HAEM5:ALK-positive anaplastic large cell lymphoma: Difference between revisions
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{{Under Construction}} | {{Under Construction}} | ||
<blockquote class= | <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]]. | ||
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|ALK-positive anaplastic large cell lymphoma | |ALK-positive anaplastic large cell lymphoma | ||
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==WHO Essential and Desirable Genetic Diagnostic Criteria== | ==WHO Essential and Desirable Genetic Diagnostic Criteria== | ||
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span> | <span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span> | ||
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!Notes | !Notes | ||
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|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 | ||
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<blockquote class= | <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. | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in: | ||
* Chromosomal Rearrangements (Gene Fusions) | * Chromosomal Rearrangements (Gene Fusions) | ||
* Individual Region Genomic Gain/Loss/LOH | * Individual Region Genomic Gain/Loss/LOH | ||
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<blockquote class= | <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>. | ||
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<blockquote class= | <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. | ||
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<blockquote class= | <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 | ||
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*ALK-NPM-STAT3 induces: | *ALK-NPM-STAT3 induces: | ||
**See Epigenomics section above | **See Epigenomics section above | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
* | * | ||
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==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> | ||
*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== | ||