Section 22: My Little Proliferative Neoplasms Flashcards
What is a Myeloproliferative Neoplasm
Clonal disorder of hematopoietic stem cell bc of genetic mutations
Reduced negative feedback systems (dysfunction of normal checks & balances
Excessive production of cells
Common Characteristics of chronic MPNs
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)
Define CML
Chronic Myeloid Leukemia
General characteristics of CML
Ph-22 Chromosome (+)
Most common over 45 yrs of age
Eosinophilic and Basophilic variants of CML exist but are rare and aggressive
Lab findings of CML
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
Characteristics of CML-AP
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
Characteristics of CML-BP
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
Define CNL
Chronic Neutrophilic Leukemia
(w/ or w/o CSF3R gene mutation)
Characteristics of CNL
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
Define CMML
Chrmonic Myelomonocytic Leukemia
(Previously called CMoL)
Myeloproliferative (MPN) and Myelodysplastic (MDS) w/ overlapping features
What mutation causes Philadephia-22 and what does the mutation result in?
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
Define PV
Polycythemia Vera
Characteristics of PV
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
PV in regards to Fe Deficiency
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
Define Post- PV-MF
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
Define Secondary Polycythemia
Polycythemia due to Hypoxia
Characteristics of Secondary Polycythemia
Due to Hypoxia
Decreased O2
Increased EPO
Normal LAP
RBC mass increased due to Increased production by BM from normal processes
Define Relative Erythrocytosis
Decreased Plasma Volume vs Normal RBC Mass
Increased Hct
Normal 02 Saturation
Normal LAP
Normal EPO
Define ET
Essential Thrombocythemia
Characteristics of ET
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
ET Blood Smear findings
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
Define PMF
Primary Myelofibrosis
General PMF Characteristics
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
Early PMF Characteristics
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
PMF Progression
Ineffective erythropoiesis and hemolysis
EM Hematopoiesis (more nrbcs and abnormal poik)
WBC and Plt decrease (immature granulocytes, megakaryo fragments, & microp-Plts
Define CEL-NOS
Chronic Eosinophilic Leukemia - Not Otherwise Specified
CEL-NOS Characteristics
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
