Myeloid Neoplasms

A. Acute Myelogenous Leukemia (AML) 1. Acute myelogenous leukemia a. Myeloblasts may have intracytoplasmic rods (stain red) called Auer rods i. Auer rods are abnormal lysosomes (primary granules) that are pathognomonic of myeloblasts and not found in ALL :

ii. Auer rods also stain positive with myeloperoxidase (MPO) or Sudan-black B stain iii. Auer rods are most commonly found in M3 AML

b. The tissue form of AML is called granulocytic sarcoma (chloroma)

c. French-American-British (FAB) classification of AML

i. MO: undifferentiated ii. Ml: myeloblastic leukemia without maturation iii. M2: myeloblastic leukemia with maturation (some promyelocytes)

iv. M3: hypergranular (microgranular) promyelocytic leukemia

• Micro: numerous cytoplasmic granules and numerous Auer rods

■ May develop disseminated intravascular coagulation (DIC) due to release of th rombo plastic substances in granules (especially when therapy kills the leukemic cells)

■ Characteristic translocation: t(15;17)

■ 15 has the polymorphonuclear leukocyte (PML) gene, whereas 17 has the retinoic acid receptor a gene (RAR-a).

• This translocation forms an abnormal retinoic acid receptor; therefore, therapy is with all-trans-retinoic acid v. M4: myelomonocytic leukemia has both myeloblasts and monoblasts vi. M5: monocytic leukemia (may have gingival infiltrates)

vii. M6: erythroleukemia (Di Guglielmo disease); as abnormal erythroid precursors (binucleate and megaloblastic changes)

viii. M7: acute megakaryocytic leukemia; associated with acute myelofibrosis due i to release of platelet-derived growth factor (PDGF)

B. Myelodysplasia

1. Myelodysplasia syndromes (MDS)

a. The classification of myelodysplastic syndromes is based on the number of blasts in the marrow b. Dysplastic changes include Pelger-Huet cells ("aviator glasses" nuclei), ring sider-oblasts, nuclear budding, and "pawn ball" megakaryocytes c. MDS patients have an increased risk of developing acute leukemia (preleukemias)


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Myeloproliferative Syndromes (MPS)

1. General a. MPSs are clonal neoplastic proliferations of multipotent myeloid stem cells b. Bone marrow is usually markedly hypercellular (hence the name myeloproliferative)

i. All cell lines are increased in number (erythroid, myeloid, and megakaryocytes)

ii. Cannot tell the MPSs apart by the histologic appearance of the bone marrow

2. Chronic myelogenous leukemia (CML)

a. Clonal proliferation of pluripotent stem cells b. A unique characteristic is the chromosomal translocation i. Philadelphia (Ph) chromosome, which has t(9;22)

ii. 9 has c-abl (an oncogene), while 22 has bcr (breakpoint cluster region)

iii. This translocation forms a new protein P210 that has tyrosine kinase activity c. Insidious onset (i.e., chronic) and massive splenomegaly d. Micro: hypercellular bone marrow with all cell lines increased in number e. Peripheral leukocytosis including i. Markedly increased numbers of neutrophils (and bands and metamyelocytes)

ii. Increased eosinophils and basophils (like the other MPSs)

f. Decreased leukocyte alkaline phosphatase (LAP) activity is diagnostic compared with leukemoid reaction, which has increased LAP

g. Treatment i. Control with hydroxyurea ii. Bone marrow transplant h. Prognosis i. Slow progression (half develop accelerated phase <5 years)

ii. Then blast crisis (very bad prognosis; doesn't respond to chemotherapy): 2/3 myeloid blasts and 1/3 lymphoid blasts

3. Polycythemia vera (P. vera)

a. Characteristic findings i. Increased erythroid precursors with increased red cell mass (primary)

ii. Increased hematocrit iii. Increased blood viscosity b. Decreased erythropoietin (EPO), but RBCs have increased sensitivity to EPO and overproliferate c. Increased basophils and increased eosinophils (like all of the MPSs)

d. Histamine release from basophils causes intense pruritus and gastric ulcers (bleeding may cause iron deficiency)

e. Increased LAP

f. Clinical characteristics: plethora (redness) and cyanosis (blue)

g. Complications i. Increased blood viscosity can cause deep vein thromboses and infarcts ii. High cell turnover can cause hyperuricemia, resulting in gout iii. P. vera may develop into a "spent phase" with myelofibrosis iv. Increased risk for acute leukemia

4. Essential thrombocythemia (ET)

a. Increased megakaryocytes (and other cell Lines) in bone marrow b. Peripheral blood smear i. Increased number of platelets (>1,000,000), some with abnormal shapes ii. Also increased numbers of leukocytes c. Clinical signs include excessive bleeding and occlusion of small vessels

5. Myelofibrosis (MF) with myeloid metaplasia a. Etiology is unknown (agnogenic)

b. Bone marrow aspiration may be a "dry tap"

c. Biopsy specimen shows hypocellular marrow with fibrosis (increased reticulin)

i. Fibroblasts are polyclonal proliferation (not neoplastic)

ii. Fibrosis is secondary to factors released from megakaryocytes, such as platelet-derived growth factor (PDGF)

d. Enlarged spleen due to extramedullary hematopoiesis (myeloid metaplasia)

e. Peripheral smear i. Leukoerythroblastosis (immature white cells and nucleated red cells)

ii. Teardrop RBCs f. High cell turnover causes hyperuricemia and gout

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