Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (346 page)

   
Cytogenetics
reveals no consistent karyotypic abnormalities, deletion of 6q may be the most common.

   
Serum protein electrophoresis
shows hypergammaglobulinemia in half the patients, rarely a monoclonal IgG gammopathy.

   
Serologic findings
: A positive RF is common, and antinuclear antibodies and circulating immune complexes are present in half the cases.

Suggested Reading

Zhang D, Loughran TP. Large granular lymphocytic leukemia: molecular pathogenesis, clinical manifestations, and treatment.
Hematology Am Soc Hematol Educ Program.
2012;2012:652–659.

CHRONIC NEUTROPHILIC LEUKEMIA

   Definition

A rare myeloproliferative disease in which the predominant blood peripheral cells are mature granulocytes.

   Who Should Be Suspected?

Patients with persistent neutrophilia in whom a chronic infection, neoplasm, or inflammatory process is excluded. Clinical picture of splenomegaly and hepatomegaly of unknown etiology. Twenty-five to 30% of patients present with mucocutaneous bleeding. Polycythemia vera, primary myelofibrosis, and essential thrombocythemia should be excluded.

   Laboratory Findings

   
CBC
: Characterized by persistent leukocytosis (WBC ≥ 2,500 × 10
⁹
/μL) due to neutrophilia (segmented neutrophils and bands are >80% of WBC). Immature granulocytes are <10% on the peripheral blood smear (PBS). Hb and platelets are normal early in the disease, but anemia and thrombocytopenia develop as the disease progresses.

   
Bone marrow
: Hypercellular with increase in mature neutrophils, but <5% myeloblasts.

   
Cytogenetics and genetic studies
: No rearrangement of BCR-ABL1, PDGFRA, PDGRFB, or FGFR1.

Suggested Reading

Bain BJ, Brunning RD, Vardiman JW, et al. Chronic neutrophilic leukaemia. In:
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
, 4th ed. Lyon, France: International Agency for Research on Cancer; 2008.

   
MULTILINEAGE DISEASES
^**

MYELOPROLIFERATIVE NEOPLASMS (MPNS)

   Definition

Chronic MPNs are a heterogeneous group of clonal malignant disorders that arise from mutations in hematopoietic stem cells/progenitors. Clonal overexpansion leads to terminal myeloid expansion, reflected by various combinations of erythrocytosis, leukocytosis, thrombocytosis, bone marrow hypercellularity/fibrosis, and splenomegaly. There is a predisposition of the progenitor cells to undergo terminal transformation into leukemic blast cells. The three most common nonleukemic MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. They are characterized by clonal dominance and unregulated increase in the circulation of erythrocytes, leukocytes, or platelets, each lineage alone, or in combination. Diagnostic challenges ensue because of the overlap of clinical and laboratory manifestations among these three disorders (phenotypic mimicry). This mimicry has been enhanced by the discovery of a common mutation
(V617F)
in
JAK2
, which belongs to the Janus family of tyrosine kinases.