Chronic Myelomonocytic Leukemia (CMML)

2016 WHO Diagnostic Criteria

Persistent peripheral blood monocytosis >1,000/μL (and accounts for ≥10% of the WBC count)
Does not meet diagnostic criteria for BCR-ABL1+ CML, PMF, PV, or ET (if you compare to the criteria for other MPNs, this is a circular argument)
No PDGFA, PDGFB, FGFR1, or JAK2-PCM1 rearrangement (specificity exclude if there is eosinophilia)
<20% blasts (blood or bone marrow); blasts defined as promonocytes, myeloblasts, or monoblasts
Myeloid dysplasia in one or more lineages, or
(If dysplasia is absent or minimal) presence of an acquired cytogenetic/molecular abnormality in the hematologic cell lineage

or, in the absence of the above criteria

At 3 months of persistent monocytosis (and)
Other causes have been excluded

CMML is unlikely if there is a previous diagnosis of a MPN, as such entities can progress to a phase with monocytosis (and this should be closely evaluated)

“Proliferative type” CMML – WBC ≥13,000/μL

“Dysplastic type” CMML – SBC <13,000/μL

CMML-0

<2% blasts in PB and
<5% blasts in BM

CMML-1

2-4% blasts in PB and/or
5-9% blasts in BM

CMML-2

5-19% blasts in PB
10-19% blasts in BM and/or
Presence of Auer rods

Immunohistochemistry

The use of immunohistochemistry (IHC) in many of the MPN/MDS neoplasms is limited. Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute myelogenous leukemia (AML). Helpful IHC markers may include:

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	CD117 is a specific myeloid marker, and marks a subset of myeloblasts. The expression is dim, and one often must look at 20-40X to clearly see expression. Mast cells (fried egg looking cell) will have very strong expression.
CD71	CD71 marks nucleated erythroid cells. This may be helpful in quantitating and differentiating erythroid cells from myeloid cells. This marker may be set-up as a double stain with CD34.
E_Cadherin	In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells. Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT	TdT is a sensitive lymphoblast (~95%) marker. It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).

References

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127: 2391–2405. doi:10.1182/blood-2016-03-643544

WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. SH Swerdlow, et al. International Agency for Research on Cancer. Lyon, 2008.