Shared Flashcard Set


BM Stem Cell Disorder Pathology

Additional Accounting Flashcards




Name the cytopenia disorders
aplastic anemia, myelodysplastic syndrome, or other causes (include infection, DIC, hypersplenism, marrow toxins, nutritional, tumors)
Aplastic anemia: def, what happens to cells?, causes
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
• Myelodysplastic Syndrome (MDS) - definition, can progress from?, diagnosis, histological findings?
– 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
Name the chronic myeloproliferative disorders
• Chronic Myelogenous Leukemia (CML)
Chronic idiopathic myelofibrosis
Essential thrombocythemia
CMPD 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
Chronic myelogenous leukemia (CML) - what shift, basophilia?, chromosome, granulocytes?, accelerated phase vs. blast crisis
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
PV - def, dominance of what?, O2 saturation?, EPO levels, complications?, mutations?
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…
Chronic idiopathic myelofibrosis - what happens to cell growth?, smear shifts with what?, mutation?
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
Essential thrombocytosis - def, how is dx made?, what is abnormal?, platelets normal or abnormal?, complications?
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
• Acute Leukemia Criteria –
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.
• Acute Leukemia Lab Dx –
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
• Acute Lymphoblastic Leukemia (ALL) – def, prevalence, subtypes, chromosome, BM biopsy shows?, peripheral smear?
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
Acute myeloblastic leukemia (AML) - def, prevalance, what histo features?, subtyping?
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
Key Dx of Acute leukemias:
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
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