillance Epidemiology and End Results (SEER) |publisher   = [[Organization:National Cancer Institute|National Cancer Institute]] |url         = http://seer.cancer.gov/csr/1975_2006/ |vauthors    = Horner MJ, Ries LG, Krapcho M, Neyman N |location    = Bethesda, MD |access-date  = 3 November 2009 |quote       = Table 1.4: Age-Adjusted SEER Incidence and U.S. Death Rates and 5-Year Relative Survival Rates By Primary Cancer Site, Sex and Time Period |url-status     = live |archive-url  = https://web.archive.org/web/20090926004001/http://seer.cancer.gov/csr/1975_2006/ |archive-date = 26 September 2009 }}</ref>

According to the [[Organization:National Institutes of Health|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.{{citation needed|date=November 2021}}

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.<ref>{{cite journal | vauthors = Tran H, Nourse J, Hall S, Green M, Griffiths L, Gandhi MK | title = Immunodeficiency-associated lymphomas | journal = Blood Reviews | volume = 22 | issue = 5 | pages = 261–281 | date = September 2008 | pmid = 18456377 | doi = 10.1016/j.blre.2008.03.009 }}</ref>

==History==
[[File:Thomas Hodgkin photo.jpg|thumb|190px|Thomas Hodgkin]]
Thomas Hodgkin published the first description of lymphoma in 1832, specifically of the form named after him.<ref name="Mauch1999">{{cite book | last = Hellman | first = Samuel |author2=Mauch, P.M. Ed.  | title = Hodgkin's Disease | publisher = Lippincott Williams & Wilkins | year = 1999 |chapter=Chapter 1 | page = 5 | isbn = 0-7817-1502-4}}</ref> 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").<ref>{{Cite web|url=https://www.etymonline.com/word/-oma?ref=etymonline_crossreference|title=-oma|website=Online Etymology Dictionary}}</ref>

==Research==
The two types of lymphoma research are clinical or [[Translational research|translational research]] and [[Basic research|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.<ref>{{cite web |url=http://www.clinicaltrials.gov/ct2/results?term=lymphoma |title=Search of: Lymphoma - List Results - ClinicalTrials.gov |access-date=2012-10-30 |url-status=live |archive-url=https://web.archive.org/web/20130106213155/http://www.clinicaltrials.gov/ct2/results?term=lymphoma |archive-date=2013-01-06 }}</ref>

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,<ref>{{cite web|website=The Leukemia & Lymphoma Society|title=Understanding Clinical Trials for Blood Cancers|url=http://www.leukemia-lymphoma.org/attachments/National/br_1162487596.pdf|publisher=Leukemia and Lymphoma Society|access-date=19 May 2010|url-status=dead|archive-url=https://web.archive.org/web/20110105213515/http://www.leukemia-lymphoma.org/attachments/National/br_1162487596.pdf|archive-date=5 January 2011}}</ref> but can improve scientists' understanding of lymphoma and form the foundation for future, more effective treatments.

==Other animals==
<!-- For a discussion of lymphoma in animals other than humans see the above link. -->

== References ==
{{Reflist|2|refs=

<ref name="Jaffe_2011_1">{{Cite book | last1=Jaffe | first1=ES | last2=Harris |first2=NL|last3=Vardiman |first3=JW|last4=Campo |first4=E|last5=Arber|first5=DA.|title=Hematopathology | publisher=Elsevier Saunders| year=2011 |edition=1st |isbn= 9780721600406}}</ref>

<ref name="Swerdlow2008">{{cite book |first1=Steven H. |last1=Swerdlow |author2=International Agency for Research on Cancer |author3=World Health Organization |title=WHO classification of tumours of haematopoietic and lymphoid tissues |url=http://apps.who.int/bookorders/anglais/detart1.jsp?codlan=1&codcol=70&codcch=4002 |year=2008 |publisher=International Agency for Research on Cancer |edition=4th |volume=2 |series=World Health Organization classification of tumours |isbn=9789283224310 |url-status=dead |archive-url=https://web.archive.org/web/20150211163852/http://apps.who.int/bookorders/anglais/detart1.jsp?codlan=1&codcol=70&codcch=4002 |archive-date=2015-02-11 }}</ref>

}}

== External links ==
* {{Curlie|Health/Conditions_and_Diseases/Cancer/Hematologic/Lymphoma/}}

{{Medical condition classification and resources| DiseasesDB       =
| ICD10            = {{ICD10|C|81||c|81}}–{{ICD10|C|96||c|81}}
| ICD9             = 202.8
| ICDO             = 9590–9999
| OMIM             =
| MedlinePlus      = 000580
| MedlinePlus_mult = {{MedlinePlus2|000581}}
| eMedicineSubj    =
| eMedicineTopic   =
| MeshID           = D008223
}}


[[Category:Anatomical pathology]]
[[Category:Hematology]]
[[Category:Pediatric cancers]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Lymphoma}}