Cutaneous lesions of leukemia cutis (LC) by chronic neutrophilic leukemia (CNL) have been merely reported due to the rare occurrences of CNL. Furthermore cutaneous lesions in relation to clinical severity have been far less studied. A 70-year-old man presented with multiple violaceous papules and excoriations on both lower extremities. The diagnosis was LC based on histologic and laboratory evaluation and the origin was elaborated as CNL with the confirmation of colony stimulating factor 3 receptor (CSF3R) mutation. Interestingly, the patient presented clinical severity in a parallel manner to the hematologic abnormality. To the best of our knowledge, there has been no reported case of CSF3R confirmed LC in CNL featuring explicit skin eruption in relation to laboratory findings.
Aged ; Colony-Stimulating Factors ; Diagnosis ; Humans ; Leukemia ; Leukemia, Neutrophilic, Chronic ; Lower Extremity ; Skin

Humans ; Leukemia, Neutrophilic, Chronic/genetics* ; Multiple Myeloma/genetics* ; Mutation ; Receptors, Colony-Stimulating Factor/genetics* ; Signal Transduction

Although neutrophilia can manifest from various causes, it is important to be able to distinguish chronic neutrophilic leukemia (CNL) from neutrophilic leukemoid reactions (NLR). In this paper, we describe four cases of leukocytosis with neutrophilia, including one case of CNL with a T618I mutation in colony stimulating factor 3 receptor (CSF3R) and three cases of NLR associated with malignancy or sepsis, which were initially suspected as CNL. Of the three NLR cases, one was associated with ovarian cancer, one with monoclonal gammopathy of undetermined significance and one with multiple myeloma with sepsis. This study demonstrated that confirming the clonality of myeloid cells with CSF3R T618I could contribute to making an accurate differential diagnosis between CNL and NLR in patients with solid cancers or plasma cell neoplasms caused by paraneoplastic syndromes and/or infection.
Colony-Stimulating Factors ; Diagnosis, Differential ; Humans ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction* ; Leukocytosis ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Myeloid Cells ; Neoplasms, Plasma Cell ; Neutrophils* ; Ovarian Neoplasms ; Paraneoplastic Syndromes ; Sepsis

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia, splenomegaly, and hypercellular bone marrow without Philadelphia chromosome. Diagnosis of CNL requires exclusion of identifiable causes of reactive neutrophilia, such as infection and tumors. Our patient presented with general weakness and weight loss. Computed tomography (CT) showed a mass in the distal rectum, which was confirmed to be an adenocarcinoma by colonoscopic biopsy. Positron emission tomography-CT showed multiple liver, bone, and lymph node metastases. Liver and lymph node biopsies revealed neutrophilic infiltration with no evidence of adenocarcinoma. The pathological findings of the bone marrow were compatible with CNL. Cytogenetic analysis revealed a normal karyotype, and molecular analysis was negative for BCR/ABL. Here, we present a 73 year-old man diagnosed with concurrent CNL and rectal cancer.
Adenocarcinoma ; Biopsy ; Bone Marrow ; Cytogenetic Analysis ; Diagnosis ; Electrons ; Humans ; Karyotype ; Leukemia ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction ; Leukocytosis ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Neutrophils ; Philadelphia Chromosome ; Rectal Neoplasms* ; Rectum ; Splenomegaly ; Weight Loss

No abstract available.
Adult ; Bone Marrow/pathology ; DNA Mutational Analysis ; Humans ; Leukemia, Myelomonocytic, Chronic/*diagnosis/genetics/therapy ; Leukemia, Neutrophilic, Chronic/*diagnosis/genetics/therapy ; Leukocyte Disorders/diagnosis ; Male ; Middle Aged ; Mutation ; Prognosis ; Receptors, Colony-Stimulating Factor/*genetics ; Recurrence ; *Stem Cell Transplantation ; Transplantation, Homologous

No abstract available.
Amyloidosis* ; Leukemia, Neutrophilic, Chronic* ; Splenic Rupture*

OBJECTIVETo observe the CSF3R, ASXL1, SETBP1, JAK2 V617F and CALR mutations in patients with chronic neutrophilic leukemia (CNL).

METHODSTwelve suspected "CNL" patients were retrospectively reviewed according the WHO criteria (2008). CSF3R,ASXL1,SETBP1 and CALR mutations were sequenced, and JAK2 V617F was tested by allele specific (AS)-PCR.

RESULTS6 of 12 cases were diagnosed as CML, and all of the 6 carried. 4 of 6 patients also had ASXL1 and SETBP1 mutations and one had a CALR mutation (c.1154-1155insTTGTC). Two patients with monoclonal gammopathy with uncertain significance (MGUS) combined with CNL-like symptoms had no CSF3R, ASXL1, SETBP1, JAK2 V617F or CALR mutation. The same results were also seen in other 4 cases with secondary neutrophilic leukocytosis.

CONCLUSIONCSF3R, ASXL1 and SETBP1 mutations differential diagnosis of CNL, and should be included in the diagnostic protocol so as to improve diagnostic accuracy for CNL.

Carrier Proteins ; Humans ; Janus Kinase 2 ; Leukemia, Neutrophilic, Chronic ; Mutation ; Nuclear Proteins ; Polymerase Chain Reaction ; Receptors, Colony-Stimulating Factor ; Repressor Proteins ; Retrospective Studies

OBJECTIVETo review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia (CNL).

DATA SOURCESData cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included. The terms "chronic neutrophilic leukemia" and "diagnosis" were used for the literature search.

STUDY SELECTIONWe identified, retrieved and reviewed the information on the clinical and laboratory features, the new genetic findings, prognosis and disease evolution and management of CNL.

RESULTSThe discovery of high-frequency granulocyte-colony stimulating factor receptor (CSF3R) mutations in CNL identifies a new major diagnostic criterion, and lends more specificity to the World Health Organization (WHO) diagnostic criteria for CNL, which are variably applied in routine clinical practice.

CONCLUSIONSIn patients for whom the cause of neutrophilia is not easily discerned, the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder, as well as providing the potential for genetically informed therapy. The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.

Carrier Proteins ; genetics ; Female ; Humans ; Leukemia, Neutrophilic, Chronic ; diagnosis ; genetics ; Male ; Mutation ; Nuclear Proteins ; genetics ; Receptors, Colony-Stimulating Factor ; genetics

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by persistent peripheral blood neutorphilia, bone marrow hypercellularity of neutrophilic granulocyte proliferation and hepatosplenomegaly. Acquired somatic mutation, JAK2 V617F, is the only molecular marker known to have association with classic BCR-ABL1 negative MPNs. However, JAK2 V617F has been detected occasionally in other MPNs such as CNL or other disease entities. We experienced a case of CNL with JAK2 V617F mutation. The patient was diagnosed according to the 2008 WHO classification criteria, and developed AML 9 months after the diagnosis of CNL. The JAK2 V617F was detected in the bone marrow throughout the clinical course. More cases are needed to establish the role of JAK2 V617F in the pathogenesis, prognosis and disease course of CNL.
Bone Marrow ; Granulocytes ; Humans ; Leukemia, Myeloid, Acute ; Leukemia, Neutrophilic, Chronic ; Neutrophils ; Prognosis

We describe here a 64-year-old woman who simultaneously presented with chronic neutrophilic leukemia (CNL) and multiple myeloma (MM). The patient presented with mature neutrophilic leukocytosis, hepatosplenomegaly, the absence of Philadelphia chromosome and the BCR-ABL fusion gene, along with IgG kappa type monoclonal gammopathy in her serum and urine. The bone marrow aspirates showed hypercellularity with marked granulocytic hyperplasia and an increase in immature plasma cells. The neutrophil function tests showed increased phagocytosis, chemotaxis and respiratory burst activity, but there was normal microbial killing activity. The patient was treated with dexamethasone and pamidronate for MM and with hydroxyurea for CNL, and she was discharged from the hospital in an improved condition.
Bone Marrow ; Chemotaxis ; Dexamethasone ; Female ; Homicide ; Humans ; Hydroxyurea ; Hyperplasia ; Immunoglobulin G ; Leukemia, Neutrophilic, Chronic* ; Leukocytosis ; Middle Aged ; Multiple Myeloma* ; Neutrophils* ; Paraproteinemias ; Phagocytosis ; Philadelphia Chromosome ; Plasma Cells ; Respiratory Burst