HAEM5:Myelodysplastic/myeloproliferative neoplasm, NOS: Difference between revisions

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{{DISPLAYTITLE:Myelodysplastic/myeloproliferative neoplasm, NOS}}
{{DISPLAYTITLE:Myelodysplastic/myeloproliferative neoplasm, NOS}}
[[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:Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN), Unclassifiable]].
<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:Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN), Unclassifiable]].
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==Definition / Description of Disease==
MDS/MPN-U are a heterogeneous group of myeloid neoplasms meeting the criteria for MDS/MPN at onset, without the defining features of one of the other categories of MDS/MPN, i.e. chronic myelomonocytic leukaemia (CMML) juvenile myelomonocytic leukaemia (JMML), atypical chronic myeloid leukaemia, ''BCR-ABL1''-negative (aCML) or myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). <ref name=":0">Orazi A, et al., (2017). Myelodysplastic / myeloproliferative neoplasm, unclassifiable, 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, p95-96.</ref><ref name=":1">{{Cite journal|last=Ti|first=Mughal|last2=Nc|first2=Cross|last3=E|first3=Padron|last4=Rv|first4=Tiu|last5=M|first5=Savona|last6=L|first6=Malcovati|last7=R|first7=Tibes|last8=Rs|first8=Komrokji|last9=Jj|first9=Kiladjian|date=2015|title=An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/26341525/|language=en|doi=10.3324/haematol.2014.114660|pmc=PMC4800699|pmid=26341525}}</ref>
MDS/MPN-U is the most poorly characterised of the MDS/MPN subgroups <ref name=":2">{{Cite journal|last=P|first=Bose|last2=A|first2=Nazha|last3=Rs|first3=Komrokji|last4=Kp|first4=Patel|last5=Sa|first5=Pierce|last6=N|first6=Al-Ali|last7=A|first7=Sochacki|last8=A|first8=Shaver|last9=W|first9=Ma|date=2018|title=Mutational landscape of myelodysplastic/myeloproliferative neoplasm-unclassifiable|url=https://pubmed.ncbi.nlm.nih.gov/30242087/|language=en|doi=10.1182/blood-2018-05-848473|pmc=PMC6236463|pmid=30242087}}</ref>.
*< 20% blasts in the peripheral blood and bone marrow
*Clinical and morphological features of a category of MDS
**'''excluding''' any case meeting the criteria for MDS with isolated del(5q)
*Platelet count of ≥ 450 ×10/L with bone marrow megakaryocytic proliferation and/or a white bood cell count of ≥ 13 × 10<sup>9</sup>/L
*Myelodysplastic / myeloproliferative features not explained by recent cytotoxic or growth factor therapy
*Excludes cases with ''PDGFRA'', ''PDGFRB'' and ''FGFR1'' rearrangement and ''PCM1-JAK2'' <ref name=":0" />
When an underlying MPN has not been identified, the category of MDS/MPN-U is appropriate. <ref name=":0" />
Cases with features of MDS/MPN-U may arise due to prior exposure to treatment and are included in the [[HAEM5:Myeloid neoplasm post cytotoxic therapy|Therapy-related myeloid neoplasms]] (t-MN).
Well-defined MPN which subsequently develop dysplastic features and progress to a more aggressive phase are excluded from this category.
Palomo ''et al.'' <ref name=":3">{{Cite journal|last=L|first=Palomo|last2=M|first2=Meggendorfer|last3=S|first3=Hutter|last4=S|first4=Twardziok|last5=V|first5=Adema|last6=I|first6=Fuhrmann|last7=F|first7=Fuster-Tormo|last8=B|first8=Xicoy|last9=L|first9=Zamora|date=2020|title=Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/32573691/|language=en|pmid=32573691}}</ref> proposed sub-categories of MDS/MPN-U based on the molecular signature. See [[Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN), Unclassifiable#Gene Mutations .28SNV.2FINDEL.29|Gene Mutations]] below.
==Synonyms / Terminology==
*Chronic myelodysplastic / myeloproliferative disease (no longer used)
*Mixed myeloproliferative / myelodysplastic syndrome, unclassifiable
*Overlap syndrome, unclassifiable <ref name=":0" /><ref name=":1" />
==Epidemiology / Prevalence==
*Less than 5% of myeloid malignancies<ref>{{Cite journal|last=L|first=Cannella|last2=M|first2=Breccia|last3=R|first3=Latagliata|last4=A|first4=Frustaci|last5=G|first5=Alimena|date=2008|title=Clinical and prognostic features of patients with myelodysplastic/myeloproliferative syndrome categorized as unclassified (MDS/MPD-U) by WHO classification|url=https://pubmed.ncbi.nlm.nih.gov/17709138/|language=en|pmid=17709138}}</ref>
*Median age: reports vary from 70 <ref name=":1" /> to 75 <ref name=":2" />
*Male:female ratio 2:1 <ref name=":1" /><ref name=":3" />
==Clinical Features==
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{| 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)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
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*Overlap with [[HAEM4:Myelodysplastic Syndromes (MDS)|MDS]] and [[HAEM4:Myeloproliferative Neoplasms (MPN)|MPN]] <ref name=":0" />
*Clinically the most heterogeneous of the MDS/MPN <ref name=":3" />
*Does not have features that define it as belonging to any of the other categories of MDS/MPN <ref name=":0" /><ref name=":1" />
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==Sites of Involvement==
*Peripheral blood and bone marrow always involved
*Extramedullary tissues may be involved <ref name=":0" />
==Morphologic Features==
Co-occurrence of myeloid lineages with (i) ineffective and/or dysplastic proliferation and (ii) effective proliferation with or without dysplasia
*Usually with anaemia, with or without macrocytosis
*Thrombocytosis (platelets ≥ 450 x 10<sup>9</sup>/L) or leucocytosis (white blood cells ≥ 13 x 10<sup>9</sup>/L)
*Dysgranulopoiesis in about 50% of cases
*Giant or hypogranular platelets in some
*Dysmegakaryopoiesis with megakaryocytes resembling those in MDS in >50% of cases, otherwise varying proportions of MDS-like and MPN-like megakaryocytes
*No dysmegakaryopoiesis in <10% of cases
*Blasts < 20% in bone marrow and peripheral blood
*Proliferation in any or all of myeloid lineages in bone marrow biopsy
*≥ 10% of at least one cell line <ref name=":0" />
Palomo ''et al.''<nowiki/>'s MDS/MPN-U sub-categories  defined by molecular profile <ref name=":3" /> (see Gene Mutations below) tend to have:
*CMML-like: higher monocyte count
*aCML-like: higher white blood cell count
*MDS/MPN-RS-T-like: higher ring sideroblast percentage
*''TP53'': more anaemia and higher blast percentage
*other: ''JAK2'' mutations correlated with thrombocytosis
==Immunophenotype==
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{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
|-
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
|}
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May be similar to that of [[HAEM4:Myelodysplastic Syndromes (MDS)|MDS]] or [[HAEM4:Myeloproliferative Neoplasms (MPN)|MPN]] <ref name=":0" />
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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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*None identified
*None identified
*''BCR-ABL1'' fusion should be excluded
*''BCR-ABL1'' fusion should be excluded
*Absence of ''PDGFRA'', ''PDGFRB'' and ''FGFR1'' rearrangements, absence of ''PCM1-JAK2'' fusion <ref name=":0" />
*Absence of ''PDGFRA'', ''PDGFRB'' and ''FGFR1'' rearrangements, absence of ''PCM1-JAK2'' fusion <ref name=":0">Orazi A, et al., (2017). Myelodysplastic / myeloproliferative neoplasm, unclassifiable, 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, p95-96.</ref>


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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:
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* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
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*Prognosis is variable and not well documented <ref name=":0" />
*Prognosis is variable and not well documented <ref name=":0" />
*There are few data regarding an appropriate prognostic scoring system <ref name=":0" />, but IPSS-R <ref name=":2" />or IPSS <ref name=":5" /> have been prognostically useful
*There are few data regarding an appropriate prognostic scoring system <ref name=":0" />, but IPSS-R <ref name=":2">{{Cite journal|last=P|first=Bose|last2=A|first2=Nazha|last3=Rs|first3=Komrokji|last4=Kp|first4=Patel|last5=Sa|first5=Pierce|last6=N|first6=Al-Ali|last7=A|first7=Sochacki|last8=A|first8=Shaver|last9=W|first9=Ma|date=2018|title=Mutational landscape of myelodysplastic/myeloproliferative neoplasm-unclassifiable|url=https://pubmed.ncbi.nlm.nih.gov/30242087/|language=en|doi=10.1182/blood-2018-05-848473|pmc=PMC6236463|pmid=30242087}}</ref>or IPSS <ref name=":5" /> have been prognostically useful
*Median overall survival (OS) from various reports: 80 months <ref name=":3" />; 21.8 months <ref name=":4" />; 12 months <ref name=":2" />
*Median overall survival (OS) from various reports: 80 months <ref name=":3">{{Cite journal|last=L|first=Palomo|last2=M|first2=Meggendorfer|last3=S|first3=Hutter|last4=S|first4=Twardziok|last5=V|first5=Adema|last6=I|first6=Fuhrmann|last7=F|first7=Fuster-Tormo|last8=B|first8=Xicoy|last9=L|first9=Zamora|date=2020|title=Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/32573691/|language=en|pmid=32573691}}</ref>; 21.8 months <ref name=":4" />; 12 months <ref name=":2" />
*Leukaemia-free survival: 18.9 months <ref name=":4" />; 10.8 months <ref name=":2" />
*Leukaemia-free survival: 18.9 months <ref name=":4" />; 10.8 months <ref name=":2" />
*Leukaemic transformation: 10% <ref name=":3" />; 16% after a median of 10.8 months <ref name=":2" />;   
*Leukaemic transformation: 10% <ref name=":3" />; 16% after a median of 10.8 months <ref name=":2" />;   
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One study identified very few recurrent gains and losses below the level of cytogenetic detection <ref name=":3" />.  
One study identified very few recurrent gains and losses below the level of cytogenetic detection <ref name=":3" />.  
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*None specific to MDS/MPN-U
*None specific to MDS/MPN-U
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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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Amongst the MDS/MPN subtypes, MDS/MPN-U has the most heterogeneous mutation profile. In one study it was most strongly correlated with ''U2AF1'' and ''TP53'' mutations <ref name=":3" />.
Amongst the MDS/MPN subtypes, MDS/MPN-U has the most heterogeneous mutation profile. In one study it was most strongly correlated with ''U2AF1'' and ''TP53'' mutations <ref name=":3" />.
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*Major drivers / early mutations in epigenetic regulators (''ASXL1, TET2)'' and splicing factors (''SRSF2'') <ref name=":2" /> <ref name=":3" />
*Major drivers / early mutations in epigenetic regulators (''ASXL1, TET2)'' and splicing factors (''SRSF2'') <ref name=":2" /> <ref name=":3" />
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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 />
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==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Myelodysplastic/myeloproliferative neoplasm, NOS”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myelodysplastic/myeloproliferative_neoplasm,_NOS</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Myelodysplastic/myeloproliferative neoplasm, NOS”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myelodysplastic/myeloproliferative_neoplasm,_NOS</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases M]]