Section 22: My Little Proliferative Neoplasms

Question 1

What is a Myeloproliferative Neoplasm

Answer 1

Clonal disorder of hematopoietic stem cell bc of genetic mutations
Reduced negative feedback systems (dysfunction of normal checks & balances
Excessive production of cells

Question 2

Common Characteristics of chronic MPNs

Answer 2

Panhyperplasia of BM
EM hematopoiesis
BM fibrosis
Overlapping disease symptoms/manifestations
Frequently terminate in acute leukemia
BM seen with increased megakaryocytes, often abnormal
Plt dysfunction

(These can all be to varying degrees)

Question 3

Define CML

Answer 3

Chronic Myeloid Leukemia

Question 4

General characteristics of CML

Answer 4

Ph-22 Chromosome (+)
Most common over 45 yrs of age
Eosinophilic and Basophilic variants of CML exist but are rare and aggressive

Question 5

Lab findings of CML

Answer 5

90% CML are Ph-22 (+)
WBC 50,000 - 800,000 (resembles BM)
Large number of mature and immature granulocytes (shift to the left)
Ph-22 causes premature cell release
May see Pseudo-Pelger-Huets
May see Psuedo-Gaucher cells
Anemia
Usually marked increase in Plts
Often increased basophils (>1-2% in PB)
Decreased LAP
Hypercellular BM, increased M:E ratio

Question 6

Characteristics of CML-AP

Answer 6

Accelerated Phase
Any of the following:
10-19% blasts in Blood or BM
Greater than or equal to 20% basophils in blood
High WBC unresponsive to treatment
Very high Plt unresponsive to treatment
Very low Plt not caused by treatment

Question 7

Characteristics of CML-BP

Answer 7

Blast Phase/Crisis
Eventual disease progression to acute leukemia
Requires blast “magic number”
Transforms to AML, often M2 but can also turn to ALL rarely
High WBC unresponsive to treatment
Very high Plt unresponsive to treatment
Very low Plt not caused by treatment

Question 8

Define CNL

Answer 8

Chronic Neutrophilic Leukemia
(w/ or w/o CSF3R gene mutation)

Question 9

Characteristics of CNL

Answer 9

Very high WBC w/ 80% or more PMNs or Bands
Hypercellular BM
Persistence of neutrophilic leukocytosis w/o left shift and w/ absence of sepsis
Can progress to AP or BP
Toxic granulation and Dohle bodies may be present
Extremely high LAP (350-400)
Slightly decreased Plt
Mild Anemia

Question 10

Define CMML

Answer 10

Chrmonic Myelomonocytic Leukemia
(Previously called CMoL)
Myeloproliferative (MPN) and Myelodysplastic (MDS) w/ overlapping features

Question 11

What mutation causes Philadephia-22 and what does the mutation result in?

Answer 11

Reiprocal translocation of long arm of 22 to long arm of 9 - t(9;22)
Results in BCR-ABL1 fusion gene (Ph-22)
Allows for production of ne protein that expresses increased tyrosine kinase activity
-Stimulates uncontrolled production of abnormal cells by BM and a loss of apoptotic functions

3% of pediatric ALL & 25% adult ALL are Ph-22 (+) or Ph-22-like

Question 12

Define PV

Answer 12

Polycythemia Vera

Question 13

Characteristics of PV

Answer 13

Malignant Increase in Red Cell Mass
JAK2 (+)
Decreased EPO
Hgb or Hct increase (M: >16.5 or >45%; F: >16.0 or >48%)
Hypercellular BM with malignant increase of erythro-, myelo-, and megakaryopoiesis
Increased granulocytes & Plts
Increased LAP
Increased aniso and poik w/ disease progression
Normal O2 Saturation
Hemostasis results can be thrown off bc of dilution factor required for some collection tubes

Question 14

PV in regards to Fe Deficiency

Answer 14

Iron deficiency can develop w/ disease progression
Leads to Plt hypofunction
Therapeutic Phelbotomy
Decreased RBC survival
Increased RBC production and Fe turnover
Iron deficiency is a desired effect bc of limiting factor
Portal vein thrombosis is classic symptom of PV

Question 15

Define Post- PV-MF

Answer 15

Post-PV-Myelofibrosis
Long term PV results in halmark teardrop cells due to increasing myelofibrosis
Signals the transition of PV to “spent phase” or post-polycythemic myeloid metaplasia

Question 16

Define Secondary Polycythemia

Answer 16

Polycythemia due to Hypoxia

Question 17

Characteristics of Secondary Polycythemia

Answer 17

Due to Hypoxia
Decreased O2
Increased EPO
Normal LAP
RBC mass increased due to Increased production by BM from normal processes

Question 18

Define Relative Erythrocytosis

Answer 18

Decreased Plasma Volume vs Normal RBC Mass
Increased Hct
Normal 02 Saturation
Normal LAP
Normal EPO

Question 19

Define ET

Answer 19

Essential Thrombocythemia

Question 20

Characteristics of ET

Answer 20

BM shows increased megakaryopoiesis and sl. increased granulopiesis
Plt count usually >600,000 (often greater than 1 million)
Spontaneous Plt aggregation & Plt fxn defects (thrombotic and hemorrhagic conditions)
30-50% have JAK2 gene mutation w/ EEC

Question 21

ET Blood Smear findings

Answer 21

Large masses of Plt aggregates
Giant and bizzare forms, small forms as well
Occ. Megakaryo fragment
Mild Normochromic, normocytic anemia (unless iron deficiency bc excessive bleeding)
Elevated WBC seen as Neutrophilia and occ. Increased Eos- and Basophils

Question 22

Define PMF

Answer 22

Primary Myelofibrosis

Question 23

General PMF Characteristics

Answer 23

Can be de novo or progression of PV or ET
Marrow fibrosis w/ increased megakaryocytes
Most are JAK2 or other mutation (+), allows for higher precursor cell count and subsequent fibrosis
Clonal cells stim release of fibroblastic growth factor
Dry Tap

Question 24

Early PMF Characteristics

Answer 24

Variety of possible WBC & Plt values
Immature granulocytes and psuedo-PH
Micromegakaryocytes
Plts may be abnormal
Pancytopenia w/ disease progression
Anemia w/ nrbcs, polychromasia, and bizarre shapes
Teardrop cells are hallmark of disease

Question 25

PMF Progression

Answer 25

Ineffective erythropoiesis and hemolysis
EM Hematopoiesis (more nrbcs and abnormal poik)
WBC and Plt decrease (immature granulocytes, megakaryo fragments, & microp-Plts

Question 26

Define CEL-NOS

Answer 26

Chronic Eosinophilic Leukemia - Not Otherwise Specified

Question 27

CEL-NOS Characteristics

Answer 27

Eosinophilia w/ no signs of outside or foreign stimuli (allergies, parasites, or other malignancies w/ eosinophilia)
Eosinophils infiltrate tissues and organs leading to organ dysfunction