HAEM5:Myelodysplastic/myeloproliferative neoplasm with neutrophilia: Difference between revisions

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{{DISPLAYTITLE:Myelodysplastic/myeloproliferative neoplasm with neutrophilia}}
{{DISPLAYTITLE:Myelodysplastic/myeloproliferative neoplasm with neutrophilia}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


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<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:Atypical Chronic Myeloid Leukemia (aCML), BCR-ABL1 Negative]].
<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:Atypical Chronic Myeloid Leukemia (aCML), BCR-ABL1 Negative]].
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==Definition / Description of Disease==
Atypical chronic myeloid leukemia, ''BCR-ABL1''-negative (aCML) presents with myelodysplastic as well as myeloproliferative features at the time of disease onset<ref name=":5" /><ref>Czader, M and Orazi, A. Chapter 45. Myelodysplastic/Myeloproliferative Neoplasms and Related Diseases. In Orazi A, Foucar K, Knowles DM. eds. Knowles Neoplastic Hematopathology. Riverwoods, IL: Wolters Kluwer Health; 2013:1148-1150.</ref>. The characteristic finding is blood leukocytosis with increase of dysplastic neutrophils and immature granulocytes. Bone marrow shows multilineage dysplasia.
*Before the diagnosis of aCML can be rendered, myeloid neoplasms with well defined genetic abnormalities such as ''[[HAEM5:Chronic myeloid leukaemia|BCR-ABL1]]'' fusion; rearrangement of [[HAEM5:Myeloid/lymphoid neoplasm with PDGFRA rearrangement|P''DGFRA'']]'', [[HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement|PDGFRB]],'' ''[[HAEM5:Myeloid/lymphoid neoplasm with FGFR1 rearrangement|FGFR1]]'', or ''[[HAEM5:Myeloid/lymphoid neoplasm with JAK2 rearrangement|PCM1-JAK2]]'' must be ruled out.
*Myeloid neoplasm with features of aCML developed after chemo or radiation therapy is classified as [[HAEM5:Myeloid neoplasm post cytotoxic therapy|therapy-related myeloid neoplasm]].
==Synonyms / Terminology==
Atypical chronic myeloid leukemia, Philadelphia chromosome-negative (Ph-)
Atypical chronic myeloid leukemia, ''BCR-ABL1''-negative
==Epidemiology / Prevalence==
The incidence of aCML is low; it is estimated that there are 1-2 aCML cases for every 100 cases of [[HAEM5:Chronic myeloid leukaemia|''BCR-ABL1''-positive chronic myeloid leukemia]]<ref>{{Cite journal|last=A|first=Orazi|last2=U|first2=Germing|date=2008|title=The Myelodysplastic/Myeloproliferative Neoplasms: Myeloproliferative Diseases With Dysplastic Features|url=https://pubmed.ncbi.nlm.nih.gov/18480833/|language=en|pmid=18480833}}</ref><ref name=":0">{{Cite journal|last=Sa|first=Wang|last2=Rp|first2=Hasserjian|last3=Ps|first3=Fox|last4=Hj|first4=Rogers|last5=Jt|first5=Geyer|last6=D|first6=Chabot-Richards|last7=E|first7=Weinzierl|last8=J|first8=Hatem|last9=J|first9=Jaso|date=2014|title=Atypical Chronic Myeloid Leukemia Is Clinically Distinct From Unclassifiable Myelodysplastic/Myeloproliferative Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/24627528/|language=en|doi=10.1182/blood-2014-02-553800|pmc=PMC4067498|pmid=24627528}}</ref>.
The median patient age at diagnosis is in the seventh or eighth decade of life<ref name=":0" /><ref name=":1">{{Cite journal|last=Jm|first=Hernández|last2=Mc|first2=del Cañizo|last3=A|first3=Cuneo|last4=Jl|first4=García|last5=Nc|first5=Gutiérrez|last6=M|first6=González|last7=G|first7=Castoldi|last8=Jf|first8=San Miguel|date=2000|title=Clinical, Hematological and Cytogenetic Characteristics of Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10847463/|language=en|pmid=10847463}}</ref><ref name=":2">{{Cite journal|last=P|first=Martiat|last2=Jl|first2=Michaux|last3=J|first3=Rodhain|date=1991|title=Philadelphia-negative (Ph-) Chronic Myeloid Leukemia (CML): Comparison With Ph+ CML and Chronic Myelomonocytic Leukemia. The Groupe Français De Cytogénétique Hématologique|url=https://pubmed.ncbi.nlm.nih.gov/2070054/|language=en|pmid=2070054}}</ref>. Rare cases of aCML has also been reported in teenagers. The reported male-to female ratio is approximately 1:1<ref name=":5">Orazi A, et al., (2017).
Atypical chronic myeloid leukaemia, BCR-ABL1-negative, 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, p87-89.</ref>.
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
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|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
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The primary symptoms are related to splenomegaly and blood cell changes like anemia and/or thrombocytopenia<ref name=":1" /><ref name=":3">{{Cite journal|last=R|first=Kurzrock|last2=Ce|first2=Bueso-Ramos|last3=H|first3=Kantarjian|last4=E|first4=Freireich|last5=Sl|first5=Tucker|last6=M|first6=Siciliano|last7=S|first7=Pilat|last8=M|first8=Talpaz|date=2001|title=BCR Rearrangement-Negative Chronic Myelogenous Leukemia Revisited|url=https://pubmed.ncbi.nlm.nih.gov/11387365/|language=en|pmid=11387365}}</ref><ref name=":2" />.
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<center><span style="color:Maroon">'''End of V4 Section'''</span>
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==Sites of Involvement==
*Blood and bone marrow are always involved.
*Involvement of spleen and liver is common.
==Morphologic Features==
====BLOOD:====
*The white blood cell count (WBC) ≥13 x 10<sup>9</sup>/L, cases >300 x 10<sup>9</sup>/L have been reported.
*Immature granulocytes, including promyelocytes, myelocytes, and metamyelocytes ≥10% of the leukocytes.
*Monocytes <10%.
*Mild basophilia.
*Dysplastic features observed in granulocytes:
**Acquired Pelger-Huët anomaly
**Other nuclear abnormalities (hypersegmentation with abnormally clumped nuclear chromatin or bizarrely segmented nuclei)
**Multiple nuclear projections
**Abnormal cytoplasmic granularity (usually hypogranularity).
*The syndrome of abnormal chromatin clumping is considered to be a morphologic variant of aCML<ref>{{Cite journal|last=Brizard|first=A.|last2=Huret|first2=J. L.|last3=Lamotte|first3=F.|last4=Guilhot|first4=F.|last5=Benz-Lemoine|first5=E.|last6=Giraud|first6=C.|last7=Desmarest|first7=M. C.|last8=Tanzer|first8=J.|date=1989|title=THREE CASES OF MYELODYSPLASTIC-MYELOPROLIFERATIVE DISORDER WITH ABNORMAL CHROMATIN CLUMPING IN GRANULOCYTES|url=http://doi.wiley.com/10.1111/j.1365-2141.1989.tb07703.x|journal=British Journal of Haematology|language=en|volume=72|issue=2|pages=294–295|doi=10.1111/j.1365-2141.1989.tb07703.x|issn=0007-1048}}</ref>.
**Neutrophil nuclei show large well-separated blocks of heterochromatin and euchromatin
*Anemia and thrombocytopenia are common.
[[File:PB 600X.jpg|thumb|Blood smear. 600X (Wright stain)|none]]
====BONE MARROW:====
*Hypercellular with markedly increased myeloid-to-erythroid ratio (usually >10:1)
*Features of trilineage dysplasia
**Dyserythropoiesis is present in about 40% of cases.
**Dysgranulopoiesis with the changes in the neutrophil lineage similar to those in the blood.
**Megakaryocytes quantitatively variable, usually normal or increased, frequently with dysmegakaryopoiesis, including micromegakaryocytes and small megakaryocytes with hypolobated nuclei.
*Mild fibrosis seen in some cases; may be more conspicuous with disease progression.
By definition, blasts <20% of blood leukocytes (usually <5%) and <20% of bone marrow nucleated cells.
[[File:BMA 200X.jpg|thumb|Bone marrow aspirate smear, 200X (Wright stain).|none]]
[[File:BMBx 100x.jpg|none|thumb|Bone marrow biopsy, 100X (H&E stain).]]
==Immunophenotype==
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!Finding!!Marker
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
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|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
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|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
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|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
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No specific immunophenotypic characteristics (flow cytometric analysis of blood and bone marrow usually report as normal, except mildly increased myeloblasts in some cases).
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<center><span style="color:Maroon">'''End of V4 Section'''</span>
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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>
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<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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The prognostic value of molecular/genetic abnormalities are not well studied yet.
The prognostic value of molecular/genetic abnormalities are not well studied yet.


Approximately 20-40% of aCML evolves to [[AML|acute myeloid leukemia]]<ref name=":0" />; most of the remaining patients die of marrow failure<ref name=":3" /><ref name=":4">{{Cite journal|last=M|first=Breccia|last2=F|first2=Biondo|last3=R|first3=Latagliata|last4=I|first4=Carmosino|last5=F|first5=Mandelli|last6=G|first6=Alimena|date=2006|title=Identification of Risk Factors in Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/17043019/|language=en|pmid=17043019}}</ref>.
Approximately 20-40% of aCML evolves to [[AML|acute myeloid leukemia]]<ref name=":0">{{Cite journal|last=Sa|first=Wang|last2=Rp|first2=Hasserjian|last3=Ps|first3=Fox|last4=Hj|first4=Rogers|last5=Jt|first5=Geyer|last6=D|first6=Chabot-Richards|last7=E|first7=Weinzierl|last8=J|first8=Hatem|last9=J|first9=Jaso|date=2014|title=Atypical Chronic Myeloid Leukemia Is Clinically Distinct From Unclassifiable Myelodysplastic/Myeloproliferative Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/24627528/|language=en|doi=10.1182/blood-2014-02-553800|pmc=PMC4067498|pmid=24627528}}</ref>; most of the remaining patients die of marrow failure<ref name=":3">{{Cite journal|last=R|first=Kurzrock|last2=Ce|first2=Bueso-Ramos|last3=H|first3=Kantarjian|last4=E|first4=Freireich|last5=Sl|first5=Tucker|last6=M|first6=Siciliano|last7=S|first7=Pilat|last8=M|first8=Talpaz|date=2001|title=BCR Rearrangement-Negative Chronic Myelogenous Leukemia Revisited|url=https://pubmed.ncbi.nlm.nih.gov/11387365/|language=en|pmid=11387365}}</ref><ref name=":4">{{Cite journal|last=M|first=Breccia|last2=F|first2=Biondo|last3=R|first3=Latagliata|last4=I|first4=Carmosino|last5=F|first5=Mandelli|last6=G|first6=Alimena|date=2006|title=Identification of Risk Factors in Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/17043019/|language=en|pmid=17043019}}</ref>.


Predictors of worse prognosis:
Predictors of worse prognosis:
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Karyotypic abnormalities are reported in as many as 80% of cases.  
Karyotypic abnormalities are reported in as many as 80% of cases.  


*Trisomy 8 and del(20q) most common.
*Trisomy 8 and del(20q) most common.
*Abnormalities of chromosomes 13, 14, 17, 19 and 12 are also common <ref name=":1" /><ref name=":2" />.
*Abnormalities of chromosomes 13, 14, 17, 19 and 12 are also common <ref name=":1">{{Cite journal|last=Jm|first=Hernández|last2=Mc|first2=del Cañizo|last3=A|first3=Cuneo|last4=Jl|first4=García|last5=Nc|first5=Gutiérrez|last6=M|first6=González|last7=G|first7=Castoldi|last8=Jf|first8=San Miguel|date=2000|title=Clinical, Hematological and Cytogenetic Characteristics of Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10847463/|language=en|pmid=10847463}}</ref><ref name=":2">{{Cite journal|last=P|first=Martiat|last2=Jl|first2=Michaux|last3=J|first3=Rodhain|date=1991|title=Philadelphia-negative (Ph-) Chronic Myeloid Leukemia (CML): Comparison With Ph+ CML and Chronic Myelomonocytic Leukemia. The Groupe Français De Cytogénétique Hématologique|url=https://pubmed.ncbi.nlm.nih.gov/2070054/|language=en|pmid=2070054}}</ref>.
*Isolated isochromosome 17q rare (most present with features of [[HAEM5:Chronic myelomonocytic leukaemia|CMML]] instead of aCML).
*Isolated isochromosome 17q rare (most present with features of [[HAEM5:Chronic myelomonocytic leukaemia|CMML]] instead of aCML).


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|}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.
|}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.


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Frequently involved:  
Frequently involved:  
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(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 />
(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 />


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==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Myelodysplastic/myeloproliferative neoplasm with neutrophilia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myelodysplastic/myeloproliferative_neoplasm_with_neutrophilia</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Myelodysplastic/myeloproliferative neoplasm with neutrophilia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myelodysplastic/myeloproliferative_neoplasm_with_neutrophilia</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases M]]