Myeloproliferative neoplasm differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Myeloproliferative disease}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Myeloproliferative_neoplasm]]
{{CMG}} {{AE}} {{MJK}}
{{CMG}} {{AE}} {{HMHJ}} {{ZAS}} {{MJK}} {{shyam}}
==Overview==
==Overview==
Myeloproliferative neoplasm must be differentiated from acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, essential thrombocytosis, hypereosinophilic syndrome, non-Hodgkin lymphoma, primary myelofibrosis, secondary thrombocytosis, splenomegaly, systemic mastocytosis, and waldenstrom macroglobulinemia.
Myeloproliferative neoplasm must be differentiated from [[myelodysplastic syndrome]], [[acute myelogenous leukemia]], [[acute lymphoblastic leukemia]], [[Waldenstrom's macroglobulinemia]], and [[lymphoproliferative disorder]]. Each of these conditions has a unique set of causes, laboratory abnormalities, physical exam findings, and investigations.
==Differentiating Myeloproliferative disease from other Diseases==
 
The lymphoid lineage may produce similar diseases, the [[lymphoproliferative disorder]]s ([[acute lymphoblastic leukemia]], [[lymphoma]]s,[[chronic lymphocytic leukemia]] and [[multiple myeloma]]).
==Differentiating Myeloproliferative Neoplasm from other Diseases==
==References==
'''ABBREVIATIONS'''
{{Reflist|2}}
 
[[Category:Hematology]]  
'''EPO''': Erythropoietin, '''FISH''': Fluorescence in situ hybridization, '''Hb''': Hemoglobin, '''LAD''': Leukocyte alkaline dehydrgenase, '''LAP''': Leukocyte alkaline phosphatase, '''LDH''': Lactate dehydrogenase, '''LFTs''': Liver function tests, '''NL''': Normal, '''PCR''': Polymerase chain reaction, '''Plt''': Platelet, '''PUD''': Peptic ulcer disease, '''RFTs''': Renal function tests, '''WBCs''': White blood cells.
{| class="wikitable"
! colspan="2" rowspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Clinical manifestations
! colspan="10" style="background:#4479BA; color: #FFFFFF;" align="center" + |Diagnosis
! rowspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! rowspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! rowspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Signs
! colspan="8" style="background:#4479BA; color: #FFFFFF;" align="center" + |CBC & Peripheral smear
! rowspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! rowspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
|-
! colspan="6" style="background:#4479BA; color: #FFFFFF;" align="center" + |WBCs
! rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
|-
! colspan="2" |[[Chronic myeloid leukemia]]<br>([[CML]])<ref name="pmid9012696">{{cite journal |vauthors=Savage DG, Szydlo RM, Goldman JM |title=Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period |journal=Br. J. Haematol. |volume=96 |issue=1 |pages=111–6 |date=January 1997 |pmid=9012696 |doi= |url=}}</ref><ref name="pmid26434969">{{cite journal |vauthors=Thompson PA, Kantarjian HM, Cortes JE |title=Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015 |journal=Mayo Clin. Proc. |volume=90 |issue=10 |pages=1440–54 |date=October 2015 |pmid=26434969 |pmc=5656269 |doi=10.1016/j.mayocp.2015.08.010 |url=}}</ref>
|
* Asymptomatic
* Constitutional
* [[Hyperviscosity]]  and/or [[anemia]] related
* [[Bleeding]]
* [[Infection]]
|
* [[Splenomegaly]]<br>(46–76%)
* [[Purpura]]
* [[Anemia]] related
* [[Priapism]]
|↑
|<2%
| +
|↑
|↑
|↑
|[[Anemia|↓]]
|NL
|
* Hypercellurarity with ↑ [[granuloscytosis]] and ↓ [[erythrocytosis]]
 
* [[Fibrosis]]
|
* [[FISH]] for t(9;22)(q34;q11.2)
* [[Reverse transcriptase]] quantitative [[PCR]] (RQ-PCR) for BCR-ABL
|
* [[Granulocytic]] [[dysplasia]] is minimal/absent
* May present with [[blast]] crisis
* Absolute [[leukocytosis]]  (median of 100,000/µL)
* Classic [[myelocyte]] bulge
* [[thrombocytopenia]] indicates advanced stage
|-
! colspan="2" |[[Polycythemia vera]]<br>([[PV]])<ref name="pmid29194068">{{cite journal |vauthors=Vannucchi AM, Guglielmelli P, Tefferi A |title=Polycythemia vera and essential thrombocythemia: algorithmic approach |journal=Curr. Opin. Hematol. |volume=25 |issue=2 |pages=112–119 |date=March 2018 |pmid=29194068 |doi=10.1097/MOH.0000000000000402 |url=}}</ref><ref name="pmid30252337">{{cite journal |vauthors=Pillai AA, Babiker HM |title= |journal= |volume= |issue= |pages= |date= |pmid=30252337 |doi= |url=}}</ref><ref name="pmid30281843">{{cite journal |vauthors=Tefferi A, Barbui T |title=Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management |journal=Am. J. Hematol. |volume=94 |issue=1 |pages=133–143 |date=January 2019 |pmid=30281843 |doi=10.1002/ajh.25303 |url=}}</ref><ref name="pmid28028026">{{cite journal |vauthors=Rumi E, Cazzola M |title=Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms |journal=Blood |volume=129 |issue=6 |pages=680–692 |date=February 2017 |pmid=28028026 |pmc=5335805 |doi=10.1182/blood-2016-10-695957 |url=}}</ref>
|
* Constitutional
 
*  [[Thromboembolism]]<br>and [[bleeding]]
 
* [[Pruritus]] after<br>a warm bath
* [[PUD]] related
|
* Facial ruddiness
* Related to underlying cause
* [[Splenomegaly]]
* [[Renal]] [[bruit]]
|NL or ↑
|None
| -
|↑ or ↓
|NL or ↑
|NL
|↑↑
 
|NL
|
* Hypercellularity for age with tri-lineage growth
 
* [[Myelofibrosis]] (in up to 20% of patients)
|
* [[Radioisotope]] studies
* [[Serum]] [[EPO]] levels
* [[LFTs]]
* [[RFTs]]
* [[Imaging]] studies
* ↓ Serum [[ferritin]]
* ↓ [[Folate]] levels
* ↑↑ [[B12]] levels
|
* May transform into [[myelofibrosis]] or [[leukemia]]
|-
! colspan="2" |[[Primary myelofibrosis]] ([[PMF]])<ref name="pmid26891375">{{cite journal |vauthors=Cervantes F, Correa JG, Hernandez-Boluda JC |title=Alleviating anemia and thrombocytopenia in myelofibrosis patients |journal=Expert Rev Hematol |volume=9 |issue=5 |pages=489–96 |date=May 2016 |pmid=26891375 |doi=10.1586/17474086.2016.1154452 |url=}}</ref><ref>{{cite book | last = Hoffman | first = Ronald | title = Hematology : basic principles and practice | publisher = Elsevier | location = Philadelphia, PA | year = 2018 | isbn = 9780323357623 }}</ref><ref name="pmid16919893">{{cite journal |vauthors=Michiels JJ, Bernema Z, Van Bockstaele D, De Raeve H, Schroyens W |title=Current diagnostic criteria for the chronic myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF) |journal=Pathol. Biol. |volume=55 |issue=2 |pages=92–104 |date=March 2007 |pmid=16919893 |doi=10.1016/j.patbio.2006.06.002 |url=}}</ref><ref>{{cite book | last = Hoffman | first = Ronald | title = Hematology : basic principles and practice | publisher = Elsevier | location = Philadelphia, PA | year = 2018 | isbn = 9780323357623 }}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding]]
* [[Infection]]
* [[Abdominal]] [[Pain]]
|
* [[Hepatosplenomegaly]]
* [[Petechiae]] & [[ecchymoses]]
* Abdominal distension
* [[Lymphadenopathy]]
|↓
|[[Erythroblasts]]
| -
|Absent
|NL
|NL
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Variable with [[fibrosis]] or hypercellularity
|
* JAK2 mutation
* [[CALR]] [[mutation]]
* [[MPL]] [[mutation]]
* [[mutation|↑]] [[LAP]]
* [[mutation|↑]] [[LAD]]
* [[mutation|↑]] [[Uric acid]]
* [[mutation|↑]] [[B12]] levels
|
* [[Bone marrow]] aspiration shows a dry tap
* Variable with [[leukocytosis]] or [[leukopenia]]
|-
! colspan="2" |[[Essential thrombocythemia]] ([[ET]])<ref name="pmidhttp://dx.doi.org/10.1182/blood-2007-04-083501">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=http://dx.doi.org/10.1182/blood-2007-04-083501 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }} </ref><ref>{{Cite journal
| author = [[Daniel A. Arber]], [[Attilio Orazi]], [[Robert Hasserjian]], [[Jurgen Thiele]], [[Michael J. Borowitz]], [[Michelle M. Le Beau]], [[Clara D. Bloomfield]], [[Mario Cazzola]] & [[James W. Vardiman]]
| title = The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia
| journal = [[Blood]]
| volume = 127
| issue = 20
| pages = 2391–2405
| year = 2016
| month = May
| doi = 10.1182/blood-2016-03-643544
| pmid = 27069254
}}</ref><ref>{{Cite journal
| author = [[A. Tefferi]], [[R. Fonseca]], [[D. L. Pereira]] & [[H. C. Hoagland]]
| title = A long-term retrospective study of young women with essential thrombocythemia
| journal = [[Mayo Clinic proceedings]]
| volume = 76
| issue = 1
| pages = 22–28
| year = 2001
| month = January
| doi = 10.4065/76.1.22
| pmid = 11155408
}}</ref>
|
* Headache
* [[Dizziness]]
* [[Visual]] disturbances
* [[Priapism]]
* Acute [[chest pain]]
|
* [[Splenomegaly]]
* [[Skin]] [[bruises]]
|
NL or ↑
|
None
| -
|
↓ or absent
|
NL
|
NL
|
[[Anemia|↓]]
|
↑↑
|
* Normal/Hypercellular
|
* [[JAK2]] [[mutation]]
* [[CALR]] [[mutation]]
* [[MPL]] [[mutation]]
|
* [[Thrombosis]]
* [[Hemorrhage]]
* [[Pregnancy]] loss
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Sign
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! rowspan="4" |[[Myelodysplastic]]<br>/[[Myeloproliferative neoplasm|myeloproliferative<br>neoplasms]] (MDS/MPN)
![[Chronic myelomonocytic leukemia]] (CMML)<ref name="pmid27185207">{{cite journal |vauthors=Patnaik MM, Tefferi A |title=Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=6 |pages=631–42 |date=June 2016 |pmid=27185207 |doi=10.1002/ajh.24396 |url=}}</ref>
: <ref name="pmid22615103">{{cite journal |vauthors=Parikh SA, Tefferi A |title=Chronic myelomonocytic leukemia: 2012 update on diagnosis, risk stratification, and management |journal=Am. J. Hematol. |volume=87 |issue=6 |pages=610–9 |date=June 2012 |pmid=22615103 |doi=10.1002/ajh.23203 |url=}}</ref><ref name="pmid25869097">{{cite journal |vauthors=Benton CB, Nazha A, Pemmaraju N, Garcia-Manero G |title=Chronic myelomonocytic leukemia: Forefront of the field in 2015 |journal=Crit. Rev. Oncol. Hematol. |volume=95 |issue=2 |pages=222–42 |date=August 2015 |pmid=25869097 |pmc=4859155 |doi=10.1016/j.critrevonc.2015.03.002 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding]]
* [[Infections]]
* [[Bone]] [[pain]]
* [[Leukemia Cutis]]
|
* [[Organomegaly]]
* [[Bruising]]
|↑
| < 20%
|
|NL
|[[Eosinophilia|↑]]
|↑↑
 
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* [[Myelodysplastic]] and [[myeloproliferative]] feature
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* ↑ [[LDH]]
|
* Overlapping of both, [[MDS]] and [[MPN]]
* Absolute [[monocytosis]] > 1 × 10<sup>9</sup>/L (defining feature)
 
* MD-CMML:[[WBC]] ≤ 13 × 10<sup>9</sup>/L (FAB)
 
*  MP-CMML:[[WBC]] > 13 × 10<sup>9</sup>/L (FAB)
 
|-
![[Atypical chronic myeloid leukemia]] (aCML), [[BCR/ABL|BCR-ABL]]1-<ref name="pmid26637732">{{cite journal |vauthors=Dao KH, Tyner JW |title=What's different about atypical CML and chronic neutrophilic leukemia? |journal=Hematology Am Soc Hematol Educ Program |volume=2015 |issue= |pages=264–71 |date=2015 |pmid=26637732 |pmc=5266507 |doi=10.1182/asheducation-2015.1.264 |url=}}</ref><ref name="pmid22289493">{{cite journal |vauthors=Muramatsu H, Makishima H, Maciejewski JP |title=Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions |journal=Semin. Oncol. |volume=39 |issue=1 |pages=67–73 |date=February 2012 |pmid=22289493 |pmc=3523950 |doi=10.1053/j.seminoncol.2011.11.004 |url=}}</ref>
|
*Asymptomatic
* Constitutional
* [[Hyperviscosity|Hyperviscosity]]  and/or [[anemia]] related
* [[Bleeding|Bleeding]]
* [[Infection|Infection]]
|
* [[Splenomegaly]]  (46–76%)
* [[Purpura]]
* [[Anemia]] related
* [[Priapism]]
|↑
|<20%
| +
|<2% of WBCs
|N/A
|N/A
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Granulocytic [[hyperplasia]] with prominent [[dysplasia]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
|
* Granulocytic [[dysplasia]] is prominent
* Absence of ''[[BCR/ABL|BCR-ABL]]'' or ''PDGFRA'', [[PDGFRB|''PDGFRB'',]] or ''[[FGFR1]]'' rearrangements
* [[WBC]] > 13 × 10<sup>9</sup>/L
|-
![[Juvenile myelomonocytic leukemia (patient information)|Juvenile myelomonocytic leukemia (]]JMML)<ref name="pmid9226148">{{cite journal |vauthors=Aricò M, Biondi A, Pui CH |title=Juvenile myelomonocytic leukemia |journal=Blood |volume=90 |issue=2 |pages=479–88 |date=July 1997 |pmid=9226148 |doi= |url=}}</ref><ref name="pmid80255132">{{cite journal |vauthors=Hasle H |title=Myelodysplastic syndromes in childhood--classification, epidemiology, and treatment |journal=Leuk. Lymphoma |volume=13 |issue=1-2 |pages=11–26 |date=March 1994 |pmid=8025513 |doi=10.3109/10428199409051647 |url=}}</ref>
|
* [[Infections]]
* [[Anemia]] related
|
* [[Hepatosplenomegaly]]
* [[Lymphadenopathy]]
* [[Rash]]
|[[Leukocytosis|↑]]
|↑
|N/A
|N/A
|N/A
|[[Monocytosis|↑]]
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Hypercelluar with  ↑ [[myeloid cells]] in stages of maturation
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* [[Flow cytometry|↓]] [[Serum]] [[Iron]]
* [[Flow cytometry|↑]] [[Vitamin B12|B12]] levels
|
* Polyclonal [[hypergammaglobulinemia]]
|-
![[MDS]]/[[MPN]] with ring sideroblasts and [[thrombocytosis]] (MDS/MPN-RS-T)<ref name="pmid28188970">{{cite journal |vauthors=Patnaik MM, Tefferi A |title=Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T): 2017 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=92 |issue=3 |pages=297–310 |date=March 2017 |pmid=28188970 |doi=10.1002/ajh.24637 |url=}}</ref><ref name="pmid30186759">{{cite journal |vauthors=Alshaban A, Padilla O, Philipovskiy A, Corral J, McAlice M, Gaur S |title=Lenalidomide induced durable remission in a patient with MDS/MPN-with ring sideroblasts and thrombocytosis with associated 5q- syndrome |journal=Leuk Res Rep |volume=10 |issue= |pages=37–40 |date=2018 |pmid=30186759 |doi=10.1016/j.lrr.2018.08.001 |url=}}</ref><ref name="pmid30524760">{{cite journal |vauthors=Bouchla A, Papageorgiou SG, Tsakiraki Z, Glezou E, Pavlidis G, Stavroulaki G, Bazani E, Foukas P, Pappa V |title=Plasmablastic Lymphoma in an Immunocompetent Patient with MDS/MPN with Ring Sideroblasts and Thrombocytosis-A Case Report |journal=Case Rep Hematol |volume=2018 |issue= |pages=2525070 |date=2018 |pmid=30524760 |pmc=6247723 |doi=10.1155/2018/2525070 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Thrombosis]]
 
|
* Variable
|NL or ↑
|NL
| -
|NL
|N/A
|N/A
|[[Anemia|↓]]
|[[Thrombocytosis|↑]]
|
* Hypercellularity with [[dyserythropoiesis]] and increased [[megakaryocytes]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* ↑ [[Serum]] [[Iron]]
|
* Large atypical [[megakaryocytes]]
 
* Ringed [[sideroblasts]]
* [[SF3B1]] [[mutation]]
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Sign
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! colspan="2" |[[Chronic neutrophilic leukemia]] ([[CNL]])<ref name="pmid29440636">{{cite journal |vauthors=Szuber N, Tefferi A |title=Chronic neutrophilic leukemia: new science and new diagnostic criteria |journal=Blood Cancer J |volume=8 |issue=2 |pages=19 |date=February 2018 |pmid=29440636 |pmc=5811432 |doi=10.1038/s41408-018-0049-8 |url=}}</ref><ref name="pmid28028025">{{cite journal |vauthors=Maxson JE, Tyner JW |title=Genomics of chronic neutrophilic leukemia |journal=Blood |volume=129 |issue=6 |pages=715–722 |date=February 2017 |pmid=28028025 |pmc=5301820 |doi=10.1182/blood-2016-10-695981 |url=}}</ref><ref name="pmid26366092">{{cite journal |vauthors=Menezes J, Cigudosa JC |title=Chronic neutrophilic leukemia: a clinical perspective |journal=Onco Targets Ther |volume=8 |issue= |pages=2383–90 |date=2015 |pmid=26366092 |pmc=4562747 |doi=10.2147/OTT.S49688 |url=}}</ref>
|
* Asymptomatic
* Constitutional symptoms
* [[Bleeding]]
* [[Infection]]
|
* [[Splenomegaly]]
* [[Heptomegaly]]
* [[Purpura]]
* [[Anemia]] related
|↑
|Minimal
| +
|NL
|NL
|NL
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Uniforme and intense hypercellularity with minimal to none [[fibrosis]]
* [[Neutrophil]] toxic granulations and [[Dohle bodies]]
|
* [[FISH]]
* Imaging for [[hepatosplenomegaly]]
* ↑  [[LDH]]
* ↑ [[B12]] levels
|
* Associationed with [[polycythemia vera]] and [[plasma cell disorders]]
* [[Leukocytosis]] with<br>[[chronic]] [[neutrophilia]]
|-
! colspan="2" |[[Chronic eosinophilic leukemia]],<br>not otherwise specified<br>(NOS)<ref name="pmid27512192">{{cite journal |vauthors=Vidyadharan S, Joseph B, Nair SP |title=Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations |journal=Indian J Dermatol |volume=61 |issue=4 |pages=437–9 |date=2016 |pmid=27512192 |pmc=4966405 |doi=10.4103/0019-5154.185716 |url=}}</ref><ref name="pmid29892549">{{cite journal |vauthors=Hofmans M, Delie A, Vandepoele K, Van Roy N, Van der Meulen J, Philippé J, Moors I |title=A case of chronic eosinophilic leukemia with secondary transformation to acute myeloid leukemia |journal=Leuk Res Rep |volume=9 |issue= |pages=45–47 |date=2018 |pmid=29892549 |pmc=5993353 |doi=10.1016/j.lrr.2018.04.001 |url=}}</ref><ref name="pmid23662039">{{cite journal |vauthors=Yamada Y, Rothenberg ME, Cancelas JA |title=Current concepts on the pathogenesis of the hypereosinophilic syndrome/chronic eosinophilic leukemia |journal=Transl Oncogenomics |volume=1 |issue= |pages=53–63 |date=2006 |pmid=23662039 |pmc=3642145 |doi= |url=}}</ref><ref name="pmid27722133">{{cite journal |vauthors=Kim TH, Gu HJ, Lee WI, Lee J, Yoon HJ, Park TS |title=Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement |journal=Blood Res |volume=51 |issue=3 |pages=204–206 |date=September 2016 |pmid=27722133 |doi=10.5045/br.2016.51.3.204 |url=}}</ref>
|
* Constitutional
* [[Rash]]
* [[Rhinitis]]
* [[Gastritis]]
* [[Thromboembolism]]<br>related
|
* [[Hypertension]]
* [[Eczema]], [[mucosal]] [[ulcers]], [[erythema]]
* [[Angioedema]]
 
* [[Ataxia]]
* [[Anemia]]
* [[Lymphadenopathy]]
* [[Hepatosplenomegaly]]
|[[Leukocytosis|↑]]
|Present
| +
|↑
|↑↑
|↑
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Hypercelluar with  ↑ [[eosinophilic]] precursors, ↑ [[eosinophils]], and atypical [[mononuclear cells]]
|
* [[FISH]]
* Cytogenetic analysis of purified [[eosinophils]] and [[X-chromosome]] inactivation analysis
* ↑ [[B12]] levels
* ↑ [[LDH]]
|
* [[Heart failure]] [[Lung fibrosis]]
* [[Encephalopathy]]
* [[Erythema annulare centrifugam]]
|-
! colspan="2" |[[Myeloproliferative neoplasm|MPN]],<br>unclassifiable
|
*Similar to other<br>[[Myeloproliferative neoplasm|myeloproliferative neoplasms]]
|
*Similar to other<br>[[Myeloproliferative neoplasm|myeloproliferative neoplasms]]
|[[Leukocytosis|↑]]
|Variable
|↑ or ↓
|↑ or ↓
|↑ or ↓
|↓
|↑
|
* ↑ [[megakaryocyte]] proliferation with variable hypercellularity in [[granulocytic]] or [[erythrocytic]] cell lines
|
* May resemble other<br>[[myeloproliferative neoplasms]]
|
*Similar to other [[myeloprolifeartive neoplasms]] but do not fulfil the criteria to be classified to a specific type
|-
! colspan="2" |[[Mastocytosis]]<ref name="pmid24262698">{{cite journal |vauthors=Carter MC, Metcalfe DD, Komarow HD |title=Mastocytosis |journal=Immunol Allergy Clin North Am |volume=34 |issue=1 |pages=181–96 |date=February 2014 |pmid=24262698 |pmc=3863935 |doi=10.1016/j.iac.2013.09.001 |url=}}</ref><ref name="pmid29494109">{{cite journal |vauthors=Macri A, Cook C |title= |journal= |volume= |issue= |pages= |date= |pmid=29494109 |doi= |url=}}</ref><ref name="pmid25031064">{{cite journal |vauthors=Lladó AC, Mihon CE, Silva M, Galzerano A |title=Systemic mastocytosis - a diagnostic challenge |journal=Rev Bras Hematol Hemoter |volume=36 |issue=3 |pages=226–9 |date=2014 |pmid=25031064 |pmc=4109736 |doi=10.1016/j.bjhh.2014.03.003 |url=}}</ref><ref name="pmid28031180">{{cite journal |vauthors=Valent P, Akin C, Metcalfe DD |title=Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts |journal=Blood |volume=129 |issue=11 |pages=1420–1427 |date=March 2017 |pmid=28031180 |pmc=5356454 |doi=10.1182/blood-2016-09-731893 |url=}}</ref>
|
* Constitutional
 
* [[Pruritus]] & [[Flushing]]
* [[Urticaria]] & [[Blisters]]
 
* [[Hypotension]] & [[PUD]]
* [[Bleeding]]
* [[Bronchoconstriction]]
 
|
* [[Mastocytosis exanthema]]
* [[Blistering]]
* [[Swelling]]
* [[Lymphadenopathy]]
* [[Bleeding]]
* [[Fibrosis]]
|[[Leukocytosis|↑]]
|None
| -
|NL
|[[Eosinophilia|↑]]
|NL
|[[Anemia|↓]]
|↓ or ↑
|
* Multifocal dense infiltrates of [[mast cells]] with atypical [[morphology]] in >25 %
|
* Cytogenetic analysis for [[c-KIT]] [[receptor]] [[mutations]]
* [[Serum]] [[tryptase]] levels
* 24-hour urine test for N-methyl [[histamine]] and 11-beta-[[prostaglandine]]
* ↑ [[Alkaline phosphatase]]
* ↑ [[LDH]]
|
* Skin most commonly involved
* Susceptibility to [[anaphylaxix]]
* [[Osteoporosis]]
|-
! colspan="2" |[[Myeloid]]/[[lymphoid]] [[neoplasms]]<br>with [[eosinophilia]] and rearrangement<br>of [[PDGFR|PDGFRA]], [[PDGFRB]], or [[FGFR1]],<br>or with [[PCM1]]-[[JAK2]]<ref name="KumarChen2015">{{cite journal|last1=Kumar|first1=Kirthi R.|last2=Chen|first2=Weina|last3=Koduru|first3=Prasad R.|last4=Luu|first4=Hung S.|title=Myeloid and Lymphoid Neoplasm With Abnormalities of FGFR1 Presenting With Trilineage Blasts and RUNX1 Rearrangement|journal=American Journal of Clinical Pathology|volume=143|issue=5|year=2015|pages=738–748|issn=1943-7722|doi=10.1309/AJCPUD6W1JLQQMNA}}</ref><ref>{{Cite journal
| author = [[Paolo Strati]], [[Guilin Tang]], [[Dzifa Y. Duose]], [[Saradhi Mallampati]], [[Rajyalakshmi Luthra]], [[Keyur P. Patel]], [[Mohammad Hussaini]], [[Abu-Sayeef Mirza]], [[Rami S. Komrokji]], [[Stephen Oh]], [[John Mascarenhas]], [[Vesna Najfeld]], [[Vivek Subbiah]], [[Hagop Kantarjian]], [[Guillermo Garcia-Manero]], [[Srdan Verstovsek]] & [[Naval Daver]]
| title = Myeloid/lymphoid neoplasms with FGFR1 rearrangement
| journal = [[Leukemia & lymphoma]]
| volume = 59
| issue = 7
| pages = 1672–1676
| year = 2018
| month = July
| doi = 10.1080/10428194.2017.1397663
| pmid = 29119847
}}</ref><ref>{{Cite journal
| author = [[Ximena Montenegro-Garreaud]], [[Roberto N. Miranda]], [[Alexandra Reynolds]], [[Guilin Tang]], [[Sa A. Wang]], [[Mariko Yabe]], [[Wei Wang]], [[Lianghua Fang]], [[Carlos E. Bueso-Ramos]], [[Pei Lin]], [[L. Jeffrey Medeiros]] & [[Xinyan Lu]]
| title = Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase
| journal = [[Human pathology]]
| volume = 65
| pages = 147–156
| year = 2017
| month = July
| doi = 10.1016/j.humpath.2017.05.008
| pmid = 28551329
}}</ref><ref>{{Cite journal
| author = [[Paola Villafuerte-Gutierrez]], [[Montserrat Lopez Rubio]], [[Pilar Herrera]] & [[Eva Arranz]]
| title = A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation
| journal = [[Case reports in hematology]]
| volume = 2018
| pages = 5724960
| year = 2018
| month =
| doi = 10.1155/2018/5724960
| pmid = 30647980
}}</ref>
|
* Asymptomatic
* Constitutional
* [[Rash]]
* [[Cough]] & breathlessness
* [[Peripheral neuropathy]]/<br>[[encephalopathy]]
|
* [[Fever]]
* [[Lymphadenopathy]]
| ↑
| NL
| -
| NL
| [[Eosinophilia|↑]]
|[[Monocytosis|↑]]
| NL
| [[Thrombocytopenia|↓]]
|
* [[Myeloid]] expansion with [[eosinophilia]]
|
* [[FISH]] shows t(8;13) and t(8;22)
|
* May present or evolve into [[acute myeloid]] or [[lymphoblastic leukemia]]
* [[Leukocytosis]] (30 - 59 × 10<sup>9</sup>/L
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Sign
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! colspan="2" |B-lymphoblastic leukemia/lymphoma<ref name="pmid30107017">{{cite journal |vauthors=Kamiya-Matsuoka C, Garciarena P, Amin HM, Tremont-Lukats IW, de Groot JF |title=B lymphoblastic leukemia/lymphoma presenting as seventh cranial nerve palsy |journal=Neurol Clin Pract |volume=3 |issue=6 |pages=532–534 |date=December 2013 |pmid=30107017 |pmc=6082360 |doi=10.1212/CPJ.0b013e3182a78ef0 |url=}}</ref><ref name="pmid29029550">{{cite journal |vauthors=Zhang X, Rastogi P, Shah B, Zhang L |title=B lymphoblastic leukemia/lymphoma: new insights into genetics, molecular aberrations, subclassification and targeted therapy |journal=Oncotarget |volume=8 |issue=39 |pages=66728–66741 |date=September 2017 |pmid=29029550 |pmc=5630450 |doi=10.18632/oncotarget.19271 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding]]
* [[Infection]]
* [[Bone pain]]
|
* [[Pallor]]
* [[Petechiae]]
* [[Organomegaly]]
* [[Lymphadenopathy]]
|NL or ↑
|>25%
|N/A
|↑ or ↓
|↑ or ↓
|↑ or ↓
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Hypercellular with [[blast]] infilterationwith or without [[myelodysplasia]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
 
* [[FISH]]
* [[Auer rod|Auer bodies]]
|
* May present as [[Extramedullary myeloid tumor|extramedullary]] disease ([[Extramedullary Myeloid Cell Tumor|Myeloid sarcoma]])
|-
! colspan="2" |[[Myelodysplastic syndrome|Myelodysplastic syndromes]]<br>([[MDS]])<ref name="pmid24300826">{{cite journal |vauthors=Germing U, Kobbe G, Haas R, Gattermann N |title=Myelodysplastic syndromes: diagnosis, prognosis, and treatment |journal=Dtsch Arztebl Int |volume=110 |issue=46 |pages=783–90 |date=November 2013 |pmid=24300826 |pmc=3855821 |doi=10.3238/arztebl.2013.0783 |url=}}</ref><ref name="pmid26769228">{{cite journal |vauthors=Gangat N, Patnaik MM, Tefferi A |title=Myelodysplastic syndromes: Contemporary review and how we treat |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=76–89 |date=January 2016 |pmid=26769228 |doi=10.1002/ajh.24253 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding]]
* [[Infection]]
|
* [[Pallor]]
* [[Petechiae]]
* [[Organomegaly]]
|[[Leukopenia|↓]]
|Variable
| -
|↓
|↓
|↓
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Hypercellular/ normocellular [[bone marrow]] with [[Dysplastic change|dysplastic]] changes
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* Macro-ovalocytes
* Basophilic stippling
* [[Howell-Jolly body|Howell-Jolly body]]
|
* [[Leukemia]] transformation
* Acquired pseudo-Pelger-Huët anomaly
|-
! colspan="2" |[[Acute myeloid leukemia]] ([[AML]])<br>and related [[neoplasms]]<ref name="pmid3864727">{{cite journal |vauthors=Islam A, Catovsky D, Goldman JM, Galton DA |title=Bone marrow biopsy changes in acute myeloid leukaemia. I: Observations before chemotherapy |journal=Histopathology |volume=9 |issue=9 |pages=939–57 |date=September 1985 |pmid=3864727 |doi= |url=}}</ref><ref name="pmid17587881">{{cite journal |vauthors=Orazi A |title=Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases |journal=Pathobiology |volume=74 |issue=2 |pages=97–114 |date=2007 |pmid=17587881 |doi=10.1159/000101709 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding|Bleeding]]
* [[Bone pain|Bone pain]]
* [[Joint pain|Joint pain]]
* [[Infections|Infections]]
|
* [[Infection]] related
 
* [[Pallor|Pallor]]
* [[Chloroma|Leukemia cutis]]
* [[Bruising]] & [[Petechia|petechiae]]
* [[Lymphadenopathy]]
 
* [[Hepatomegaly|Hepatosplenomegaly]]
|NL or ↑
|↑
|N/A
|↑ or ↓
|↑ or ↓
|↑ or ↓
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Increased  immature[[myeloid]] [[cells]]
with [[Dysplastic change|dysplasia]]     
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* [[FISH]]
* ↑ [[Potassium]]
* ↑ [[Uric acid]]
* ↑ [[Phosphorus]]
* ↓ [[Calcium]]
* ↑ [[LDH]]
|
* Common in [[Down syndrome]]
|-
! colspan="2" |[[Blastic plasmacytoid dendritic cell neoplasm|Blastic plasmacytoid<br>dendritic cell neoplasm]]<ref>{{Cite journal
| author = [[F. Julia]], [[T. Petrella]], [[M. Beylot-Barry]], [[M. Bagot]], [[D. Lipsker]], [[L. Machet]], [[P. Joly]], [[O. Dereure]], [[M. Wetterwald]], [[M. d'Incan]], [[F. Grange]], [[J. Cornillon]], [[G. Tertian]], [[E. Maubec]], [[P. Saiag]], [[S. Barete]], [[I. Templier]], [[F. Aubin]] & [[S. Dalle]]
| title = Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients
| journal = [[The British journal of dermatology]]
| volume = 169
| issue = 3
| pages = 579–586
| year = 2013
| month = September
| doi = 10.1111/bjd.12412
| pmid = 23646868
}}</ref><ref>{{Cite journal
| author = [[Livio Pagano]], [[Caterina Giovanna Valentini]], [[Alessandro Pulsoni]], [[Simona Fisogni]], [[Paola Carluccio]], [[Francesco Mannelli]], [[Monia Lunghi]], [[Gianmatteo Pica]], [[Francesco Onida]], [[Chiara Cattaneo]], [[Pier Paolo Piccaluga]], [[Eros Di Bona]], [[Elisabetta Todisco]], [[Pellegrino Musto]], [[Antonio Spadea]], [[Alfonso D'Arco]], [[Stefano Pileri]], [[Giuseppe Leone]], [[Sergio Amadori]] & [[Fabio Facchetti]]
| title = Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study
| journal = [[Haematologica]]
| volume = 98
| issue = 2
| pages = 239–246
| year = 2013
| month = February
| doi = 10.3324/haematol.2012.072645
| pmid = 23065521
}}</ref><ref>{{Cite journal
| author = [[Joseph D. Khoury]]
| title = Blastic Plasmacytoid Dendritic Cell Neoplasm
| journal = [[Current hematologic malignancy reports]]
| volume = 13
| issue = 6
| pages = 477–483
| year = 2018
| month = December
| doi = 10.1007/s11899-018-0489-z
| pmid = 30350260
}}</ref><ref>{{Cite journal
| author = [[Shinichiro Sukegawa]], [[Mamiko Sakata-Yanagimoto]], [[Ryota Matsuoka]], [[Haruka Momose]], [[Yusuke Kiyoki]], [[Masayuki Noguchi]], [[Naoya Nakamura]], [[Rei Watanabe]], [[Manabu Fujimoto]], [[Yasuhisa Yokoyama]], [[Hidekazu Nishikii]], [[Takayasu Kato]], [[Manabu Kusakabe]], [[Naoki Kurita]], [[Naoshi Obara]], [[Yuichi Hasegawa]] & [[Shigeru Chiba]]
| title = &#91;Blastic plasmacytoid dendritic cell neoplasm accompanied by chronic myelomonocytic leukemia successfully treated with azacitidine&#93;
| journal = <nowiki>[[[Rinsho ketsueki] The Japanese journal of clinical hematology]]</nowiki>
| volume = 59
| issue = 12
| pages = 2567–2573
| year = 2018
| month =
| doi = 10.11406/rinketsu.59.2567
| pmid = 30626790
}}</ref>
|
* [[Cutaneous]] symptoms (brown/purple nodular lesions) on [[face]], [[scalp]], [[lower limb]] & [[trunk]]
|
* Brown/violaceous [[bruise]] like lesions
* [[Lymphadenopathy]]
* [[Splenomegaly]]
| NL
| ↑
|
|NL
| NL
| NL
| [[Anemia|↓]]
| [[Thrombocytopenia|↓]]
|
* [[Malignant|Malignant cells]]
|
* [[Immunohistochemistry]] or [[flow cytometry]] for [[CD4]] & [[CD56]]
* [[Neutropenia]]
|
* TdT expression positive
* May develop [[chronic myelomonocytic leukemia]] (CMML)
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Sign
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! rowspan="3" |T-lymphoblastic leukemia/<br>lymphoma
*
*
!T-lymphoblastic leukemia/<br>lymphoma<ref name="pmid26276771">{{cite journal |vauthors=You MJ, Medeiros LJ, Hsi ED |title=T-lymphoblastic leukemia/lymphoma |journal=Am. J. Clin. Pathol. |volume=144 |issue=3 |pages=411–22 |date=September 2015 |pmid=26276771 |doi=10.1309/AJCPMF03LVSBLHPJ |url=}}</ref><ref name="pmid19284608">{{cite journal |vauthors=Patel KJ, Latif SU, de Calaca WM |title=An unusual presentation of precursor T cell lymphoblastic leukemia/lymphoma with cholestatic jaundice: case report |journal=J Hematol Oncol |volume=2 |issue= |pages=12 |date=March 2009 |pmid=19284608 |pmc=2663564 |doi=10.1186/1756-8722-2-12 |url=}}</ref><ref name="pmid24822133">{{cite journal |vauthors=Elreda L, Sandhu M, Sun X, Bekele W, Cohen AJ, Shah M |title=T-cell lymphoblastic leukemia/lymphoma: relapse 16 years after first remission |journal=Case Rep Hematol |volume=2014 |issue= |pages=359158 |date=2014 |pmid=24822133 |pmc=4005062 |doi=10.1155/2014/359158 |url=}}</ref>
|
* Constitutional
* [[Anemia]] Related
* [[Bleeding]]
* [[Superior vena cava syndrome]]
|
* [[Lymphadenopathy]]
* [[Mediastinal mass]]
*  [[Pleural effusions]]
* [[Trachea|Tracheal]] obstruction
* [[Pericardial effusions]]
|↑
|>25% [[Blast|blasts]] ([[Leukemia]])
 
<25% [[Blast|blasts]] ([[Lymphoma]])
|↑ or ↓
|↑ or ↓
|↑ or ↓
|↓
|↓
|
* Hypercelluarity with increased [[T cells]] precursors
|
* [[Cytogenetic analysis]][[Flow cytometry]]
* [[FISH]]
* ↑ [[LDH]]
* Positive for TdT
|
* May involve [[brain]], [[skin]], and [[testes]].
|-
!Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph<ref name="pmid28868017">{{cite journal |vauthors=Sedick Q, Alotaibi S, Alshieban S, Naheet KB, Elyamany G |title=Natural Killer Cell Lymphoblastic Leukaemia/Lymphoma: Case Report and Review of the Recent Literature |journal=Case Rep Oncol |volume=10 |issue=2 |pages=588–595 |date=2017 |pmid=28868017 |doi=10.1159/000477843 |url=}}</ref>
|
* Constitutional
* [[Anemia]] Related
* [[Bleeding]]
* [[Superior vena cava syndrome]]
|
* [[Lymphadenopathy]]
* [[Mediastinal mass]]
*  [[Pleural effusions]]
* [[Trachea|Tracheal]] obstruction
* [[Pericardial effusions]]
|↑
|↑
|↑ or ↓
|↑ or ↓
|↑ or ↓
|↓
|↓
|
* N/A
|
* [[Cytogenetic analysis]]
 
* [[FISH]]
* [[Flow cytometry]]
* ↑ [[LDH]]
|
* Similar to [[T-cell]] lymphoblastic [[leukemia]] but may have more aggressive clinical course.
* [[Diagnosis]] is usually based on presence of [[CD56]] expression, and  [[T-cell]]-associated markers such as [[CD2]] and [[CD7]].
*  [[B cell|B-cell]] markers are absent.
|-
!Provisional entity: Early T-cell precursor lymphoblastic leukemia<ref name="pmid26747249">{{cite journal |vauthors=Jain N, Lamb AV, O'Brien S, Ravandi F, Konopleva M, Jabbour E, Zuo Z, Jorgensen J, Lin P, Pierce S, Thomas D, Rytting M, Borthakur G, Kadia T, Cortes J, Kantarjian HM, Khoury JD |title=Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype |journal=Blood |volume=127 |issue=15 |pages=1863–9 |date=April 2016 |pmid=26747249 |pmc=4915808 |doi=10.1182/blood-2015-08-661702 |url=}}</ref><ref name="pmid23695450">{{cite journal |vauthors=Haydu JE, Ferrando AA |title=Early T-cell precursor acute lymphoblastic leukaemia |journal=Curr. Opin. Hematol. |volume=20 |issue=4 |pages=369–73 |date=July 2013 |pmid=23695450 |pmc=3886681 |doi=10.1097/MOH.0b013e3283623c61 |url=}}</ref>
|
* Constitutional
* [[Anemia]] Related
* [[Bleeding]]
* [[Superior vena cava syndrome]]
|
* [[Lymphadenopathy]]
* [[Mediastinal mass]]
*  [[Pleural effusions]]
* [[Trachea|Tracheal]] obstruction
* [[Pericardial effusions]]
|↑
|↑
|↑ or ↓
|↑ or ↓
|↑ or ↓
|↓
|↓
|
* Hypercelluarity with increased [[T cells]] precursors
|
* [[Cytogenetic analysis]]
* [[FISH]]
* [[Flow cytometry]]
* ↑ [[LDH]]
|
* Similar to [[T cell|T-cell]] lymphoblastic [[leukemia]] but is more aggressive clinically and cell are characterized by [[Flow cytometry|cytometry]] as [[CD1a]]<sup>−</sup>, [[CD8]]<sup>−</sup>, [[CD5]]<sup>−</sup> (dim), and positivity for 1 or more stem cell or [[myeloid]] [[antigens]].
* [[Gene expression]] indicates more immature [[cells]] as compared to other subtypes of [[T cell|T-cell]] [[neoplasms]].
|}


[[Category: Disease]]
==Differentiating Myeloproliferative neoplasm from other Diseases==


{{WH}}
{| class="wikitable"
{{WS}}
!Characteristic
!Causes
!Physical examination
!Laboratory abnormalities
!Therapy
!Other associations
|-
!Myeloproliferative neoplasm
|
* ''JAK2'' mutation
* ''CALR'' mutation
* ''MPL'' mutation
* ''BCR-ABL'' translocation
* ''CSF3R'' mutation
* ''SETBP1'' mutation
* ''PDGFRA'' or ''PDGFRB'' rearrangement
|
* Splenomegaly
* Hepatomegaly
* Evidence of infection
* Pallor
|
* Elevated hemoglobin
* Elevated [[white blood cell]] count
* Elevated [[platelet]] count
* Elevated [[eosinophil]] and/or [[neutrophil]] count
* Bone marrow fibrosis
|
* Ruxolitinib
* Hydroxyurea
* Anagrelide
* Imatinib
* Midostaurin
* Stem cell transplant
|
* Variable features based on the subtype of myeloproliferative neoplasm
|-
!Myelodysplastic syndrome
|
* Prior exposure to alkylating agents
* Prior exposure to topoisomerase II inhibitors
* Age-related changes in hematopoietic stem cells
* Deletion of chromosome 5q or 7
* Gain of chromosome 8
|
* [[Mucosal bleeding]]
* Petechiae
* Ecchymoses
* Evidence of infection
* Pallor
|
* Dysplasia in at least 10% of cells of at least 1 cell line
* Low [[white blood cell]] count
* [[Anemia]]
* [[Neutropenia]]
* [[Thrombocytopenia]]
|
* Lenalidomide
* Decitabine
* Azacitidine
* Erythropoiesis-stimulating agents (ESAs)
* Granulocyte colony-stimulating factor (G-CSF)
* Transfusion support
* Stem cell transplant for high-risk myelodysplastic syndrome
|
* Age-related changes in the bone marrow contribute to myelodysplastic syndrome
|-
!Acute myeloid leukemia
|
* Chromosomal instability
* Sporadic mutations
* Prior exposure to benzene
* Prior exposure to alkylating agents
* Prior exposure to topoisomerase II inhibitors
* Germline ''RUNX1'' mutation
|
* Pyrexia
* Evidence of infection
* Pallor
* Mucosal bleeding
* Bruising
|
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Neutropenia]]
* Elevated LDH
* Elevated uric acid
* Elevated phosphorus
* Elevated potassium
* Low calcium
* Greater than 20% myeloblasts on bone marrow aspirate<ref name="pmid27895058">{{cite journal| author=Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al.| title=Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | journal=Blood | year= 2017 | volume= 129 | issue= 4 | pages= 424-447 | pmid=27895058 | doi=10.1182/blood-2016-08-733196 | pmc=5291965 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27895058  }} </ref>
|
* Cytarabine
* Anthracycline
* Enasidenib
* Liposomal daunorubicin plus cytarabine
* Gemtuzumab ozogamycin
* Midostaurin
* [[Stem cell transplant]]
|
* Variable prognosis based on cytogenetic and molecular profile
* Four new FDA-approved therapies became available in 2017
|-
!Acute lymphoblastic leukemia
|
* Chromosomal instability
* Sporadic mutations
|
* Neurologic deficits
* Pallor
* Lymphadenopathy
|
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Neutropenia]]
* Elevated LDH
* Elevated uric acid
* Elevated phosphorus
* Elevated potassium
* Low calcium
* Greater than 20% lymphoblasts on bone marrow aspirate
|
* HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)<ref name="pmid28665419">{{cite journal| author=Terwilliger T, Abdul-Hay M| title=Acute lymphoblastic leukemia: a comprehensive review and 2017 update. | journal=Blood Cancer J | year= 2017 | volume= 7 | issue= 6 | pages= e577 | pmid=28665419 | doi=10.1038/bcj.2017.53 | pmc=5520400 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28665419  }} </ref>
* R-HyperCVAD (inclusion of rituximab)
* Peg-asparaginase
* Intrathecal methotrexate
* Intrathecal cytarabine
* Blinatumomab (bispecific T cell engager)
* Inotuzumab ozogamycin (anti-CD22 antibody)
* Tisagenlecleucel (chimeric antigen receptor T (CAR-T) cell therapy)
* [[Stem cell transplant]]
|
* Sanctuary sites include the central nervous system (CNS) and testes<ref name="pmid23523389">{{cite journal| author=Inaba H, Greaves M, Mullighan CG| title=Acute lymphoblastic leukaemia. | journal=Lancet | year= 2013 | volume= 381 | issue= 9881 | pages= 1943-55 | pmid=23523389 | doi=10.1016/S0140-6736(12)62187-4 | pmc=3816716 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23523389  }} </ref>
|-
!Waldenstrom's macroglobulinemia
|
* ''MYD88'' mutation
* Lymphoplasmacytic cell proliferation
|
* Hepatomegaly
* Splenomegaly
* Retinal vascular dilation and thrombosis
* Decreased visual acuity
* Headache
|
* Elevated [[immunoglobulin M]] (IgM) [[paraprotein]]
* Presence of M-spike on protein electrophoresis
* Elevated serum free light chains (''kappa'' and ''lambda'')
* Increased serum viscosity
|
* [[Rituximab]]
* [[Ibrutinib]]
* [[Plasmapheresis]]
|
* ''MYD88'' mutation testing is standard-of-care
* Plasmapheresis should be initiated if symptoms of hyperviscosity are present
* Typically does not require [[stem cell transplant]]
|-
![[Lymphoproliferative disorder]]<ref name="pmid28102226">{{cite journal| author=Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG et al.| title=Chronic lymphocytic leukaemia. | journal=Nat Rev Dis Primers | year= 2017 | volume= 3 | issue=  | pages= 16096 | pmid=28102226 | doi=10.1038/nrdp.2016.96 | pmc=5336551 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28102226  }} </ref>
|
* [[Epstein-Barr virus]] (EBV)
* [[Human immunodeficiency virus]] (HIV)
* [[Human T cell lymphotrophic virus-1]] (HTLV-1)
* Post-transplant status ([[post-transplant lymphoproliferative disorder]] (PTLD))
* Chromosomal instability
* Sporadic mutations
* Rheumatologic disease
|
* [[Lymph node enlargement]]
* [[Splenomegaly]]
* [[Hepatomegaly]]
|
* Elevated lymphocyte count with presence of clonality
* Anemia
* Thrombocytopenia
* Neutropenia
|
* Variable based on the etiology
* Cytotoxic chemotherapy
* Antiviral agents
* Biologic therapy with anti-CD20 monoclonal antibodies
* Tapering immunosuppressive medications (for post-transplant lymphoproliferative disorder)
|
* Can be due to a variety of causes
* Variable prognosis
|}
==References==
{{reflist|2}}
[[Category:Up-To-Date]]
[[Category:Medicine]]
[[Category:Oncology]]
[[Category:Hematology]]
[[Category:Differential diagnosis]]

Latest revision as of 20:15, 6 March 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2] Zahir Ali Shaikh, MD[3] Mohamad Alkateb, MBBCh [4] Shyam Patel [5]

Overview

Myeloproliferative neoplasm must be differentiated from myelodysplastic syndrome, acute myelogenous leukemia, acute lymphoblastic leukemia, Waldenstrom's macroglobulinemia, and lymphoproliferative disorder. Each of these conditions has a unique set of causes, laboratory abnormalities, physical exam findings, and investigations.

Differentiating Myeloproliferative Neoplasm from other Diseases

ABBREVIATIONS

EPO: Erythropoietin, FISH: Fluorescence in situ hybridization, Hb: Hemoglobin, LAD: Leukocyte alkaline dehydrgenase, LAP: Leukocyte alkaline phosphatase, LDH: Lactate dehydrogenase, LFTs: Liver function tests, NL: Normal, PCR: Polymerase chain reaction, Plt: Platelet, PUD: Peptic ulcer disease, RFTs: Renal function tests, WBCs: White blood cells.

Disease Clinical manifestations Diagnosis Other features
Symptoms Signs CBC & Peripheral smear Bone marrow biopsy Other investigations
WBCs Hb Plt
WBC Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Chronic myeloid leukemia
(CML)[1][2]
<2% + NL
Polycythemia vera
(PV)[3][4][5][6]
  • Constitutional
NL or ↑ None - ↑ or ↓ NL or ↑ NL ↑↑ NL
  • Hypercellularity for age with tri-lineage growth
Primary myelofibrosis (PMF)[7][8][9][10] Erythroblasts - Absent NL NL
  • Variable with fibrosis or hypercellularity
Essential thrombocythemia (ET)[11][12][13]

NL or ↑

None

-

↓ or absent

NL

NL

↑↑

  • Normal/Hypercellular
Disease Symptoms Sign WBC Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Hb Plt Bone marrow biopsy Other investigations Other features
Myelodysplastic
/myeloproliferative
neoplasms
(MDS/MPN)
Chronic myelomonocytic leukemia (CMML)[14]
[15][16]
< 20% NL ↑↑
  • Overlapping of both, MDS and MPN
  • Absolute monocytosis > 1 × 109/L (defining feature)
  • MD-CMML:WBC ≤ 13 × 109/L (FAB)
  •  MP-CMML:WBC > 13 × 109/L (FAB)
Atypical chronic myeloid leukemia (aCML), BCR-ABL1-[17][18] <20% + <2% of WBCs N/A N/A
Juvenile myelomonocytic leukemia (JMML)[19][20] N/A N/A N/A
MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)[21][22][23]
  • Variable
NL or ↑ NL - NL N/A N/A
Disease Symptoms Sign WBC Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Hb Plt Bone marrow biopsy Other investigations Other features
Chronic neutrophilic leukemia (CNL)[24][25][26] Minimal + NL NL NL
Chronic eosinophilic leukemia,
not otherwise specified
(NOS)[27][28][29][30]
Present + ↑↑
MPN,
unclassifiable
Variable ± ↑ or ↓ ↑ or ↓ ↑ or ↓
Mastocytosis[31][32][33][34]
  • Constitutional
None - NL NL ↓ or ↑
Myeloid/lymphoid neoplasms
with eosinophilia and rearrangement
of PDGFRA, PDGFRB, or FGFR1,
or with PCM1-JAK2[35][36][37][38]
NL - NL NL
  • FISH shows t(8;13) and t(8;22)
Disease Symptoms Sign WBC Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Hb Plt Bone marrow biopsy Other investigations Other features
B-lymphoblastic leukemia/lymphoma[39][40] NL or ↑ >25% N/A ↑ or ↓ ↑ or ↓ ↑ or ↓
Myelodysplastic syndromes
(MDS)[41][42]
Variable -
  • Leukemia transformation
  • Acquired pseudo-Pelger-Huët anomaly
Acute myeloid leukemia (AML)
and related neoplasms[43][44]
NL or ↑ N/A ↑ or ↓ ↑ or ↓ ↑ or ↓

with dysplasia

Blastic plasmacytoid
dendritic cell neoplasm
[45][46][47][48]
NL NL NL NL
Disease Symptoms Sign WBC Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Hb Plt Bone marrow biopsy Other investigations Other features
T-lymphoblastic leukemia/
lymphoma
T-lymphoblastic leukemia/
lymphoma[49][50][51]
>25% blasts (Leukemia)

<25% blasts (Lymphoma)

± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • Hypercelluarity with increased T cells precursors
Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph[52] ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • N/A
Provisional entity: Early T-cell precursor lymphoblastic leukemia[53][54] ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • Hypercelluarity with increased T cells precursors

Differentiating Myeloproliferative neoplasm from other Diseases

Characteristic Causes Physical examination Laboratory abnormalities Therapy Other associations
Myeloproliferative neoplasm
  • JAK2 mutation
  • CALR mutation
  • MPL mutation
  • BCR-ABL translocation
  • CSF3R mutation
  • SETBP1 mutation
  • PDGFRA or PDGFRB rearrangement
  • Splenomegaly
  • Hepatomegaly
  • Evidence of infection
  • Pallor
  • Ruxolitinib
  • Hydroxyurea
  • Anagrelide
  • Imatinib
  • Midostaurin
  • Stem cell transplant
  • Variable features based on the subtype of myeloproliferative neoplasm
Myelodysplastic syndrome
  • Prior exposure to alkylating agents
  • Prior exposure to topoisomerase II inhibitors
  • Age-related changes in hematopoietic stem cells
  • Deletion of chromosome 5q or 7
  • Gain of chromosome 8
  • Lenalidomide
  • Decitabine
  • Azacitidine
  • Erythropoiesis-stimulating agents (ESAs)
  • Granulocyte colony-stimulating factor (G-CSF)
  • Transfusion support
  • Stem cell transplant for high-risk myelodysplastic syndrome
  • Age-related changes in the bone marrow contribute to myelodysplastic syndrome
Acute myeloid leukemia
  • Chromosomal instability
  • Sporadic mutations
  • Prior exposure to benzene
  • Prior exposure to alkylating agents
  • Prior exposure to topoisomerase II inhibitors
  • Germline RUNX1 mutation
  • Pyrexia
  • Evidence of infection
  • Pallor
  • Mucosal bleeding
  • Bruising
  • Cytarabine
  • Anthracycline
  • Enasidenib
  • Liposomal daunorubicin plus cytarabine
  • Gemtuzumab ozogamycin
  • Midostaurin
  • Stem cell transplant
  • Variable prognosis based on cytogenetic and molecular profile
  • Four new FDA-approved therapies became available in 2017
Acute lymphoblastic leukemia
  • Chromosomal instability
  • Sporadic mutations
  • Neurologic deficits
  • Pallor
  • Lymphadenopathy
  • Anemia
  • Thrombocytopenia
  • Neutropenia
  • Elevated LDH
  • Elevated uric acid
  • Elevated phosphorus
  • Elevated potassium
  • Low calcium
  • Greater than 20% lymphoblasts on bone marrow aspirate
  • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)[56]
  • R-HyperCVAD (inclusion of rituximab)
  • Peg-asparaginase
  • Intrathecal methotrexate
  • Intrathecal cytarabine
  • Blinatumomab (bispecific T cell engager)
  • Inotuzumab ozogamycin (anti-CD22 antibody)
  • Tisagenlecleucel (chimeric antigen receptor T (CAR-T) cell therapy)
  • Stem cell transplant
  • Sanctuary sites include the central nervous system (CNS) and testes[57]
Waldenstrom's macroglobulinemia
  • MYD88 mutation
  • Lymphoplasmacytic cell proliferation
  • Hepatomegaly
  • Splenomegaly
  • Retinal vascular dilation and thrombosis
  • Decreased visual acuity
  • Headache
  • Elevated immunoglobulin M (IgM) paraprotein
  • Presence of M-spike on protein electrophoresis
  • Elevated serum free light chains (kappa and lambda)
  • Increased serum viscosity
  • MYD88 mutation testing is standard-of-care
  • Plasmapheresis should be initiated if symptoms of hyperviscosity are present
  • Typically does not require stem cell transplant
Lymphoproliferative disorder[58]
  • Elevated lymphocyte count with presence of clonality
  • Anemia
  • Thrombocytopenia
  • Neutropenia
  • Variable based on the etiology
  • Cytotoxic chemotherapy
  • Antiviral agents
  • Biologic therapy with anti-CD20 monoclonal antibodies
  • Tapering immunosuppressive medications (for post-transplant lymphoproliferative disorder)
  • Can be due to a variety of causes
  • Variable prognosis

References

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