HAEM5:Myeloid sarcoma: Difference between revisions

Myeloid sarcoma may occur ''de novo'' in about one quarter of cases. Its detection should be considered as the equivalent of a diagnosis of AML. It may precede or coincide with AML or represent acute blastic transformation of MDS, MPN or MDS/MPN. Myeloid sarcoma may also be the initial manifestation of relapse in a patient with previously diagnosed AML, regardless of peripheral blood or bone marrow findings. In addition, isolated myeloid sarcoma occurs in 8-20% of patients who have undergone allogenic stem cell transplantation (reason still unclear), or in patients with simultaneously or previously treated non-Hodgkin lymphoma or a previous history of non-hematopoietic tumor (therapy-related)<ref>{{Cite journal|last=Pileri|first=S. A.|last2=Ascani|first2=S.|last3=Cox|first3=M. C.|last4=Campidelli|first4=C.|last5=Bacci|first5=F.|last6=Piccioli|first6=M.|last7=Piccaluga|first7=P. P.|last8=Agostinelli|first8=C.|last9=Asioli|first9=S.|date=2007|title=Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients|url=https://www.ncbi.nlm.nih.gov/pubmed/17170724|journal=Leukemia|volume=21|issue=2|pages=340–350|doi=10.1038/sj.leu.2404491|issn=0887-6924|pmid=17170724}}</ref><ref name=":0">Pileri SA, et al., (2017). Myeloid sarcoma, 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 D, Hasserjian R, Le Beau M, Orazi A, Siebert R, Editors. IARC Press: Lyon, France, p167-168.</ref>.

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==Sites of Involvement==

On immunohistochemistry in paraffin sections, tumors with more mature myeloid profile express CD33, CD34, CD68 (KP1) and CKIT. Staining for terminal deoxynucleotidyl transferase (TdT), MPO and CD45 are inconsistent.

Cases that meet criteria for mixed phenotype acute leukemia are not classified as myeloid sarcoma<ref name=":0" />.

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==Chromosomal Rearrangements (Gene Fusions)==

FISH and/or karyotypic aberrations are detected in about 55% of cases.

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

The clinical behavior and response to therapy seem ''not'' to be influenced by any of the following factors: age, sex, anatomical site(s) involved, ''de novo'' presentation, clinical history related to AML, MDS or MPN, histological features, immunophenotype or cytogenetic findings. Patients who undergo allogeneic or autologous bone marrow transplantation seem to have a higher probability of prolonged survival or cure. In one study the 5-year overall survival rate among 51 patients with myeloid sarcoma treated with allogenic bone marrow transplantation was 47%<ref>{{Cite journal|last=Chevallier|first=Patrice|last2=Labopin|first2=Myriam|last3=Cornelissen|first3=Jan|last4=Socié|first4=Gérard|last5=Rocha|first5=Vanderson|last6=Mohty|first6=Mohamad|last7=ALWP of EBMT|date=2011|title=Allogeneic hematopoietic stem cell transplantation for isolated and leukemic myeloid sarcoma in adults: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation|url=https://www.ncbi.nlm.nih.gov/pubmed/21685467|journal=Haematologica|volume=96|issue=9|pages=1391–1394|doi=10.3324/haematol.2011.041418|issn=1592-8721|pmc=3166114|pmid=21685467}}</ref>.

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

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==Characteristic Chromosomal Patterns==

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Complex karyotype is associated with poor outcome<ref name=":1">{{Cite journal|last=Mirza|first=M. Kamran|last2=Sukhanova|first2=Madina|last3=Stölzel|first3=Friedrich|last4=Onel|first4=Kenan|last5=Larson|first5=Richard A.|last6=Stock|first6=Wendy|last7=Ehninger|first7=Gerhard|last8=Kuithan|first8=Friederike|last9=Zöphel|first9=Klaus|date=2014|title=Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays|url=https://www.ncbi.nlm.nih.gov/pubmed/25088808|journal=Leukemia Research|volume=38|issue=9|pages=1091–1096|doi=10.1016/j.leukres.2014.05.004|issn=1873-5835|pmc=4157130|pmid=25088808}}</ref>.  

Gains and losses, see below

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==Gene Mutations (SNV / INDEL)==

Some studies have reported genetic abnormalities in various AML-associated genes encoding tyrosine kinases (''FLT3'', ''KIT'', and ''KRAS''), tumor suppressors (''WT1'' and ''TP53''), epigenetic modifiers (''TET2'' and ''ASXL1''), spliceosome proteins (''SF3B1'' and ''SRSF2''), and transcription factors (''RUNX1''). One study highlights that almost one-third of MS harbor a targetable mutation, in particular ''KIT'' D816V, ''IDH2'' R140Q, and ''BRAF'' V600E. These mutations can also be found in non infiltrated bone marrows suggesting the existence of preleukemic clones in the bone marrow from MS patients<ref>{{Cite journal|last=Falini|first=B.|last2=Lenze|first2=D.|last3=Hasserjian|first3=R.|last4=Coupland|first4=S.|last5=Jaehne|first5=D.|last6=Soupir|first6=C.|last7=Liso|first7=A.|last8=Martelli|first8=M. P.|last9=Bolli|first9=N.|date=2007|title=Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas|url=https://www.ncbi.nlm.nih.gov/pubmed/17443224|journal=Leukemia|volume=21|issue=7|pages=1566–1570|doi=10.1038/sj.leu.2404699|issn=0887-6924|pmid=17443224}}</ref><ref>{{Cite journal|last=Li|first=Z.|last2=Stölzel|first2=F.|last3=Onel|first3=K.|last4=Sukhanova|first4=M.|last5=Mirza|first5=M. K.|last6=Yap|first6=K. L.|last7=Borinets|first7=O.|last8=Larson|first8=R. A.|last9=Stock|first9=W.|date=2015|title=Next-generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma|url=https://www.ncbi.nlm.nih.gov/pubmed/25787914|journal=Leukemia|volume=29|issue=10|pages=2113–2116|doi=10.1038/leu.2015.81|issn=1476-5551|pmc=4575593|pmid=25787914}}</ref><ref>{{Cite journal|last=Pastoret|first=Cedric|last2=Houot|first2=Roch|last3=Llamas-Gutierrez|first3=Francisco|last4=Boulland|first4=Marie-Laure|last5=Marchand|first5=Tony|last6=Tas|first6=Patrick|last7=Ly-Sunnaram|first7=Beatrice|last8=Gandemer|first8=Virginie|last9=Lamy|first9=Thierry|date=2017|title=Detection of clonal heterogeneity and targetable mutations in myeloid sarcoma by high-throughput sequencing|url=https://www.ncbi.nlm.nih.gov/pubmed/27659839|journal=Leukemia & Lymphoma|volume=58|issue=4|pages=1008–1012|doi=10.1080/10428194.2016.1225208|issn=1029-2403|pmid=27659839}}</ref>.

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==Epigenomic Alterations==