ABSTRACT
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.
Subject(s)
Aged , Humans , Colony-Stimulating Factors , Diagnosis , Leukemia , Leukemia, Neutrophilic, Chronic , Lower Extremity , SkinABSTRACT
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.
Subject(s)
Humans , Colony-Stimulating Factors , Diagnosis, Differential , Leukemia, Neutrophilic, Chronic , Leukemoid Reaction , Leukocytosis , Monoclonal Gammopathy of Undetermined Significance , Multiple Myeloma , Myeloid Cells , Neoplasms, Plasma Cell , Neutrophils , Ovarian Neoplasms , Paraneoplastic Syndromes , SepsisABSTRACT
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.
Subject(s)
Humans , Adenocarcinoma , Biopsy , Bone Marrow , Cytogenetic Analysis , Diagnosis , Electrons , Karyotype , Leukemia , Leukemia, Neutrophilic, Chronic , Leukemoid Reaction , Leukocytosis , Liver , Lymph Nodes , Neoplasm Metastasis , Neutrophils , Philadelphia Chromosome , Rectal Neoplasms , Rectum , Splenomegaly , Weight LossABSTRACT
No abstract available.
Subject(s)
Amyloidosis , Leukemia, Neutrophilic, Chronic , Splenic RuptureABSTRACT
No abstract available.
Subject(s)
Adult , Humans , Male , Middle Aged , Bone Marrow/pathology , DNA Mutational Analysis , Leukemia, Myelomonocytic, Chronic/diagnosis , Leukemia, Neutrophilic, Chronic/diagnosis , Leukocyte Disorders/diagnosis , Mutation , Prognosis , Receptors, Colony-Stimulating Factor/genetics , Recurrence , Stem Cell Transplantation , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia (CNL).</p><p><b>DATA SOURCES</b>Data 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.</p><p><b>STUDY SELECTION</b>We identified, retrieved and reviewed the information on the clinical and laboratory features, the new genetic findings, prognosis and disease evolution and management of CNL.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>In 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.</p>
Subject(s)
Female , Humans , Male , Carrier Proteins , Genetics , Leukemia, Neutrophilic, Chronic , Diagnosis , Genetics , Mutation , Nuclear Proteins , Genetics , Receptors, Colony-Stimulating Factor , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To observe the CSF3R, ASXL1, SETBP1, JAK2 V617F and CALR mutations in patients with chronic neutrophilic leukemia (CNL).</p><p><b>METHODS</b>Twelve 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.</p><p><b>RESULTS</b>6 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.</p><p><b>CONCLUSION</b>CSF3R, ASXL1 and SETBP1 mutations differential diagnosis of CNL, and should be included in the diagnostic protocol so as to improve diagnostic accuracy for CNL.</p>
Subject(s)
Humans , Carrier Proteins , Janus Kinase 2 , Leukemia, Neutrophilic, Chronic , Mutation , Nuclear Proteins , Polymerase Chain Reaction , Receptors, Colony-Stimulating Factor , Repressor Proteins , Retrospective StudiesABSTRACT
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.
Subject(s)
Humans , Bone Marrow , Granulocytes , Leukemia, Myeloid, Acute , Leukemia, Neutrophilic, Chronic , Neutrophils , PrognosisABSTRACT
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.
Subject(s)
Female , Humans , Middle Aged , Bone Marrow , Chemotaxis , Dexamethasone , Homicide , Hydroxyurea , Hyperplasia , Immunoglobulin G , Leukemia, Neutrophilic, Chronic , Leukocytosis , Multiple Myeloma , Neutrophils , Paraproteinemias , Phagocytosis , Philadelphia Chromosome , Plasma Cells , Respiratory BurstABSTRACT
We present the case of a 44 years man who presented to us with persistent leucocytosis. Following relevant investigations, we diagnosed him to have Chronic Neutrophilic Leukaemia (CNL); a rare haematological disorder. Ten months later, he remains non-responsive to standard line of treatment.
Subject(s)
Adult , Allopurinol/therapeutic use , Humans , Hydroxyurea/therapeutic use , Leukemia, Neutrophilic, Chronic/diagnosis , Leukocytosis/diagnosis , Male , Prognosis , Vitamins/therapeutic useABSTRACT
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by clonal proliferation of mature neutrophils, hepatosplenomegaly, elevated leukocyte alkaline phosphatase score (ALP score) and a negative Philadelphia chromosome. To date, approximately 150 cases have been reported in the literature, including some cases presenting with a 'leukemic' state reflected by a neutrophilic reaction. The term 'true' CNL, recently introduced by Reilly, highlights the need for more experience with CNL cases to improve the diagnostic criteria. In Korea, about 10 cases have been reported in the literature and some of those cases did not meet the WHO diagnostic criteria for CNL. We present a typical case of CNL in a 66-year-old man who complained of general weakness and weight loss. On admission, the white blood cell count from the peripheral blood was 175,600/L with 80% segmented neutrophils. The cytogenic study was negative for the Philadelphia chromosome and had a normal karyotype.
Subject(s)
Aged , Humans , Alkaline Phosphatase , Karyotype , Korea , Leukemia, Neutrophilic, Chronic , Leukocyte Count , Leukocytes , Myeloproliferative Disorders , Neutrophils , Philadelphia Chromosome , Weight LossABSTRACT
Introducción: La leucemia neutrofílica crónica es un desorden mieloproliferativo poco frecuente (sólo se han descrito 143 casos)que se caracteriza por esplenomegalia, leve leucocitosis, marcada neutrofilia sin basofilia, cromosoma Filadelfia BCR/ABL negativos y anormalidades cromosómicas hasta en el 10 porciento de los casos; en el caso clínico descrito se encontró tetrasomía 8. El diagnóstico diferencial de la leucemia neutrofílica crónica es difícil e incluye la reacción leucemiode, la leucemia mieloide crónica y la policitemia vera. Descripción del caso: apaciente de 73 años con síntomas clínicos y hallazgos hematopatológicos de leucemia neutrofílica crónica, con tetrasomía 8 en el estudio citogenético. Discusión: de junio de 1977 a junio de 2003, en el Instituto Nacional de Cancerología se diagnosticaron 318 casos de leucemia mieloide crónica. entre los pacientes afectados se encontró uno que cumplió con todos los criterios clínicos, genéticos y patológicos para ser clasificado como víctima de una leucemia neutrofílica crónica. Este es nuestro primer caso de leucemia neutrofílica crónica que se presenta la anormalidad cromosómica tetrasomía 8
Subject(s)
Cytogenetics , Leukemia, Neutrophilic, ChronicABSTRACT
Chronic Neutrophilic Leukemia (CNL) is a rare myeloproliferative disorder characterized by a persistent increase of mature peripheral neutrophils, myeloid hyperplasia in bone marrow, hepatosplenomegaly, elevated neutrophil alkaline phosphatase (NAP) and absence of Philadelphia chromosome, with no evidence of infection or malignancy sufficient to mimic a leukemoid reaction. CNL has been associated with multiple myelomas in many reported cases, but transition of Polycythemia Vera (PV) to CNL is very rare. An 81-year-old female patient, who had undergone intermittent phlebotomy following the diagnosis of PV 8 years previously, was admitted to our hospital due to lower back pain. A physical examination showed a splenomegaly 2cm below the costal margin, with tenderness of the thoracic and lumbar spine area. A peripheral blood examination showed a WBC count of 91, 800/micro L (neutrophil 88%) with a rare immature form, hemoglobin of 9.1 g/dL and a platelet count of 1, 661, 000/micro L. Her NAP score was 58. The bone marrow examination showed 95% cellularity, with an M: E ratio of 10: 1, increased megakaryocytes with normal morphology and the absence of myelofibrosis. Chromosomal studies showed no Philadelphia chromosome. A radiological examination showed compression fractures of the vertebrae and spinal cord compression. No underlying disease causing a leukemoid reaction was detected. With iron replacement, the hemoglobin level failed to increase over 12 g/dL. Therefore, it was concluded to be a transition of PV to CNL. After administration of hydroxyurea and vertebroplasty, the symptom improved and the WBC count was sustained below 40, 000/micro L.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Leukemia, Neutrophilic, Chronic/etiology , Polycythemia Vera/complicationsABSTRACT
Se describe un caso de leucemia neutrofílica crónica asociada a leucemia de piel, en una paciente de 49 años de edad, sexo femenino, diagnosticada en julio de 2001; con presencia de 43.605/mm3 neutrófilos en sangre periférica y médula ósea hipercelular con serie granulocítica hiperplástica. el estudio histopatológico de la piel reveló infiltrado del 70 porciento de blastos tipo mieloide. Fue tratada con hidroxiurea, siendo favorable la resuesta clínica y laboratorial. el hemograma de diciembre de 2001 presentó 5.656/mm3 neutrófilos.
Subject(s)
Humans , Female , Adult , Skin , Leukemia , Leukemia, Neutrophilic, Chronic/diagnosis , Leukemia, Neutrophilic, Chronic/genetics , Leukemia, Neutrophilic, Chronic/therapyABSTRACT
Chronic neutrophilic leukemia is a rare hematological disorder with hepatosplenomegaly and sustained mature neutrophilic leucocytosis. Increased serum vitamin B12, increased serum urine acid levels and increased leukocyte alkaline phosphatase activity are the associated features in the absence of fever or any other underlying disorder to cause leukemoid reaction. We report one such rare case.
Subject(s)
Aged , Alkaline Phosphatase/metabolism , Humans , Leukemia, Neutrophilic, Chronic/diagnosis , Male , Uric Acid/blood , Vitamin B 12/bloodABSTRACT
Chronic neutrophilic leukemia is a rare myeloproliferative disorder. We have experienced a typical case of chronic neutrophilic leukemia in a 76-year-old man who complained abdominal distension due to hepatosplenomegaly. White blood cell count of peripheral blood was 50,500/nL with 90% segmented neutrophils. The underlying disease for a leukemoid reaction had not been detected. Leukocyte alkaline phosphatase score and the serum levels of vitamin B12 and uric acid were elevated. Chromosome study showed a normal karyotype without Philadelphia chromosome or bcr/abl rearrangement. Phorbol myristate acetate-activated respiratory burst activity of neutrophils measured with chemiluminescence showed increased activity.
Subject(s)
Aged , Humans , Alkaline Phosphatase , Karyotype , Leukemia, Neutrophilic, Chronic , Leukemoid Reaction , Leukocyte Count , Leukocytes , Luminescence , Myeloproliferative Disorders , Myristic Acid , Neutrophils , Philadelphia Chromosome , Respiratory Burst , Uric Acid , Vitamin B 12ABSTRACT
Chronic neutrophilic leukemia(CNL) is a rare disorder characterized by persistent neutrophilia of mature cell type without evidence of infection, hepatosplenomegaly, elevated neutrophil alkaline phosphatase score and the absence of Philadelphia chromosome We report a typical case of CNL with multiple myeloma(IgG-lambda type) in 68 years old female. Many neutrophils had toxic granule and vacuole. The peripheral blood smear showed neutrophlic leukocytosis(50,940/microliter, neutrophil 94%) with rare immature form. The cytogenetic study showed normal karyotype without Philadelphia chromosome. She was diagnosed as multiple myeloma with paraproteinemia, lytic bone lesion of skull, and immature plasma cells in bone marrow.