Myeloid Neoplasms

MYELOID NEOPLASMS

Acute Myelogenous Leukemia

Acute myelogenous leukemia is a cancer of the myeloid line of blood cells. Median age at diagnosis is age 50. Symptoms include fatigue, unusual bleeding, and infec-tions.

Lab findings: Myeloid blasts or promyelocytes represent at least 20% of the marrow cells. Auer rods (linear condensations of cytoplasmic granules) are characteristic of AML and are not found in normal myeloid precursors.

The WHO classification of AML (2008) is as follows:

•         AML with recurrent genetic abnormalities (for some of these entities, the karyotype is diagnostic regardless of the blast percentage)

o   Promyelocytic leukemia has t(15;17)(q22;q12) with fusion gene PML/RARA and responds to all-transretinoic acid (ATRA); DIC is common

o   AML with either t(8;21)(q22;q22) or inv(16)(p13.1;q22)

•         AML with myelodysplasia-related changes

•         Therapy-related myeloid neoplasms

•         AML, not otherwise specified

Myelodysplastic Syndromes (MDS)

MDS are classified according to the number of blasts in the marrow. Dysplastic changes include Pelger-Huët cells (“aviator glasses” nuclei), ring sideroblasts, nuclear budding, and “pawn ball” megakaryocytes. MDS are considered preleukemias, so patients are at increased risk for developing acute leukemia.

MDS mainly affect older adults (age 50–70); they also predispose to infection, hem-orrhage and anemia. Transformation to AML is common.

Myeloproliferative Neoplasms (MPN)

MPN are clonal neoplastic proliferations of multipotent myeloid stem cells. The bone marrow is usually markedly hypercellular (hence the name myeloproliferative). All cell lines are increased in number (erythroid, myeloid, and megakaryocytes).

Chronic myelogenous leukemia (CML) is a clonal proliferation of pluripotent granulocytic precursor stem cells. In most cases it is associated with a BCR-ABL fusion gene due to a balanced (9;22) translocation; however, this Phila-delphia chromosome is not specific to CML.

CML has an insidious onset (i.e., chronic) and causes massive spleno-megaly. Progression is typically slow (50% develop accelerated phase <5 years), unless blast crisis develops (very poor prognosis; doesn’t respond to chemotherapy). In blast crisis, 70% of cases show myeloid blasts and 30% show lymphoid blasts.

Microscopically, the bone marrow is hypercellular, with all cell lines increased in number. Peripheral leukocytosis is present, including mark-edly increased neutrophils (and bands and metamyelocytes), as well as increased eosinophils and basophils (as in the other MPS).

Treatment is imatinib mesylate, which blocks the P210 tyrosine kinase protein produced by the translocation. Hematopoietic stem cell trans-plantation is also used.

Polycythemia vera is a stem cell disorder with trilineage (erythroid, granulo-cytic, megakaryocytic) proliferation. It may develop into a “spent phase” with myelofibrosis. It causes an increased risk for acute leukemia. Phlebotomy is therapeutic.

Polycythemia vera characteristically shows the following:

•         Increased erythroid precursors with increased red cell mass

•         Increased hematocrit

•         Increased blood viscosity, which can cause deep vein thrombosis and infarcts

•         Decreased erythropoietin, but erythrocytes have increased sensitivity to erythropoietin and overproliferate

•         Increased basophils. Histamine release from basophils can cause intense pruritus and gastric ulcer (bleeding may cause iron deficiency).

•         Increased eosinophils (like all of the MPS)

•         High cell turnover can cause hyperuricemia, resulting in gout. Other clinical characteristics include plethora (redness) and cyanosis (blue).

Essential thrombocythemia is characterized by increased megakaryocytes (and other cell lines) in bone marrow. Peripheral blood smear shows increased platelets, some with abnormal shapes. There are also increased leukocytes. Clinical signs include excessive bleeding and occlusion of small vessels.

Myelofibrosis (MF) with myeloid metaplasia has unknown etiology (agnogenic).

•         Marrow fibrosis is secondary to factors released from megakaryocytes, such as platelet-derived growth factor (PDGF).

•         Bone marrow aspiration may be a “dry tap.” The biopsy specimen shows hypocellular marrow with fibrosis (increased reticulin). The fibroblasts are a polyclonal proliferation and are not neoplastic.

•         There is an enlarged spleen due to extramedullary hematopoiesis (myeloid metaplasia). Peripheral smear shows leukoerythroblastosis (immature white cells and nucleated red cells) with teardrop RBCs. High cell turnover causes hyperuricemia and gout.