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

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*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>

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==Sites of Involvement==

==Morphologic Features==

[[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>:

*'''BCL2-negative'''

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==Chromosomal Rearrangements (Gene Fusions)==

*ALK(+) ALCL is characterized by chromosomal translocations involving ''ALK'' gene, a receptor tyrosine kinase domain at 2p23.

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* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

Diagnosis

**'''''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" />'''''

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==Individual Region Genomic Gain / Loss / LOH==

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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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==Characteristic Chromosomal Patterns==

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See other sections.

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==Gene Mutations (SNV / INDEL)==

*Limited literature on somatic mutations in ALK+ ALCL

*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 />

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==Epigenomic Alterations==

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*ALK-NPM-STAT3 induces:

**See Epigenomics section above

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*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>

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==Genetic Diagnostic Testing Methods==