Sesions 51-55
Terms
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- Neutropenia
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Increased neutrophil utilization
Differential: overwhelming bacterial/fungal infection, drugs, autoimmune, splenic sequestration - Lymphopenia DDX
- Congenital immunodeficiency, HIV, steroids, chemo, autoimmune, malnutrition, acute infection
- Neutrophilia
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Absolute neutrophil count >8000
Toxic granulation, vacuolization, Dohle bodies - Neutrophilia DDX
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Acute bacterial infection
Physiologic stress - Leukemoid Reaction
- extreme neutrophilia with immature granulocyte precursors (left shift) that simulates leukemia
- Leukoerythroblastosis
- Immature granuloctyes and nucleated RBC precursos in peripheral blood
- Leukoeryhtroblastosis DDX
-
Severe acute infection or bleeding
Infiltrate BM processes
Myeloproliferative syndromes (CML)
Extramedullary hematopoiesis - Lymphocytosis
- Absolute lymphocyte count >4000 (8000 in kids)
- Lymphocytosis DDX
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Chronic inflammation
Viral infection
Lymphoid neoplasms (CLL) - Monocytosis
- Absolute monocyte count >1000
- Monocytosis DDX
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Chronic infection/inflammation
Recovery from neutropenia
Myeloplastic/myeloproliferative overlap syndromes - Eosinophilia
- Absolute eosinophil count >500
- Eosinophilia DDX
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Allergic disorder
Drug effects
Parasitic infection
Skin disease
Myeloproliferative syndrome
Neoplasm - Basophilia
- Absolute basophil count >250
- Basophilia DDX
- Myeloproliferative syndrome (CML)
- Reactive Changes in Leukocytes
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Toxic granulation
Vacoulization
Dohle bodies
Acute bacterial ifnection
Neutrophilia - Syndromes due to morphologically abnormal WBCs
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Pelger-Huet anomaly
May-Hegglin anomaly
Alder-Reily syndrome
Chediak-Higashi syndrome - Translocation in CML
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Philadelphia chromsome t(9;22)
BCR/ABL gene fusion product - Abnormal enzyme in CML
- Leukocyte Alkaline Phosphatase is always decreased
- CML Peripheral Blood Findings
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Leukoerythocytosis
Leukocytosis with basophilia, eosinophilia
Normal or increased PLT count
Anemia
Myeloid hyperplasia
Myeloblasts <10%
Thrombocytopenia, thrombocytosis - Polycytehmia Vera Findings
-
NO philadelphia chromsome
Increased RBC mass
Increased Hg
Thrombocytosis and/or leukocytosis
Serum erythropoietin is normal or Low
Clonal proliferation of RBCs - Polycythemic Phase
- Increased RBC mass lead to thromboitc events, headaches, dizzines, splenomegaly, thrombocytosis, leukocytosis, increased Hg
- Spent Phase
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Reticulin fibrosis of marrow
Decreased RBC mass
Increased splenomegaly
Leukoerythroblastosis
Extramedullary hematopoiesis -
Essential Thrombocythemia
Clinical Manifestations -
Thrombotic Events
Paradoxical bleeding episodes -
Essential Thrombocythemia
Blood Findings -
Thrombocytosis
PLT > 600,000
Giant platelets
Increased WBC, no basophilia
Megakaryotic hyperplasia
Enlarged, mature megakaryocytes in clusters -
Chronic Idiopathic Myelofibrosis
Pathology - Clonal proliferation of primarily granulocytic and megakaryotic elements with prominent reactive myelofibrosis and extramedullary hematopoiesis
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CMF Pre Fibrotic Stage
Blood/BM Findings -
Blood: anemia with teardrop cells, thrombocytosis with large atypical platelets, mild to no leukoerythoblasts
BM: hypercellular, clusters of atypical megakaryocytes, granulocytic Left shift -
CMF Fibrotic Stage
Blood/BM Findings -
Blood: anemia with numerous teardrop cells, leukoerythroblastosis, variable WBC and PLT
BM: hypocellular with greatly increased reticulin and collagen fibrosis, prominent megakaryotic hyperplasia, osteosclerosis (new bone formation) -
CMF
Clinical Presentation -
Hepatosplenomegaly due to EMH
Severe anemia
Fatigue, dyspnea, weight loss, night sweats, fever, bleeding - Chronic Myelodysplastic Syndromes
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clonal stem cell diseases with ineffective hematopoiesis
-morphologically abnormal hematopoietic cells which do no migrate from well -
Chronic Myelodysplastic Syndromes
Hematologic Findings -
peripheral blood cytopenias
BM hypercellularity -
Chronic Myelodysplastic Syndromes
Clinical Presentation -
Idiopathic
Drug effects
Irradiation
Heavey metal intoxication
Viral infections
Megaloblastic anemias
Congenital dyserythropoietc anemia
Paroxysmal noctural hemoglobinuria - Dyserythropoiesis Morphology
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Irregular nuclear borders
Bi or multinucleated
Megabloblastic change/dyssynchrony
Ringed sideroblasts
Vaculoziation
PAS positivity - Dysgranulopoiesis Morphology
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Small cell size
Hypogranulation
Nuclear hypersegmentation
Hypolobation (pseudo Pelger-Huet cells)
Pseudo Chediak-Higashi granules - Dysmegakaryocytopoeisis Morphology
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Hypolobation
Multinucleation
Hypogranular platelets - ALIP
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Atypical localization of immature precursors
-clusters of myeloblasts and promyelocytes away from vascular structures
-most commonly in higher grade MDS - MDS
-
Low grade: refractory anemia with or without ringed sideroblasts
High grade: Refractory cytopenia with multilinage dysplasia, refractory anemia with excess blasts - Refractory Anemia
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-ineffective erythropoeisis
-unresponsive to iron, B12, folate
-dysplasia limited to dyserthropoeisis - Refractory Anemia with Ringed Sideroblasts
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15%+ erythroid precursors in BM are ringed sideroblasts
Dysplasia limited to dyserythropoiesis - Refractory Anemia with Excess Blasts
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Dysplasia in all 3 lineages
Auer rods - Refractory Cytopenia with Multilineage Dysplasia
- Bi or pancytopenia with dysplastic changes in BM celss of 2 or 3 lineages
- Myelodysplastic/myeloproliferative overlap diseases
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diseases with myelodysplastic features (abnormal dysplastic morphologic forms) but also myeloproliferative features (usually leukocytosis and/or splenomegaly)
No philadelphia chromosome
CMML-1 and CMML-2 - Acute Myeloid Leukemia
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not of lymphoid origin
granulocytic, monocytic, erythroid, megaloblastic - Causes of AML
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idiopathic
MDS, chronic myeloproliferative syndromes, ionizing radiation, cytotoxic drugs, benzene, viral infection, smoking - AML Peripheral Blood Findings
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20%+ BLASTS
Thrombocytopenia and/or anemia
WBC count variable, often high - AML BM Findings
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20%+ Blasts
Extremely hypercellular
Monomorphic blast population - AML Clinical Presentation
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Symptoms of BM failure
-easy bleeding/bruising (thrombocytopenia)
-fatigue, pallor (anemia)
-fever/infection (neutropenia) - AML Progonoses
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Poor: secondary to MDS, previous chemo, advanced age, high WBC count
Favorable: cytogenetic - Myeloblasts Markers
- CD13, CD33, myeloperoxidase
- Lymphoblasts Markers
- CD10, T and B Cell, TdT
- Auer Rods
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abnormal needle shaped myeloperoxidase crystals
-definitive evidence of myeloid (granulocytic) differentiation
-not present in AML - AML Subtypes with Auer Rods
- M1, M2, M3
- AML-M3
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Acute Promyelocytic Leukemia
Many Auer rods per cell
Younger patients
DIC
t(15;17)
Favorable long term prognosis - AML-M4
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Acute myelomonocytic leukemia (myelo and monoblasts)
Myeloblasts are positive for CD13 and myeloperoxidase (Auer rods)
Monoblasts are positive for CD14, CD65, non-specific esterase
inv(16)--> abnormal eosinophil precursors in BM
Favorable prognosis - AML-M6
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Myeloblasts >20%
Dysplastic eryhtroid precursors
More than half of BM cells
Ring-shaped perinuclear vaculoes
Profound anemia
Erythroid precursors in peripheral blood - AML-M7
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Acute megakaryocytic leukemia
CD41a
Platelet specific antibody against GP IIb/IIIa or vWF
Increased BM fibrosis
Down syndrome patients