Difference between revisions of "Anaplastic Large Cell Lymphoma, ALK-Negative"

From Compendium of Cancer Genome Aberrations
Jump to: navigation, search
(Cancer Sub-Classification / Subtype)
(Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications))
(6 intermediate revisions by the same user not shown)
Line 8: Line 8:
 
==Cancer Category/Type==
 
==Cancer Category/Type==
  
Mature T-cell neoplasm
+
Mature peripheral T-cell neoplasm
  
 
==Cancer Sub-Classification / Subtype<ref name=":0" />==
 
==Cancer Sub-Classification / Subtype<ref name=":0" />==
 
Three major molecular subtypes
 
Three major molecular subtypes
  
* DUSP22-positive subtype (30%)
+
*DUSP22-positive subtype (30%)
* TP63-positive subtype  (8%)
+
*TP63-positive subtype  (8%)
* Triple-negative subtype  (DUSP22 negative, TP63 negative, Alk negative) with emerging sub-classifications
+
*Triple-negative subtype  (DUSP22 negative, TP63 negative, Alk negative) with emerging sub-classifications
  
 
==Definition / Description of Disease<ref>{{Cite journal|last=Ad|first=Attygalle|last2=J|first2=Cabeçadas|last3=P|first3=Gaulard|last4=Es|first4=Jaffe|last5=D|first5=de Jong|last6=Yh|first6=Ko|last7=J|first7=Said|last8=W|first8=Klapper|date=2014|title=Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology|url=https://pubmed.ncbi.nlm.nih.gov/24128129/|language=en|doi=10.1111/his.12251|pmc=PMC6364972|pmid=24128129}}</ref><ref>{{Cite journal|last=Sh|first=Swerdlow|last2=E|first2=Campo|last3=Sa|first3=Pileri|last4=Nl|first4=Harris|last5=H|first5=Stein|last6=R|first6=Siebert|last7=R|first7=Advani|last8=M|first8=Ghielmini|last9=Ga|first9=Salles|date=2016|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/26980727/|language=en|doi=10.1182/blood-2016-01-643569|pmc=PMC4874220|pmid=26980727}}</ref>==
 
==Definition / Description of Disease<ref>{{Cite journal|last=Ad|first=Attygalle|last2=J|first2=Cabeçadas|last3=P|first3=Gaulard|last4=Es|first4=Jaffe|last5=D|first5=de Jong|last6=Yh|first6=Ko|last7=J|first7=Said|last8=W|first8=Klapper|date=2014|title=Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology|url=https://pubmed.ncbi.nlm.nih.gov/24128129/|language=en|doi=10.1111/his.12251|pmc=PMC6364972|pmid=24128129}}</ref><ref>{{Cite journal|last=Sh|first=Swerdlow|last2=E|first2=Campo|last3=Sa|first3=Pileri|last4=Nl|first4=Harris|last5=H|first5=Stein|last6=R|first6=Siebert|last7=R|first7=Advani|last8=M|first8=Ghielmini|last9=Ga|first9=Salles|date=2016|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/26980727/|language=en|doi=10.1182/blood-2016-01-643569|pmc=PMC4874220|pmid=26980727}}</ref>==
  
*Anaplastic large cell lymphomas, alk-negative, belong to the general class of peripheral T cell lymphomas, a subtype of Non-Hodgin's lymphoma
+
*Anaplastic large cell lymphomas (ALCL), alk-negative, belong to the general class of peripheral T cell lymphomas, a subtype of Non-Hodgin's lymphoma
*This distinct entity is morphologically and phenotypically indistinguishable from Alk-Positive anaplastic large cell lymphoma.
+
*This distinct entity is morphologically and phenotypically indistinguishable from Alk-positive anaplastic large cell lymphoma, although prognosis is generally poorer in the latter*.
 +
**When stratified for age, prognosis between Alk- and Alk+ ALCL appears similar <ref>{{Cite journal|last=Kj|first=Savage|last2=Nl|first2=Harris|last3=Jm|first3=Vose|last4=F|first4=Ullrich|last5=Es|first5=Jaffe|last6=Jm|first6=Connors|last7=L|first7=Rimsza|last8=Sa|first8=Pileri|last9=M|first9=Chhanabhai|date=2008|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|url=https://pubmed.ncbi.nlm.nih.gov/18385450/|language=en|pmid=18385450}}</ref><ref>{{Cite journal|last=D|first=Sibon|last2=M|first2=Fournier|last3=J|first3=Brière|last4=L|first4=Lamant|last5=C|first5=Haioun|last6=B|first6=Coiffier|last7=S|first7=Bologna|last8=P|first8=Morel|last9=J|first9=Gabarre|date=2012|title=Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials|url=https://pubmed.ncbi.nlm.nih.gov/23045585/|language=en|pmid=23045585}}</ref>
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
Line 26: Line 27:
 
*N/A
 
*N/A
  
==Epidemiology / Prevalence==
+
==Epidemiology / Prevalence<ref name=":1">{{Cite journal|last=G|first=Hapgood|last2=Kj|first2=Savage|date=2015|title=The biology and management of systemic anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25869285/|language=en|pmid=25869285}}</ref>==
  
*More common in adults than children
+
*More common in adults than children (peak incidence 6th decade of life)
 
*Less than 3% of all Non-Hodgkin's lymphoma
 
*Less than 3% of all Non-Hodgkin's lymphoma
 
*M:F 1.5:1
 
*M:F 1.5:1
  
==Clinical Features==
+
==Clinical Features<ref name=":1" />==
  
 
*B symptoms of weight loss, fevers, chills
 
*B symptoms of weight loss, fevers, chills
Line 40: Line 41:
 
==Sites of Involvement==
 
==Sites of Involvement==
  
*Nodal (predominantly abdominal lymphadenopathy
+
*Nodal (predominantly abdominal lymphadenopathy)
*Extranodal (skin, bone, gastrointestinal)
+
*Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases
  
 
==Morphologic Features==
 
==Morphologic Features==
Line 51: Line 52:
 
*Eosinophils common
 
*Eosinophils common
  
==Immunophenotype==
+
==Immunophenotype<ref name=":1" />==
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 57: Line 58:
 
!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
|Positive (universal)||strong CD30, CD43 (almost universally)
+
|Positive (universal)||CD30*, CD43 (almost universally)
 
|-
 
|-
|Positive (subset)||CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin
+
|Positive (subset)||CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, EMA
 
|-
 
|-
 
|Negative (universal)||ALK, EBER, LMP-1
 
|Negative (universal)||ALK, EBER, LMP-1
Line 65: Line 66:
 
|Negative (DUSP22 rearranged subset)||CD2, CD3, CD5, TIA1, granzyme B, perforin
 
|Negative (DUSP22 rearranged subset)||CD2, CD3, CD5, TIA1, granzyme B, perforin
 
|}
 
|}
 +
<nowiki>*</nowiki>Strong CD30 staining is apparent on cell membrane and on Golgi apparatus.
  
 
==Chromosomal Rearrangements (Gene Fusions)<ref>{{Cite journal|last=Pileri|first=Stefano|date=2011-05-01|title=Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing.|url=http://dx.doi.org/10.3410/f.10182958.10970056}}</ref><ref>{{Cite journal|last=Wisell|first=J.|date=2012-01|title=Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies|url=http://dx.doi.org/10.1016/j.ypat.2011.11.134|journal=Yearbook of Pathology and Laboratory Medicine|volume=2012|pages=83–84|doi=10.1016/j.ypat.2011.11.134|issn=1077-9108}}</ref>==
 
==Chromosomal Rearrangements (Gene Fusions)<ref>{{Cite journal|last=Pileri|first=Stefano|date=2011-05-01|title=Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing.|url=http://dx.doi.org/10.3410/f.10182958.10970056}}</ref><ref>{{Cite journal|last=Wisell|first=J.|date=2012-01|title=Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies|url=http://dx.doi.org/10.1016/j.ypat.2011.11.134|journal=Yearbook of Pathology and Laboratory Medicine|volume=2012|pages=83–84|doi=10.1016/j.ypat.2011.11.134|issn=1077-9108}}</ref>==
Line 72: Line 74:
 
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Prevalence
 
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Prevalence
 
|-
 
|-
|t(6;7)(p25.3;q32.3)||DUSP22/IRF4||30%<ref name=":0">{{Cite journal|last=Er|first=Parrilla Castellar|last2=Es|first2=Jaffe|last3=Jw|first3=Said|last4=Sh|first4=Swerdlow|last5=Rp|first5=Ketterling|last6=Ra|first6=Knudson|last7=Js|first7=Sidhu|last8=Ed|first8=Hsi|last9=S|first9=Karikehalli|date=2014|title=ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/24894770/|language=en|doi=10.1182/blood-2014-04-571091|pmc=PMC4148769|pmid=24894770}}</ref>
+
|t(6;7)(p25.3;q32.3)||DUSP22/FRA7H||30%<ref name=":0">{{Cite journal|last=Er|first=Parrilla Castellar|last2=Es|first2=Jaffe|last3=Jw|first3=Said|last4=Sh|first4=Swerdlow|last5=Rp|first5=Ketterling|last6=Ra|first6=Knudson|last7=Js|first7=Sidhu|last8=Ed|first8=Hsi|last9=S|first9=Karikehalli|date=2014|title=ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/24894770/|language=en|doi=10.1182/blood-2014-04-571091|pmc=PMC4148769|pmid=24894770}}</ref>
 
|-
 
|-
 
|t(3;3)(q22;q26.2)||P63/TBL1XR1||8%<ref name=":0" />
 
|t(3;3)(q22;q26.2)||P63/TBL1XR1||8%<ref name=":0" />
|}
+
|}
+
<nowiki>*</nowiki> These rearrangements are mutually exclusive
 +
 
 
==Characteristic Chromosomal Aberrations / Patterns==
 
==Characteristic Chromosomal Aberrations / Patterns==
  
Line 135: Line 138:
  
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
===Other Mutations===
+
===Other Mutations<ref name=":2">{{Cite journal|last=R|first=Crescenzo|last2=F|first2=Abate|last3=E|first3=Lasorsa|last4=F|first4=Tabbo'|last5=M|first5=Gaudiano|last6=N|first6=Chiesa|last7=F|first7=Di Giacomo|last8=E|first8=Spaccarotella|last9=L|first9=Barbarossa|date=2015|title=Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25873174/|language=en|doi=10.1016/j.ccell.2015.03.006|pmc=PMC5898430|pmid=25873174}}</ref>===
  
 
*TET2
 
*TET2
Line 145: Line 148:
 
*N/A
 
*N/A
  
==Genes and Main Pathways Involved==
+
==Genes and Main Pathways Involved <ref name=":2" />==
  
 
JAK-STAT
 
JAK-STAT
Line 156: Line 159:
 
==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
 
==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
  
*3-gene model (TNFRSF8, BATF3, and TMOD1) distinguishes Alk- ALCL from PTCL with > 97% accuracy<ref>{{Cite journal|date=2020-02-10|title=ALK-negative anaplastic large cell lymphoma|url=http://dx.doi.org/10.32388/xalv0h|journal=Definitions|publisher=Qeios}}</ref>
+
*3-gene model (TNFRSF8, BATF3, and TMOD1) distinguishes Alk- ALCL from PTCL, NOS with > 97% accuracy<ref>{{Cite journal|date=2020-02-10|title=ALK-negative anaplastic large cell lymphoma|url=http://dx.doi.org/10.32388/xalv0h|journal=Definitions|publisher=Qeios}}</ref>
 +
*Leukocyte common antigen (LCA) expression may help distinguish from primary cutaneous Anaplastic Large-Cell Lymphoma
 
*5 year overall survival > 90% for DUSP22 rearranged Alk- ALCL, 17% for TP63-rearranged Alk- ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK<ref name=":0" />
 
*5 year overall survival > 90% for DUSP22 rearranged Alk- ALCL, 17% for TP63-rearranged Alk- ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK<ref name=":0" />
  

Revision as of 19:52, 28 July 2020

This page is under construction
We need your help!
Please consider joining in the project and submitting a review

Primary Author(s)*

Derick Okwan-Duodu, MD, PhD; Sumire Kitahara, MD

Cancer Category/Type

Mature peripheral T-cell neoplasm

Cancer Sub-Classification / Subtype[1]

Three major molecular subtypes

  • DUSP22-positive subtype (30%)
  • TP63-positive subtype (8%)
  • Triple-negative subtype (DUSP22 negative, TP63 negative, Alk negative) with emerging sub-classifications

Definition / Description of Disease[2][3]

  • Anaplastic large cell lymphomas (ALCL), alk-negative, belong to the general class of peripheral T cell lymphomas, a subtype of Non-Hodgin's lymphoma
  • This distinct entity is morphologically and phenotypically indistinguishable from Alk-positive anaplastic large cell lymphoma, although prognosis is generally poorer in the latter*.
    • When stratified for age, prognosis between Alk- and Alk+ ALCL appears similar [4][5]

Synonyms / Terminology

  • N/A

Epidemiology / Prevalence[6]

  • More common in adults than children (peak incidence 6th decade of life)
  • Less than 3% of all Non-Hodgkin's lymphoma
  • M:F 1.5:1

Clinical Features[6]

  • B symptoms of weight loss, fevers, chills
  • Peripheral and/or abdominal lymphadenopathy
  • Most patients present with advanced stage disease

Sites of Involvement

  • Nodal (predominantly abdominal lymphadenopathy)
  • Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases

Morphologic Features

  • Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells
  • Prominent nucleoli
  • Hallmark cells
  • High nuclear-cytoplasmic ratio
  • Eosinophils common

Immunophenotype[6]

Finding Marker
Positive (universal) CD30*, CD43 (almost universally)
Positive (subset) CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, EMA
Negative (universal) ALK, EBER, LMP-1
Negative (DUSP22 rearranged subset) CD2, CD3, CD5, TIA1, granzyme B, perforin

*Strong CD30 staining is apparent on cell membrane and on Golgi apparatus.

Chromosomal Rearrangements (Gene Fusions)[7][8]

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Prevalence
t(6;7)(p25.3;q32.3) DUSP22/FRA7H 30%[1]
t(3;3)(q22;q26.2) P63/TBL1XR1 8%[1]

* These rearrangements are mutually exclusive

Characteristic Chromosomal Aberrations / Patterns

Genomic Gain/Loss/LOH[9]

  • In general, recurrent lesions are more common in Alk- than Alk+ disease
Chromosome Number Gain/Loss/Amp/LOH Region Genes Prevalence
1q Gain numerous
6p Gain
8q Gain 24.22 NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1 23%
12q Gain
6q Loss 21 56%
13q Loss 32.3-q33.3 23%
16q Loss 23.2 MAF, WWOX 29%
17p Loss 13.3-p12 TP53 42%

Gene Mutations (SNV/INDEL)

Other Mutations[10]

  • TET2
  • FAS
  • STIM2

Epigenomics (Methylation)

  • N/A

Genes and Main Pathways Involved [10]

JAK-STAT

Diagnostic Testing Methods

  • ERBB4 and COL29A1 co-expressing subtype[11]
  • DUSP22- IRF4[12]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • 3-gene model (TNFRSF8, BATF3, and TMOD1) distinguishes Alk- ALCL from PTCL, NOS with > 97% accuracy[13]
  • Leukocyte common antigen (LCA) expression may help distinguish from primary cutaneous Anaplastic Large-Cell Lymphoma
  • 5 year overall survival > 90% for DUSP22 rearranged Alk- ALCL, 17% for TP63-rearranged Alk- ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK[1]

Familial Forms

  • Not described

Other Information

Put your text here

Links

Put your links here (use "Link" icon at top of page)

References

(use "Cite" icon at top of page)

  1. 1.0 1.1 1.2 1.3 Er, Parrilla Castellar; et al. (2014). "ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes". doi:10.1182/blood-2014-04-571091. PMC 4148769. PMID 24894770.CS1 maint: PMC format (link)
  2. Ad, Attygalle; et al. (2014). "Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology". doi:10.1111/his.12251. PMC 6364972. PMID 24128129.CS1 maint: PMC format (link)
  3. Sh, Swerdlow; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.CS1 maint: PMC format (link)
  4. Kj, Savage; et al. (2008). "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". PMID 18385450.
  5. D, Sibon; et al. (2012). "Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials". PMID 23045585.
  6. 6.0 6.1 6.2 G, Hapgood; et al. (2015). "The biology and management of systemic anaplastic large cell lymphoma". PMID 25869285.
  7. Pileri, Stefano (2011-05-01). "Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing".
  8. Wisell, J. (2012-01). "Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies". Yearbook of Pathology and Laboratory Medicine. 2012: 83–84. doi:10.1016/j.ypat.2011.11.134. ISSN 1077-9108. Check date values in: |date= (help)
  9. M, Boi; et al. (2013). "PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma". PMID 24004669.
  10. 10.0 10.1 R, Crescenzo; et al. (2015). "Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma". doi:10.1016/j.ccell.2015.03.006. PMC 5898430. PMID 25873174.CS1 maint: PMC format (link)
  11. I, Scarfò; et al. (2016). "Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts". PMID 26463425.
  12. Al, Feldman; et al. (2011). "Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing". doi:10.1182/blood-2010-08-303305. PMC 3035081. PMID 21030553.CS1 maint: PMC format (link)
  13. "ALK-negative anaplastic large cell lymphoma". Definitions. Qeios. 2020-02-10.

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.