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

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(Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications))
(Other Mutations)
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{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!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/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(3;3)(q22;q26.2)||P63/TBL1XR1|| ||8%<ref name=":0" />
+
|t(3;3)(q22;q26.2)||P63/TBL1XR1||8%<ref name=":0" />
 
|}
 
|}
 
 
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|
 
|
 
|-
 
|-
|8q||Gain||
+
|8q||Gain||24.22
 
|-
 
|-
 
|12q
 
|12q
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|
 
|
 
|-
 
|-
|6q
+
|16q
 
|Loss
 
|Loss
|
+
|23.2
 
|-
 
|-
 
|13q
 
|13q
 
|Loss
 
|Loss
|
+
|32.3-q33.3
 
|-
 
|-
 
|17p
 
|17p
 
|Loss
 
|Loss
 +
|13.3-p12
 +
|}
 +
 +
{| class="wikitable"
 +
!Lesion/Cytoband
 +
!Start*
 +
!Size, kb*
 +
!RefSeq genes†
 +
!ALCL %
 +
!ALK<sup>−</sup>ALCL %
 +
!ALK<sup>+</sup>ALCL %
 +
!''P''
 +
|-
 +
|'''Losses'''
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|-
 +
| 17p13.3-p12
 +
|526
 +
|11 747.22
 +
|>20 (TP53)
 +
|25
 +
|42
 +
|9
 +
|.002
 +
|-
 +
| 6q21
 +
|105 944 900
 +
|951.75
 +
|''ATG5'', ''PRDM1''
 +
|19
 +
|56
 +
|6
 +
|<.001
 +
|-
 +
| 13q32.3-q33.3
 +
|99 090 837
 +
|9349.42
 +
|>20
 +
|16
 +
|23
 +
|9
 +
|ns
 +
|-
 +
| 16q23.2
 +
|78 371 498
 +
|11 642
 +
|''MAF'', ''WWOX''
 +
|16
 +
|29
 +
|3
 +
|.004
 +
|-
 +
|'''Gains'''
 
|
 
|
|}
+
|
+
|
 +
|
 +
|
 +
|
 +
|
 +
|-
 +
| 1q
 +
|121 344 093
 +
|127 880.29
 +
|>20
 +
|23
 +
|32
 +
|15
 +
|ns
 +
|-
 +
| 8q24.22
 +
|133 799 280
 +
|919.4
 +
|''NDRG1'', ''PHF20L1'', ''SLA'', ''ST3GAL1'', ''TG'', ''WISP1''
 +
|17
 +
|23
 +
|12
 +
|ns
 +
|}
 +
 
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
  
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!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
 
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
 
|-
 
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
+
|PRDM1
 +
|
 +
|Transcriptional Repressor
 +
|LOF
 +
|56%
 +
|-
 +
|TP53|| ||Tumor Suppressor||EXAMPLE LOF||42%
 
|}
 
|}
 
 
 
===Other Mutations===
 
===Other Mutations===
 +
 +
* PRDM1
 +
* TP53
 +
* TET2
 +
* FAS
 +
* STIM2
 +
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-

Revision as of 18:00, 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

Definition / Description of Disease

This entity of anaplastic large cell lymphoma 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)[1][2]

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

Characteristic Chromosomal Aberrations / Patterns

Genomic Gain/Loss/LOH

Put your text here and/or fill in the table

Chromosome Number Gain/Loss/Amp/LOH Region
1q Gain
6p Gain
8q Gain 24.22
12q Gain
4q Loss
16q Loss 23.2
13q Loss 32.3-q33.3
17p Loss 13.3-p12
Lesion/Cytoband Start* Size, kb* RefSeq genes† ALCL % ALKALCL % ALK+ALCL % P
Losses
 17p13.3-p12 526 11 747.22 >20 (TP53) 25 42 9 .002
 6q21 105 944 900 951.75 ATG5, PRDM1 19 56 6 <.001
 13q32.3-q33.3 99 090 837 9349.42 >20 16 23 9 ns
 16q23.2 78 371 498 11 642 MAF, WWOX 16 29 3 .004
Gains
 1q 121 344 093 127 880.29 >20 23 32 15 ns
 8q24.22 133 799 280 919.4 NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1 17 23 12 ns

Gene Mutations (SNV/INDEL)

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
PRDM1 Transcriptional Repressor LOF 56%
TP53 Tumor Suppressor EXAMPLE LOF 42%

Other Mutations

  • PRDM1
  • TP53
  • TET2
  • FAS
  • STIM2
Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

  • N/A

Genes and Main Pathways Involved

JAK-STAT

Diagnostic Testing Methods

ERBB4 and COL29A1 co-expressing subtype[4]

DUSP22- IRF4[5]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • 3-gene model (TNFRSF8, BATF3, and TMOD1) distinguishes Alk- ALCL from PTCL with > 97% accuracy[6]
  • 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[3]

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. 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".
  2. 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)
  3. 3.0 3.1 3.2 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)
  4. I, Scarfò; et al. (2016). "Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts". PMID 26463425.
  5. 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)
  6. "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.