Path/Myeloproliferatives

Question 1

What is the big problem with myeloproliferative diseases?

Answer 1

Chronic proliferation of clones that differentiate to circulating blood cells

Question 2

What cell dysfunctions occur in CML?

Answer 2

High WBC

All stages of granulocytes in blood

Question 3

What is the main difference between CML and CMML?

Answer 3

CMML shows abnormal monocyte lineages also

Question 4

PV defect?

Answer 4

Erythroid lineage overactive –> elevated RBC count

Question 5

ET and myelofibrosis main defect

Answer 5

Mutant megs cause elevated platelet count

Question 6

Factors that help you distinguish infection from myeloproliferative disease?

Answer 6

Left shift
Toxic granulation
Symptoms
Check smear
WBC - myeloid bulge (more myelocytes than metamyelocytes )

Question 7

CML

Answer 7

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

Question 8

PV what is the predominant cause?

Answer 8

JAK2V617F mutation

Question 9

Mastocytosis cause

Answer 9

C-KIT or PDGF-RA activation

Question 10

Mastocytosis immunophenotype

Answer 10

Tryptase!
CD117+
CD25+ usually

Question 11

Mastocytosis treatment

Answer 11

Imatinib

Question 12

Myelofibrosis cause

Answer 12

Jak2 mutation on chrmo 9

Question 13

Myelofibrosis pathogenesis

Answer 13

Abnormal megs make cytokines –> collagen deposition from activated fibroblasts

Question 14

JAK2 is mutated in these myeloproliferative diseases

Answer 14

Myelofibrosis, ET, PV

Question 15

90% of cases of this disease involve JAK2 mutations

Answer 15

PV

Question 16

Mastocytosis - what is the cause of the symptoms?

Answer 16

Histamine everywhere! flushing, rashes, urticaria

Question 17

What is the very definitive, necessary way to diagnose mastocytosis?

Answer 17

Immunophenotype

**Serum Tryptase!! + (mast cell granule marker)
CD117+ for c-Kit cases

Question 18

Myelofibrosis

Answer 18

> 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

Question 19

What is the differential diagnosis for primary myelofibrosis vs ET (vs iron def vs inflamm)?

Answer 19

Reticulin fibers in BM
+ = myelofibrosis
- = ET

Platelet count
very elevated –> myelofibrosis
norm/low –> thrombocythemia

TPO
Normal –> ET
Not –> other

Question 20

What is the treatment for ET?

Answer 20

Hydroxyurea

Question 21

How to PV patients present?

Answer 21

Thrombosis/HT/Stroke/MI from inc RBCs

Question 22

PV morphology

Answer 22

Hypercellular marrow
Erythroid hyperplasia
inc megs

Question 23

What is the typical ET presentation?

Answer 23

Thrombosis (inc platelets)

Question 24

What do you worry about in myelodysplasia

Answer 24

Progression to acute leukemia

Question 25

Refractory cytopenia with unilineage dysplasia - presentation and morphology

Answer 25

Unexplained cytopenia in elderly Binucleated RBCs Hypercellular marrow

Question 26

Refractory anemia with Ring sideroblasts - how to Dx?

Answer 26

Morphology + iron stain results (looking for signs of overload)

Question 27

Refractory anemia w ring sideroblasts - presentation and morphology

Answer 27

Unexplained cytopenia in elderly Ring sideroblasts (nucleated RBCs with granules of iron accumulated in perinuclear mitochondria)

Question 28

Which myelodysplasias are at significant risk for progressing to acute leukemia?

Answer 28

Refractory cytopenia w multilineage dysplasia MDS with del(5q) Refractory anemia with excess blasts

Question 29

MDS with del(5q) - morphology, cytogenetics, presentation, prognosis, tx?

Answer 29

Severe anemia in elderly women Loss of large arm of 5 ALL megs are mononuclear Treat w/ lenalidomide

Question 30

Refractory cytopenia with multilineage dysplasia

Answer 30

Severe anemia 2+ lineages with dysplasia Abnormal granulocyte degranulation Abnormal nuclei lobulation

Question 31

Refractory anemia with excess blasts

Answer 31

Cytopenia with elderly patients RAEB-1: 5-9% blasts RAEB-2: 10-19% blasts Blasts and dyspoietic maturation CD34+ +/- CD117+

Question 32

How does refractory anemia with excess blasts differ from acute leukemia?

Answer 32

AML develops from blasts with translocations that halt differentiation Here, mutation results in clonal expansion, more like a true malignancy