Which morphologic and cytochemical feature best distinguishes chronic myelomonocytic leukemia (CMML) from chronic myeloid leukemia (CML)?

Question

Accepted Answer

D. Monocytosis ≥1,000/μL with dysplastic features and absence of Philadelphia chromosome. ## CMML vs CML — Morphologic and Cytogenetic Distinction ### Core Diagnostic Difference **Key Point:** CMML is a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) characterized by **monocytosis ≥1,000/μL** with dysplastic features and **absence of Philadelphia chromosome**. CML is a pure myeloproliferative neoplasm driven by BCR-ABL1. This distinction is critical because CMML has worse prognosis and different treatment approach. ### Comparison Table: CMML vs CML | Feature | CMML | CML | |---------|------|-----| | **Monocyte count** | **≥1,000/μL (absolute)** | **<1,000/μL (usually)** | | **Philadelphia chromosome** | **Absent** | **Present (>95%)** | | **BCR-ABL1** | Absent | Present | | Dysplastic features | Present (hypogranular neutrophils, abnormal monocytes) | Absent or minimal | | Blast percentage | 0–19% (defines CMML-0, -1, -2) | <5% in chronic phase | | Myeloid maturation | Abnormal (dysplasia) | Normal left shift | | Median survival | 12–24 months | >5 years (with TKI) | | Treatment | Hypomethylating agents, allogeneic HSCT | Tyrosine kinase inhibitors | | Transformation risk | High (to AML) | Lower in chronic phase | ### Why Monocytosis + Dysplasia + Absence of Philadelphia Chromosome Is Diagnostic 1. **Monocytosis ≥1,000/μL is a hallmark:** CML rarely has absolute monocytosis; CMML requires it by definition. 2. **Dysplastic changes are key:** CMML shows abnormal monocyte morphology (pseudo-Pelger nuclei, hypogranularity), abnormal neutrophils, and left shift with dysplasia. CML shows orderly left shift without dysplasia. 3. **Philadelphia chromosome absence:** This single finding excludes CML and points toward CMML or other MDS/MPN entities. 4. **WHO/ICC classification:** CMML is now classified as MDS/MPN overlap, reflecting its hybrid myelodysplastic and myeloproliferative features. **High-Yield:** CMML is defined by the combination of monocytosis + dysplasia + absence of BCR-ABL1. Any patient with monocytosis >1,000/μL and no Philadelphia chromosome should raise suspicion for CMML. **Clinical Pearl:** CMML patients often present with higher blast burden at diagnosis (median 5–10% blasts) compared to CML in chronic phase (<5% blasts). This contributes to worse prognosis and higher risk of transformation to AML. **Mnemonic:** **CMML = Monocytosis + Myelodysplasia + Missing Philadelphia** (absent BCR-ABL1). [cite:Robbins 10e Ch 13]

Answer

A. Splenomegaly and elevated leukocyte count

Answer

B. Presence of >1% blasts in peripheral blood

Answer

C. Positive myeloperoxidase (MPO) staining in myeloid cells

Which morphologic and cytochemical feature best distinguishes chronic myelomonocytic leukemia (CMML) from chronic myeloid leukemia (CML)?

Explanation

CMML vs CML — Morphologic and Cytogenetic Distinction

Core Diagnostic Difference

Comparison Table: CMML vs CML

Why Monocytosis + Dysplasia + Absence of Philadelphia Chromosome Is Diagnostic

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Feature	CMML	CML
Monocyte count	≥1,000/μL (absolute)	<1,000/μL (usually)
Philadelphia chromosome	Absent	Present (>95%)
BCR-ABL1	Absent	Present
Dysplastic features	Present (hypogranular neutrophils, abnormal monocytes)	Absent or minimal
Blast percentage	0–19% (defines CMML-0, -1, -2)	<5% in chronic phase
Myeloid maturation	Abnormal (dysplasia)	Normal left shift
Median survival	12–24 months	>5 years (with TKI)
Treatment	Hypomethylating agents, allogeneic HSCT	Tyrosine kinase inhibitors
Transformation risk	High (to AML)	Lower in chronic phase