Compendium of Cancer Genome Aberrations

HAEM5:ALK-positive anaplastic large cell lymphoma: Difference between revisions

[unchecked revision][checked revision]
← Older edit
VisualWikitext
No edit summary
 
(18 intermediate revisions by 3 users not shown)
Line 1: Line 1:
{{DISPLAYTITLE:ALK-positive anaplastic large cell lymphoma}}
{{DISPLAYTITLE:ALK-positive anaplastic large cell lymphoma}}
 
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class="blockedit">{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Anaplastic Large Cell Lymphoma, ALK-Positive]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Anaplastic Large Cell Lymphoma, ALK-Positive]].
}}</blockquote>
}}</blockquote>


<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>


==Primary Author(s)*==
==Primary Author(s)*==
Line 15: Line 14:


Sumire Kitahara, MD, Cedars-Sinai, Los Angeles, CA
Sumire Kitahara, MD, Cedars-Sinai, Los Angeles, CA
==WHO Classification of Disease==


__TOC__
==Cancer Category / Type==
*[[HAEM4:Mature T- and NK-cell Neoplasms]]
==Cancer Sub-Classification / Subtype==
*Systemic T-cell lymphoma
==Definition / Description of Disease==
Anaplastic Large Cell Lymphoma, ALK-Positive (ALK+ ALCL) is a T-cell lymphoma characterized by usually large lymphoma cells with abundant cytoplasm and pleomorphic nuclei, often horse-shoe shaped (see Morphologic Features below), with a chromosomal rearrangement involving the ALK gene resulting in expression of ALK protein and CD30
==Synonyms / Terminology==
*Ki-1 (CD30) lymphoma - obsolete
==Epidemiology / Prevalence==
*ALCL ([[ALK]]+, ALK-, and primary cutaneous) account for <5% of all cases of non-Hodgkin lymphoma (NHL)<ref name=":0" />
*ALK+ ALCL<ref name=":0">Arber DA, et al., (2017). Anaplastic large cell lymphoma, ALK-positive, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p413-418.</ref>
**~3% of adult NHL
**10-20% of childhood lymphomas
**Most frequent in the first three decades of life
**Male:female = 1.5:1
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
!Structure
|Most patients (70%) present with advanced (stage III-IV) disease and B-symptoms.<ref name=":19" />
!Disease
|-
|-
|'''Laboratory Findings'''
|Book
|Noncontributory
|Haematolymphoid Tumours (5th ed.)
|}
 
 
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
 
*Most patients (70%) present with advanced (stage III-IV) disease and B-symptoms.<ref name=":19">{{Cite journal|last=Savage|first=Kerry J.|last2=Harris|first2=Nancy Lee|last3=Vose|first3=Julie M.|last4=Ullrich|first4=Fred|last5=Jaffe|first5=Elaine S.|last6=Connors|first6=Joseph M.|last7=Rimsza|first7=Lisa|last8=Pileri|first8=Stefano A.|last9=Chhanabhai|first9=Mukesh|date=2008-06-15|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/|journal=Blood|volume=111|issue=12|pages=5496–5504|doi=10.1182/blood-2008-01-134270|issn=1528-0020|pmid=18385450}}</ref>
 
</blockquote>
==Sites of Involvement==
 
 
*Lymph nodes and extranodal sites (most commonly skin, bone, soft tissue, lungs and liver)<ref name=":0" />
*Bone marrow involvement detected in 30% when using immunohistochemistry (CD30 and EMA). Can miss marrow involvement by H&E evaluation alone, which detects involvement with ~10% incidence.<ref>{{Cite journal|last=M|first=Fraga|last2=P|first2=Brousset|last3=D|first3=Schlaifer|last4=C|first4=Payen|last5=A|first5=Robert|last6=H|first6=Rubie|last7=F|first7=Huguet-Rigal|last8=G|first8=Delsol|date=1995|title=Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance|url=https://pubmed.ncbi.nlm.nih.gov/7817951/|language=en|pmid=7817951}}</ref>
 
 
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /></blockquote>
==Morphologic Features==
 
"Hallmark cells"<ref>{{Cite journal|last=Stein|first=H.|last2=Foss|first2=H. D.|last3=Dürkop|first3=H.|last4=Marafioti|first4=T.|last5=Delsol|first5=G.|last6=Pulford|first6=K.|last7=Pileri|first7=S.|last8=Falini|first8=B.|date=2000-12-01|title=CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features|url=https://pubmed.ncbi.nlm.nih.gov/11090048/|journal=Blood|volume=96|issue=12|pages=3681–3695|issn=0006-4971|pmid=11090048}}</ref><ref>{{Cite journal|last=Benharroch|first=D.|last2=Meguerian-Bedoyan|first2=Z.|last3=Lamant|first3=L.|last4=Amin|first4=C.|last5=Brugières|first5=L.|last6=Terrier-Lacombe|first6=M. J.|last7=Haralambieva|first7=E.|last8=Pulford|first8=K.|last9=Pileri|first9=S.|date=1998-03-15|title=ALK-positive lymphoma: a single disease with a broad spectrum of morphology|url=https://pubmed.ncbi.nlm.nih.gov/9490693/|journal=Blood|volume=91|issue=6|pages=2076–2084|issn=0006-4971|pmid=9490693}}</ref>
 
*Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
*Usually large in size, but may also be smaller
*Present in varying proportions
*Seen in all morphological variants/patterns of ALK+ ALCL
 
Morphological variants/patterns
 
#Common (60%): predominant population of large hallmark cells
#Lymphohistiocytic (10%): lymphoma cells are admixed with numerous reactive histiocytes that may obscure the lymphoma cells; lymphoma cells often cluster around vessels and are often smaller than in the common pattern
#Small cell (5-10%): predominant population of smaller lymphoma cells; hallmark cells are often concentrated around vessels; may also see "fried egg cells" (pale cytoplasm with central nucleus) or signet ring-like cells; can misdiagnose of peripheral T-cell lymphoma, NOS
#Hodgkin-like (3%): mimics nodular sclerosis classic Hodgkin lymphoma
#Composite (15%): more than one pattern in a single lymph node
 
When lymph node is only partially involved, lymphoma characteristically grows in the sinuses, which may mimic a metastatic tumor.
 
==Immunophenotype==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
CD30 expression on ALCL (ALK+ or ALK-) allows for targeted therapy<ref name=":2" />
 
*First-line therapy: [https://www.fda.gov/drugs/fda-approves-brentuximab-vedotin-previously-untreated-salcl-and-cd30-expressing-ptcl Brentuximab] (anti-CD30) vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone)
 
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
|Category
|T-cell and NK-cell lymphoid proliferations and lymphomas
|-
|-
|Positive (universal) - Cell membrane and Golgi; large lymphoma cells show strongest staining; smaller cells may show weak, partial to negative staining||CD30
|Family
|Mature T-cell and NK-cell neoplasms
|-
|-
|Positive (universal) - Cellular location of ALK staining varies depending on ALK translocation partner. In the most common t(2;5), most cases show both cytoplasmic and nuclear||ALK
|Type
|Anaplastic large cell lymphoma
|-
|-
|Positive (subset)||EMA
|Subtype(s)
|ALK-positive anaplastic large cell lymphoma
|}
==Related Terminology==
 
{| class="wikitable"
|+
|Acceptable
|Anaplastic large cell lymphoma, ALK-positive
|-
|-
|Negative - >75% of cases are CD3-negative||CD3
|Not Recommended
|N/A
|}
 
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
|-
|-
|Positive (70%)
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
|CD4
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Negative in majority of cases
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|CD8
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
|Positive in majority of cases
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|CD2
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
|Positive in majority of cases
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|CD5
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
 
 
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
 
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
|Positive
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|TIA1
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|Positive
|
|Granzyme B
|
|-
|
|Positive
|
|Perforin
|
|-
|
|Variably positive
|
|CD45
|
|-
|Positive (universal)
|CD25
|-
|Negative (universal)
|BCL2
|}
|}


<blockquote class="blockedit">{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
[[ALK]]+ ALCL show the following staining pattern<ref>{{Cite journal|last=Montes-Mojarro|first=Ivonne A.|last2=Steinhilber|first2=Julia|last3=Bonzheim|first3=Irina|last4=Quintanilla-Martinez|first4=Leticia|last5=Fend|first5=Falko|date=2018-04-04|title=The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)|url=https://pubmed.ncbi.nlm.nih.gov/29617304/|journal=Cancers|volume=10|issue=4|pages=E107|doi=10.3390/cancers10040107|issn=2072-6694|pmc=5923362|pmid=29617304}}</ref><ref>{{Cite journal|last=Stein|first=H.|last2=Foss|first2=H. D.|last3=Dürkop|first3=H.|last4=Marafioti|first4=T.|last5=Delsol|first5=G.|last6=Pulford|first6=K.|last7=Pileri|first7=S.|last8=Falini|first8=B.|date=2000-12-01|title=CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features|url=https://pubmed.ncbi.nlm.nih.gov/11090048/|journal=Blood|volume=96|issue=12|pages=3681–3695|issn=0006-4971|pmid=11090048}}</ref>:
*'''CD30+:''' Cell membrane and Golgi; large lymphoma cells show strongest staining; smaller cells may show weak, partial to negative staining
*'''ALK+:''' cellular location of ALK staining varies depending on ALK translocation partner. In the most common t(2;5), most cases show both cytoplasmic and nuclear ALK staining. In the small cell variant, staining is usually restricted to the nucleus
*EMA+: some cases show positivity in only a proportion of lymphoma cells
*'''CD3(-):''' >75% of cases are CD3-negative
*CD4>>>CD8
*CD2 and CD5: Majority positive
*Cytotoxic marker(s)+: TIA1, granzyme B and/or perforin
*'''CD45: variably positive'''
*CD25+
*'''BCL2-negative'''
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==


FISH is not required for diagnosis in routine practice <ref name=":27" /><ref name=":28" />.
FISH is not required for diagnosis in routine practice <ref name=":27" /><ref name=":28" />.
Line 167: Line 118:
!Notes
!Notes
|-
|-
|t(2;5)(p23;q35)||3' ''ALK'' / 5' ''NPM1''<ref name=":20" />||''NPM1::ALK'' fusion protein||84%<ref name=":0" />
|t(2;5)(p23;q35)||3' ''ALK'' / 5' ''NPM1''<ref name=":20" />||''NPM1::ALK'' fusion protein||84%<ref name=":0">Arber DA, et al., (2017). Anaplastic large cell lymphoma, ALK-positive, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p413-418.</ref>
|No
|No
|No
|No
Line 174: Line 125:




'''<u>Of note, identifying the ''ALK'' fusion partner is not considered necessary in routine clinical practice.</u>'''
<u>Of note, identifying the ''ALK'' fusion partner is not considered necessary in routine clinical practice.</u>




Line 270: Line 221:


<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>


*ALK(+) ALCL is characterized by chromosomal translocations involving ''ALK'' gene, a receptor tyrosine kinase domain at 2p23.
*ALK(+) ALCL is characterized by chromosomal translocations involving ''ALK'' gene, a receptor tyrosine kinase domain at 2p23.
Line 333: Line 284:
|}
|}
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>


Line 340: Line 294:
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
* Gene Mutations (SNV/INDEL)}}</blockquote>
Diagnosis
Diagnosis


Line 370: Line 324:
**'''''NOTCH1 inhibition by γ-secretase inhibitors (GSI) in combination with crizotinib may provide synergistic anti-tumor activity, or as a single agent in ALK-inhibitor resistant cell lines<ref name=":5" />'''''
**'''''NOTCH1 inhibition by γ-secretase inhibitors (GSI) in combination with crizotinib may provide synergistic anti-tumor activity, or as a single agent in ALK-inhibitor resistant cell lines<ref name=":5" />'''''


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Individual Region Genomic Gain / Loss / LOH==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
chr7
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|
|
|
|
|
|
|
|}


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 383: Line 391:
!Notes
!Notes
|-
|-
|2q
|17p
|Gain
|17p11-pter
|
|No
|Unclear
|No
|
|-
|17p
|Gain
|Gain
|Chr 2:29,192,774-29,921,586
|17q24 -qter
|EXAMPLE
|
 
chr7
|No
|No
|Yes
|Unclear
|No
|No
|EXAMPLE
|
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|EXAMPLE
|4q
 
|Loss
8
|4q13-q28
|EXAMPLE Gain
|
|EXAMPLE
|No
 
|Unclear
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
|No
|No
|
|-
|11q
|Loss
|11q14-q23
|
|No
|No
|Unclear
|No
|No
|EXAMPLE
|
 
Common recurrent secondary finding for t(8;21) (add reference).
|}
|}


<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>


Frequent secondary chromosomal imbalances are seen in ALK+ ALCL (58% of cases), as based on comparative genomic hybridization analysis<ref>{{Cite journal|last=I|first=Salaverria|last2=S|first2=Beà|last3=A|first3=Lopez-Guillermo|last4=V|first4=Lespinet|last5=M|first5=Pinyol|last6=B|first6=Burkhardt|last7=L|first7=Lamant|last8=A|first8=Zettl|last9=D|first9=Horsman|date=2008|title=Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18275429/|language=en|pmid=18275429}}</ref>.
Frequent secondary chromosomal imbalances are seen in ALK+ ALCL (58% of cases), as based on comparative genomic hybridization analysis<ref>{{Cite journal|last=I|first=Salaverria|last2=S|first2=Beà|last3=A|first3=Lopez-Guillermo|last4=V|first4=Lespinet|last5=M|first5=Pinyol|last6=B|first6=Burkhardt|last7=L|first7=Lamant|last8=A|first8=Zettl|last9=D|first9=Horsman|date=2008|title=Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18275429/|language=en|pmid=18275429}}</ref>.
Line 463: Line 477:
|}
|}
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Characteristic Chromosomal Patterns==


Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
==Characteristic Chromosomal or Other Global Mutational Patterns==


Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
Co-deletion of 1p and 18q
Co-deletion of 1p and 18q
|Yes
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|No
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE:
|
 
|
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
|}


<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>


See other sections.
See other sections.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Gene Mutations (SNV / INDEL)==
==Gene Mutations (SNV/INDEL)==
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
 
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC /  TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
Line 550: Line 628:




<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>


*Limited literature on somatic mutations in ALK+ ALCL
*Limited literature on somatic mutations in ALK+ ALCL
Line 597: Line 675:
*Gain in ALK copy number and loss of ALK gene rearrangement have also been implicated in the development of acquired resistance to crizotinib.<ref name=":7" /><ref name=":8" /><ref name=":9" /><br />
*Gain in ALK copy number and loss of ALK gene rearrangement have also been implicated in the development of acquired resistance to crizotinib.<ref name=":7" /><ref name=":8" /><ref name=":9" /><br />


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==


Line 613: Line 695:
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 619: Line 701:
|-
|-
|ALK; fusion protein derivatives
|ALK; fusion protein derivatives
|Ras-ERK
|Ras-ERK<ref name=":30" />
|Increased cell growth and proliferation
|Increased cell growth and proliferation
|-
|-
|ALK; fusion protein derivatives
|ALK; fusion protein derivatives
|JAK/STAT3
|JAK/STAT3<ref name=":30" />
|Cell survival and phenotypic changes
|Cell survival and phenotypic changes
|-
|-
|ALK; fusion protein derivatives
|ALK; fusion protein derivatives
|PI3K/AKT/mTOR
|PI3K/AKT/mTOR<ref name=":30" />
|Cell survival and phenotypic changes
|Cell survival and phenotypic changes
|}
|}


<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">
*ALK-NPM-STAT3 induces:
**See Epigenomics section above
**TGF beta, IL-10, PD-L1/CD274 to create immunosuppressive microenvironment and evasion of immune system<ref name=":31" /><ref name=":32" /><ref name=":33" />
**ICOS expression (CD28 costimulatory receptor superfamily)
**HIF1α expression induces expression of VEGF (tumor angiogenesis); allows lymphoma cells to adapt to hypoxic conditions<ref name=":34" />
*Expression of embryonic genes (SOX2, SALL4) promoting stem cell-like program
*Deregulation of microRNAs (miR-155, miR-101, miR-17-92 cluster, miR-26a, miR-16)<ref name=":35" /><ref name=":36" /><ref name=":37" /><ref name=":38" /><ref name=":39" />
 
</blockquote>
 
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>


*
*
*Activation of the ALK catalytic domain leads to the oncogenic properties of the ALK protein, leading to activation of multiple signaling cascades including<ref>{{Cite journal|last=M|first=Boi|last2=E|first2=Zucca|last3=G|first3=Inghirami|last4=F|first4=Bertoni|date=2015|title=Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/25559471/|language=en|pmid=25559471}}</ref>:
*Activation of the ALK catalytic domain leads to the oncogenic properties of the ALK protein, leading to activation of multiple signaling cascades including<ref name=":30">{{Cite journal|last=M|first=Boi|last2=E|first2=Zucca|last3=G|first3=Inghirami|last4=F|first4=Bertoni|date=2015|title=Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/25559471/|language=en|pmid=25559471}}</ref>:
**RAS-ERK
**RAS-ERK
**JAK/STAT
**JAK/STAT
Line 643: Line 736:
*ALK-NPM-STAT3 induces:
*ALK-NPM-STAT3 induces:
**See Epigenomics section above
**See Epigenomics section above
**TGF beta, IL-10, PD-L1/CD274 to create immunosuppressive microenvironment and evasion of immune system<ref>{{Cite journal|last=Marzec|first=Michal|last2=Zhang|first2=Qian|last3=Goradia|first3=Ami|last4=Raghunath|first4=Puthiyaveettil N.|last5=Liu|first5=Xiaobin|last6=Paessler|first6=Michele|last7=Wang|first7=Hong Yi|last8=Wysocka|first8=Maria|last9=Cheng|first9=Mangeng|date=2008-12-30|title=Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)|url=https://pubmed.ncbi.nlm.nih.gov/19088198|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=105|issue=52|pages=20852–20857|doi=10.1073/pnas.0810958105|issn=1091-6490|pmc=2634900|pmid=19088198}}</ref><ref>{{Cite journal|last=Kasprzycka|first=Monika|last2=Zhang|first2=Qian|last3=Witkiewicz|first3=Agnieszka|last4=Marzec|first4=Michal|last5=Potoczek|first5=Magdalena|last6=Liu|first6=Xiaobin|last7=Wang|first7=Hong Yi|last8=Milone|first8=Michael|last9=Basu|first9=Samik|date=2008-08-15|title=Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes|url=https://pubmed.ncbi.nlm.nih.gov/18684941|journal=Journal of Immunology (Baltimore, Md.: 1950)|volume=181|issue=4|pages=2506–2512|doi=10.4049/jimmunol.181.4.2506|issn=1550-6606|pmc=2586884|pmid=18684941}}</ref><ref>{{Cite journal|last=Yamamoto|first=Ryo|last2=Nishikori|first2=Momoko|last3=Tashima|first3=Masaharu|last4=Sakai|first4=Tomomi|last5=Ichinohe|first5=Tatsuo|last6=Takaori-Kondo|first6=Akifumi|last7=Ohmori|first7=Katsuyuki|last8=Uchiyama|first8=Takashi|date=2009-11|title=B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19703193|journal=Cancer Science|volume=100|issue=11|pages=2093–2100|doi=10.1111/j.1349-7006.2009.01302.x|issn=1349-7006|pmid=19703193}}</ref>
**TGF beta, IL-10, PD-L1/CD274 to create immunosuppressive microenvironment and evasion of immune system<ref name=":31">{{Cite journal|last=Marzec|first=Michal|last2=Zhang|first2=Qian|last3=Goradia|first3=Ami|last4=Raghunath|first4=Puthiyaveettil N.|last5=Liu|first5=Xiaobin|last6=Paessler|first6=Michele|last7=Wang|first7=Hong Yi|last8=Wysocka|first8=Maria|last9=Cheng|first9=Mangeng|date=2008-12-30|title=Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)|url=https://pubmed.ncbi.nlm.nih.gov/19088198|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=105|issue=52|pages=20852–20857|doi=10.1073/pnas.0810958105|issn=1091-6490|pmc=2634900|pmid=19088198}}</ref><ref name=":32">{{Cite journal|last=Kasprzycka|first=Monika|last2=Zhang|first2=Qian|last3=Witkiewicz|first3=Agnieszka|last4=Marzec|first4=Michal|last5=Potoczek|first5=Magdalena|last6=Liu|first6=Xiaobin|last7=Wang|first7=Hong Yi|last8=Milone|first8=Michael|last9=Basu|first9=Samik|date=2008-08-15|title=Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes|url=https://pubmed.ncbi.nlm.nih.gov/18684941|journal=Journal of Immunology (Baltimore, Md.: 1950)|volume=181|issue=4|pages=2506–2512|doi=10.4049/jimmunol.181.4.2506|issn=1550-6606|pmc=2586884|pmid=18684941}}</ref><ref name=":33">{{Cite journal|last=Yamamoto|first=Ryo|last2=Nishikori|first2=Momoko|last3=Tashima|first3=Masaharu|last4=Sakai|first4=Tomomi|last5=Ichinohe|first5=Tatsuo|last6=Takaori-Kondo|first6=Akifumi|last7=Ohmori|first7=Katsuyuki|last8=Uchiyama|first8=Takashi|date=2009-11|title=B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19703193|journal=Cancer Science|volume=100|issue=11|pages=2093–2100|doi=10.1111/j.1349-7006.2009.01302.x|issn=1349-7006|pmid=19703193}}</ref>
**ICOS expression (CD28 costimulatory receptor superfamily)
**ICOS expression (CD28 costimulatory receptor superfamily)
**HIF1α expression induces expression of VEGF (tumor angiogenesis); allows lymphoma cells to adapt to hypoxic conditions<ref>{{Cite journal|last=Martinengo|first=Cinzia|last2=Poggio|first2=Teresa|last3=Menotti|first3=Matteo|last4=Scalzo|first4=Maria Stella|last5=Mastini|first5=Cristina|last6=Ambrogio|first6=Chiara|last7=Pellegrino|first7=Elisa|last8=Riera|first8=Ludovica|last9=Piva|first9=Roberto|date=2014-11-01|title=ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis|url=https://pubmed.ncbi.nlm.nih.gov/25193384|journal=Cancer Research|volume=74|issue=21|pages=6094–6106|doi=10.1158/0008-5472.CAN-14-0268|issn=1538-7445|pmid=25193384}}</ref>
**HIF1α expression induces expression of VEGF (tumor angiogenesis); allows lymphoma cells to adapt to hypoxic conditions<ref name=":34">{{Cite journal|last=Martinengo|first=Cinzia|last2=Poggio|first2=Teresa|last3=Menotti|first3=Matteo|last4=Scalzo|first4=Maria Stella|last5=Mastini|first5=Cristina|last6=Ambrogio|first6=Chiara|last7=Pellegrino|first7=Elisa|last8=Riera|first8=Ludovica|last9=Piva|first9=Roberto|date=2014-11-01|title=ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis|url=https://pubmed.ncbi.nlm.nih.gov/25193384|journal=Cancer Research|volume=74|issue=21|pages=6094–6106|doi=10.1158/0008-5472.CAN-14-0268|issn=1538-7445|pmid=25193384}}</ref>
*Expression of embryonic genes (SOX2, SALL4) promoting stem cell-like program
*Expression of embryonic genes (SOX2, SALL4) promoting stem cell-like program
*Deregulation of microRNAs (miR-155, miR-101, miR-17-92 cluster, miR-26a, miR-16)<ref>{{Cite journal|last=Rodriguez|first=Antony|last2=Vigorito|first2=Elena|last3=Clare|first3=Simon|last4=Warren|first4=Madhuri V.|last5=Couttet|first5=Philippe|last6=Soond|first6=Dalya R.|last7=van Dongen|first7=Stijn|last8=Grocock|first8=Russell J.|last9=Das|first9=Partha P.|date=2007-04-27|title=Requirement of bic/microRNA-155 for normal immune function|url=https://pubmed.ncbi.nlm.nih.gov/17463290|journal=Science (New York, N.Y.)|volume=316|issue=5824|pages=608–611|doi=10.1126/science.1139253|issn=1095-9203|pmc=2610435|pmid=17463290}}</ref><ref>{{Cite journal|last=Merkel|first=Olaf|last2=Hamacher|first2=Frank|last3=Laimer|first3=Daniela|last4=Sifft|first4=Eveline|last5=Trajanoski|first5=Zlatko|last6=Scheideler|first6=Marcel|last7=Egger|first7=Gerda|last8=Hassler|first8=Melanie R.|last9=Thallinger|first9=Christiane|date=2010-09-14|title=Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK)+ and ALK- anaplastic large-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/20805506|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=37|pages=16228–16233|doi=10.1073/pnas.1009719107|issn=1091-6490|pmc=2941277|pmid=20805506}}</ref><ref>{{Cite journal|last=Spaccarotella|first=Elisa|last2=Pellegrino|first2=Elisa|last3=Ferracin|first3=Manuela|last4=Ferreri|first4=Cristina|last5=Cuccuru|first5=Giuditta|last6=Liu|first6=Cuiling|last7=Iqbal|first7=Javeed|last8=Cantarella|first8=Daniela|last9=Taulli|first9=Riccardo|date=2014-01|title=STAT3-mediated activation of microRNA cluster 17~92 promotes proliferation and survival of ALK-positive anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23975180|journal=Haematologica|volume=99|issue=1|pages=116–124|doi=10.3324/haematol.2013.088286|issn=1592-8721|pmc=4007939|pmid=23975180}}</ref><ref>{{Cite journal|last=Zhu|first=Haifeng|last2=Vishwamitra|first2=Deeksha|last3=Curry|first3=Choladda V.|last4=Manshouri|first4=Roxsan|last5=Diao|first5=Lixia|last6=Khan|first6=Aarish|last7=Amin|first7=Hesham M.|date=2013-05|title=NPM-ALK up-regulates iNOS expression through a STAT3/microRNA-26a-dependent mechanism|url=https://pubmed.ncbi.nlm.nih.gov/23338972|journal=The Journal of Pathology|volume=230|issue=1|pages=82–94|doi=10.1002/path.4171|issn=1096-9896|pmc=3940725|pmid=23338972}}</ref><ref>{{Cite journal|last=Dejean|first=E.|last2=Renalier|first2=M. H.|last3=Foisseau|first3=M.|last4=Agirre|first4=X.|last5=Joseph|first5=N.|last6=de Paiva|first6=G. R.|last7=Al Saati|first7=T.|last8=Soulier|first8=J.|last9=Desjobert|first9=C.|date=2011-12|title=Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/21778999|journal=Leukemia|volume=25|issue=12|pages=1882–1890|doi=10.1038/leu.2011.168|issn=1476-5551|pmid=21778999}}</ref>
*Deregulation of microRNAs (miR-155, miR-101, miR-17-92 cluster, miR-26a, miR-16)<ref name=":35">{{Cite journal|last=Rodriguez|first=Antony|last2=Vigorito|first2=Elena|last3=Clare|first3=Simon|last4=Warren|first4=Madhuri V.|last5=Couttet|first5=Philippe|last6=Soond|first6=Dalya R.|last7=van Dongen|first7=Stijn|last8=Grocock|first8=Russell J.|last9=Das|first9=Partha P.|date=2007-04-27|title=Requirement of bic/microRNA-155 for normal immune function|url=https://pubmed.ncbi.nlm.nih.gov/17463290|journal=Science (New York, N.Y.)|volume=316|issue=5824|pages=608–611|doi=10.1126/science.1139253|issn=1095-9203|pmc=2610435|pmid=17463290}}</ref><ref name=":36">{{Cite journal|last=Merkel|first=Olaf|last2=Hamacher|first2=Frank|last3=Laimer|first3=Daniela|last4=Sifft|first4=Eveline|last5=Trajanoski|first5=Zlatko|last6=Scheideler|first6=Marcel|last7=Egger|first7=Gerda|last8=Hassler|first8=Melanie R.|last9=Thallinger|first9=Christiane|date=2010-09-14|title=Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK)+ and ALK- anaplastic large-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/20805506|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=37|pages=16228–16233|doi=10.1073/pnas.1009719107|issn=1091-6490|pmc=2941277|pmid=20805506}}</ref><ref name=":37">{{Cite journal|last=Spaccarotella|first=Elisa|last2=Pellegrino|first2=Elisa|last3=Ferracin|first3=Manuela|last4=Ferreri|first4=Cristina|last5=Cuccuru|first5=Giuditta|last6=Liu|first6=Cuiling|last7=Iqbal|first7=Javeed|last8=Cantarella|first8=Daniela|last9=Taulli|first9=Riccardo|date=2014-01|title=STAT3-mediated activation of microRNA cluster 17~92 promotes proliferation and survival of ALK-positive anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23975180|journal=Haematologica|volume=99|issue=1|pages=116–124|doi=10.3324/haematol.2013.088286|issn=1592-8721|pmc=4007939|pmid=23975180}}</ref><ref name=":38">{{Cite journal|last=Zhu|first=Haifeng|last2=Vishwamitra|first2=Deeksha|last3=Curry|first3=Choladda V.|last4=Manshouri|first4=Roxsan|last5=Diao|first5=Lixia|last6=Khan|first6=Aarish|last7=Amin|first7=Hesham M.|date=2013-05|title=NPM-ALK up-regulates iNOS expression through a STAT3/microRNA-26a-dependent mechanism|url=https://pubmed.ncbi.nlm.nih.gov/23338972|journal=The Journal of Pathology|volume=230|issue=1|pages=82–94|doi=10.1002/path.4171|issn=1096-9896|pmc=3940725|pmid=23338972}}</ref><ref name=":39">{{Cite journal|last=Dejean|first=E.|last2=Renalier|first2=M. H.|last3=Foisseau|first3=M.|last4=Agirre|first4=X.|last5=Joseph|first5=N.|last6=de Paiva|first6=G. R.|last7=Al Saati|first7=T.|last8=Soulier|first8=J.|last9=Desjobert|first9=C.|date=2011-12|title=Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/21778999|journal=Leukemia|volume=25|issue=12|pages=1882–1890|doi=10.1038/leu.2011.168|issn=1476-5551|pmid=21778999}}</ref>


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Line 660: Line 756:


==Additional Information==
==Additional Information==
This disease is <u>defined/characterized</u> as detailed below:
Anaplastic Large Cell Lymphoma, ALK-Positive (ALK+ ALCL) is a T-cell lymphoma characterized by usually large lymphoma cells with abundant cytoplasm and pleomorphic nuclei, often horse-shoe shaped (see Morphologic Features below), with a chromosomal rearrangement involving the ALK gene resulting in expression of ALK protein and CD30
The <u>epidemiology/prevalence</u> of this disease is detailed below:
*ALCL ([[ALK]]+, ALK-, and primary cutaneous) account for <5% of all cases of non-Hodgkin lymphoma (NHL)<ref name=":0" />
*ALK+ ALCL<ref name=":0" />
**~3% of adult NHL
**10-20% of childhood lymphomas
**Most frequent in the first three decades of life
**Male:female = 1.5:1
The <u>clinical features</u> of this disease are detailed below:
Signs and symptoms - Most patients (70%) present with advanced (stage III-IV) disease and B-symptoms.<ref name=":19">{{Cite journal|last=Savage|first=Kerry J.|last2=Harris|first2=Nancy Lee|last3=Vose|first3=Julie M.|last4=Ullrich|first4=Fred|last5=Jaffe|first5=Elaine S.|last6=Connors|first6=Joseph M.|last7=Rimsza|first7=Lisa|last8=Pileri|first8=Stefano A.|last9=Chhanabhai|first9=Mukesh|date=2008-06-15|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/|journal=Blood|volume=111|issue=12|pages=5496–5504|doi=10.1182/blood-2008-01-134270|issn=1528-0020|pmid=18385450}}</ref>
Laboratory findings - Noncontributory
The <u>sites of involvement</u> of this disease are detailed below:
*Lymph nodes and extranodal sites (most commonly skin, bone, soft tissue, lungs and liver)<ref name=":0" />
*Bone marrow involvement detected in 30% when using immunohistochemistry (CD30 and EMA). Can miss marrow involvement by H&E evaluation alone, which detects involvement with ~10% incidence.<ref>{{Cite journal|last=M|first=Fraga|last2=P|first2=Brousset|last3=D|first3=Schlaifer|last4=C|first4=Payen|last5=A|first5=Robert|last6=H|first6=Rubie|last7=F|first7=Huguet-Rigal|last8=G|first8=Delsol|date=1995|title=Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance|url=https://pubmed.ncbi.nlm.nih.gov/7817951/|language=en|pmid=7817951}}</ref>
The <u>morphologic features</u> of this disease are detailed below:
"Hallmark cells"<ref>{{Cite journal|last=Stein|first=H.|last2=Foss|first2=H. D.|last3=Dürkop|first3=H.|last4=Marafioti|first4=T.|last5=Delsol|first5=G.|last6=Pulford|first6=K.|last7=Pileri|first7=S.|last8=Falini|first8=B.|date=2000-12-01|title=CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features|url=https://pubmed.ncbi.nlm.nih.gov/11090048/|journal=Blood|volume=96|issue=12|pages=3681–3695|issn=0006-4971|pmid=11090048}}</ref><ref>{{Cite journal|last=Benharroch|first=D.|last2=Meguerian-Bedoyan|first2=Z.|last3=Lamant|first3=L.|last4=Amin|first4=C.|last5=Brugières|first5=L.|last6=Terrier-Lacombe|first6=M. J.|last7=Haralambieva|first7=E.|last8=Pulford|first8=K.|last9=Pileri|first9=S.|date=1998-03-15|title=ALK-positive lymphoma: a single disease with a broad spectrum of morphology|url=https://pubmed.ncbi.nlm.nih.gov/9490693/|journal=Blood|volume=91|issue=6|pages=2076–2084|issn=0006-4971|pmid=9490693}}</ref>


*None
*Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
*Usually large in size, but may also be smaller
*Present in varying proportions
*Seen in all morphological variants/patterns of ALK+ ALCL
 
Morphological variants/patterns
 
#Common (60%): predominant population of large hallmark cells
#Lymphohistiocytic (10%): lymphoma cells are admixed with numerous reactive histiocytes that may obscure the lymphoma cells; lymphoma cells often cluster around vessels and are often smaller than in the common pattern
#Small cell (5-10%): predominant population of smaller lymphoma cells; hallmark cells are often concentrated around vessels; may also see "fried egg cells" (pale cytoplasm with central nucleus) or signet ring-like cells; can misdiagnose of peripheral T-cell lymphoma, NOS
#Hodgkin-like (3%): mimics nodular sclerosis classic Hodgkin lymphoma
#Composite (15%): more than one pattern in a single lymph node
 
When lymph node is only partially involved, lymphoma characteristically grows in the sinuses, which may mimic a metastatic tumor.
 
The <u>immunophenotype</u> of this disease is detailed below:
 
* CD30 expression on ALCL (ALK+ or ALK-) allows for targeted therapy<ref name=":2" />. First-line therapy: [https://www.fda.gov/drugs/fda-approves-brentuximab-vedotin-previously-untreated-salcl-and-cd30-expressing-ptcl Brentuximab] (anti-CD30) vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone)
 
CD30+''':''' Positive (universal) - cell membrane and Golgi; large lymphoma cells show strongest staining; smaller cells may show weak, partial to negative staining
 
ALK: Positive (universal) - cellular location of ALK staining varies depending on ALK translocation partner. In the most common t(2;5), most cases show both cytoplasmic and nuclear
 
EMA: positive (subset)
 
CD3: Positive (subset)
 
CD4: Positive (70%)
 
CD5: Negative in majority of cases
 
CD8: Positive in majority of cases
 
CD2: Positive in majority of cases
 
TIA1: Positive
 
Granzyme B: Positive
 
Perforin: Positive
 
CD45: Variably positive
 
CD25: Positive (universal)
 
BCL2: Negative (universal)


==Links==
==Links==
Line 668: Line 837:


==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />


<br />
<br />


==Notes==
==Notes==
<nowiki>*</nowiki>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.
<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
 
<nowiki>*</nowiki>''Citation of this Page'': “ALK-positive anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:ALK-positive_anaplastic_large_cell_lymphoma</nowiki>.
==Other Sections==
Primary Authors*


Prior Author(s): 


Miguel Gonzalez Mancera, MD
       


Sumire Kitahara, MD
<nowiki>*</nowiki>''Citation of this Page'': “ALK-positive anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:ALK-positive_anaplastic_large_cell_lymphoma</nowiki>.
 
Cedars-Sinai, Los Angeles, CA
 
__TOC__
 
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases A]]
Retrieved from "https://test.ccga.io/index.php/HAEM5:ALK-positive_anaplastic_large_cell_lymphoma"