With reference to the November/December 2016 Image Challenge, the case of the 68-year-old woman with neutrophilic leukocytes of a longstanding duration is very instructive. I am wondering if the pseudo Pelger-Huët anomaly seen in the circled neutrophils is a manifestation of chronic neutrophilic leukemia (CNL)?

— John J. Akabutu, MD, Canadian Cord Blood Registry, Edmonton, Alberta, Canada

Authors’ Reply

We appreciate your query regarding the Image Challenge. In this case of CNL, we agree that infrequent neutrophils are present with morphology resembling the acquired (or pseudo) Pelger-Huët anomaly. This morphologic feature consists of bilobed nuclei that may be connected by a thin filament of chromatin and mimics the congenital Pelger-Huët anomaly, which is an autosomal dominant-inherited disorder due to mutations in the gene encoding the lamin B receptor. The acquired Pelger-Huët anomaly may be observed in a variety of states, including myelodysplastic disorders (MDS), MDS/myeloproliferative neoplasms (MPN) (e.g., chronic myelomonocytic leukemia or atypical chronic myeloid leukemia [CML]), acute myeloid leukemia, leukemoid reactions, chemotherapy or other drug exposures, vitamin B12 or folate deficiency, myxedema, and viral infections.

One of the diagnostic criteria of World Health Organization (WHO) -defined CNL is absence of dysgranulopoeisis; in contradistinction, “prominent” dysgranulopoiesis (e.g., >10% of observed leukocytes) is considered a major feature defining atypical CML, which was absent in this case.1  We additionally favored a diagnosis of CNL because of the lack of myeloid immaturity, the presence of the CSF3R T618I mutation (identified in approximately 80%-90% of CNL cases, but <10% of atypical CML cases),1,2  and morphologic findings of toxic granulation and Döhle bodies in the neutrophils — recurrent findings in CNL. However, we have encountered similar cases that exist on a morphologic spectrum between CNL and atypical CML. Although some of these examples may ultimately be assigned a diagnosis of MPN-unclassifiable, or MDS/MPN-unclassifiable, the application of WHO laboratory, morphologic, and genetic criteria should provide diagnostic specificity in most cases.


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Author notes

Dr. Jason Gotlib and Dr. John H. Baird respond to a comment/letter to the editor by Dr. John J. Akabutu regarding the Nov/Dec 2016 image challenge, “A Stimulating Case of Leukocytosis.”

Competing Interests

Dr. Gotlib is a principal investigator on a trial of the JAK1/JAK2 inhibitor ruxolitinib in patients with CNL and atypical CML. He has received research funding and honoraria from Incyte, Inc., manufacturer of ruxolitinib and sponsor of the trial.