Term
| Name the cytopenia disorders |
|
Definition
| aplastic anemia, myelodysplastic syndrome, or other causes (include infection, DIC, hypersplenism, marrow toxins, nutritional, tumors) |
|
|
Term
| Aplastic anemia: def, what happens to cells?, causes |
|
Definition
caused by scarcity of hematopoietic stem cells in bone marrow
o Pancytopenia – most common symptom, due to lack of adequate blood cell production (nphils <500, platelets <20,000, retic < 50,000)
o Bone marrow hypocellularity – Dx of aplastic anemia, could be from radiation. Needs SC transplants…
o 1o Idiopathic AA – approximately half of cases
o 2o AA – due to drugs, radiation, marrow toxins |
|
|
Term
| • Myelodysplastic Syndrome (MDS) - definition, can progress from?, diagnosis, histological findings? |
|
Definition
– progenitor cells w/ abnormal differentiation (and thus function)
o Cytopenia – can have one, several, or all cell lineages down, depending on stage affected
o Acute Myelocytic Leukemia – MDS progression if myeloblasts spill into blood to level >20%
o Refractory anemia/cytopenia – different subtypes of MDS
o Diagnosis – made through lab smears, cytogenics, and exclusion of nutritional disorders:
Lab Dx – made thru blood & marrow smears dysplasia, high blasts
Cytogenetics – genotype to assess for clonality
Exclude folate/B12 deficiency – can mimic MDS
o Histological Findings – ringed sideroblasts, dysmorphic granulocytes/megakaryoctes/platelets
Dysmorphic erythroid precursors – nuclear irregularity, weird granularity
Ringed sideroblasts –blasts have trouble handling Fe accumulate in ring around cell
Dysmorphic granulocytes – hypogranular, hyposegmented nuclei
Dysmorphic megakaryocytes – two small nuclei (multinuclear = normal)
Dysmorphic platelets – giant, hypogranular |
|
|
Term
| Name the chronic myeloproliferative disorders |
|
Definition
• Chronic Myelogenous Leukemia (CML)
PV
Chronic idiopathic myelofibrosis
Essential thrombocythemia |
|
|
Term
|
Definition
involves progenitor cells with unregulated growth but normal differentiation (at least initially)
o Elevated peripheral counts – unlike MDS cytopenia, CMPD presents w/ elevated counts
o Distinguish CMPD from neutrophilia/leukemoid reaction, secondary polycythemia, reactive thrombocytosis
o No dysplasia – in most cases, dysplasia is not prominent
o Vs. Reactive proliferation – these occur on reactive basis; CMPD occurs on neoplastic basis
Leukemoid Reaction – elevated WBC count in response to physiologic stress/infection
• Toxic granulation – neutrophils will granulate in mounting active immune response
• Dohle bodies – very dark blue blotches stacks of RER (revved up to fight infection)
• Normal cytogenetics – no preponderance of a clonal progenitor cell
Secondary Polycythemia – hypoxic patient (smoker, high altitude) will generate more cells
Reactive thrombocytosis – more platelets due to surgery, infection, hyposplenism, or hemorrhage
Mimic CMPD – a reactive proliferation must be distinguished from a CMPD
o Vs. Acute leukemia – AL has very increased proportion of blasts, rapidly fatal if no Tx |
|
|
Term
| Chronic myelogenous leukemia (CML) - what shift, basophilia?, chromosome, granulocytes?, accelerated phase vs. blast crisis |
|
Definition
blood & bone marrow proliferation of myeloid cells
o Slight left shift – earlier lineages present in blood, but few blasts (mostly normal differentiation)
o Basophilia – unsure why, but high basophil count distinctive characteristic of CML
o “Philadelphia chromosome” – virtually all CMLs have this genetic marker (balanced translocation of part of 22 to 9) or BCR/ABL fusion
o Granulocyte dominance – CMLs affect multipotent stem cells, but granulocyte lineage dominant
o Accelerated Phase – if blasts in blood are 10-19%
o Blast Crisis – if over 20% blasts in blood; 2/3 myeloid, 1/3 lymphoid multipotent stem cells |
|
|
Term
| PV - def, dominance of what?, O2 saturation?, EPO levels, complications?, mutations? |
|
Definition
bone marrow disease producing primarily excess RBCs (also WBCs/platelets)
o Erythroid dominance – although affecting multipotent stem cells, erythroid lineage dominates
o Normal O2 saturation – unlike 2o polycythemia reactive proliferation caused by hypoxia
o Decreased EPO – low erythropoietin level due to feedback, unlike 2o polycthemia (elevated EPO from hypoxia)
o Thrombotic/hemorrhagic complications – due to increased viscosity & platelet dysfunction
o JAK2/V617F – mutated in nearly all cases; late phase nearly indistinguishable from… |
|
|
Term
| Chronic idiopathic myelofibrosis - what happens to cell growth?, smear shifts with what?, mutation? |
|
Definition
disorder of displaced proliferation (bone marrow hypocellular)
o Displaced proliferation – spleen and liver take over hematopoiesis processes (“extramedullary”)
o Bone marrow – progressively hypocellular & fibrotic
o Bone thickening – abnormally thickened bony trabeculae
o Splenomegaly – gross enlargment due to hematopoiesis in liver and spleen
o Leukoerythroblastic peripheral blood smear – left shifted blood smear with:
Teardrop erythrocytes – from having to migrate through liver & splenic sinuses
Myeloblasts – from left-shift, lack of marrow maturation environment
o JAK2/V617F – mutated in about 50% of cases |
|
|
Term
| Essential thrombocytosis - def, how is dx made?, what is abnormal?, platelets normal or abnormal?, complications? |
|
Definition
sustained platelet count > 4.5 X10^9/L
o Exclusion Diagnosis – must exclude other CMPDs:
Not reactive thrombocytosis – no infection, Fe deficiency, malignancy, or splenectomy
No RBC mass – unlike polycthemia vera
No “Philadelphia Chromosome” – not a CML
No marrow fibrosis – unlike chronic idiopathic myelofibrosis
JAK2/V617F – mutated in 50% of cases but if detected then only need count >450k to diagnose
o Abnormal megakaryocytes – numerous abnormal megakaryocytes in bone marrow
o Dysfunctional platelets – numerous platelets are morphologically bizarre & dysfunctional
o Thrombosis/hemorrhage – due to large numbers of dysfunctional platelets |
|
|
Term
| • Acute Leukemia Criteria – |
|
Definition
blast content of blood must be >20%
o Bone marrow – largely replaced with blast forms that remain undifferentiated
o Elevated WBC – leukemic blasts in the blood may cause this
o Leukemic infiltration – leukemic cells may infiltrate liver, spleen, lymph nodes, skin, etc. |
|
|
Term
| • Acute Leukemia Lab Dx – |
|
Definition
based on CBC differential, bone marrow & blood smears
o CBC – can show anemia, neutropenia, thrombocytopenia from blast forms only, few mature cells
o Lymphocytic/Myelogenous – use cytochemistry, flow cytometry, cytogenetics to subclassify
Myeloperoxidase – evidence of granulocytic differentiation
Non-specific esterase – evidence of monocytic differentiation
o Hemorhage/thrombosis – can also be caused by acute leukemia |
|
|
Term
| • Acute Lymphoblastic Leukemia (ALL) – def, prevalence, subtypes, chromosome, BM biopsy shows?, peripheral smear? |
|
Definition
leukemia of lymphoblasts (>20%)
o Children Prevalence – ALL much more common in children than adults (think hi lymphocytes)
o B/T subtypes – can assess B/T lineages thru flow cytometry; may have prognostic significance
o Philadelphia chromosome – has bad prognosis if cytogenetics confirms this
o Bone marrow biopsy – shows montonous accumulation of all blasts
o Peripheral smear – will show blasts in smear |
|
|
Term
| Acute myeloblastic leukemia (AML) - def, prevalance, what histo features?, subtyping? |
|
Definition
leukemia of myeloblasts (>20%)
o Adult Prevalence – AML much more common in adults (think lower lymphocytes)
o Azurophilic cytoplasmic granules – myeloblasts have these, unlike lymphoblasts
o QUIZ: Auer rods – crystalline structure in cytoplasm formed by myeloperoxidase Dx AML
o Subtyping – several subtypes of AML, with prognostic/therapeutic significance
M3-acute promyelocyte leukemia – will see multiple Auer rods, heavy granulation of promyelocytes, risk of DIC, Tx retinoic acid, Ch 15-17 translocate |
|
|
Term
| Key Dx of Acute leukemias: |
|
Definition
1) Smear morphology & cytochemistry – accurate classification of majority of acute leukemias
• Myeloperoxidase granulocytic differentiation
• Nonspecific esterase monocytic differentiation
2) Immunophenotyping (flow cytometry) – confirms Dx of ALL; may be needed in some AMLs
3) Cytogenetics/molecular genetics – important supplemental prognostic & Dx information |
|
|
