CMML

*Cases of MPN can be associated with monocytosis or they can develop it during the course of the disease. These cases may simulate CMML. In these rare instances, a previous documented history of MPN excludes CMML, whereas the presence of MPN features in the BM and/or of MPN-associated mutations (JAK2, CALR, or MPL) tend to support MPN with monocytosis rather than CMML. †Blasts and blast equivalents include myeloblasts, monoblasts, and promonocytes. Promonocytes are monocytic precursors with abundant light gray or slightly basophilic cytoplasm with a few scattered, fine lilac-colored granules, finely distributed, stippled nuclear chromatin, variably prominent nucleoli, and delicate nuclear folding or creasing. Abnormal monocytes, which can be present both in the PB and BM, are excluded from the blast count. ‡The presence of mutations in genes often associated with CMML (eg, TET2, SRSF2, ASXL1, SETBP1) in the proper clinical contest can be used to support a diagnosis. It should be noted however, that many of these mutations can be age-related or be present in subclones. Therefore, caution would have to be used in the interpretation of these genetic results

*Cases of MPN can be associated with monocytosis or they can develop it during the course of the disease. These cases may simulate CMML. In these rare instances, a previous documented history of MPN excludes CMML, whereas the presence of MPN features in the BM and/or of MPN-associated mutations (JAK2, CALR, or MPL) tend to support MPN with monocytosis rather than CMML. †Blasts and blast equivalents include myeloblasts, monoblasts, and promonocytes. Promonocytes are monocytic precursors with abundant light gray or slightly basophilic cytoplasm with a few scattered, fine lilac-colored granules, finely distributed, stippled nuclear chromatin, variably prominent nucleoli, and delicate nuclear folding or creasing. Abnormal monocytes, which can be present both in the PB and BM, are excluded from the blast count. ‡The presence of mutations in genes often associated with CMML (eg, TET2, SRSF2, ASXL1, SETBP1) in the proper clinical contest can be used to support a diagnosis. It should be noted however, that many of these mutations can be age-related or be present in subclones. Therefore, caution would have to be used in the interpretation of these genetic results

• Although CMML is a biologically distinct entity from MDS with mixed myelodysplastic and myeloproliferative features, it has traditionally been considered a subtype of MDS, IPSS-R accurately stratifies prognosis of patients with this disease.
• The natural history of patients with CMML is distinct than that of patients with classic MDS. Patients tend to have higher frequency of B symptoms and extramedullary manifestations of the disease. Tissue infiltration causing hepatic or renal dysfunction is common.
• Divided into myelodysplastic and myeloproliferative subtypes based on a WBC level of 13000/μL using recommendations by the FAB group.
  • Constitutional symptoms (fever, weight loss, night sweats) are more frequent in the myeloproliferative group, while fatigue, infection, and bleeding are more common in the myelodysplastic subtype.
• The peripheral blood may demonstrate cytopenias and dysplastic changes more typical of MDS, or dysplastic changes may be minimal. Cases showing dysplastic changes tend to have a WBC count <13000/μL and are associated with RUNX1 mutations and have a worse prognosis.
• The bone marrow is usually hypercellular and may demonstrate monocytic or granulocytic hyperplasia. Erythroid precursors and megakaryocytes may demonstrate prominent dysplastic changes, but often these cell types are normal in appearance. Ring sideroblasts are present in increased numbers in some cases. Blasts and promonocytes may be elevated up to 19%.
  • Increased blasts correlate with poor prognosis.
  • Variable marrow fibrosis may also be seen in nearly 30% of cases.
• Approximately 20% to 40% of CMML will have detectable clonal abnormalities.
  • The most frequent recurring cytogenetic abnormalities include trisomy 8, monosomy 7/deletion (7q), structural abnormalities of 12p, and i(17q).
  • JAK2 mutations have been detected in ~3% of patients.
  • Mutations of RAS are detected in approximately one-third of CMML cases.
  • Other genes commonly mutated in CMML include SRSF2, TET2, and ASXL1.
  • Mutations occur less frequently in SETBP1, NRAS, RUNX1, CBL, and EZH2.

Classification

• CMML-0: < 2% blasts in PB and < 5% blasts in BM.
• CMML-1: 2% to 4% blasts in PB and/or 5% to 9% blasts in BM.
• CMML-2: 5% to 19% blasts in PB, 10% to 19% in BM, and/or when any Auer rods are present.
• Oligomonocytic CMML (O-CMML): presence of clinical and pathological features of CMML, relative monocytosis (≥10% monocytes) but absolute monocyte count (AMC) < 500 or 1000/μL; clinicopathologic and mutational profile of O-CMML were similar to overt CMML.

aCML

• A misnomer with no relation to CML.
• Affects elderly patients with an apparent male predominance.