WBC & LN: Part 4: MDS and Myeloproliferative Disorders Flashcards
what is Myelodysplastic Syndrome?
it has an increased risk for what?
it usually presents how?
group of ‘clonal stem cell’ disorders characterized by maturation defects associated with ineffective hematopoiesis
increased risk of cytopenias, and transformation to acute myelogenous leukemia (AML)
presents as peripheral blood cytopenias (fall in total counts) as a result of exaggerated apoptosis of marrow precursor cells
On what part of the population does MDS afect?
what may cause it?
older age group (exception: following chemotherapy/associated with Down’s Syndrome)
causes
- Chemicals: benzene, alkylating agents
- radiation
what are the 2 types of MDS?
what is the pathogenesis of MDS?
- Idiopathic Primary MDS
- Therapy related MDS (t-MDS)
- ineffective hematopoiesis
- possibly due to stem cell damage
what can be expected in a lab report of a patient with MDS?
Peripheral Blood smear will show what?
pancytopenia, neutropenia, thrombocytopenia
Peripheral Blood Smear = hypogranular granulocytes, pseudo Pelger-Huet cells
what is this?
MDS: peripheral blood smear showing ‘bilobed’ (pseudo Pelger Huet) neutrophils
What can we find out by looking at a Bone Marrow with Myelodysplastic Syndrome?
how much myeloblasts will be seen in the bone marrow?
- dysplastic maturation affecting all non lymphoid lineage: erythroid, granulocytic, monocytic, megakaryocyctic
- Erythroid series: ringed sideroblasts, megaloblastoid cells
- Myeloid series: pseudo Pelger-Huet cells; neutrophils with 2 nuclear lobes
- Megakaryocyte: pawn ball megakaryocytes (single nuclear lobes)
- myeloblasts less than 20% in bone marrow
what is this?
MDS: bone marrow showing ‘pawn ball’ megakaryocytes
What age group will myelodysplastic syndrome affect?
what will be the clinical presentation?
what can MDS progress into?
what is the prognosis for MDS?
- older age group (> 60 years)
- weakness, infections, hemorrhages
- progression to AML in 10 to 40%
- t- MDS has very poor prognosis
what is this?
What disease is it related to?
ringed sideroblasts
MDS
what is this?
What disease is it related to?
pseudo Pelger-Huet cells
MDS
what is this?
What disease is it related to?
Pawn ball megakaryocyte
MDS
Myeloproliferative disorders
what characterizes myeloproliferative disorders?
how do you classify MPD?
what are the common features we can expect to see in MPD?
- neoplastic cell proliferation associated with cell maturation involving all cell lines
- classified on the predominant cell type affected
- association with JAK-2 mutation
- increased cell turnover (exception ET)
- marrow fibrosis (exception ET)
- transformation to acute leukemias, mostly AML, but some end with ALL (transformation to acute leukemia not seen with ET)
Myeloproliferative Disorders
what are the 4 types of MPD?
- Chronic Myeloid Leukemia (CML)
- Polycythemia vera
- Essential thrombocytosis
- Primary myelofibrosis
Chronic Myeloid Leukemia
who does it affect?
what is the Pathophysiology involved?
- adults between 25 to 60 yrs
- presence of a distinctive molecular abnormality
translocation involving ABL gene on chromosome 9 and BCR gene on chromosome 22 (philadelphia ch.)
activates multiple downstream pathways: RAS, JAK/STAT, AKT
Labs for Chronic Myeloid Leukemia
total WBC?
Platelet count?
what can be seen in the Peripheral Blood Smear?
Bone Marrow?
Biochemistry?
Molecular Diagnosis?
total WBC = more than 100, 000
Platelet count = increased first, later thrombocytopenia
Peripheral Blood Smear = moderate anemia, most cells present are:
myelocytes, metamyelocytes, band forms, eosinophils and basophils
Bone Marrow =
- marked hypercellularity
- myeloid and megakaryocytic lineage
- eosinophils and basophils are increased
- myeloblasts are less than 5% (increase over 10% signifies onset of accelerated phase)
- later stages show collagen proliferation
Biochemistry =
- hyperuricemia
- LAP score is low
Molecular Diagnosis = Philadelphia chromosome (95%)
what is seen here?
Chronic Myeloid Leukemia
Note: numerous granulocytes; mature neutrophils seen, and numerous platelets
what disease is this?
what can be seen in this bone marrow aspiration?
CML
increase in myeloid elements including basophils and eosinophils.
What are the clinical signs of CML?
during what stage do we see enlarged spleen?
- massive splenomegaly
- rapidly increasing percentage of blasts (myeloblasts)
- anemia, thrombocytopenia, basophilia
enlarged spleen is seen during the blast crisis or accelerated phase.
Myeloblasts in blast crisis or accelerated phase lack what?
What is used to treat CML? what does it do?
Auer rods
Imatinib mesylate; blocks the effects of the BCR-ABL fusion product
on who does polycythemia vera happen?
what is a cause that leads to polycythemia vera?
Reactive Polycythemia vera is associated with what? What are the clinical findings?
Ectopic Polycythemia vera is associated with what? what are the clinical findings?
what is seen in a lab report for Polycythemia Vera?
adults
neoplasm arising in a multipotent myeloid stem cell
lung diseases; Sa O2 is low, and EPO is high
paraneoplastic syndromes like renal cell carcinoma; SaO2 is normal, EPO is high
SaO2 is normal, and EPO is decreased
what characterizes polycythemia vera?
what is the pathogenesis of polycythemia vera?
characterized by increased marrow production of: erythroid, granulocytic and megakaryocytic elements
- erythroid proliferation not regulated by erythropoietin due to decreased erythropoietin levels; the little EPO present drives red cell expansion as erythrocytes are sensitive to erythropoietin
- JAK2 mutation in chromosome 9
- gets activated and causes proliferation
what can be expected for the following values during polycythemia vera?
RBC count?
Hb?
Hematocrit?
WBC?
platelets?
bone marrow?
peripheral blood smear?
biochemical?
RBC count = increased
Hb = increased
Hematocrit = increased
WBC = leukocytosis
platelets = increased (thrombocytopenia)
bone marrow = hypercellular (late stage = fibrosis)
peripheral blood smear = increased basophils & large platelets
biochemical = hyperuricemia
why do most clinical features in polycythemia vera happen?
what are the clinical features of polycythemia vera?
- mostly due to expanded total blood volume and slowing of blood flow due to increased viscosity
C/F:
- headache, dizziness, tinnitus, visual disturbances
- “ruddy” color of skin, especially face
- DVT, infarcts, and bleeding (increased red cell mass, and abnormal platelet function)
- transient ischemic attack, stroke, pulmonary thrombo-embolism, Budd-Chiari syndrome
- pruritus (release of histamine from mast cells/basophils), ‘aquagenic pruritus’
- peptic ulceration (histamine release)
- hyperuricemia (gout)
what is a complication of polycythemia vera?
myelofibrosis, acute leukemia
what is primary myelofibrosis?
what is its pathogenesis?
a disease of adults (over 60 years), presenting with anemia, bone marrow fibrosis and splenomegaly
pathogenesis:
- extensive deposition of collagen (cause of fibrosis)
- fibrogenic cytokines (factors): PDGF and TGF-β
released from neoplastic megakaryocytes
- JAK-2 mutation
- extramedullary hematopoiesis (spleen and liver)
what can we expect for these values in primary myelofibrosis:
Hemoglobin?
WBC count?
Peripheral blood smear?
Bone Marrow?
Biochemistry?
Hemoglobin = reduced
WBC count = elevated in early stage
Peripheral blood smear = normocytic normochromic anemia and tear drop’ rbc (dacrocytes) + leukoerythroblastic reaction
Bone Marrow = early: hypercellular; later: hypocellular
Biochemistry = hyperuricemia
what disease is this?
what are the cells in the bottom?
what is the cell on the right?
primary myelofibrosis
tear drop cells RBC
nucelated RBC
what is this?
fibrosis in the bone marrow
Essential Thrombocytosis
how common is it, among the myeloproliferative disorders?
what is essential thrombocytosis?
it is associated with what complications?
what is the pathogenesis of this condition?
what differs essential thrombocytosis from polycythemia or marrow fibrosis?
uncommon
is a clonal hematopoietic stem cell disorder characterized by an isolated thrombocytosis and
associated with thrombotic and hemorrhagic complications
pathogenesis:
- JAK2 mutation
- leads to proliferation of platelets
no evidence of polycythemia, nor marrow fibrosis seen in ET
what can we expect for these values for essential thrombocytosis:
total WBC
total platelet count
peripheral smear
bone marrow
bleeding time
platelet defect
total WBC = elevated
total platelet count = elevated
peripheral smear = anemia, basophilia, leukocytosis, thrombocytosis (increased number), platelets are larger
bone marrow = increased cellularity, megakaryocytic hyperplasia
bleeding time = may be abnormal
platelet defect = present
what can be seen in this peripheral smear?
In what disease do we see this?
platelets increased
seen in essential thrombocytosis
what are the clinical features for essential thrombocytosis?
what can induce the symptoms?
- deep vein thrombosis, portal and hepatic vein thrombosis
- myocardial infarction
- tendency to bleed, GI bleed
- splenomegaly
- Erythromyalgia ( intense burning or throbbing pain of hand and feet)
****associated with warmth, duskiness, and mottled erythemia
—— induced by exercise ——
