Chronic Neutrophilic Leukemia



Chronic Neutrophilic Leukemia


Kaaren K. Reichard, MD





Key Facts


Terminology



  • Chronic neutrophilic leukemia (CNL)


Etiology/Pathogenesis



  • Unknown


  • Extremely rare disease


Clinical Issues



  • Hepatosplenomegaly


  • Bleeding, gout, pruritus


Microscopic Pathology



  • PB neutrophilia; blasts < 1%, WBC ≥ 25 × 109/L, immature granulocytes < 10% of WBC


  • BM hypercellular with granulocytic predominance; blasts < 5%, occasional erythroid and megakaryocytic proliferation


  • No dysplasia, overt basophilia, or monocytosis


Ancillary Tests



  • Genetics



    • Absence of BCR-ABL1 fusion


    • No rearrangement of PDGFRA, PDGFRB, and FGFR1


    • Cytogenetics most often normal


    • JAK2 V617F mutation has been reported


Top Differential Diagnoses



  • Reactive neutrophilia



    • Infection, inflammation, collagen vascular disease, underlying neoplasm


    • Myeloma may lead to “CNL-like” picture


  • CML, BCR-ABL1 positive



    • Particularly neutrophilic variant


    • p230 variant of BCR-ABL1 fusion


  • BCR-ABL1 negative MPNs


  • Survival ranges from < 1 year to > 20 years


  • Median survival < 2 years






This peripheral blood smear demonstrates the typical neutrophilic leukocytosis with minimal left shift in a case of chronic neutrophilic leukemia.






This bone marrow core biopsy shows the classic granulocytic predominance and hypercellularity in a case of chronic neutrophilic leukemia. The bone and megakaryocyte morphology is normal.


TERMINOLOGY


Abbreviations



  • Chronic neutrophilic leukemia (CNL)


Definitions



  • Clonal hematopoietic neoplasm manifesting predominantly in granulocytic lineage


  • Persistent peripheral blood (PB) neutrophilia


  • Persistent bone marrow (BM) granulocytic proliferation


  • Reactive neutrophilia and other myeloproliferative neoplasms (MPNs) must be completely excluded


  • BCR-ABL1 negative


ETIOLOGY/PATHOGENESIS


Unknown



  • Rare disease



    • < 500 cases reported in the literature


  • CNL neutrophils may be dysfunctional



    • Decreased stimulation with granulocyte colony stimulating factor (G-CSF)


    • Insufficiency of some inflammatory cytokinespecific signaling


CLINICAL ISSUES


Epidemiology



  • Age



    • Median: 6th decade


  • Gender



    • Slight male predominance


Presentation



  • Abnormal complete blood cell count (CBC)


  • Hepatomegaly


  • Splenomegaly


  • Neutrophilia


  • Majority of patients asymptomatic


  • Gout


  • Pruritus


  • Mucocutaneous bleeding


Laboratory Tests



  • CBC


  • PB and BM examination


  • Cytogenetics


Treatment



  • Variable



    • Depends on symptomatology


    • Watchful waiting



      • If indolent


    • Cytoreductive agents (e.g., hydroxyurea)


    • Toxic chemotherapy



      • If progressive or symptomatic disease


    • Allogeneic stem cell transplant in rare cases


  • Progressive disease



    • Development of myelodysplasia or acute leukemia


    • Unclear, in some cases, if result of prior toxic treatment


Prognosis



  • Heterogeneous


  • May be indolent


  • Disease progression



    • Progressive neutrophilia refractory to therapy


    • Progressive splenomegaly


    • Refractory thrombocytopenia with bleeding complications


    • Cytogenetic clonal evolution


    • Myelodysplasia may develop


    • Rare leukemic transformation


    • Death from



      • Intracranial hemorrhage


      • Infection


      • Bone marrow failure



IMAGE FINDINGS


Radiographic Findings



  • Hepatomegaly


  • Splenomegaly


MICROSCOPIC PATHOLOGY


Peripheral Blood



  • Neutrophilia and increased band forms


  • WBC ≥ 25 × 109/L


  • Toxic changes with prominent granules may be seen



    • Must exclude reactive condition


  • Absence of dysplasia


  • No significant basophilia


  • No significant monocytosis


  • Immature granulocytes (metamyelocytes, myelocytes, and promyelocytes) constitute < 10% of WBC


  • Blasts comprise < 1% of WBC


  • Variable anemia and thrombocytopenia


  • Erythrocytes and platelets morphologically normal


Bone Marrow



  • Hypercellular; granulocytic predominance; blasts < 5%


  • May see megakaryocytic &/or erythroid proliferation


  • May see histiocytic neutrophilic phagocytosis


  • No dysplasia


  • No significant reticulin fibrosis


  • Normal bony trabeculae


Ancillary Studies

Tags:
Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Chronic Neutrophilic Leukemia

Full access? Get Clinical Tree
Get Clinical Tree app for offline access