Pathology of Myeloid Disorders

Question 1

an auer rod is indicative of…

Answer 1

acute myeloid leukemia (AML)

Question 2

pathogenesis of myeloid neoplasms: genetic abnormalities

Answer 2

*chromosomal translocations
ex. t(15;17) KML/RARalpha; t(9;22) BCR/ABL)

*acquired mutations
ex. JAK2; FLT3; NPM1]

*karyotypic abnormalities
ex. monosomies, trisomies, deletions or additions

Question 3

pathogenesis of myeloid neoplasms: host factors

Answer 3

*hereditary
-genomic instability, Down’s Syndrome, neurofibromatosis, familial predisposition

*chronic marrow dysfunction/failure
-antecedent clonal stem disorder
-aplastic anemia
-paroxysmal nocturnal hemoglobinuria

Question 4

pathogenesis of myeloid neoplasms: mutagenic factors

Answer 4

*chemical/drugs: ex. CHEMO
*ionizing radiation

Question 5

myeloid “left shift” - defined

Answer 5

increase in less mature circulating neutrophils (blasts, promyelocytes, myelocytes, metamyelocytes)

Question 6

causes of myeloid “left shift”

Answer 6

1. INFECTIONS
2. tissue necrosis/inflammation
3. drugs/hormones
4. miscellaneous (pregnancy, smoking, stress, post-splenectomy)
5. bone marrow fibrosis
6. leukemias

Question 7

myeloproliferative neoplasms (MPNs) - overview

Answer 7

*clonal stem cell disorders
*neoplasm of multipotent progenitor cell
*hematopoiesis effective and ordered; cells show ALL stages of differentiation
*involve the bone marrow and peripheral blood; often have a cytosis w/ organomegaly

Question 8

examples of myeloproliferative neoplasms (MPNs)

Answer 8

1. chronic myeloid leukemia (CML)
2. polycythemia vera (PV)
3. essential thrombocythemia (ET)
4. primary myelofibrosis (PMF)

Question 9

buzz words for CML

Answer 9

*BCR-ABL1 positive
*t(9;22) translocation, aka Philadelphia chromosome
*proliferation primarily of neutrophil series
*leukocytosis with granulocytic left shift

Question 10

Pseudo-Pelger-Huet Anomaly

Answer 10

*neutrophils with bilobed (“duet”) nuclei
*associated with myelodysplastic syndromes or drugs (eg. immunosuppressants)

Question 11

myelodysplastic syndromes (MDS) - overview

Answer 11

*stem cell disorders involving ineffective hematopoiesis → defects in cell maturation of nonlymphoid lineages
*clonal stem cell disorders
*neoplasm of multipotent progenitor cell
*hematopoiesis is INEFFECTIVE and DISORDERDED (dysplastic cells show all stages of differentiation)
*involve the bone marrow and peripheral blood; often have cytopenias w/o organomegaly

Question 12

myelodysplastic syndromes (MDS) - clinical features

Answer 12

*older adults, between 60-75 years
*symptoms related to cytopenias - fatigue, infections, hemorrhage
*organomegaly absent

Question 13

myelodysplastic syndromes (MDS) - diagnosis

Answer 13

consider in any adult patent with unexplained blood cytopenia; diagnosis of exclusion:
1. peripheral blood/bone marrow examination
2. rule out vitamin deficiencies: B12, folate
3. rule out toxic exposures: heavy metal (arsenic)
4. rule out drug therapies: chemo, colony stimulating factor
5. cytogenic studies

Question 14

myelodysplastic syndromes (MDS) - peripheral blood

Answer 14

*anemia - macrocytic, reticulocytopenia
*thrombocytopenia - big ass platelets
*neutropenia
*blasts < 20%

Question 15

myelodysplastic syndromes (MDS) - bone marrow

Answer 15

*hypercellular for patient age
*uni/multi-lineage dysplasia (cells look weird)
*blasts < 20%
*abnormal karyotype

Question 16

dyserythropoiesis

Answer 16

*asynchronous nucleus:cytoplasm maturation of RBCs
*nuclear alterations: budding, internuclear bridging, multinuclearity
*ringed sideroblasts: nucleated RBC with Fe granules circling nucleus

Question 17

dysgranulopoiesis

Answer 17

*asynchronous nucleus:cytoplasm maturation
*nuclear alterations: hypolobated (Pseudo Pelger Huet) or hyperlobated
*cytoplasmic granules: hypogranular; inclusion like granules

Question 18

dysmegakaryocytopoiesis

Answer 18

*megakaryocytic clustering (increase in #)
*hypolobated / monolobated:
-micromegakaryocytes = “dwarf”