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| __NOTOC__
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| {{Angioimmunoblastic T-cell lymphoma}}
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| {{CMG}}; {{AE}} {{RT}}
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|
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| ==Overview==
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| '''Angioimmunoblastic T-cell lymphoma (AILT)''' is a mature [[T-cell]] [[lymphoma]] characterized by a polymorphous [[lymph node]] infiltrate showing a marked increase in [[follicular dendritic cells]] (FDCs) and [[high endothelial venules]] (HEVs) and systemic involvement.<ref name="who1"/> It is also known as '''immunoblastic lymphadenopathy''' (Lukes-Collins Classification) and '''AILD-type (lymphogranulomatosis X) T-cell lymphoma''' (Kiel Classification)<ref name="who1">[http://www.iarc.fr/WHO-BlueBooks/BBwebsite/bb3.html] Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds): '''World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues.''' IARC Press: Lyon 2001 </ref>.
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|
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|
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| ==Overview==
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| AILT comprises 15-20% of peripheral [[T-cell lymphomas]] and 1-2% of all [[non-Hodgkin lymphomas]].<ref name="anon1">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9166827&query_hl=8&itool=pubmed_ExternalLink]
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| Anon. "A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project." '''Blood'''. 1997 Jun 1;89(11):3909-18. PMID: 9166827</ref>
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|
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| ==Age==
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| The typical patient with angioimmunoblastic T-cell lymphoma (AILT) is either middle-aged or elderly.
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|
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| ==Gender==
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| No gender preference for this disease has been observed.
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|
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| ==Symptoms==
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| Patients with this disease usually present at an advanced stage and show systemic involvement. The clinical findings typically include
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| * A pruritic skin [[rash]]
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| * [[Edema]]
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| * [[Ascites]]
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| * [[Pleural effusions]]
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| * [[Arthritis]].<ref name="sie1">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8664186&query_hl=11&itool=pubmed_ExternalLink]
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| Siegert W, Nerl C, Agthe A, Engelhard M, Brittinger G, Tiemann M, Lennert K, Huhn D. "Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group." '''Ann Oncol'''. 1995 Sep;6(7):659-64. PMID: 8664186</ref><ref name="jaf1">
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| [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8664181&query_hl=13&itool=pubmed_ExternalLink]
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| Jaffe ES. "Angioimmunoblastic T-cell lymphoma: new insights, but the clinical challenge remains." Ann Oncol. 1995 Sep;6(7):631-2. PMID: 8664181</ref>
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| ==Laboratory Findings==
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| The classical laboratory finding is polyclonal [[hypergammaglobulinemia]]
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|
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| Other [[immunoglobulin]] derrangements are also seen, including
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| * [[Hemolytic anemia]] with [[cold agglutinins]]
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| * [[Circulating immune complexes]]
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| * [[Anti-smooth muscle antibodies]]
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| * Positive [[rheumatoid factor]]
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|
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| ==Treatment==
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|
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| ==References==
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| {{reflist|2}}
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|
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| {{reflist|2}}
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| {{reflist|2}}
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| [[Category:Hematology]]
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| [[Category:Types of cancer]]
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| [[Category:Oncology]]
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| [[Category:Disease]]
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| [[Category:Needs content]]
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| {{WikiDoc Help Menu}}
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| {{WikiDoc Sources}}
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| __NOTOC__
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| {{SI}}
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| {{DiseaseDisorder infobox |
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| Name = auses
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|
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| Anaplastic large cell lymphoma, ALK positive
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|
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| ls|
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| ICD10 = {{ICD10|C|84|4|c|81}} |
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| OMIM = |
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| MedlinePlus = |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| }}
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| {{CMG}}; {{AE}} {{AP}}
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|
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| {{SK}} ALCL-ALK(+); ALK-positive ALCL; ALK positive ALCL; ALK positive anaplastic large cell lymphoma
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|
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| ==Overview==
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| The anaplastic large cell lymphoma (ALCL) ALK-positive ('''A'''naplastic '''L'''lymphoma '''K'''inase) is a [[peripheral T-cell lymphoma]] ([[non-Hodgkin lymphoma]]) characterized by the proliferation of [[CD30]]-positive T-cells which have an abundant cytoplasm, a pleomorphic nucleus (horseshoe-shaped nucleus), and an eosinophilic paranuclear region.<ref name="pmid9490693">{{cite journal| author=Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugières L, Terrier-Lacombe MJ et al.| title=ALK-positive lymphoma: a single disease with a broad spectrum of morphology. | journal=Blood | year= 1998 | volume= 91 | issue= 6 | pages= 2076-84 | pmid=9490693 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9490693 }} </ref> This type of ALK-positive lymphoma is associated with a translocation in the ALK gene [T(2;5)(p23;q35)] which expresses the ALK protein.<ref name=Swerdlow>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
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|
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| ==Classification==
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| ===Morphologic Classification<ref>{{cite web|url=http://go.galegroup.com/ps/retrieve.do?sgHitCountType=None&sort=RELEVANCE&inPS=true&prodId=HRCA&userGroupName=mlin_b_bethidmc&tabID=T002&searchId=R1&resultListType=RESULT_LIST&contentSegment=&searchType=AdvancedSearchForm¤tPosition=1&contentSet=GALE%7CA188154738&&docId=GALE|A188154738&docType=GALE&role=|title=The anaplastic lymphoma kinase in the pathogenesis of cancer}}</ref>===
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| ====Classical Variants====
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| *'''Common pattern''' ALK positive anaplastic large cell lymphoma
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|
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| ====Atypical Variants====
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| *'''Small cell''' ALK positive anaplastic large cell lymphoma
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| *'''Lymphohistiocytic''' ALK positive anaplastic large cell lymphoma
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| *'''Giant cell''' ALK positive anaplastic large cell lymphoma
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| *'''Hodgkin's like''' ALK positive anaplastic large cell lymphoma
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|
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| ====Rare Variants====
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| *'''Sarcomatoid''' ALK positive anaplastic large cell lymphoma
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|
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|
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| ==Causes==
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|
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| ALK positive anaplastic large cell lymphoma is associated with a rearrangement in the anaplastic lymphoma kinase (ALK) gene. The most frequent gene translocation is T(2;5)(p23;q35).<ref name="pmid8122112">{{cite journal| author=Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL et al.| title=Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. | journal=Science | year= 1994 | volume= 263 | issue= 5151 | pages= 1281-4 | pmid=8122112 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8122112 }} </ref> This translocation leads to a chimeric protein between the nucleolar phosphoprotein (NPM) gene (5q35) and ALK gene (2p23), which has structural similarity to the insulin growth factor receptor.<ref>{{cite web|url=http://go.galegroup.com/ps/retrieve.do?sgHitCountType=None&sort=RELEVANCE&inPS=true&prodId=HRCA&userGroupName=mlin_b_bethidmc&tabID=T002&searchId=R2&resultListType=RESULT_LIST&contentSegment=&searchType=AdvancedSearchForm¤tPosition=1&contentSet=GALE%7CA15341631&&docId=GALE|A15341631&docType=GALE&role=|title=Fusion of kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma}}</ref> Normal [[T-cell]]s require [[IL-2]] as a growth factor; [[T-cell]]s of patients with ALK positive anaplastic large cell lymphoma have a constitutive activation of [[IL-2 receptor]] caused by the new NMP-ALK chimeric protein.<ref>{{cite web|url=http://go.galegroup.com/ps/retrieve.do?sgHitCountType=None&sort=RELEVANCE&inPS=true&prodId=HRCA&userGroupName=mlin_b_bethidmc&tabID=T002&searchId=R3&resultListType=RESULT_LIST&contentSegment=&searchType=AdvancedSearchForm¤tPosition=1&contentSet=GALE%7CA15341631&&docId=GALE|A15341631&docType=GALE&role=|title=Fusion of kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma}}</ref>
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|
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| Other gene mutations include:<ref>{{cite web|url=http://www.nature.com/nrc/journal/v8/n1/abs/nrc2291.html|title=The anaplastic lymphoma kinase in the pathogenesis of cancer}}</ref>
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| *T(1;2), encoding a tropomyosin3 (TPM3)/ALK fusion protein (10 to 20%)
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| *T(2;3), encoding a TRK fusion gene (TFP)/ALK fusion protein (2 to 5%)
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| *Inv(2), encoding a ATIC (Pur H gene)/ALK fusion protein (2 to 5%)
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| *T(2;17), encoding a clathrin heavy (CLTC)/ALK fusion protein (2 to 5%)
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| *T(2;17), encoding a ALO17/ALK fusion protein (2 to 5 percent of cases)
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| *T(2;19), encoding a tropomyosin 4 (TPM4)/ALK fusion protein (<1%)
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| *T(2;22), encoding a non-muscle myosin (MYH9)/ALK fusion protein (<1%)
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|
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| == Differential Diagnosis ==
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| *[[ALCL ALK negative]]
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| *Primary cutaneous ALCL
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| *Diffuse large B-cell lymphoma, anaplastic type
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| *Diffuse large B-cell lymphoma, plasmablastic type
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| *[[Hodgkin lymphoma]]
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|
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| == Epidemiology and Demographics==
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| ALK positive anaplastic large cell lymphoma affects primarily young (between 10 and 29 years), male patients<ref name="pmid11090048">{{cite journal| author=Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K et al.| title=CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. | journal=Blood | year= 2000 | volume= 96 | issue= 12 | pages= 3681-95 | pmid=11090048 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11090048 }} </ref> and accounts for 3% of all [[NHL]], 40% of all large cell lymphomas<ref>{{cite web|url=http://www.bloodjournal.org/content/93/8/2697?sso-checked=true|title=ALK+ Lymphoma: Clinico-Pathological Findings and Outcome}}</ref> and 10%-20% of childhood lymphomas.<ref>{{cite web|url=http://www.bloodjournal.org/content/93/8/2697?sso-checked=true|title=ALK+ Lymphoma: Clinico-Pathological Findings and Outcome}}</ref>
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|
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| According to a study on 1,320 cases of [[peripheral T-cell lymphomas]] and NK cell lymphomas between 1990 and 2002 in 22 different centers, ALK-Positive ALCL is the fifth most common type of peripheral T cell lymphoma (6.6% of total patients).<ref>{{cite web|url=http://jco.ascopubs.org/content/26/25/4124.full.pdf|title=International Peripheral T-Cell and Natural Killer/T-Cell Lymphoma Study: Pathology Findings and Clinical Outcomes}}</ref> In the United states, ALK-Positive ALCL is the most frequent type of [[peripheral T-cell lymphoma]].
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|
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| ==Natural History, Complications and Prognosis==
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|
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| ===Prognosis===
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| The '''I'''nternational '''P'''rognostic '''I'''index (IPI) is used to estimate the prognosis of patients.<ref>{{cite web|url=http://www.uptodate.com/contents/image?imageKey=HEME%2F70850&topicKey=HEME%2F4705&rank=1%7E150&source=see_link&search=Anaplastic+large+cell+lymphoma%2C+ALK+positive&utdPopup=true|title=International Prognostic Index for non-Hodgkin lymphoma}}</ref> The IPI takes into account 5 variables:
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| *Patient's age (>60 years)
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| *Elevated serum [[lactate dehydrogenase]] ([[LDH]])
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| *Eastern Cooperative Oncology Group (ECOG) performance status
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| *Ann Arbor clinical stage III or IV
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| *Number of involved extra nodal sites > 1
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|
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| If any of this criteria is met, one point is awarded for the IPI. The interpretation of the total score is as follows:
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| *0 to 1: Low risk
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| *2: Low-intermediate risk
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| *3: High-intermediate risk
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| *4 to 5: High risk
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|
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| According to the International Peripheral T cell Lymphoma Project, the estimated 5-years survival for each of the IPI stages are as follows:<ref>{{cite web|url=http://www.bloodjournal.org/content/111/12/5496.abstract?sso-checked=true|title=ALK− anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project}}</ref>
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|
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| *Low risk (IPI 0-1): 90%
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| *Low-intermediate risk (IPI 2): 68%
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| *High-intermediate risk (IPI 3): 23%
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| *High risk (IPI 4-5): 33%
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|
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| However, recently, the International peripheral T-cell lymphoma Project score (IPTCLP) has demonstrated to be the most accurate score to predict overall survival in patients. <ref>{{cite web|url=http://annonc.oxfordjournals.org/content/early/2010/07/14/annonc.mdq359.full.pdf+html|title=Comparison of four prognostic scores in peripheral T-cell lymphoma}}</ref>
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|
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| This score includes:
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| *Age
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| *Eastern Cooperative Oncology Group (ECOG) performance status
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| *Platelet count
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|
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| == Diagnosis ==
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|
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| ===History and Symptoms===
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| Most adult patients present with painless [[lymphadenopathy]]. Although retroperitoneal and peripheral [[lymphadenopathy]] is very common,<ref name="pmid25674293">{{cite journal| author=Yu G, Gao Z, Huang X| title=ALK-positive anaplastic large cell lymphoma with an unusual alveolar growth pattern. | journal=Int J Clin Exp Pathol | year= 2014 | volume= 7 | issue= 12 | pages= 9086-9 | pmid=25674293 | doi= | pmc=PMC4314028 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25674293 }} </ref> other possible locations for enlarged lymph nodes include the gastrointestinal tract, the breast,<ref name="pmid25490539">{{cite journal| author=Gidengil CA, Predmore Z, Mattke S, van Busum K, Kim B| title=Breast implant-associated anaplastic large cell lymphoma: a systematic review. | journal=Plast Reconstr Surg | year= 2014 | volume= | issue= | pages= | pmid=25490539 | doi=10.1097/PRS.0000000000001037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25490539 }} </ref> the spleen,<ref name="pmid11097375">{{cite journal| author=Hebeda KM, MacKenzie MA, van Krieken JH| title=A case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma presenting with spontaneous splenic rupture: an extremely unusual presentation. | journal=Virchows Arch | year= 2000 | volume= 437 | issue= 4 | pages= 459-64 | pmid=11097375 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11097375 }} </ref> the liver,<ref name="pmid17396261">{{cite journal| author=Grewal JS, Smith LB, Winegarden JD, Krauss JC, Tworek JA, Schnitzer B| title=Highly aggressive ALK-positive anaplastic large cell lymphoma with a leukemic phase and multi-organ involvement: a report of three cases and a review of the literature. | journal=Ann Hematol | year= 2007 | volume= 86 | issue= 7 | pages= 499-508 | pmid=17396261 | doi=10.1007/s00277-007-0289-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17396261 }} </ref> the bone,<ref name="pmid17396261">{{cite journal| author=Grewal JS, Smith LB, Winegarden JD, Krauss JC, Tworek JA, Schnitzer B| title=Highly aggressive ALK-positive anaplastic large cell lymphoma with a leukemic phase and multi-organ involvement: a report of three cases and a review of the literature. | journal=Ann Hematol | year= 2007 | volume= 86 | issue= 7 | pages= 499-508 | pmid=17396261 | doi=10.1007/s00277-007-0289-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17396261 }} </ref> the heart,<ref name="pmid16313264">{{cite journal| author=Lim ZY, Grace R, Salisbury JR, Creamer D, Jayaprakasam A, Ho AY et al.| title=Cardiac presentation of ALK positive anaplastic large cell lymphoma. | journal=Eur J Haematol | year= 2005 | volume= 75 | issue= 6 | pages= 511-4 | pmid=16313264 | doi=10.1111/j.1600-0609.2005.00542.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16313264 }} </ref> and the respiratory tract.<ref name="pmid18670314">{{cite journal| author=Tan DS, Eng PC, Lim ST, Thye LS, Tao M| title=Primary tracheal lymphoma causing respiratory failure. | journal=J Thorac Oncol | year= 2008 | volume= 3 | issue= 8 | pages= 929-30 | pmid=18670314 | doi=10.1097/JTO.0b013e318180271d | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18670314 }} </ref>
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|
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| Common symptoms include typical [[B symptoms]]: [[fever]], [[weight loss]], and [[night sweats]].<ref>{{cite web|url=http://www.lymphomas.org.uk/sites/default/files/pdfs/T-cell-lymphomas.pdf|title=T-cell lymphomas (Lymphoma Association)}}</ref>
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|
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| ===Laboratory Findings===
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| *[[Anemia]]
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| *[[Thrombocytopenia]]
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| *Elevated [[lactate dehydrogenase]] ([[LDH]])<ref>{{cite web|url=http://www.bloodjournal.org/content/111/12/5496|title=ALK− anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project}}</ref>
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|
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| == Treatment ==
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| ====CHOP-E Regimen====
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| The CHOP-E regimen includes:
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| *[[Cyclophosphamide]]
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| *[[Doxorubicin]]
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| *[[Vincristine]]
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| *[[Prednisone]]
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| *[[Etoposide]]
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|
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| [[Crizotinib]] has successfully treated patients with ALK positive ALCL refractory to CHOP therapy.<ref>{{cite web|url=http://www.ascopost.com/ViewNews.aspx?nid=12946|title=Crizotinib Produces Durable Responses in Small Study of Patients With Advanced, Chemoresistant ALK-Positive Lymphoma}}</ref> [[Crizotinib]] was administered twice daily, each dose of 250mg.
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|
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| ==References==
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| {{Reflist|2}}
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|
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| __NOTOC__
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| {{SI}}
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| {{DiseaseDisorder infobox |
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| Name = auses
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|
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| Anaplastic large cell lymphoma, ALK negative
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|
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| ls|
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| ICD10 = {{ICD10|C|84|4|c|81}} |
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| OMIM = |
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| MedlinePlus = |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| }}
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| {{CMG}}; {{AE}} {{AP}}
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|
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| {{SK}} ALCL-ALK(-); ALK-negative ALCL; ALK negative ALCL; ALK negative anaplastic large cell lymphoma
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|
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| ==Overview==
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| ALK negative anaplastic large cell lymphoma (ALCL) is a type of [[peripheral T-cell lymphoma]] ([[non-Hodgkin's lymphoma]]). ALK negative ALCL [[T-cell]]s express [[CD30]], but not the ALK ('''A'''naplastic '''L'''ymphoma '''K'''inase) chimeric protein,<ref name=Swerdlow>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref> which explains the difference in clinical outcome compared to that of [[ALK(+)-ALCL]].<ref name="pmid25461779">{{cite journal| author=Xing X, Feldman AL| title=Anaplastic large cell lymphomas: ALK positive, ALK negative, and primary cutaneous. | journal=Adv Anat Pathol | year= 2015 | volume= 22 | issue= 1 | pages= 29-49 | pmid=25461779 | doi=10.1097/PAP.0000000000000047 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461779 }} </ref> [[T-cell]]s in ALK negative ALCL have a chromosomal rearrangement that involves DUSP22 and TP63 gene. ALK negative ALCL patients with DUSP22 mutation have a higher five-year overall survival rate in comparison with ALK positive ALCL.<ref name="pmid24894770">{{cite journal| author=Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA et al.| title=ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. | journal=Blood | year= 2014 | volume= 124 | issue= 9 | pages= 1473-80 | pmid=24894770 | doi=10.1182/blood-2014-04-571091 | pmc=PMC4148769 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24894770 }} </ref>
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|
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| ==Historical Perspective==
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| In 2008, the World Health Organization (WHO) added ALK negative ALCL as a provisional entity in the [[peripheral T-cell lymphoma]] classification.<ref name="ALK">{{cite web|url=http://www.sciencedirect.com/science/article/pii/S104084281200131X|title=Anaplastic large cell lymphoma, ALK-negative}}</ref>
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|
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| ==Causes==
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| ALK negative ALCL is characterized by a translocation T(6;7)(p25.3;q32.3), which inactivates the DUSP22 gene and leads to a higher proliferation rate.<ref name="pmid21030553">{{cite journal| author=Feldman AL, Dogan A, Smith DI, Law ME, Ansell SM, Johnson SH et al.| title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. | journal=Blood | year= 2011 | volume= 117 | issue= 3 | pages= 915-9 | pmid=21030553 | doi=10.1182/blood-2010-08-303305 | pmc=PMC3035081 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21030553 }} </ref> In healthy people, the product of the DUSP22 gene, the DUSP22 protein (also known as the <i>JNK pathway-associated phosphatase</i> or <i>JKAP</i>), inactivates the LCK tyrosine kinase protein during T-cell receptor signaling.<ref>{{cite web|url=http://www.nature.com/ncomms/2014/140409/ncomms4618/full/ncomms4618.html|title=The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck}}</ref>
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|
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| DUSP22 mutations are also associated with breast cancer (the UDSMP22 protein can also block [[estrogen receptors]])<ref>{{cite web|url=http://www.bloodjournal.org/content/117/3/915?sso-checked=true|title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing}}</ref> and primary cutaneous ALCL.<ref name="pmid25461779">{{cite journal| author=Xing X, Feldman AL| title=Anaplastic large cell lymphomas: ALK positive, ALK negative, and primary cutaneous. | journal=Adv Anat Pathol | year= 2015 | volume= 22 | issue= 1 | pages= 29-49 | pmid=25461779 | doi=10.1097/PAP.0000000000000047 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461779}} </ref>
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|
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| == Differential Diagnosis==
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| *Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)<ref name="pmid22789917">{{cite journal| author=Ferreri AJ, Govi S, Pileri SA, Savage KJ| title=Anaplastic large cell lymphoma, ALK-negative. | journal=Crit Rev Oncol Hematol | year= 2013 | volume= 85 | issue= 2 | pages= 206-15 | pmid=22789917 | doi=10.1016/j.critrevonc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22789917 }} </ref><ref name="ALK+/ALK-">{{cite web|url=http://www.bloodjournal.org/content/111/12/5496?sso-checked=true|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project}}</ref>
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| *Classical [[Hodgkin's lymphoma]]<ref name="pmid22789917">{{cite journal| author=Ferreri AJ, Govi S, Pileri SA, Savage KJ| title=Anaplastic large cell lymphoma, ALK-negative. | journal=Crit Rev Oncol Hematol | year= 2013 | volume= 85 | issue= 2 | pages= 206-15 | pmid=22789917 | doi=10.1016/j.critrevonc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22789917 }} </ref>
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| *Primary cutaneous anaplastic large cell lymphoma<ref name=Swerdlow>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
| |
| *[[Anaplastic large cell lymphoma, ALK positive]]<ref name="ALK+/ALK-">{{cite web|url=http://www.bloodjournal.org/content/111/12/5496?sso-checked=true|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project}}</ref>
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|
| |
| == Epidemiology and Demographics==
| |
| ALK negative ALCL represents 2%-3% of all [[non-Hodgkin's lymphomas]] ([[NHL]]) and 12% of all [[T-cell NHL]].<ref name="ALK">{{cite web|url=http://www.sciencedirect.com/science/article/pii/S104084281200131X|title=Anaplastic large cell lymphoma, ALK-negative}}</ref>
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|
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| ===Age===
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| ALK negative ALCL affects primarily adults between 40-60 years old.
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|
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| ===Gender===
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| There is a modest male predominance in the prevalence of the disease.<ref name=Swerdlow>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
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|
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| ==Risk Factors==
| |
| *Breast implants<ref name="pmid22789917">{{cite journal| author=Ferreri AJ, Govi S, Pileri SA, Savage KJ| title=Anaplastic large cell lymphoma, ALK-negative. | journal=Crit Rev Oncol Hematol | year= 2013 | volume= 85 | issue= 2 | pages= 206-15 | pmid=22789917 | doi=10.1016/j.critrevonc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22789917 }} </ref>
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|
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| ==Natural History, Complications and Prognosis==
| |
|
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| ===Prognosis===
| |
| The '''I'''nternational '''P'''rognostic '''I'''ndex (IPI) is used to estimate the prognosis of patients.<ref>{{cite web|url=http://www.uptodate.com/contents/image?imageKey=HEME%2F70850&topicKey=HEME%2F4705&rank=1%7E150&source=see_link&search=Anaplastic+large+cell+lymphoma%2C+ALK+positive&utdPopup=true|title=International Prognostic Index for non-Hodgkin lymphoma}}</ref> The IPI takes into account 5 variables:
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| *Patient's age (>60 years)
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| *Elevated serum [[lactate dehydrogenase]] ([[LDH]])
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| *Eastern Cooperative Oncology Group (ECOG) performance status
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| *Ann Arbor clinical stage III or IV
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| *Number of involved extra nodal sites > 1
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|
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| If any of this criteria is met, one point is awarded for the IPI. The interpretation of the total score is as follows:
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| *0 to 1: Low risk
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| *2: Low-intermediate risk
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| *3: High-intermediate risk
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| *4 to 5: High risk
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|
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| ==Diagnosis==
| |
|
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| ===History and Symptoms===
| |
| Patients typically present [[B symptoms]] ([[fever]], [[weight loss]] and [[lymphadenopathy]]). ALK negative ALCL patients have a higher incidence of cutaneous, hepatic and gastrointestinal involvement than [[ALK positive ALCL]].<ref name="ALK+/ALK-">{{cite web|url=http://www.bloodjournal.org/content/111/12/5496?sso-checked=true|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project}}</ref> Other sites of involvement include the [[bronchus]]<ref name="pmid24427373">{{cite journal| author=Xu X| title=ALK-negative anaplastic large cell lymphoma primarily involving the bronchus: a case report and literature review. | journal=Int J Clin Exp Pathol | year= 2014 | volume= 7 | issue= 1 | pages= 460-3 | pmid=24427373 | doi= | pmc=PMC3885507 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24427373 }} </ref>, [[central nervous system]],<ref name="pmid24649224">{{cite journal| author=Nomura M, Narita Y, Miyakita Y, Ohno M, Fukushima S, Maruyama T et al.| title=Clinical presentation of anaplastic large-cell lymphoma in the central nervous system. | journal=Mol Clin Oncol | year= 2013 | volume= 1 | issue= 4 | pages= 655-660 | pmid=24649224 | doi=10.3892/mco.2013.110 | pmc=PMC3915681 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24649224 }} </ref> [[pancreas]],<ref name="pmid16273656">{{cite journal| author=Savopoulos CG, Tsesmeli NE, Kaiafa GD, Zantidis AT, Bobos MT, Hatzitolios AI et al.| title=Primary pancreatic anaplastic large cell lymphoma, ALK negative: a case report. | journal=World J Gastroenterol | year= 2005 | volume= 11 | issue= 39 | pages= 6221-4 | pmid=16273656 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16273656 }} </ref> [[rectum]],<ref>{{citeweb|url=http://dx.doi.org/10.4236/ojpathology.2013.31007|title=
| |
| Anaplastic Large Cell Lymphoma, ALK-Negative Presenting in the Rectum: A Case Report and Review of the Literature}}</ref> [[breast]] peri-implant seromas,<ref name="pmid25490535">{{cite journal| author=Brody GS, Deapen D, Taylor CR, Pinter-Brown L, House-Lightner SR, Andersen J et al.| title=Anaplastic Large Cell Lymphoma (ALCL) Occuring in Women with Breast Implants: Analysis of 173 Cases. | journal=Plast Reconstr Surg | year= 2014 | volume= | issue= | pages= | pmid=25490535 | doi=10.1097/PRS.0000000000001033 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25490535 }} </ref> [[skeletal muscle]],<ref name="pmid25292453">{{cite journal| author=Kubo Y, Aoi J, Johno T, Makino T, Sakai K, Masuguchi S et al.| title=A case of anaplastic large cell lymphoma of skeletal muscle. | journal=J Dermatol | year= 2014 | volume= 41 | issue= 11 | pages= 999-1002 | pmid=25292453 | doi=10.1111/1346-8138.12641 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25292453 }} </ref> and [[bone]].<ref name="pmid25346119">{{cite journal| author=Yu G, Huang X, Li M, Ding Y, Wang X, Lai Y et al.| title=[Clinicopathologic features and prognosis of primary bone anaplastic large cell lymphoma]. | journal=Zhonghua Bing Li Xue Za Zhi | year= 2014 | volume= 43 | issue= 8 | pages= 512-5 | pmid=25346119 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25346119 }} </ref>
| |
|
| |
| ===Cytology Findings===
| |
| According to the World Health Organization (WHO), the most important factor to diagnose a ALK negative ALCL is morphology and immunophenotype:<ref>{{cite web|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704299/|title=Anaplastic large cell lymphoma: changes in the World Health Organization classification and perspectives for targeted therapy}}</ref>
| |
|
| |
| ====Morphologic criteria====
| |
| *Absence of small-to-medium sized lymphocytes.
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|
| |
| ====Immunophenotype criteria====
| |
| *[[CD30]] expression
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| *Nuclear negativity for the [[PAX5]] transcription factor (usually expressed in [[Hodgkin’s lymphoma]] classic variant)
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| *Negativity for the [[EBV]] markers EBER and LMP1 (which may be expressed in [[Hodgkin’s lymphoma]] classic variant)
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| *Presence of clonal [[T-cell receptor]] rearrangements (usually absent in [[Hodgkin’s lymphoma]] classic variant).
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|
| |
| ===Laboratory Findings<ref name="ALK+/ALK-">{{cite web|url=http://www.bloodjournal.org/content/111/12/5496?sso-checked=true|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project}}</ref>===
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| *[[Anemia]]
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| *[[Thrombocytopenia]]
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| *Increased [[LDH]]
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|
| |
| == Treatment ==
| |
| Although the [[peripheral T-cell lymphomas]] are a heterogenous group of pathologies, the treatment is the same:<ref name="pmid24615779">{{cite journal| author=Moskowitz AJ, Lunning MA, Horwitz SM| title=How I treat the peripheral T-cell lymphomas. | journal=Blood | year= 2014 | volume= 123 | issue= 17 | pages= 2636-44 | pmid=24615779 | doi=10.1182/blood-2013-12-516245 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24615779 }} </ref>
| |
| ===CHOP Regimen===
| |
| *This regimen includes:
| |
| **[[Cyclophosphamide]]
| |
| **[[Doxorubicin]]
| |
| **[[Vincristine]]
| |
| **[[Prednisone]]
| |
|
| |
| Some evidence suggest that although CHOP regimen is effective in treating the ALK(-) ALCL, a short 2-year event-free survival requires extra management<ref name="pmid24428090">{{cite journal| author=Rattarittamrong E, Norasetthada L, Tantiworawit A, Chai-Adisaksopha C, Nawarawong W| title=CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital. | journal=J Med Assoc Thai | year= 2013 | volume= 96 | issue= 11 | pages= 1416-22 | pmid=24428090 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24428090 }} </ref>, reason why CHOP regimen must then be followed by an autologous stem cell transplant during remission.<ref name="pmid24615779">{{cite journal| author=Moskowitz AJ, Lunning MA, Horwitz SM| title=How I treat the peripheral T-cell lymphomas. | journal=Blood | year= 2014 | volume= 123 | issue= 17 | pages= 2636-44 | pmid=24615779 | doi=10.1182/blood-2013-12-516245 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24615779 }} </ref>
| |
|
| |
| ===Alternative Therapy===
| |
| A novel drug, [[Brentuximab]], has effectively treated refractory, [[CD30]] positive ALCL in the japanese population.<ref name="pmid24814862">{{cite journal| author=Ogura M, Tobinai K, Hatake K, Ishizawa K, Uike N, Uchida T et al.| title=Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma. | journal=Cancer Sci | year= 2014 | volume= 105 | issue= 7 | pages= 840-6 | pmid=24814862 | doi=10.1111/cas.12435 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24814862 }} </ref> The most common side effects associated with [[brentuximab]] are [[peripheral sensory neuropathy]] and [[neutropenia]].<ref name="pmid23831822">{{cite journal| author=Terriou L, Bonnet S, Debarri H, Demarquette H, Morschhauser F| title=[Brentuximab vedotin: new treatment for CD30+ lymphomas]. | journal=Bull Cancer | year= 2013 | volume= 100 | issue= 7-8 | pages= 775-9 | pmid=23831822 | doi=10.1684/bdc.2013.1778 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23831822 }} </ref>
| |
|
| |
| ==References==
| |
| {{Reflist|2}}
| |