Path/Myeloproliferatives Flashcards
What is the big problem with myeloproliferative diseases?
Chronic proliferation of clones that differentiate to circulating blood cells
What cell dysfunctions occur in CML?
High WBC
All stages of granulocytes in blood
What is the main difference between CML and CMML?
CMML shows abnormal monocyte lineages also
PV defect?
Erythroid lineage overactive –> elevated RBC count
ET and myelofibrosis main defect
Mutant megs cause elevated platelet count
Factors that help you distinguish infection from myeloproliferative disease?
Left shift Toxic granulation Symptoms Check smear WBC - myeloid bulge (more myelocytes than metamyelocytes )
CML
t(9;22) BCR-ABL1 Tyr kinase overactivity
carcinogen exposure-related
30-60 yo
Imatinib (if no resp use Dadat- and nilotinib)
Use PCR Low LAP (nonfunctioning lymphocytes)
Hypercellular
No blasts
Basophilia in PB
PV what is the predominant cause?
JAK2V617F mutation
Mastocytosis cause
C-KIT or PDGF-RA activation
Mastocytosis immunophenotype
Tryptase!
CD117+
CD25+ usually
Mastocytosis treatment
Imatinib
Myelofibrosis cause
Jak2 mutation on chrmo 9
Myelofibrosis pathogenesis
Abnormal megs make cytokines –> collagen deposition from activated fibroblasts
JAK2 is mutated in these myeloproliferative diseases
Myelofibrosis, ET, PV
90% of cases of this disease involve JAK2 mutations
PV
Mastocytosis - what is the cause of the symptoms?
Histamine everywhere! flushing, rashes, urticaria
What is the very definitive, necessary way to diagnose mastocytosis?
Immunophenotype
**Serum Tryptase!! + (mast cell granule marker)
CD117+ for c-Kit cases
Myelofibrosis
> 50 yo
pres w thrombosis
Abnormal megs cytokines deposit collagen –> extramedullary hematopoiesis (spleen!)
**Splenomegaly
Reticulin fibers platelets up (mutant megs)
BM full of Collagen III
TEAR DROPS on “myelo” guitar
nucleated RBCs
Tx: transfusion
What is the differential diagnosis for primary myelofibrosis vs ET (vs iron def vs inflamm)?
Reticulin fibers in BM
+ = myelofibrosis
- = ET
Platelet count
very elevated –> myelofibrosis
norm/low –> thrombocythemia
TPO
Normal –> ET
Not –> other
What is the treatment for ET?
Hydroxyurea
How to PV patients present?
Thrombosis/HT/Stroke/MI from inc RBCs
PV morphology
Hypercellular marrow
Erythroid hyperplasia
inc megs
What is the typical ET presentation?
Thrombosis (inc platelets)
What do you worry about in myelodysplasia
Progression to acute leukemia
Refractory cytopenia with unilineage dysplasia - presentation and morphology
Unexplained cytopenia in elderly
Binucleated RBCs
Hypercellular marrow
Refractory anemia with Ring sideroblasts - how to Dx?
Morphology + iron stain results (looking for signs of overload)
Refractory anemia w ring sideroblasts - presentation and morphology
Unexplained cytopenia in elderly
Ring sideroblasts (nucleated RBCs with granules of iron accumulated in perinuclear mitochondria)
Which myelodysplasias are at significant risk for progressing to acute leukemia?
Refractory cytopenia w multilineage dysplasia
MDS with del(5q)
Refractory anemia with excess blasts
MDS with del(5q) - morphology, cytogenetics, presentation, prognosis, tx?
Severe anemia in elderly women
Loss of large arm of 5
ALL megs are mononuclear
Treat w/ lenalidomide
Refractory cytopenia with multilineage dysplasia
Severe anemia
2+ lineages with dysplasia
Abnormal granulocyte degranulation
Abnormal nuclei lobulation
Refractory anemia with excess blasts
Cytopenia with elderly patients
RAEB-1: 5-9% blasts
RAEB-2: 10-19% blasts
Blasts and dyspoietic maturation
CD34+ +/- CD117+
How does refractory anemia with excess blasts differ from acute leukemia?
AML develops from blasts with translocations that halt differentiation
Here, mutation results in clonal expansion, more like a true malignancy
