Reactive and Neoplastic Myeloid Processes CC Flashcards
In order to make a diagnosis of acute leukemia, how many blasts (at a minimum) would you have to see in a peripheral blood (or bone marrow) smear?
20%
What is the dominant cell on this slide?
Neutrophils
In steptococcall tonsilitis, what is the dominant cell we expect to see?
What about in INfectious mono or whooping cough?
What about cutaneous larva migrans?
strep we expect to see neutrophils
In whooping cough or mono = lymphocytosis
cutaenous larva migrans = eosinophils
What test do we order to confirm strep?
for mono?
Throat culture for strep
monospot for mono
What do the following lab tests dx or confirm?
JAK2 mutational analysis
Cytogenetics for Philidelphia chromosome
Flow cytometry for TdT+ cells
JAK2 mutational analysis = neoplastic condidions
Cytogenetics for Philidelphia chromosome = CML
Flow cytometry for TdT+ cells= ALL
What is the significance of
“toxic change” in the peripheral blood
neutrophils?
Indicates the presence of primary granules
What is the difference between primary and secondary granules?
Primary granules = purple and seein in BM or in mature neutrophils in reactive conditions
Secondary granules are more pink and are the mature form
When do we see Auer rods?
In AML
The patient is a 60-year-old lady with a past medical history significant for hypertension.
Her labs show these concerns:
WBC: 122,000 (normal 4-10,000)
Plates = 550,000 (nomral is 160-370,000)
Neutros = 86,000 (normal is 1,800 to 7,700)
Baso = 1,220 (normal is 0-80)
Negative for infection/medications/ last CBC with normal spleen and lymph nodes; what does this indicate?
Chronic myelogenous leukemia
We see hyper/hyocellular BM and
effective or ineffective hematopoesis in CML
CML
. Hypercellular bone marrow
with effective hematopoiesis
What is the differnce between effective and ineffective hematopoiesis?
efficetive is if precursors are being made in the BM and being released to periphery~ you would see elevated counts, this does not mean cells released are mature
Ineffecitve is when the cells are not released to the periphery thus we will see cytopenias
Leukocytes positive for the
Philadelphia chromosome are often indicitive of
Chronic myelogenous leukemia; 9:22 translocation that leads to constituitively active JAK/STAT path
What is the functional defect that is associated with the product of the BCR-ABL
fusion gene?
A constitutively activated tyrosine kinase
Clonal myeloproliferative disorder of pluripotent
stem cells
•____ proliferation, _____apoptosis
Increased proliferation
decreased apoptosis
CML Hallmarks
– Cytogenetic:
– Molecular:
Ph-chromosome
BCR/ABL
Boring statistics on CML
7% to 15% of adult leukemias
• Incidence 1.5/105; prevalence 5/105
• 2009 statistics: 5050 new patients, 470 deaths
• Etiology: Irradiation in <5%
Unknown in 95%
What are the three phases in CML?
Chronic phases = Ph+ and pts live 3-5 years
Accelerated Phase= cytogenetic changes w/ increasing blasts; live 12-24 mo
Blast phase = increase blasts; live 3-6 months
What type of therapy is recommended for patient with CML?
A tryosine kinase inhibitor like Imatinib
What are the tryosine kinase inhibitors used to tx CML?
Imatinib
Oral = Dasatinib, Nilotinib, bsutinib, Ponatinib
If a pt is controlling their CML with a tryosine kinase inhibitor and decides to go off it, what will most likely occur?
. The patient will likely progress
to acute leukemia
68 yo male comes in with history of abdominal pain;
An upper intestinal endoscopy reveals peptic ulcer disease and an abdominal ultrasound demonstrates hepatic vein thrombosis and splenomegaly.
• A JAK2 mutational analysis is homozygous for
the V617F mutation.
we expect to see decreased or increased EPO?
DECREASED erythropoietin
**patient has polycythemia vera
The patient is a 22-year-old man who presented to his PCP with weakness and now has blood oozing from his nose and mouth.
• On physical examination, he shows petechiae and ecchymoses over most of his body.
• Laboratory studies show a WBC count of 50,000/mL (reference range: 4,000-10,000/mL), and increases in D-dimers, prothrombin time, and partial thromboplastin time, consistent with disseminated intravascular coagulation (DIC).
HE has bilobed nuclie, chromatin dispersed w/ prominent granules and lots of Auer rods. Dx?
Acute myeloid leukemia
What cytogenetic abnormality is most
likely associated with the type of AML in our 22 yo pt?
choices are:
t(8;21)
inv(16)
t(15;17)
t(9;11)
t15;17
***this is APL and you see auer rods, DIC and is an emergecy
What is the functional defect that is associated with the product of the PML-RARa
fusion gene?
A block in terminal differentiationdue to retinoic acid receptor disruption
What tx would you recommend to patient with a t(15;17) cytogenetic abnormality?
This is APL
Tx is All-trans retinoic acid (ATRA)
What cytogenetic / molecular abnormalities have a similar prognostic significance to t(15;17), in a patient with AML?
t (8;21): AML1/ETO
inv(16): CBF/ MYH11
76-year-old woman presenting with
weakness and pancytopenia.
• A bone marrow examination shows a
hypercellular bone marrow with frequent
hypogranular and hypolobated neutrophils,
and small, hypolobated megakaryocytes.
What is the most likely diagnosis based on these findings?
Myelodysplastic syndrome
- Which is the most important diagnostic
criterion in differentiating a myelodysplastic syndrome
from an acute myeloid leukemia with myelodysplasiaassociated
changes a patient?
The bone marrow blast percentage
- A karyotype is performed and shows
abnormal findings. What cytogenetic abnormality
is most likely to be found in this patient that was dx with myelodysplastic syndrome?
Monosomy 7
What kind of therapy is recommended for patients with myelodysplastic syndrome?
A hypomethylating agent, Lenalidomide, Histone Deacetylase inhibitors
you can delier stem cell transplant but IG these patients are older and would have a hard time undergoing transplant
Why do hypOmethlyating agents work for patients with MDS?
MDS is HYPERmethlyated DNA thus there is less gene expression because methylation silences gene expression
hypOmethlyation will remove the methly groups from the DNA thus we have gene expression
50% will respond and this lasts 12-18 months
50 year old male c/o fatigue
• CBC-D:
– Hb:9 MCV: 100
– Plt: 30,000
– WBC: 80,000 Blasts: 60,000 (60,000/80,000 = 75% blasts!)
• Normal fibrinogen
Flow cytometry shows; CD13 +, CD33 +, HLA-DR +, CD34 +, CD117 +, MPO +
DX?
Acute myeloid leukemia
(90% pt we don’t know why they get this, 10% had prior chemo)
What is the prognosis for AML based on?
age and cytogenetics
What are the “Good” cytogeneti associations for AML?
t(8;21),
t(15,17),
inv(16),
or with FAB type M3 (28%)
What are the ‘poor’ cyotogenetic abnormalities associated with AML?
Any patient with adverse karyotypic abnormalities, i.e. -5, -7,
del(5q), abn(3q), complex, or with resistant disease, i.e. >15%
blasts in the bone marrow performed after course 1 In the
absence of favourable karyotypic abnormalities and not FAB
type M3 (20%)
What is the recommended Therapy for AML?
7 + 3
Ara-C + Daunorubicin for induction
Then HIDAC or Ara-C for Consolidation
60 year old gentlemen
• c/o fatigue and night sweats. On exam; fatigue cachexia, bone pain and night sweats
• Labs: Hemoglobin 11 gm/dl
• Exam: Spleen palpable 4 cm at MCL
• Labs: Otherwise unremrkable
Below is his blood smear
DX?
Primary myelofibrosis
What lab finding would confirm a PMF diagnosis?
JAK2 mutational analysis or JAK2 V617F (seen in 50% of cases)
= constantaly on!
How often is the JAK2 mutation seen in :
Polycythemia vera?
Essential thrombocythemia?
Primary meylofibrosis?
Polycythemia vera? 100%
Essential thrombocythemia? 50%
Primary meylofibrosis? 50%
What is staging like for Myelofibrosis?
based on Age, hemoglobbin levels, size of spleen and B symptoms
If you have all 4 = 2 year survival
If you ahve none = 9 year survival
How do you stage MDS?
There are 4 groups and are based on % blasts adn number of cytopenias and chromosomes
Low has 10 year survival
Intermediate 1 and 2 are inbetween
High = 3 month survival
How do you stage AML?
Good: 60-70% survival
Intermediate: 40-50% survival
Poor cytogenetics= 10-20%
