MDS/MPN (2021)

Myelodysplastic/Myeloproliferative
Neoplasms (MDS/MPN)
By:
Ahmed Makboul Ahmed
M.B.B.Ch, M.Sc
Assistant Lecturer, Clinical Pathology Department, South Egypt Cancer Institute

TERMINOLOGY:
Definition:
• De novo clonal chronic myeloid neoplasm characterized by hybrid myelodysplastic and
myeloproliferative features manifested by at least 1 cytopenia and at least 1 cytosis in
blood.
• Maturation is intact; mature cells predominate.
• Blasts and blast equivalents are ≤ 20% in blood and bone marrow.
• Multiple subtypes defined with specific criteria.
• Multiple exclusionary criteria.

CLINICAL FEATURES:
Incidence:
• All MDS/MPN are rare.
• JMML affects 1 per million children.
Age:
• Aside from JMML, MDS/MPNs affect predominately older adults.
• JMML affects children, and 75% of cases manifest by 3 years of age.
Gender:
• Clear-cut male predominance in JMML and CMML.
• No significant gender differences in aCML, MDS/MPN-RS-T.

Clinical Presentation:
• Aside from JMML, patients with MDS/MPN are generally older adults who manifest with
gradual symptoms of progressive cytopenias (notably anemia) and splenomegaly.
• Children with JMML often present with constitutional symptoms and secondary
infections.
oHepatosplenomegaly common.
oMay also have pulmonary disease.
• Splenomegaly is common in all types of MDS/MPN.
• Abnormal myelomonocytic infiltrates can be apparent in skin, lymph nodes, or mucosal
sites.

NATURAL HISTORY:
Prognosis:
• CMML is linked to intermediate prognosis.
• aCML has poor prognosis; response to therapy not significant.
• JMML is usually rapidly fatal without aggressive therapy.
• MDS/MPN-RS-T often relatively indolent.

CLASSIFICATION:
The 2016 WHO Classification of MDS/MPN
1. Chronic myelomonocytic leukemia (CMML).
2. Atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML).
3. Juvenile myelomonocytic leukemia (JMML).
4. MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
5. Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U).

1. Chronic Myelomonocytic Leukemia
(CMML)
• Chronic myelomonocytic leukemia (CMML) is a
MDS/MPN.
oLike other entities in this "overlap" category, it
combines features of both MDS and MPN.
• The current diagnostic criteria of CMML require a
persistent, unexplained absolute monocytosis
≥ 1 x 109/L, as well as monocytes representing ≥
10% of PB leukocytes.

Clinical features:
• Age: CMML mostly occurs in older adults (median age at diagnosis, 70 years).
• Gender: Moderate male predominance.
• Manifestations:
oHepatosplenomegaly more common in those with leukocytosis.
oSymptoms of cytopenia(s).
oMany patients may be asymptomatic.
oIn a subset of patients, CMML may be associated with immune-mediated processes and/or
autoimmune disorders, such as systemic vasculitis, immune thrombocytopenia, psoriasis,
and gout.

MICROSCOPIC PATHOLOGY:
Features of blast equivalents in CMML:
Monoblasts o Chromatin: Quite open and consistent with blast stage.
o Nucleus:
§ Nuclear contours are round with only minimal
irregularity or folding.
§ Prominent nucleoli.
o Cytoplasm: Relatively abundant with variable sparse
granules or fine vacuoles.
Promonocytes
(Blast equivalents)
o Intermediate form of maturation between monoblast
and monocyte.
o Chromatin: More dispersed than that of monocyte.
o Nucleus:
§ Nuclear contours are lightly folded and creased.
§ Nucleoli often present.
o Cytoplasm: Cytoplasm is lightly basophilic and
vacuolated.

Peripheral Blood:
WBCs:
• WBC count may be increased or normal.
• Absolute monocytosis ≥ 1 x 109/L.
oMonocytes representing ≥ 10% of PB leukocytes.
oThe monocytes in PB are typically mature, with
minimal morphologic abnormality.
oHowever, they can exhibit abnormal granulation,
unusual nuclear lobation, more cytoplasmic vacuoles
and delicate nuclear chromatin.
• Dysplasia, especially involving granulocytic lineage.
• Blast percentage < 20%.
• Some cases also show mild basophilia or eosinophilia.
RBCs: Anemia may be present.
Platelets: Thrombocytopenia may be present

Bone Marrow Examination:
Cellularity: Hypercellular BM in more than 75% of cases.
Erythroid Series: Erythroid dysplasia (megaloblastoid changes or ring sideroblasts) in
about 25% of cases.
Granulocytic Series:
• Granulocytic proliferation with a significant increase in the myeloid-to-erythroid ratio
(The most prominent feature).
• Granulocytic dysplasia.
• < 20% blasts/blast equivalents.
Megakaryocytic Series: Dysplastic megakaryocytes (micro-megakaryocytes or
megakaryocytes with abnormal nuclear lobation) in about 75% of patients.

• The updated WHO Classification divides CMML into three categories, CMML-0, CMML-
1, and CMML-2, based on the percentage of myeloid blasts (including promonocytes) in
peripheral blood and bone marrow.
oThe value of subdividing CMML into three subgroups is based on the different
survivals of these patients.
• The finding of ≥20% blasts in the blood or the bone marrow indicates AML with
monocytic differentiation rather than CMML.

There are 2 subtypes of CMML (not included in WHO classification):
1. “Myelodysplastic” type of CMML:
oWBC of <13 x 109/L.
oProminent dysplasia.
2. “Proliferative” type of CMML:
oWBC count of ≥13 x 109/L
oFrequent hepatosplenomegaly.
oWBC is increased due to monocytosis and, occasionally, neutrophilia.

DIFFERENTIAL DIAGNOSIS:
1. Reactive Monocytosis:
• Especially in cases without significant dysplasia or clonal genetic abnormality, it is
essential to exclude all other causes of reactive monocytosis:
oChronic infection.
oAutoimmune syndrome.
oUnrelated neoplasm.
oOther causes of inflammation.

Steps of evaluation:
1. A careful review of the clinical history:
o For evidence of an underlying inflammatory or neoplastic disorder.
2. Physical examination:
o To determine whether organomegaly is present (which would favor CMML).
3. CBC and inspection of the blood smear:
o For evidence of dysplasia and morphologically abnormal or immature monocytes.
o For the absence of findings that would support a different diagnosis, such as lymphoma cells.
4. BM examination with appropriate genetic studies:
o If, after these steps have been taken, the diagnosis of CMML is still being considered.
5. Flow cytometric immunophenotyping:
o Multiple aberrancies, such as overexpression of CD56 and underexpression of myeloid antigens on the same
cells support the diagnosis of CMML.
6. Give a descriptive diagnosis and to defer a definitive diagnosis until after an observation period of 3-6
months:
o If dysplasia is lacking or minimal in PB and BM and there is no myeloid-related karyotypic abnormality or other
genetic abnormality.

2. AML with monocytic differentiation:
• A bone marrow examination is essential prior to rendering a diagnosis of CMML:
oPresence of greater than 20% blasts and promonocytes in the bone marrow
establishes a diagnosis of AML, even if there are few or no circulating blast
equivalents in the blood.
oDiagnosis of CMML requires demonstration that there are <20% blasts/blast
equivalents in the bone marrow.
3. Chronic Myeloid Leukemia, BCR-ABL1(+):
• In particular, CML with p190 form of chimeric protein may show significant monocytosis,
mimicking CMML.
• CML must always be excluded by testing for BCR-ABL1 rearrangement by karyotype,
FISH, and/or RT-PCR.

DIAGNOSTIC CRITERIA:
The 2016 WHO Diagnostic Criteria of CMML
1. Persistent PB monocytosis > 1 x 10⁹/L and monocytes >10%.
2. < 20% blasts (including blast equivalents) in blood and BM.
3. No Philadelphia chromosome, BCR-ABL1 fusion, or myeloproliferative neoplasm.
4. No rearrangement of PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2.
5. Dysplasia in 1 or more myeloid lineage.
6. If dysplasia is absent or minimal, CMML may still be diagnosed if:
oclonal cytogenetic or molecular abnormality present *; or
oif monocytosis has persisted for at least 3 months and other causes of monocytosis are
excluded.
* The presence of mutations in genes often associated with CMML (e.g., TET2, SRSF2, ASXL1, SETBP1) in the proper
clinical context can be used to support a diagnosis. However, some of the mutations can be age related or be present in
subclones. Therefore, caution would have to be used in the interpretation of these genetic results.

Blood Features BM Features Genetics/Other Features
Chronic Myelomonocytic Leukemia (CMML):
Monocytosis: sustained (≥ 1 ×
109/L), monocytes > 10% in PB.
Hypercellular BM with predominance
of myeloid/monocytic lineage.
May have clonal cytogenetic abnormality.
Cytopenia: Anemia or
thrombocytopenia.
Maturation intact. Many molecular genetic exclusionary
criteria.
Dysplasia of at least 1 lineage. Dysplasia of at least 1 lineage. - Exclude benign causes of monocytosis
for cases lacking clonal cytogenetic
abnormality.
- Persistence of monocytosis without
apparent cause supports diagnosis even
when cytogenetics normal.
≤ 20% blasts/promonocytes. ≤ 20% blasts/promonocytes. 3 subtypes: CMML 0, 1 and 2
o based on blast percentage in blood
and BM.
SUMMARY:

2. Juvenile Myelomonocytic Leukemia
(JMML)
• Rare, highly aggressive clonal hematopoietic disorder
of infancy and early childhood characterized by
proliferation of myelomonocytic cells.
• The peripheral blood shows marked leukocytosis with
absolute monocytosis (at least 1 x 109/L), as well as
neutrophilia and presence of myeloid left-shift.
• Patients may have anemia and thrombocytopenia.

Clinical features:
• Age: JMML mostly occurs in children younger than 3 years.
• Gender: Male predominance.
• Manifestations:
oPatients usually present with pallor and fever and may have a skin rash.
oThere is leukocytosis
oThe clinical features are relatively nonspecific and may closely resemble viral illness.
oThere is usually hepatosplenomegaly and often lymphadenopathy.
oCafé au lait spots are seen in patients with neurofibromatosis type 1 (NF1).

Peripheral Blood:
PB is the most important specimen for suspecting diagnosis of JMML.
WBCs: Leukocytosis.
• Absolute monocytosis > 1 x 10⁹/L.
oMay show dysplasia, including nuclear atypia.
oImmature monocytes (monoblasts and promonocytes) should be included in blast
percentage.
• Neutrophilia with some immature forms (left shifted maturation).
• Dysplasia: Granulocytes may show dysplasia, including nuclear hypolobation and
hypogranulation.
• Eosinophilia and basophilia may be present.
• Blasts < 20%; usually < 5%.
RBCs & Platelets: Anemia & thrombocytopenia often present.

Bone Marrow Examination: (nonspecific findings)
Cellularity: Hypercellular BM.
Erythroid Series: Non-specific findings. May show megaloblastoid changes.
• Granulocytic proliferation.
• Monocytes typically account for 5-10% of cellularity.
• < 20% blasts/blast equivalents.
• Significant dysplasia is not a feature of JMML.
Megakaryocytic Series: Non-specific findings.
Other findings: BM fibrosis may be present.

The 2016 WHO Diagnostic Criteria of JMML
I. Clinical and hematologic features (all four features mandatory):
o PB monocyte count ≥1 x 109/L.
o Blast percentage in PB and BM <20%.
o Splenomegaly.
o Absence of Philadelphia chromosome (BCR-ABL1 rearrangement).
II. Genetic studies (1 finding sufficient):
o Somatic mutation in PTPN11 or KRAS or NRAS
o Clinical diagnosis of NF1 or NF1 mutation
o Germline CBL mutation and loss of heterozygosity of CBL
III. For patients without genetic features, besides the clinical and hematologic features listed under I, the
following criteria must be fulfilled:
o Monosomy 7 or any other chromosomal abnormality or at least two of the following criteria:
§ Hemoglobin F increased for age.
§ Myeloid or erythroid precursors on PB smear.
§ GM-CSF hypersensitivity in colony assay.
§ Hyperphosphorylation of STAT5.
Cases must satisfy all 4 morphologic features and either 1 genetic finding or chromosomal abnormality
and at least 2 additional features.

SUMMARY:
Juvenile Myelomonocytic Leukemia (JMML):
Leucocytosis, anemia and
thrombocytopenia.
Hypercellular BM. Detection of somatic or germline
mutation in RAS family.
Monocytosis: sustained (≥ 1 ×
109/L).
≤ 20% blasts/promonocytes. 5 gene panel: PTPN11, NRAS, KRAS,
NF1 and CBL.
≤ 20% blasts/promonocytes. Variable features. Many additional criteria for cases
lacking one of these mutations include:
o Monosomy 7.
o Increased HbF for age.
o Hyperphosphorylation of STAT5.
Variable dysplasia of monocytes and
neutrophils.
Increased monocytic lineage cells. BCR-ABL1 negative.
KMT2A/MLL negative

DIAGNOSTIC ALGORITHM FOR A CASE OF MONOCYTOSIS:

3. Atypical CML, BCR-ABL1 negative
• Leukemic disorder with myelodysplastic as well as
myeloproliferative features at time of initial diagnosis.
oOften has splenomegaly.
oDysplastic neutrophilic leukocytosis with left-shifted
neutrophilic precursors (≥10%) in PB is the hallmark
of this disease.
oNo significant monocytosis or basophilia.
oOften with severe anemia and thrombocytopenia.
oNo t(9;22) or BCR-ABL1 fusion.
oNo PDGFRA, PDGFRB, or FGFR1 rearrangements
or PCM1-JAK2 translocation.
oAssociated with SETBP1 mutations in up to 1/3 of
cases.
oDoes not meet diagnostic criteria for any MPN.

Clinical features:
• Age: Typically elderly with a median age at presentation of 72 years.
• Gender: Male predominance (M:F ratio= 2:1).
• Manifestations:
oOrganomegaly (45%)
oAnemia, thrombocytopenia and leukocytosis.
oaCML is an aggressive disease, with a median overall survival of 14–30 months.
oApproximately 15–40% of cases progress to AML, and the median transformation
time is 18 months.
§ Older age (>65 years) and leukocytosis (> 50 x 109/L) have been reported to be
associated with shorter overall survival.
§ Organomegaly, monocytosis, BM blasts > 5%, and transfusion dependency have
been linked to increased rate of AML progression.

Peripheral Blood:
WBCs:
• Leukocytosis with WBC ≥ 13 x 10⁹/L with median of 40.8
x 10⁹/L.
• Increased neutrophils and their precursors including
promyelocytes, myelocytes, and metamyelocytes
comprising ≥ 10% of WBC.
• Prominent dysgranulopoiesis:
oAcquired Pelger-Huët abnormality.
oAbnormally clumped chromatin.
oHypolobated or abnormal segmentation of nuclei.
oHypogranular cytoplasm.
• < 20% blasts in PB.
• Absent or minimal absolute basophilia.
• Absent or minimal absolute monocytosis.
RBCs & platelets: anemia and thrombocytopenia common.

Cellularity: Hypercellular BM.
Erythroid Series: Dyserythropoiesis is seen in about 50% of cases.
• Increased neutrophils and precursors; increased M:E ratio to over 10:1
• Prominent dysgranulopoiesis is present in all cases.
• May have increased blasts but < 20%.
Megakaryocytic Series: Dysmegakaryopoiesis common including small or
micromegakaryocytes and hypolobated forms.
Other findings: BM fibrosis may be present.

1. Chronic Myeloid Leukemia, BCR-ABL1(+):
• Critical to distinguish aCML from CML as CML is highly responsive to tyrosine kinase
inhibitors such as imatinib, dasatinib etc. while aCML is not responsive to any therapy.
• t(9;22) or BCR-ABL1 fusion by routine cytogenetic karyotype, FISH, or PCR studies is
diagnostic of CML.
• Neutrophilic precursors often exceed 20% of total nucleated cells.
• Absolute basophilia is almost always present in CML.
• Absolute eosinophilia is almost always present in CML.
• No significant dysplasia in stable phase of CML.
• aCML usually lacks basophilia or eosinophilia.

2. Chronic Myelomonocytic Leukemia (CMML):
• Persistent absolute monocytosis, often significantly increased.
• Monocytes > 10% of WBC.
• Lacks severe dysgranulopoiesis.
• Relatively indolent disease.
• Major distinction is PB:
oMonocytes account for > 10% of WBC and absolute monocytosis in CMML.
oaCML may have minimal absolute monocytosis but monocyte percentage < 10%.
• Gene mutations:
oMutations of TET2, SRSF2, or ZRSR2 are associated with CMML.
oPresence of SETBP1 mutations favor diagnosis of aCML.

3. Chronic Neutrophilic Leukemia (CNL):
• Morphology:
oPersistent leukocytosis with predominantly neutrophils (> 80%), left shift (< 10%)
typical of CNL.
oaCML has > 10% myeloid precursors.
• Gene mutations:
oCSF3R mutation seen in 90% of CNL and presence favors diagnosis of CNL.
oPresence of SETBP1 mutations favors diagnosis of aCML.

The 2016 WHO Diagnostic Criteria of aCML
1. PB leukocytosis with neutrophils and neutrophilic precursors (promyelocytes,
myelocytes, metamyelocytes) comprising ≥10% of WBCs.
2. Dysgranulopoiesis, which may include abnormal chromatin clumping.
3. No or minimal absolute basophilia; basophils typically <2% of WBCs.
4. No or minimal absolute monocytosis; monocytes <10% of WBCs.
5. Hypercellular BM with dysplastic granulocytic hyperplasia, with or without erythroid
and megakaryocytic dysplasia.
6. <20% blasts in the PB and BM.
7. No evidence of BCR-ABL1, PDGFRA, PDGFRB, or FGFR1 rearrangement or PCM1-
JAK2.
8. Not meeting WHO criteria for PMF, PV, or ET and no previous history of these
diseases.

SUMMARY:
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative:
Leucocytosis with neutrophilia
with left shift comprising ≥ 10%
of WBCs.
Hypercellular BM with predominance
of myeloid lineage.
No recurrent genetic features.
≤ 20% blasts ≤ 20% blasts Must be de novo with no history of
prior MPN.
Prominent neutrophil dysplasia. Maturation intact. Diagnosis of exclusion.
Minimal or absent basophilia (<
2% of WBCs).
Dysplasia of at least 1 lineage. Must not meet criteria for other
myeloid neoplasms.
Minimal or absent monocytosis
(< 10% of WBCs).
Granulocytic lineage dysplasia most
common; followed by megakaryocytic
lineage dysplasia.
Must not have prior MPN or
antecedent hematologic neoplasm.

4. MDS/MPN with ring sideroblasts and
thrombocytosis (MDS/MPN-RS-T)
• MDS/MPN characterized by anemia, abnormal
erythroid iron incorporation with ring sideroblasts,
and increased platelets.
• Hybrid myeloproliferative and myelodysplastic
features.
• SF3B1 mutated.
• The diagnosis of MDS/MPN-RS-T requires:
oAnemia with persistent thrombocytosis (platelet
count ≥ 450 x 109/L).
oBlasts: < 1% blasts in PB, < 5% myeloblasts in
BM.
oDysplastic, ineffective erythropoiesis with ≥ 15%
ring sideroblasts.

Clinical features:
• Age: Old age with median age 71 – 75 years.
• Gender: Slight female predominance.
• Manifestations:
oSymptoms are usually related to anemia that can be severe
oSymptoms related to excessive thrombocytosis, with bleeding or thrombosis.
oSplenomegaly has been reported in about 40% of cases, and hepatomegaly can
also occur.
oThe frequency of thrombotic events in MDS/MPN-RS-T is similar to that of ET.

Peripheral Blood:
WBCs:
• WBC count normal or only slightly increased.
• Differential counts usually normal.
• Circulating blasts < 1%.
RBCs:
• Normochromic normocytic or macrocytic anemia.
• Often shows significant anisopoikilocytosis.
• May show dimorphic population.
Platelets:
• Significant thrombocytosis (≥ 450 x 10⁹/L).
• May show large or giant platelets.
• Agranular platelets may be present.

Cellularity: Hypercellular; with increased erythroid and megakaryocytic lineage.
Erythroid Series:
• Erythroid hyperplasia.
• Dyserythropoiesis (megaloblastoid changes, nuclear budding, multinucleation).
• Ring sideroblasts by iron stain: ≥ 15% (even if SF3B1 mutation is present).
• Dysplasia may be present.
• BM blasts < 5%.
Megakaryocytic Series:
• Increased megakaryocytes.
• Large, hyperlobulated megakaryocytes
• Show similar morphology to megakaryocytes in MPN.
Other findings: BM fibrosis may be present at presentation.

1. MDS with Ring Sideroblasts (MDS-RS):
• No thrombocytosis.
• Lower hemoglobin and WBC count than patients with MDS/MPN-RS-T.
• Not have MPN-associated mutations, such as JAK2 V617F.
2. MDS With Isolated del(5q):
• Associated with thrombocytosis.
• Presence of dwarf monolobated megakaryocytes.
• Presence of del(5q) by cytogenetics or FISH.

3. Essential Thrombocythemia (ET):
• Does not show significant anemia.
• No significant dysplasia.
• Platelet count often higher than in MDS/MPN-RS-T.
• Presence of CALR and MPL mutations.
4. Reactive Thrombocytosis:
• Associated with tissue injury, infection, and inflammation.
• Not sustained over time.
• Not show ring sideroblasts.
5. Sideroblastic Anemia:
• No thrombocytosis.
• No SF3B1 mutation.

The 2016 WHO Diagnostic Criteria of MDS/MPN-RS-T
1. Anemia, often macrocytic, with <1% blasts in PB.
2. Persistent thrombocytosis with platelet count ≥ 450 x 109/L.
3. Bone marrow:
oErythroid lineage dysplasia with or without multilineage dysplasia.
o≥ 15% ring sideroblasts.
o< 5% blasts in BM.
4. Presence of SF3B1 mutation.
oIn the absence of SF3B1 mutation, no history of recent cytotoxic or growth factor
therapy that could explain the myelodysplastic/myeloproliferative features
5. No BCR-ABL1 fusion gene; no rearrangement of PDGFRA, PDGFRB, FGFR1, or
PCM1-JAK2; and no isolated del(5q), t(3;3) or inv(3).
6. No preceding history of MPN, MDS (except for MDS-RS), or other types of MDS/MPN.

SUMMARY:
MDS/MPN with Ring Sideroblasts and Thrombocytosis:
Anemia with erythroid
dysplasia.
Hypercellular BM with increased
erythroid and megakaryocytic
lineages.
SF3B1 and JAK2 mutations in
most of cases.
< 1% blast. Dyserythropoiesis with ≥ 15% ring
sideroblasts.
Many other mutations described in
subset of cases.
Sustained thrombocytosis (≥
450 × 109/L)
Increased large, hyperlobated
megakaryocytes (MPN-like).
Many molecular exclusionary
material.
Variable WBCs. Blasts not increased; ≤ 5%. Must be de novo without
antecedent MPN, MDS or other
type of MDS/MPN.

5. MDS/MPN, Unclassifiable
Unclassifiable subtype of clonal chronic myeloid
neoplasm, which is characterized by:
• De novo presentation; not related to prior
chemotherapy.
• Hybrid myelodysplastic and myeloproliferative features
at presentation:
• At least 1 cytopenia in blood.
• At least 1 cytosis in blood:
oWBC ≥ 13 x 10⁹/L.
oPLT ≥ 450 x 10⁹/L.
• Blasts/blast equivalents < 20% in PB and BM.
• Does not meet criteria for other MDS/MPN subtypes.
• Does not meet criteria for other myeloid neoplasm.

Clinical features:
• Age: Old age with median age 71 – 73 years.
• Gender: Slight male predominance (M:F ratio= 1.4 – 2 : 1).
• Manifestations:
oNo distinctive clinical manifestations.
oSymptoms from cytopenias.
oSplenomegaly in 1/3 of patients.

Peripheral Blood:
WBCs:
• Variable white blood cell (WBC) count.
• Leukocytosis common (median WBC 19 x 10⁹/L).
• Some cases may show increased circulating granulocyte
precursors (promyelocytes, myelocytes, and
metamyelocytes) but they are either <10% of WBC or not
in conjunction with dysgranulopoiesis
• Granulocytic dysplasia usually present.
• Variable blast percentage (< 20%).
RBCs:
• Anemia often present, variable anisopoikilocytosis.
Platelets:
• Thrombocytopenia in 1/3; thrombocytosis in 1/3.

Cellularity: Hypercellular; with dysplasia in 1 or more lineage.
Erythroid Series:
• Some cases may show erythroid hyperplasia
• Variable dysplasia.
• BM blasts/blast equivalents < 20%.
Megakaryocytic Series:
• Increased megakaryocytes.
• MDS-like: Dysplastic, with small hypolobated forms or widely separated nuclear lobes.
• MPN-like: in 20-30% of cases large hypersegmented megakaryocytes with loose clustering.
Other findings: BM fibrosis may be present in 20-30% of patients at presentation.

1. Chronic myelomonocytic leukemia (CMML):
• Persistent absolute monocytosis (≥ 1 × 109/L) with monocytes > 10% in PB favors
CMML.
• This is because borderline or transient monocytosis may be seen in some cases of
MDS/MPN-U.
2. Atypical chronic myeloid leukemia (aCML):
• It shares overlapping features with at least a subset of MDS/MPN-U, and in some
cases, this separation is arbitrary.
oFor example, if there is marked leukocytosis with marked dysgranulopoiesis but the
PB has < 10% neutrophil precursors or, conversely, if there is leukocytosis but the
PB shows ≥ 10% neutrophil precursors and no dysgranulopoiesis despite the
presence of dyspoietic features in other lineages, diagnostic criteria for aCML are
not fulfilled, and the features are more in keeping with MDS/MPN-U.

SUMMARY:
MDS/MPN Unclassifiable:
Blood features of MDS/MPN
with cytopenia and cytoses.
Hypercellular with variable
features.
No distinctive molecular or
cytogenetic features.
≤ 20% blasts Myeloid lineage predominance. De novo presentation.
Dysplasia often present. Intact maturation. MDS with isolated del(5q)
excluded.
Dysplasia of at least 1 lineage. Not fulfill criteria of other
MDS/MPN.
≤ 20% blasts Diagnosis of exclusion.

MDS/MPN (2021)

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