Cancer stuffs - MPNs and MDS Flashcards
MDS
Neoplastic clonal population from STEM CELLS → take over marrow → failure to make normal cells in 1/m lineages → ineffective hematopoiesis → AML risk
MPNs
Neoplastic clonal population from NORMAL cells → take over marrow (Hypercellular marrow) → make too many normal cells in 1/m lineages → splenomegaly and/or hepatomegaly →
can escalate to marrow fibrosis → BM failure → MDS or AML
Is MDS or MPNs due to persistant cytopenias in 1/m lineages?
MDS
Marrow findings of MDS
- Dysplasia:
- dyserythropoiesis
- dysgranulopoiesis
- dysmegakaryopoiesis - ringed sideroblasts
- bi-lobed PMNs : pseudo-pelger huet cells
- small megakaryocytes
Types of MDS
- Primary/idiopathic
2. Secondary/ Therapy related
Types of MPNs
- Chronic Myelogenous leukemias (CML)
- Polycythemia Vera
- Primary Myelofibrosis (PMF)
- Essential Thrombocytopenia (ET)
Onset of Primary vs Secondary MDS
primary: insidious
secondary: 2-8 yr latency
Cytogenic abnormality of primary/idiopathic MDS
- Monosomy 5 or 7
- del 7q or 5q
- trisomy 8
MDS vs MPNs Pt population target
MDS: >50, median: 70
MPNs: 40-60yrs
Neoplastic causes of secondary (T-MDS)
whole/partial del ch 5 or 7
in conjunction w/ use of alkylating agents and ionizing radiation
Non-neoplastic causes of secondary (T-MDS)
- chemo drugs
- Vit Def.
- Viral infection
- toxin/heavy metals
Low grade MDS
Myeloblasts <5% of marrow cells
- RC-UD
- RC-MD
High grade MDS
Myeloblasts >5
and/or >2% of peripheral blood cells
(CML of MPNs have >20% blasts)
Types of low grade MDS and prognosis
- Refractory Cytopenia with Unilineage Dysplasia (RC-UD)
- good prognosis - Refractory Cytopenia with Multilineage Dysplasia (RC-MD)
- worse prognosis
Types of high grade MDS and prognosis
- Refractory Anemia with Excess Blasts-1 (RAEB-1)
- dismal prognosis - Refractory Anemia with Excess Blasts-2 (RAEB-2)
- very dismal prognosis
Chromosomal abnormalities of:
CML
BCR-ABL t(9;22) p(210)
Chromosomal abnormalities of:
Polycythemia Vera
Jak2
- V617 point mutation
Chromosomal abnormalities of: Primary myelofibrosis (PMF)
Jak2 in 50%
or CALR or MPL
Chromosomal abnormalities of: Essential thromocytopenia (ET)
Jak2 in 50%
or CALR or MPL
Prognosis of:
- Polycythemia Vera
- Primary Myelofibrosis (PMF)
- Essential Thrombocytopenia (ET)
Polycythemia Vera - Good (10-20 yrs) Primary Myelofibrosis (PMF) - poor (~5 yrs) Essential Thrombocytopenia (ET) - Good (10-15 yrs)
Stages/phases of:
CML
Initial phase
(accelerated phase)
Blast phase
Stages/phases of:
PV
Polycythemic stage
Spent phase
Stages/phases of:
PMF
Prefibrotic stage
Fibrotic stage
Observations in CML:
- Initial phase
- Blast phase
Initial phase: (Hypercellular bone marrow): - ↑neutrophils (neutrophilia) - ↑ basophils - ↑platelets - Small megakaryocytes (w round, non lobulated nuclei)
Blast phase:
- > 20% blasts in marrow/blood
Can progress to AML
Observations in PV:
- Polycythemic stage
- Spent phase
Polycythemic stage
- ↑ cell count (hypercellularity)
- trilineage hyperplasia (erythrocytosis, neutrophilia, thrombocytosis)
Spent phase
- ↓ cell count
- marrow fibrosis
- Large macrophages
Observations in PMF:
- Prefibrotic stage
- Fibrotic stage
Prefibrotic stage (hypercellular marrow) - ↑neutrophils (neutrophilia) (no ↑ basophils) - ↑platelets - Large megakaryocytes (bizarre)
Fibrotic stage
- reticulin fibrosis of marrow
- dacrocytes
- extramedullary hematopoiesis
- leukoerythroblastosis
histo findings in ET
- normocellular
- Thrombocytosis (↑platelets)
- Large megakaryocytes (bizzare)
Symptoms of CML
- Splenomegaly
- Fatigue
- Anemia
- Weight loss
- Night Sweats
Symptoms of PV
- Hepato/splenomegaly
- Headaches
- dizziness
- Visual problems
- Paresthesia
- Plethora (redness)
- Itching
Symptoms of ET
- No splenomegaly
- Usually asymptomatic (Usu diagnosed from - ↑platelets)
- transient ischemic attack
Which of the MPNs is at risk for thrombosis? Of which arteries? how do you treat it?
Polycythemia Vera
- Portal
- Mesenteric
- Splenic
–> treat w/ serial phlebotomy
