Table 1.
Diagnostic work up and diagnostic criteria for CNL.
| Work up | Diagnostic criteria |
|---|---|
| Confirm persistent leukocytosis/neutrophilia | Repeated blood counts should confirm WBC >25 x 109/L in repeated evaluations |
| Exclude all reactive or secondary causes of neutrophilia | Complete survey must not reveal any cause of secondary neutrophilia and if revealed, a CSF3R mutation should also be present |
| Evaluate peripheral blood findings and morphology | >80% of the WBC should be neutrophils or bands, with less mature forms <10% and blasts <1% |
| Evaluate the clinical and biochemical profile | Hepatosplenomegaly is common, and serum LDH, uric acid, B12, and liver cholestatic enzymes are usually increased |
| Evaluate cytochemical profile | LAP score is elevated or markedly elevated |
| Evaluate bone marrow findings and morphology | Marrow cellularity is highly increased with granulocytic hyperplasia without evident dysplasia or excess of blasts |
| Evaluate bone marrow histology and immunophenotype | A clear myeloproliferative syndrome pattern without an increase of monocytes, eosinophils, basophils or mast cells |
| Exclude BCR/ABL positive Chronic Myelogenous Leukemia | PCR for BCR/ABL transcripts should be negative and karyotype should not exhibit Ph chromosome |
| Exclude BCR/ABL negative myeloproliferative neoplasms | Diagnostic criteria for polycythemia vera, primary myelofibrosis and essential thrombocythemia should not be confirmed |
| Exclude chronic myelomonocytic leukemia | The absolute monocyte count in the blood should be <1 x 109/L |
| Exclude a classical myelodysplastic syndrome | Dysplastic changes should be absent |
| Exclude atypical BCR/ABL-negative chronic myelogenous leukemia | Dysplastic changes should be absent. Multilineage dysplastic changes and >10% immature cells in the PB are prominent in aCML. CSF3R mutation should be demonstrated |
| Perform direct molecular characterization of the disease | There should be a mutation in the CSF3R gene, but with NGS additional mutations may also be revealed |
| Investigate for presence of commonly coexisted conditions | Extramedullary infiltration, vasculitic syndromes or plasma cell dyscrasias might be present. CSF3R mutations necessary to be confirmed |