title: Neutrophilic progression in a case of polycytemia vera mimicking chronic neutrophilic leukemia: clinical and molecular characterization.
abstract: BACKGROUND
  In a small subset of polycytemia vera (PV), neutrophilia not secondary to reactive conditions or treatment can develop and persist. Clinical significance and morphogenetic alterations associated with this uncommon phenomenon are not well defined.
  
  
  METHODS
  An 81-year-old Caucasian woman, affected by polycytemia vera lasting 17 years, presented in March 2012 with hyperleukocytosis, absolute neutrophilia, and thrombocytosis despite hydroxyurea treatment. All other laboratory parameters were normal, except for an increased neutrophil alkaline phosphatase and lactate dehydrogenase. Reactive neutrophilia due to infection or neoplasia have been ruled out by a total body computerized tomography scan, and by low levels of C reactive protein. Re-evaluation of bone marrow showed hypercellular smears with expansion of granulopoiesis while immature granulocytes were <10% and myeloblasts were <1%. Bone marrow trephine biopsy showed hypercellular marrow, with panmyelosis, increased myeloid/erithroid ratio, polymorphic clusters of megakaryocytes. A loose network of reticulin fibers with many intersections was identified by means of Gomori's silver impregnation. There were no hybrid BCR/ABL gene transcripts of p210, p190 and p230, no mutations in platelet derived growth factor receptors alpha and beta. Flow cytometry on the aspirate showed that CD34+ CD117+ myeloblasts constituted less than 1% of total marrow nucleated cells, mature granulocytes demonstrated persistent expression of CD33. Mutational analysis of the gene CSF3R by PCR amplification revealed no alterations in exons 14-17, including codons 615 and 618. The case presented here represents a possible evolution of PV, albeit very rare.
  
  
  CONCLUSIONS
  The condition described here differs from the CNL for the persistence of morphological pictures typical of myeloproliferative diseases, for absence of CSF3R gene mutations and for the hyper expansion of the mature granulopoietic series. The clinical significance and morphogenetic alterations associated with this uncommon phenomenon are not well defined.
authors.affiliation: Department of Medicine and Medical Specialities, Ca' Granda Foundation IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy and Department of Clinical Sciences and Community Health, University of Milan, Via F. Sforza, 20122 Milan, Italy. Electronic address: roberto.castelli@unimi.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Castelli
authors.affiliation: Department of Medicine and Medical Specialities, Ca' Granda Foundation IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy and Department of Clinical Sciences and Community Health, University of Milan, Via F. Sforza, 20122 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
authors.affiliation: Pathology Unit, Department of Pathophysiology and Transplantation, University of Milan School of Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pancrazzi
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Alessandro Maria
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000235:genetics; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D015467:Leukemia, Neutrophilic, Chronic / Q000235:genetics / Q000473:pathology*; D011087:Polycythemia Vera / Q000235:genetics / Q000473:pathology*; D035583:Rare Diseases; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics
chemical_list: C517047:CSF3R protein, human; D016184:Receptors, Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase
keywords: Chronic neutrophilic leukemia like-evolution; Mutational analysis of the gene encoding colony-stimulating factor 3 receptor; Myeloproliferative neoplasms; Polycythemia vera