Definition
Neutrophilic leukemic disorder with myeloproliferative and myelodysplastic features but lacking specific cytogenetic abnormalities
Diagnostic Criteria
Peripheral blood leukocytosis must be >13 x 109 /μL
May be marked (>300 x 109 /μL)
Primarily due to neutrophils and neutrophilic precursors
Promyelocytes, myelocytes and metamyelocytes usually make up 10-20% of WBC
Monocytes must be <10% of WBC (may rarely slightly exceed 1 x 109 /μL)
Basophils usually <2% of WBC
Blasts <20% in blood and marrow
Hypercellular bone marrow, predominantly granulocytic
Erythrocytic and megakaryocytic hyperplasia may also be present
Prominent granulocytic dysplasia must be present in blood and marrow
Erythrocytic and megakaryocytic dysplasia may also be present
Ph chromosome, BCR-ABL1, PDGFRA, PDGFRB, FGFR1 abnormalities and acute myeloid leukemia-defining translocations (e.g. inv(16), t(8;21)) must be absent
Nonspecific karyotypic abnormalities and/or mutations are present in most cases
Myelodysplasia is defined by morphologic features of abnormal cellular maturation in at least one bone marrow lineage
Not all features are applicable to all disorders
Dyserythropoeisis
Peripheral blood erythrocyte abnormalities
Normocytic, normochromic anemia
Macrocytosis
Dimorphic red blood cells (RBC)
Mixture of normal RBC and hypochromic microcytic RBC
Basophilic stippling
Poikilocytosis
Varying shapes, frequently macro-ovalocytes
Bone marrow erythroid lineage abnormalties
Erythroid hyperplasia or hypoplasia
Megaloblastoid / megaloblastic changes
Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
Nucleus lags behind cytoplasm
Ring sideroblasts
≥5 iron granules encircling ≥1/3 of the nucleus
Usually either many or none
Cytoplasmic vacuoles
Also seen in copper deficiency
Nuclear changes
Multinuclearity
Nuclear budding, hyperlobulation and satellite nuclei
Internuclear bridging
Dysgranulopoiesis
Peripheral blood and/or bone marrow findings (easier seen in peripheral blood)
Hypogranularity
Pale cytoplasm almost indistinguishable from background on slide
Nuclear hypolobation or irregular hypersegmentation (>5 lobes)
Pseudo Pelger-Huet anomaly
Two equal size nuclear lobes connected by a thin strand of chromatin
Infrequent findings
Abnormal cytoplasmic granules (pseudo Chediak-Higashi granules)
Giant grey to red granules
Dohle bodies
Small blue cytoplasmic inclusions
Often found at periphery of cell
Auer rods
Rod-like structures formed by fusion of primary granules
May be found in blasts or maturing granulocytes
Dysmegakaryopoiesis
Peripheral blood platelet abnormalities
Giant
Larger than a red blood cell
Bizarre
Irregular shapes and protrusions
Hypogranularity
Compare to normal platelets with purple granules
Bone marrow megakaryocyte abnormalities
Micromegakaryocytes
Smaller than a promyelocyte
Nuclear hypolobation
Prominent in 5q- syndrome
A single lobe is typically seen in a small megakaryocyte
Multinucleation
Distinct nuclei without a connecting strand of chromatin
Cytoplasmic hypogranularity
Dita Gratzinger MD PhD
Original posting: 11/6/11
Supplemental Studies
Special stains Nonspecific esterase, and CD68PG may be useful for identifying monocytes in tissue sections (to exclude CMML)
Genetic studies
Ph chromosome, BCR-ABL1, PDGFRA, PDGFRB translocations must not be present
Nonspecific karyotypic abnormalities and/or mutations are present in most cases
Most frequent cytogenetic abnormalities include +8 and del(20q)
Mutations in NRAS and KRAS may be present; JAK2 V617F generally absent
Differential Diagnosis
Myeloproliferative and Mixed MDS/MPNs with Neutrophilia and/or Monocytosis
CML -CPAtypical CML CMML-1 CNL
Ph Chromosome and/or BCR-ABL1 Translocation
Almost 100%
Absent
Absent
Absent
WBC
Left shifted neutrophilia*
Left shifted neutrophilia
Monocytosis, may have left shifted neutrophilia
Neutrophilia
B lood basophilsIncreased
Not increased
Not increased
Not increased
Blood monocytes
Variable,** <1x103 /μL
Variable, <1x103 /μL
Always >1x103 /μL
<1x103 /μL
Blood immature granulocytes
>20%
10-20%
Usually <10%
<10%
Blood blasts
Usually <2%
>2%
<5%
<1%
Granulocytic dysplasia
Absent
++
+/-
Absent
*rare p230 BCR-ABL1 isoform may show mature neutrophilia, **rare p190 BCR-ABL1 isoform associated with monocytosis
Clinical
Median age 60-80 years
Has been reported between 10-20 years
Hepatosplenomegaly
Median survival 14-29 months
Death due to marrow failure or evolution to AML
Classification / Lists
WHO 2008 Classification of Myeloid Neoplasms
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
Bibliography
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2008
Xubo G et al, Eur J Haematol. 2009 Oct;83(4):292-301.. The role of peripheral blood, bone marrow aspirate and especially bone marrow trephine biopsy in distinguishing atypical chronic myeloid leukemia from chronic granulocytic leukemia and chronic myelomonocytic leukemia.
Hall J, Foucar K, Diagnosing myelodysplastic/myeloproliferative neoplasms: laboratory testing strategies to exclude other disorders, International Journal of Laboratory Hematology, 2010, 32
Orazi A, Germing U. (2008) The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia, 22, 1308–1319.
