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

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(Genomic Gain/Loss/LOH)
(Cancer Sub-Classification / Subtype)
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Mature T-cell neoplasm
 
Mature T-cell neoplasm
  
==Cancer Sub-Classification / Subtype==
+
==Cancer Sub-Classification / Subtype<ref name=":0" />==
 +
Three major molecular subtypes
  
==Definition / Description of Disease==
+
* DUSP22-positive subtype (30%)
 +
* TP63-positive subtype  (8%)
 +
* Triple-negative subtype  (DUSP22 negative, TP63 negative, Alk negative) with emerging sub-classifications
  
This entity of anaplastic large cell lymphoma is morphologically and phenotypically indistinguishable from Alk-Positive anaplastic large cell lymphoma.
+
==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
 +
*This distinct entity is morphologically and phenotypically indistinguishable from Alk-Positive anaplastic large cell lymphoma.
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
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==Characteristic Chromosomal Aberrations / Patterns==
 
==Characteristic Chromosomal Aberrations / Patterns==
  
==Genomic Gain/Loss/LOH==
+
==Genomic Gain/Loss/LOH<ref>{{Cite journal|last=M|first=Boi|last2=A|first2=Rinaldi|last3=I|first3=Kwee|last4=P|first4=Bonetti|last5=M|first5=Todaro|last6=F|first6=Tabbò|last7=R|first7=Piva|last8=Pm|first8=Rancoita|last9=A|first9=Matolcsy|date=2013|title=PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24004669/|language=en|pmid=24004669}}</ref>==
  
* In general, recurrent lesions are more common in Alk- than Alk+ disease
+
*In general, recurrent lesions are more common in Alk- than Alk+ disease
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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==Diagnostic Testing Methods==
 
==Diagnostic Testing Methods==
  
ERBB4 and COL29A1 co-expressing subtype<ref>{{Cite journal|last=I|first=Scarfò|last2=E|first2=Pellegrino|last3=E|first3=Mereu|last4=I|first4=Kwee|last5=L|first5=Agnelli|last6=E|first6=Bergaggio|last7=G|first7=Garaffo|last8=N|first8=Vitale|last9=M|first9=Caputo|date=2016|title=Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts|url=https://pubmed.ncbi.nlm.nih.gov/26463425/|language=en|pmid=26463425}}</ref>
+
*ERBB4 and COL29A1 co-expressing subtype<ref>{{Cite journal|last=I|first=Scarfò|last2=E|first2=Pellegrino|last3=E|first3=Mereu|last4=I|first4=Kwee|last5=L|first5=Agnelli|last6=E|first6=Bergaggio|last7=G|first7=Garaffo|last8=N|first8=Vitale|last9=M|first9=Caputo|date=2016|title=Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts|url=https://pubmed.ncbi.nlm.nih.gov/26463425/|language=en|pmid=26463425}}</ref>
 
+
*DUSP22- IRF4<ref>{{Cite journal|last=Al|first=Feldman|last2=A|first2=Dogan|last3=Di|first3=Smith|last4=Me|first4=Law|last5=Sm|first5=Ansell|last6=Sh|first6=Johnson|last7=Jc|first7=Porcher|last8=N|first8=Ozsan|last9=Ed|first9=Wieben|date=2011|title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing|url=https://pubmed.ncbi.nlm.nih.gov/21030553/|language=en|doi=10.1182/blood-2010-08-303305|pmc=PMC3035081|pmid=21030553}}</ref>
DUSP22- IRF4<ref>{{Cite journal|last=Al|first=Feldman|last2=A|first2=Dogan|last3=Di|first3=Smith|last4=Me|first4=Law|last5=Sm|first5=Ansell|last6=Sh|first6=Johnson|last7=Jc|first7=Porcher|last8=N|first8=Ozsan|last9=Ed|first9=Wieben|date=2011|title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing|url=https://pubmed.ncbi.nlm.nih.gov/21030553/|language=en|doi=10.1182/blood-2010-08-303305|pmc=PMC3035081|pmid=21030553}}</ref>
 
  
 
==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 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>
*5 year overall survival > 90% for DUSP22 rearranged Alk- ALCL, 17% for TP63-rearranged Alk- ALCL, and 42% for cases lacking 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" />
  
 
==Familial Forms==
 
==Familial Forms==

Revision as of 18:46, 28 July 2020

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Primary Author(s)*

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

Cancer Category/Type

Mature 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, 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.

Synonyms / Terminology

  • N/A

Epidemiology / Prevalence

  • More common in adults than children
  • Less than 3% of all Non-Hodgkin's lymphoma
  • M:F 1.5:1

Clinical Features

  • 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, bone, gastrointestinal)

Morphologic Features

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

Immunophenotype

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

Chromosomal Rearrangements (Gene Fusions)[4][5]

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Prevalence
t(6;7)(p25.3;q32.3) DUSP22/IRF4 30%[1]
t(3;3)(q22;q26.2) P63/TBL1XR1 8%[1]

Characteristic Chromosomal Aberrations / Patterns

Genomic Gain/Loss/LOH[6]

  • 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

  • TET2
  • FAS
  • STIM2

Epigenomics (Methylation)

  • N/A

Genes and Main Pathways Involved

JAK-STAT

Diagnostic Testing Methods

  • ERBB4 and COL29A1 co-expressing subtype[7]
  • DUSP22- IRF4[8]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • 3-gene model (TNFRSF8, BATF3, and TMOD1) distinguishes Alk- ALCL from PTCL with > 97% accuracy[9]
  • 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

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Links

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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. 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".
  5. 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)
  6. M, Boi; et al. (2013). "PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma". PMID 24004669.
  7. I, Scarfò; et al. (2016). "Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts". PMID 26463425.
  8. 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)
  9. "ALK-negative anaplastic large cell lymphoma". Definitions. Qeios. 2020-02-10.

Notes

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