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Myeloproliferative neoplasms (MPN) Clinical manifestations Diagnosis Other features
Symptoms Physical examination CBC & Peripheral smear Bone marrow biopsy Gold standard Other investigations
WBCs RBCs Platelets
Leukocytosis Blasts Left shift Basophilia Eosinophilia Monocytosis Others
Chronic myeloid leukemia

(CML), BCR-ABL1+[1][2]

  • Asymptomatic
  • Constitutional symptoms
  • Hyperviscosity and/or anemia related
  • Bleeding
  • Infection
  • Splenomegaly (46–76%)
  • Purpura
  • Anemia related
  • Priapism
Absolute leukocytosis (median of 100,000/µL) Usually <2% but may present with blast crisis Left shift with classic myelocyte bulge (myelocytes > metamyelocytes on the blood smear)
Absolute basophilia is almost always present Absolute eosinophilia in 90% of patients Often present Anemia Platelet count is usually normal or elevated but thrombocytopenia indicates advanced stage or an alternative diagnosis
  • Hypercellurarity with ↑ granuloscytosis and ↓ erythrocytosis
  • Fibrosis
Marrow aspirate & unilateral biopsy with cytogenetics and flow cytometry
  • FISH for t(9;22)(q34;q11.2)
  • Reverse transcriptase quantitative PCR (RQ-PCR) for BCR-ABL
Chronic neutrophilic leukemia (CNL)[3][4][5]
  • Asymptomatic
  • Constitutional symptoms
  • Bleeding
  • Infection
  • Splenomegaly
  • Heptomegaly
  • Purpura
  • Anemia related
Leukocytosis with chronic neutrophilia Minimal to none Significantly less than that of CML Absent Absent Absent ↑ Lactate dehydrogenase (LDH)

↑ Vitamin B12 levels

Anemia Thrombocytopenia Uniforme and intense hypercellularity with minimal to none fibrosis

Neutrophil toxic granulations and Dohle bodies

FISH

Imaging for hepatosplenomegaly

Associationed with polycythemia vera and plasma cell disorders
Polycythemia vera (PV)[6][7][8][9]
  • Constitutional
  • Thromboembolism and bleeding
  • Pruritus after a warm bath
  • PUD related
  • Facial ruddiness
  • Related to underlying cause
  • Splenomegaly
  • Renal bruit
Normal to mild None None May be present May be present Usually absent ↓ Serum ferritin ↓ Folate levels

↑↑B12 levels

↑↑ Hb and Hct levels (> 16 and 48%) None to moderate Hypercellularity for age with tri-lineage growth

Myelofibrosis (in up to 20% of patients)

JAK2 mutation studies are diagnostic in 95% of patients Radioisotope studies

Serum EPO levels

LFTs

RFTs

Imaging studies

May transform into myelofibrosis or leukemia
Primary myelofibrosis (PMF)[10][11][12][13]
  • Constitutional
  • Anemia related
  • Bleeding
  • Infection
  • Abdominal Pain
  • Hepatosplenomegaly
  • Petechiae & ecchymoses
  • Abdominal distension
  • Lymphadenopathy
Variable with leukocytosis or leukopenia Erythroblasts may be seen None Abset Absent Absent ↑ LAP

↑ LAD

uric acid

↑ vitamin B12

Normochromic normocytic anemia Thrombocytopenia Variable with fibrosis or hypercellularity JAK2 mutation

CALR mutation

MPL mutation

Bone marrow aspiration shows a dry tap
Essential thrombocythemia (ET)[14][15][16]
  • Headache
  • Dizziness
  • Visual disturbances
  • Priapism
  • Acute chest pain
  • Splenomegaly
  • Skin bruises

None/may be

None

None

decreased or absent basophils

None

None

None

Normocytic,

normochrmoic

Marked thrombocytosis

Normal/Hypercellular

WHO diagnostic criteria for essential thrombocythemia

JAK2 mutation

CALR mutation

MPL mutation

Thrombosis

Hemorrhage

Pregnancy loss

Chronic eosinophilic leukemia, not otherwise specified (NOS)[17][18][19][20]
  • Constitutional
  • Rash
  • Rhinitis
  • Gastritis
  • Thromboembolism related
  • Hypertension
  • Eczema, mucosal ulcers, erythema
  • Angioedema
  • Ataxia
  • Anemia
  • Lymphadenopathy
  • hepatosplenomegaly
Leukocytosis Present Present Mild basophilia Severe eosinophilia Mildly increased

monocytes

↑ B12 levels

LDH

Anemia Thrombocytopenia Hypercelluar with ↑ eosinophilic precursors, ↑ eosinophils, and atypical mononuclear cells Biopsy combined with peripheral eosinophilia and absence of Philadelphia chromosome FISH

Cytogenetic analysis of purified eosinophils and X-chromosome inactivation analysis

  • Heart failure
  • Lung fibrosis
  • Encephalopathy
  • Erythema annulare centrifugam
MPN, unclassifiable Similar to other myeloproliferative neoplasms Similar to other myeloproliferative neoplasms Leukocytosis Variable Variable Variable Variable Variable May resemble other myeloproliferative neoplasms Variable Thrombocytosis in most cases ↑ megakaryocyte proliferation with variable hypercellularity in granulocytic or erythrocytic cell lines None Similar to other myeloprolifeartive neoplasms but do not fulfil the criteria to be classified to a specific type
Mastocytosis[21][22][23][24]
  • Constitutional
  • Pruritus & Flushing
  • Urticaria & Blisters
  • Hypotension & PUD
  • Bleeding
  • Bronchoconstriction
  • Mastocytosis exanthema
  • Blistering
  • Swelling
  • Lymphadenopathy
  • Bleeding
  • Fibrosis
Leukocytosis None None Eosinophilia ↑ Alkaline phosphatase

↑ LDH

Anemia Thrombocytopenia or thrombocytosis Multifocal dense infiltrates of mast cells with atypical morphology in >25 % Bone marrow or lesional (Cutaneous mastocytosis) biopsyand histopathological studies Cytogenetic analysis for c-KIT receptor mutations

Serum tryptase levels

24-hour urine test for N-methyl histamine and 11-beta-prostaglandine

  • Skin most commonly involved
  • Susceptibility to anaphylaxix
  • Osteoporosis
Myeloproliferative neoplasms (MPN) Clinical manifestations Diagnosis Other features
Symptoms Physical examination CBC & Peripheral smear Bone marrow biopsy Gold standard Other investigations
WBCs RBCs Platelets
Leukocytosis Blasts Left shift Basophilia Eosinophilia Monocytosis Others
Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of

PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2

  • Myeloid/lymphoid neoplasms with PDGFRA rearrangement
  • Myeloid/lymphoid neoplasms with PDGFRB rearrangement
  • Myeloid/lymphoid neoplasms with FGFR1 rearrangement
  • Provisional entity: Myeloid/lymphoid neoplasms with PCM1-JAK
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) Chronic myelomonocytic leukemia (CMML)[25]
[26][27]
  • Constitutional
  • Anemia related
  • Bleeding
  • Infections
  • Bone pain
  • Leukemia Cutis
  • Organomegaly
  • Bruising
MD-CMML: WBC ≤ 13 × 109/L

 MP-CMML: WBC > 13 × 109/L (FAB)

< 20% blasts Eosinophilia Absolute monocytosis > 1 × 109/L (defining feature) ↑ LDH Anemia Thrombocytopenia Myelodysplastic and myeloproliferative feature Exclusion of distinctive rearrangements and translocation i.e; Ph chromosome and presence of monocytosis Cytogenetic analysis

Flow cytometry

Overlapping of both, MDS and MPN
Atypical chronic myeloid leukemia (aCML), BCR-ABL1-
Juvenile myelomonocytic leukemia (JMML)[28]
  • Infections
  • Anemia related
  • Hepatosplenomegaly
  • Lymphadenopathy
  • Rash
Leukocytosis Present Monocytosis ↓Serum Iron

↑vitamin B12

Anemia Thrombocytopenia Hypercelluar with ↑ myeloid cells in stages of maturation Cytogenetic analysis

Flow cytometry

Polyclonal hypergammaglobulinemia
MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)
MDS/MPN, unclassifiable
Myelodysplastic syndromes (MDS) MDS with single lineage dysplasia
MDS with ring sideroblasts (MDS-RS)
MDS-RS and single lineage dysplasia
MDS-RS and multilineage dysplasia
MDS with multilineage dysplasia
MDS with excess blasts
MDS with isolated del(5q)
MDS, unclassifiable
Provisional entity: Refractory cytopenia of childhood
Myeloid neoplasms with germ line predisposition
Acute myeloid leukemia (AML) and related neoplasms
  • AML with recurrent genetic abnormalities
  1. AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
  2. AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11
  3. APL with PML-RARA
  4. AML with t(9;11)(p21.3;q23.3);MLLT3-KMT2A
  5. AML with t(6;9)(p23;q34.1);DEK-NUP214
  6. AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM
  7. AML (megakaryoblastic) with t(1;22)(p13.3;q13.3);RBM15-MKL1
  8. Provisional entity: AML with BCR-ABL1
  9. AML with mutated NPM1
  10. AML with biallelic mutations of CEBPA
  11. Provisional entity: AML with mutated RUNX1
  • AML with myelodysplasia-related changes
  • Therapy-related myeloid neoplasms
  • AML, NOS
  1. AML with minimal differentiation
  2. AML without maturation
  3. AML with maturation
  4. Acute myelomonocytic leukemia
  5. Acute monoblastic/monocytic leukemia
  6. Pure erythroid leukemia
  7. Acute megakaryoblastic leukemia
  8. Acute basophilic leukemia
  9. Acute panmyelosis with myelofibrosis
  • Myeloid sarcoma
  • Myeloid proliferations related to Down syndrome
  1. Transient abnormal myelopoiesis (TAM)
  2. Myeloid leukemia associated with Down syndrome
Blastic plasmacytoid dendritic cell neoplasm
Acute leukemias of ambiguous lineage Acute undifferentiated leukemia
Mixed phenotype acute
leukemia (MPAL) with t(9;22)(q34.1;q11.2);BCR-ABL1
MPAL with t(v;11q23.3);KMT2A rearranged
MPAL, B/myeloid, NOS
MPAL, T/myeloid, NO
B-lymphoblastic leukemia/lymphoma
  • B-lymphoblastic leukemia/lymphoma, NOS
  • B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
  • B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2);BCR-ABL1
  • B-lymphoblastic leukemia/lymphoma with t(v;11q23.3);KMT2A rearranged
  • B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1);ETV6-RUNX1
  • B-lymphoblastic leukemia/lymphoma with hyperdiploidy
  • B-lymphoblastic leukemia/lymphoma with hypodiploidy
  • B-lymphoblastic leukemia/lymphoma with t(5;14)(q31.1;q32.3) IL3-IGH
  • B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3);TCF3-PBX1
  • Provisional entity: B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like
  • Provisional entity: B-lymphoblastic leukemia/lymphoma with iAMP
T-lymphoblastic leukemia/lymphoma
T-lymphoblastic leukemia/lymphoma
Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph
Provisional entity: Early T-cell precursor lymphoblastic leukemia
  • 50% of patients are asymptomatic
  • Clinical features are generally nonspecific such as left upper quadrant pain, early satiety, fatigue & lethargy (most common presenting symptom), weight loss, and night sweats.
  • symptoms of anemia
  • bleeding
  • priapism
  • bone pain
  • Abdominal mass or fullness
  • Infection
  • Headache
  • Dyspnoea
  • Visual disturbances
  • Weakness
  • Arthralgia
  • Cough
  • Malaise
  • Dizziness
  • Nausea/vomiting
  • Ankle oedema
  • Mental change

References

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  2. Thompson PA, Kantarjian HM, Cortes JE (October 2015). "Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015". Mayo Clin. Proc. 90 (10): 1440–54. doi:10.1016/j.mayocp.2015.08.010. PMC 5656269. PMID 26434969.
  3. Szuber N, Tefferi A (February 2018). "Chronic neutrophilic leukemia: new science and new diagnostic criteria". Blood Cancer J. 8 (2): 19. doi:10.1038/s41408-018-0049-8. PMC 5811432. PMID 29440636.
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  5. Menezes J, Cigudosa JC (2015). "Chronic neutrophilic leukemia: a clinical perspective". Onco Targets Ther. 8: 2383–90. doi:10.2147/OTT.S49688. PMC 4562747. PMID 26366092.
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  7. Pillai AA, Babiker HM. PMID 30252337. Missing or empty |title= (help)
  8. Tefferi A, Barbui T (January 2019). "Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management". Am. J. Hematol. 94 (1): 133–143. doi:10.1002/ajh.25303. PMID 30281843.
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  15. Daniel A. Arber, Attilio Orazi, Robert Hasserjian, Jurgen Thiele, Michael J. Borowitz, Michelle M. Le Beau, Clara D. Bloomfield, Mario Cazzola & James W. Vardiman (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. PMID 27069254. Unknown parameter |month= ignored (help)
  16. A. Tefferi, R. Fonseca, D. L. Pereira & H. C. Hoagland (2001). "A long-term retrospective study of young women with essential thrombocythemia". Mayo Clinic proceedings. 76 (1): 22–28. doi:10.4065/76.1.22. PMID 11155408. Unknown parameter |month= ignored (help)
  17. Vidyadharan S, Joseph B, Nair SP (2016). "Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations". Indian J Dermatol. 61 (4): 437–9. doi:10.4103/0019-5154.185716. PMC 4966405. PMID 27512192.
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