Intro to WBC disorders Flashcards
Monocytes, neutrophils, eosinophils, basophils all come from what type of blast?
Myeloblast
What three cell lines result from myeloid blasts?
Eyrthroid precursor, megakaryocyte, myeloblast
What areas are white blood cells distributed in?
Bone Marrow, Peripheral blood (granulocytes/monocytes/lymphocytes)
Lymph nodes, thymus, spleen, tonsils, adenoids, Peyer Patches
MALT–in lung and GI tract
Benign Leukocyte disorders are NOT neoplastic thus not:
Clonal
In benign leukocyte disorders, we see Qualitative and Quantitative disorders…
What types of quantitative disorders do we see?
Increased: cytoses
Decrease: cytopenias
Normal range for WBCs
4,000 to 10,000
Reference range for :
Neutrophils
Lymphocytes
Monocytes
Neutrophils = 1,500 – 6,000
Lymphocytes = 1,000 – 3,500
Monocytes = 100 – 600
Reference range for:
Eosinophils
Basophils
Eosinophils = 0 – 450
Basophils = 0 – 200
NOT leukemia (benign, exaggeratedresponse to infection)
Absolute leukocyte count > 50,000/mL
May involve neutrophils, lymphocytes oreosinophils
Leukemoid reaction
Three causes of leukemoid reactions?
Perforating appendicitis (neutrophils)
Whooping cough (lymphocytes)
Cutaneous larva migrans (eosinophils)
Describe leukoerythroblastic reaction
immature bone marrow cells in the PB d/t BM infiltrative disease (such as fibrosis or metestatic breast cancer) or from severe BM stress (such as sepsis or Growth factor)
What defines neutrophilia and when do we see it?
absolute neutrophil count > 7,000
seen in sterile inflammation with necrosis (acute MI)
Infection (like acute appendicitis)
Drugs (steroids or catecholamines, lithium)
What is the pathogeneis of neutrophilia?
Increased production and decreased margination
Define Neutropenia:
Etiology:
Pathogenesis
Absolute neutrophil count: <1,500
Etiology of neutropenia: chemo, aplastic anemia, immune destruction, septic shock
Pathogeneis of neutrophenia: decreased production, increased destruction/margination
Describe Eosinophilia:
Etiotology
Absoulte eosino count >700
Type I hypersensitivity (e.g., bronchialasthma, penicillin allergy, hay fever)
Invasive helminths (e.g., strongiloidiasis, hookworm)
Hypocortisolism (e.g., Addison’s disease)
Neoplasms (e.g., Hodgkin lymphoma)
Pathogenesis of eosinophilia
Increased produciton (induced by interleukins)
Increased tissue rectruitement by chemotactic factors
Describe Basophilia:
Etiology of Basophilia:
absoulte basophil count of >200
Chronic myelogenous leukemia or CML (and otherchronic myeloproliferative neoplasms)
Chronic kidney disease
Proliferation of neoplastic cells, primarily in BM and PB
Leukemia
Proliferation of neoplastic cells, primarily in LNs and extramedullary lymphoid tissue
Lymphoma
Myeloid neoplasms are neoplastic _______ disorders
stem cell
**can involve more then one cell lineage
What are the 4 key WHO classification criteria in Myeloid neoplasms?
Morphology
Immunophenotype
Genetic Features
Clinical features
What are the three types of myeloid neoplasms?
Myeloproliferative neoplasms (MPN)
Myelodysplastic syndromes (MDS)
Acute myeloid leukemia (AML)
What are the four myeloproliferative disorders we need to know?
Chronic myelogenous leukemia: BCR ABLpositive (CML)
Polycythemia vera (PV)
Primary myelofibrosis (PMF)
Essential thrombocythemia (ET)
Myeloproliferative neoplasms, General features:
______hematopoietic stem cell disorders
Proliferation of one or more of the follwing myeloid lineages:
Clonal hematopoeitic stem cell disorders
Lineages: Granulocytic/ Erythroid/ Megakaryocytic/ Mast cell
MPN is common in what decade?
How common?
MPN seen in 5th - 7th decade
Incidence: 6-10/100,000/year
MPN is:
Hyper or Hypocellular BM
with
effective or ineffective hematopoesis
Hypercellular BM with effective
hematopoiesis (increased PB counts =
cytoses) <= clonal abnormalities
increase cell proliferation
MDS is:
Hyper or Hypocellular BM
with
effective or inneffective hematopoesis
Hypercellular BM with ineffective
hematopoiesis (decreased PB counts =
cytopenias) <= clonal abnormalities
promote cell death
Chronic Myelogenous Leukemia (type of myloproliferative disease)
Epidemiology:
Pathogenesis:
peak at 40-60 years
Pathogenesis:
- Neoplastic expansion of the pluripotentialstem cell
- BCR-ABL fusion gene (produces protein with tyrosine kinase activity)
What 5 key clincal findings do we see in CML?
Hepatosplenomegaly, fatigue, weight loss, weakness, anorexia
Lab findings show Leukocytosis with immature myeloid cells, few myeloblasts (2-3%) and basophilia… what would we expect to find on FISH or RT-PCR?
BCR-ABL fusion gene~~ common in CML
expected lab findings for CML
Leukocytosis with immature myeloid cells
Few myeloblasts (2-3%)
Basophilia
Thrombocytosis (40-50% cases) or thrombocytopenia
Hypercellular BM (~100%) with granulocytic hyperplasia
Chromosome and gene responsible for CML
Philadeplphia Chromosome: t(9;22)
BCR-ABL fusion gene (FISH or RT-PCR)
What should a normal bone marrow core biopsy look like?
100-age rule
ex: if you are 30 yo you should have 70% cellularity and there should be adipocytes in there
What are the three stages seen in CML if left untreated?
Chronic phase~ 3 years
Accelerated phase~ 1 year
Blast phase = acute leukemia (meloid or lymphoblastic)
*all end up in blast phase if left untreated
What is the ideal type of treatement for CML?
BCR-ABL tyrosine kinase inhibitors
- Gleevec
- Dasatinib
- Nilotinib
*can’t cure CML but staying on this therapy you can see 95% event free survival
Pathogenesis:
Neoplastic expansion of the pluripotential
stem cell
Increase in RBCs, granulocytes and
platelets
Janus 2 kinase gene (JAK2) mutation in
virtually all cases
Polcythemia Vera
We see expansion of ___, _____ and _____ in polycythemia Vera
increase in RBC, granulocytic, and platelets
What mutation is present in virtually all cases of polycythemia vera?
Janus 2 kinase gene (JAK2)
–constitutional activation of JAK/STAT will cause activation of genes important in proliferation and survival~ in this case constant proliferation of red cells
PV – Clinical findings
Splenomegaly
Thrombotic events due to hyperviscosity (e.g. hepatic vein thrombosis)
Gout (increased uric acid due toincreased cell breakdown)
Signs of increased histamine (releasedfrom mast cells in the skin)
Ruddy face
Pruritus after bathing
Peptic ulcer disease
Your patient comes in with splenomegaly, is itchy after they bathe and was recently diagnosed with peptic ulcer disease. The Lab shows they ahve increased RBC mass. What would you suspect of their EPO and SaO2 levels
This is describing polycythemia vera
EPO is decreased
Normal oxygen saturation
In most polycythemias, there is an increase in EPO, why is polycythemia vera different?
In the other polycythemias, the increased EPO is driving the overproduciton of RBCs
In PV, it is the JAK/STAT2 mutation that is upregulating the transcription of RBCs, NOT the EPO
What are the major criteria for polycythemia vera?
Hemoglobin > 18.5 g/dL in men, 16.5 g/dL in
women or other evidence of increased RBC volume
Presence of JAK2 mutation
PV – Clinical course
Conservative treatment (e.g., phlebotomy); median survival of:
Most patients die of:
> 10 years
thrombosis or hemorrhage
In PV, 15-20% of pts evolve to what phase?
2-3% of PV pts develope what diseases?
evolved to ‘spent phase’
devo MDS or AML
Rapid development of BM fibrosis and extramedulary hematopoiesis (EMH) in the spleen, liver and lymph nodes
Primary myelofibrosis (PMF)
~ type of myeloproliferative neoplasm
What are the clinical findings seen in: Primary myelofibrosis (PMF)
Splenomegaly with portal hypertension
Splenic infarcts with left-sided pleural effusions
What mutation is found 50% of the time in PMF?
JAK2 seen in 50% cases
What do we see on a blood smear in a patient with Primary myelofibrosis?
BM fibrosis and clusters of atypical megakaryocytes
Peripheral blood leukocytosis (early stage)
Variable platelet count
Normochromic, normocytic anemia
*Teardrop cells
*Leukoerythroblastic reaction
Median Survival for PMF:
3-7 years in fibrotic stage
>10 years in early (prefibrotic) stage
5-30% of patients with PMF will develop:
AML
Major causes of morbidity and mortality in PMF:
BM failure (infection, hemorrhage)
Thromboembolic events
Portal hypertension
Cardiac failure
AML
Essential thrombocythemia (ET):
Neoplastic stem cell disorder with proliferation of__________
megakaryocytes
Platelet count in Essential throbmocythemia is:
> 450,000/mL
In this disease we see atypical platelet morphology
Mild neutrophilic leukocytosis
Hypercellular BM with abnormal megakaryocytes
Essential Thrombocytopenia
Describe what you see in Essential Thrombocythemia on HE
more platelets that are larger in size (they shouldn’t be larger then RBCs)
See large/giant, hypogranular platelets
Clinical findings of essential thrombocythemia
bleeding or throbmosis
splenomegaly
Jak2 mutation in 50% pts
Common mutation in ET pts?
Median survival:
Tx for ET
JAK2 in 50% pts
median survival: 12-15 years
Tx: alkylating agents or simular drugs to lower platelet count
