Chronic Myeloid Neoplasms
MDS / MPN
Chronic myelomonocytic leukemia (CMML)

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 8 March 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Chronic myelomonocytic leukemia [title] (CMML)

Cite this page: Chronic myelomonocytic leukemia (CMML). PathologyOutlines.com website. http://pathologyoutlines.com/topic/myeloproliferativecmml.html. Accessed March 28th, 2017.
Definition / General

Variable clinical and hematologic presentations:
  1. Myelodysplastic features of blood cytopenias, ineffective hematopoiesis, dysplastic changes and increased blasts resembling refractory anemia, refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts; plus monocytosis (monocytes may have dysplastic features)
  2. Marked leukocytosis with monocytosis, organomegaly, normal hematopoiesis, normal red blood cell and platelet counts, no / minimal dysplastic changes or excess blasts; previously called Philadelphia chromosome negative CML

  • 80% of cases arise de novo; 20% arise from prior myelodysplasia, occasionally with monocytosis (Am J Clin Pathol 2006;126:789)
  • Splenomegaly in 30 - 50% with rare rupture (Am J Hematol 2007;82:405, Am J Surg Pathol 1983;7:197), hepatomegaly in 20%
  • May have tumor forming accumulations of CD123+ plasmacytoid monocytes in lymph nodes, bone marrow or skin (Am J Surg Pathol 2004;28:585)
  • More closely related to myelodysplasia than myeloproliferative neoplasms using loss of heterozygosity evaluation (Mod Pathol 2007;20:1166)
  • Type 1: < 5% blasts in blood or < 10% blasts in bone marrow
  • Type 2: 5 - 19% blasts in blood, 10 - 19% blasts in bone marrow or Auer rods present; also < 20% blasts in blood or marrow; poorer prognosis
  • If blasts + promonocytes are 20% of more of bone marrow differential count, classify as AML
Diagnosis
  • Persistent peripheral blood monocytosis of more than 109/L, with monocytes > 10% of WBCs
  • No BCR-ABL1 gene fusion
  • No rearragement of PDGFRA or PDGFRB
  • < 20% blasts (includes myeloblasts, monoblasts and promonocytes)
  • Peripheral blood may have dysplastic changes typical of myelodysplasia in one or more myeloid lineages, or dysplasia may be limited to monocytes
  • Usually no marrow monocytosis (Mod Pathol 2006;19:1536)
  • In absence of myelodysplasi, diagnosis can be established if the process is clonal, if monocytosis is > 3 months and other causes for monocytosis are excluded
Case Reports
Treatment
  • Decitabine
  • Median survival 19 months (Cancer 2007;109:713)
  • Predictors of course of disesase include percentage of peripheral / marrow blasts, degree of leukocytosis, extent of anemia and splenomegaly / organomegaly
Micro Description
  • Peripheral blood: cytopenia(s), monocytes may be normal appearing or have dysplastic features of increased basophilic cytoplasm, abnormal granulation, hyperlobulated nuclei; other lineage cells may have dysplastic changes – the most common being granulocytes
  • Bone marrow: hypercellular marrow with mildly increased monocytes (but not diagnostic by itself) and increased granulocytes; may have increased reticulin fibers; variable dysplastic changes in erythroid cells and megakaryocytes; cases with eosinophilia need screening for PDGFRA, PDGFRB and FGFR1 gene abnormalities in addition to looking for causes of eosinophilia
Micro Images

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Images hosted on PathOut server:

Peripheral blood:

Three mature monocytes

Blast with Auer rod

Increase in mature monocytes and neutrophils



Bone marrow biopsy:

Markedly hypercellular marrow



Bone marrow smear:

Increased monocytes and monocyte precursors

Increase in monocyte
precursors and erythroid
cytoplasmic vacuoles

Promonocytes and
monocytes, neutrophils
and erythroid precursors



Stains:

Alpha naphthyl acetate
and methyl green
stains (non specific esterase)



Images hosted on other servers:

Other sites:

Kidney suburothelial tissue; various images



Nature images:

Bone marrow biopsy:

Plasmacytoid monocyte nodules: H&E and CD123

Comparison with CML and atypical CML



Other sites:

Colonic infiltration



Stains:

H&E and alpha naphthyl butyrate esterase

Plasmacytoid monocyte nodules: H&E and CD123

Positive Stains
Flow Cytometry Description
  • Monocytosis with two or more aberrant phenotypes such as decreased CD14, CD13, HLA-DR, CD64 or CD36, overexpression of CD56
  • Or abnormal antigen expression of 2+ antigens plus 20% of marrow monocytes showing CD14+ expression, which is specific for CMML versus reactive monocytosis (Am J Clin Pathol 2005;124:799)
Electron Microscopy Images

Images hosted on PathOut server:

Monocytes are atypical with large granules

Molecular / Cytogenetics Description
Molecular description:
Cytogenetics description:
  • Abnormalities in 20 - 40%, including trisomy 8, monosomy 7, 7q-, abnormalities of 12p
  • Occasionally t(5;12)(q33;p13)
Differential Diagnosis
  • CML (BCR-ABL1 gene fusion) and atypical CML (few monocytes identified by nonspecific esterase, no peripheral monocytosis, no CD123+ plasmacytoid monocytic nodules)