Stanford School of Medicine

Surgical Pathology Criteria

 use browser back button to return

Chronic Myelomonocytic Leukemia (CMML)


  • Malignant neoplasm exhibiting both myelodysplastic and myeloproliferative features and characterized by peripheral monocytosis

Diagnostic Criteria

  • Diagnosis requires ALL of the following five criteria
    • Persistent blood monocytosis, >1 x 103/μL AND
      • Usually mature but may have abnormal granules or nuclei (abnormal monocytes)
      • Neutrophilia and/or eosinophilia (see below) may be present
    • No Philadelphia chromosome or BCR-ABL1 fusion AND
    • No abnormalities of PDGFRA or PDGFRB or 11q23 (which suggest AML) AND
    • Blasts plus promonocytes <20% in both bone marrow and peripheral blood AND
      • If ≥20%, diagnose as AML
    • Any one of the below features:
      • Dysplasia in one or more myeloid lineages (most common)
      • Demonstration of an aquired clonal cytogenetic or molecular genetic abnormality in the marrow
      • At least 3 months duration of monocytosis, with other causes ruled out (see Differential Diagnosis)
  • Systemic mastocytosis may coexist with CMML
    • (WHO category SM-AHNMD)
  • CMML should be divided into prognostic groups:
    • CMML-1
      • Blasts + promonocytes <5% in blood and <10% in marrow
    • CMML-2
      • Blasts + promonocytes 5-19% in blood and 10-19% in marrow OR
      • Auer rods present in blood or marrow
  • CMML with eosinophilia may be diagnosed if blood eosinophils >1.5 x 103/μL
    • All other CMML criteria must be fulfilled, including lack of PDGFRA and PDGFRB abnormalities
    • May exhibit tissue damage from eosinophilia (see Clinical)
  • Bone marrow is usually hypercellular with dysplastic features
    • Occasional cases may be hypocellular
    • Nodules of plasmacytoid dendritic cells present in 20% of cases
      • Monomorphous cells with sharp borders and round nuclei
      • Inconspicuous nucleoli, fine chromatin
      • CD123 positive
    • Reticulin stain may show mild to moderate fibrosis
  • Spleen frequently shows red pulp involvement
  • Any of the following may be found in extramedullary sites such as skin and lymph nodes
    • CMML
    • Plasmacytoid dendritic cell nodules
    • Blastic transformation

Dita Gratzinger MD PhD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting: 11/6/11

General Criteria for Myelodysplasia

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)
      • 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

Supplemental Studies

  • Immunologic stains (flow and sections)
    • Leukemic cells
      • Positive: CD33, CD13, CD163
      • Variable: CD14, CD68, CD64
      • Occasional aberrant expression:
        • Decreased CD13, CD14, CD15, CD64, CD36, HLA-DR
        • Overexpression of CD2, CD56
    • Increased CD34 may indicate transformation to AML
      • CAUTION - monoblasts and promonocytes are often CD34 negative
        • Morphologic assessment is more important than simple CD34 count
    • Plasmacytoid dendritic cells
      • Positive: CD123, CD14, CD43, CD68, CD68R, CD45A, CD4, Granzyme B
      • Weak: CD33
      • Variable: CD56, CD2, CD5
      • Negative: TIA1, perforin
  • Nonspecific clonal cytogenetic abnormalities present in 20-40%
    • Following are not present, by definition
      • BCR-ABL1 (including p190 isoform), PDFGRA, PDFGRB
  • Nonspecific molecular abnormalities present in up to 70%, including
    • RAS (40%), TET2, CBL, JAK2, RUNX1

Differential Diagnosis

  CML-CP CMML-1 Myeloid Neoplasm with PDGFRB
Ph Chromosome and/or BCR-ABL1 Translocation Almost 100% Absent Absent


Left shifted neutrophilia* Monocytosis, may have left shifted neutrophilia Variable, may have left shifted neutrophilia, monocytosis, eosinophilia
Blood eosinophils Often increased Not increased Variable
Blood basophils Increased Not increased Variable
Blood monocytes Variable,** <1x103/μL Always >1x103/μL often <1x103/μL
Blood immature granulocytes >20% Usually <10% often <10%
Blood blasts Usually <2% <5% Variable
Granulocytic dysplasia Absent +/- Variable
*rare p230 BCR-ABL1 isoform may show mature neutrophilia, **rare p190 BCR-ABL1 isoform associated with monocytosis

Non-neoplastic Monocytosis

  • Infectious
  • Inflammatory
  • Reaction to another maligancy, such as lymphoma


  • Median age 65-75
  • Increased blasts (CMML-2) associated with increased risk of transformation to AML and poorer prognosis
  • High risk cytogenetics (chromosome 7 abnormalities and complex karyotypes) correlate with poor survival
  • "Myeloproliferative variant" (WBC > 13 x 103/μL) has poorer survival than "myelodysplastic variant" (WBC < 13 x 103/μL)
    • Not clear if this is independent of blast count and cytogenetic predictors
  • Understanding of prognostic significance of molecular alterations is rapidly evolving
    • RAS and RUNX1 mutations likely are poor prognosis factors

Classification / Lists

WHO 2008 Classification of Myeloid Neoplasms

Myeloproliferative Neoplasms (MPN)

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

Myelodysplastic Syndromes (MDS)

Therapy Related Myeloid Neoplasms



  • 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
  • Orazi A, Germing U. (2008) The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia, 22, 1308–1319.
  • Bacher U, Haferlach T, Schnittger S, Kreipe H, Kröger N. Recent advances in diagnosis, molecular pathology and therapy of chronic myelomonocytic leukaemia. Br J Haematol. 2011 Mar 9. doi: 10.1111/j.1365-2141.2011.08631.x. [Epub ahead of print] PubMed PMID: 21401573.
Printed from Surgical Pathology Criteria:
© 2010  Stanford University School of Medicine