Chronic neutrophilic leukemia differential diagnosis
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Differentiating Chronic neutrophilic leukemia from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Chronic neutrophilic leukemia (CNL) must be differentiated from other diseases that cause neutrophilia, such as, leukemoid reaction, chronic myeloid leukemia (CML), neutrophilic-chronic myelogenous leukemia (CML-N), myeloproliferative neoplasms/ myelodysplastic syndromes (MPN/MDS) disorders, polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
Differentiating [Disease name] from other Diseases
CNL must be differentiated from other diseases that cause neutrophilia.
Differentiating CNL from other diseases on the basis of neutrophilia:
- Leukemoid reaction: leukemoid reaction is responsible for the most of neutrophilia. Notable neutrophilia, bone marrow hypercellularity, normal cytogenetics, and absence of BCR-ABL gene are seen in both leukemoid reaction and neutrophilia. WBC count may be more modestly elevated in leukemoid reaction, though there have been some reports of WBC counts up to 100 × 109/L in this context34. Meticulous history-taking along with a thorough clinical examination to exclude alternate diagnoses, including occult malignancy or infection, and a period of observation is often recommended before formally determining the diagnosis. The demonstration of clonality including identification of a CSF3R mutation or other molecular or cytogenetic abnormality is clearly valuable in aligning the diagnosis in favor of CNL. CML is invariably associated with a BCR-ABL fusion gene and displays a disproportionally higher percentage of myelocytes. CML also commonly presents with basophilia, thrombocytosis, or eosinophilia. While the absence of the Philadelphia chromosome is implicit to CNL diagnosis, a rare form of CML termed neutrophilic-CML, or CML-N, has been described which shares morphological features of CNL, specifically a prominent neutrophilic proliferation35. CML-N, however, is characterized by an uncommon BCR-ABL translocation which results in the transcription of an e19/a2 type BCR-ABL messenger RNA yielding a 230-kD BCR-ABL protein (p230)12,36. The clinical correlate is a lower total WBC count, less severe anemia, less prominent splenomegaly, and blastic transformation occurring much later in CML-N patients35. The attenuated phenotype and indolent course of CMLN, specifically in patients without additional cytogenetic abnormalities, is now postulated to be due to low p230 mRNA and protein levels37. The diagnosis of CNL also requires that molecular testing be negative for defining markers of alternate neoplasms including not only the BCR-ABL1 fusion gene but also rearrangements in PDGFRA/B or FGFR1, characteristic of eosinophilic leukemia.
- Leukemoid reaction is the most common cause of neutrophilia. A detailed clinical history is useful to rule out underlying chronic infection or malignancy. The neutrophilia associated with malignancies could result from several factors, such as bone marrow metastasis, inflammatory reaction to necrosis, or production of cytokines by the tumour or in response to it.33 The white cell count is modestly elevated; however, rare cases with white cell count up to 100×109/L have been reported.34 Several cytokines are reported to play role including granulocyte-monocyte CSF (GM-CSF), interleukin-1 (IL-1), G-CSF and interleukin-6 (IL-6). The possibility of underlying occult malignancy should be excluded in all cases of sustained and unexplained neutrophilia. A careful clinical history, a thorough clinical evaluation and a period of observation are usually helpful to rule out these reactive causes. Detection of CSF3R mutation can be of great value in cases with unexplained persistent neutrophilia.
- CML
- CML-N
- MPN/MDS disorders: such as aCML (atypical chronic myeloid leukemia) and CMML (chronic myelomonocytic leukemia)
- Polycythemia vera
- Essential thrombocythemia
- Primary myelofibrosis