MDS and AML Flashcards
Cytopenias, dysplasia (one or more
myeloid cell lineages), ineffective
hematopoiesis, and increased risk of
development of AML
Myelodysplastic syndromes
Myelodysplastic syndromes are what kind of disorders?
Clonal hematopoietic stem cell disorders
Myelodysplastic Syndromes
Enhanced degree of apoptosis contributes to_________
Myeloblasts :
cytopenias
Myeloblasts < 20% (PB or BM)
What chromosomal abnormalities do we see in myelodysplastic syndromes in 50% of the cases
-5 or del5q, +8, -7 or del7q
What lab findings do we see associated with MDS?
Cytopenias (uni-, bi-, or pancytopenia)
Leukoerythroblastic reaction
Dysplastic features
Hypercellular BM
Ring sideroblasts
Increased myeloblasts
What do we see on a blood smear in a patient with MDS?
Hypolobulated and hypogranular neutrophils
GIANT platelets and large hypogranular platelets
What do we see on bone marrow aspirate in a patient with Myleodysplastic syndrome
dysplastic megakaryocyte (in picture)
dysplastic erythroid precursors
Ring sideroblasts are seen in what disease?
Myleodysplastic syndrome
(seen in other conditions as well, so you need to pair this with lab findings and clincal story)
what is wrong in this G banding and what disease is it characteristic of?
Monosomy 7
Seen in MDS
How do patients with MDS usually present and what age group?
Weaknes, infections, hemorrhage or asymptomatic
In the elderly (50s-80s)
In MDS, what is the median survival?
9-29 months
t-MDS is only 4-8 months
What do we worry that MDS will progress to?
What do MDS patients usually die of?
Progress to AML in 30% of the cases
Mortality often due to: infection or bleeding as a result of the cytopenias
Therapy for MDS (Three different categories)
Supportive: blood products, antibiotics, GFs
Hypomethylating agents: not curative
-Decitabine or Azacitidine
Allogenic stem cell transplant
Define Acute leukemia
Neoplastic proliferation of immature
cells (blasts) recapitulating progenitor
cells of the hematopoietic system
(AML or ALL)
What is the difference between Acute and Chronic leukemias
Acute = weeks to months with IMMATURE cells
Chronic = months to years with MATURE cells
How common is accute myleodysplatic leukemia and what population do we see it in?
3/100,000 per year
seen around 60 yo, 1:1 ratio on male to female
increasing incidence with age: AML = 80-90% of acute adult leukemias
What patient population do we see Acute Lymphoid Leukemia in and how common is it?
most common in children; 75% under 18 yo
represents 85% of leukemias in this age group and most common cancer in children
1.4/100,000 a year
M:F is 1.4:1
How do we differentiate ALL and AML besides age and why is it important?
Different Tx regimens
baesd on:
Morphology
Cytochemistry
Immunophenotyping
Genetics
Auer rods and myelodysplasia are present in AML or ALL
Auer rods = AML!
myelodyspalisa also seen in AML
Neither present in ALL
Describe the following in AML
Blast size
Chromatin
Nucleoli
Cytoplasm
Blasts are large and uniform
Chromatin are finely dispersed
Nuceoli: 1 to 4 often prominent
Cytoplasm: Moderately abundant and granules often present
Describe the following in ALL
Blast size
Chromatin
Nucleoli
Cytoplasm
Blast are small to medium; varialbe
Chromatin are course
Nucleoli are absent or 1 to 2 (indisitinct)
Cytoplasm is scant to moderate, no granules
Example of AML HE
blasts are large and uniform with 1 to 4 nucleoli, moderately abundant cytoplasm with granules present
(not shown but you do see auer rods 60-70% of the time
HE of ALL
Small to medium blasts with coarse chromatin. Absent or indistince nucleoli with scant cytoplasma and no granules in cytoplasm.
What is the purpose of cytochemical stains and what are the two most common?
Exploit the presence of intracellular
enzymes that produce a colored product
Most useful
Myeloperoxidase (MPO): myeloblasts
Non-specific esterase (NSE): monocytic
blasts in AMLs with monocytic
differentiation
What’s going on in this HE?
This is an MPO staining.. stains AML cells black
What is the purpose of Immunotyping?
Differentiates ALL from AML
Distinguishes B-ALL from T-ALL
Identifies subtypes of AML: megakaryocytic,
monocytic, etc.
Treatment and prognostic groups determined
partly by immunophenotype
Fingerprint for minimal residual disease (MRD)
assessment
Immunotyping in situ is:
Immunotyping of single cells is:
in situ is immunohistochemistry, done with tissue and only for one antiG or stain at a time
Of singles cells is Flow Cytometry: done of PB or BM and can do several antiG at a time
Key CDs in T linegae
CD1a
CD2
CD3
CD4
CD5
CD7 and 8
Key CDs for B cell lineage
CD 19
CD20
CD22
Key generic myeloid CDs
CD13, CD15, CD33, CD117, MPO
CD41 and CD 61 are associated with
megakaryocytes
CD 14 is associated with
monocytes
CD34 is seen in what diseases?
Marker of immaturity in AML and ALL
TdT is a marker of immaturity seen in
ALL
CD117 is marker of immaturity seen in:
AML
CD1a is a marker of immaturity seen in:
immature T cells
This technique helps classifaction of AML vs ALL associated abnormalities and can define sub-groups within them
Cytogenetics (key for biologic and prognostic purposes)
AML is a ________ set of disorders with generally poor outcome.
What is overall long term survival?
Heterogenous
only 25% survival
What type of progenitor cells are invovlved in AML and where do we see it in the body?
Myeloid progenitors
mostly in blood and bone marrow but can involve extramedullary sites
What type of general symptoms do we see in AML and what is the cause?
we see fatigue, weakness, petechiae and infections.. these are a results of the PANCYTOPENIAS
What are less common findings of AML
organomegaly, lymphadenopathy, infilitration of extramedullary tissues
~ coagulopathy seen in specific variants
Key diagnostic criteria for AML
Greater then 20% myeloid BLASTS in blood or bone marrow
Pathologic features of AML
Marrow usually hypercellular
Variable (but by definition, limited) ability of leukemic clone to mature beyond blast stage
Variable blast morphology, depending on sub-type
Maturation may be towards any of the myeloid lineages (sometimes more than one)
What key hematologic features do we see in AML
Severe leukopenia to markedleukocytosis
Anemia and thrombocytopenia are the norm
Maturing/mature cells of all myeloid
lineages may be dysplastic
WHO classifications of AML
AML with recurrent cytogenetic
abnormalities
AML with myelodysplasia-associated
changes
AML and MDS, therapy related
AML not otherwise categorized
AML with recurrent cytogenetic abnormalities (“de
novo” AML) have what kind of outcomes?
generally favorable
Generally reciprocal translocations
Generally flat incidence rate over different age groups
Distinctive morphologic features
Dysplasia of maturing lineages not prominent
No antecedent myelodysplastic syndrome
AML with recurrent cytogenetic abnormalities (“de
novo” AML)
In AML with myelodysplastic associated changes, they are likely related to:
MDS!!!
*see MDS-type cytogenetic abnormatilies
such as complex karyotypes and losses od chromosomes or part of chromosomes
AML with myelodysplasia associated changes;
increasing indicence with ______
prominent _______ dysplasia
______prognosis
Increasing incidence with age
Prominent multilineage dysplasia
Poor prognosis
Recurrent cytogenetic abnormalities of AML:
list the three favorable ones
t(8;21): AML1/ETO
inv(16): CBFb/MYH11
t(15;17): PML/RARa
What cytogenetic abnormality is associated with intermediate/unfavorable outcomes?
11q23 (MLL) rearrangements
What type of AML is associated with t(15;17)
Acute promyelocytic leukemia or APL
Acute promyelocytic leukemia (APL)
Generally hypo/hypergranular?
Describe nuclei seen
Single cells with multiple ______
Generally hypergranular
Reniform nuclei
Single cells with multiple Auer rods (Faggot cells)
APL represents ____% of AMLs
5-8%
What type of AML is this describing?
Usually leukopenic
Frequent DIC at diagnosis causing early morbidity and mortality
APL
treatement for APL?
Responds to all-trans retinoic acid (ATRA)
Role of t(15;17)
Produces PML-RARa fusion gene
Retinoic acid important for myeloid maturation;
disruption of receptor produces maturation arrest
at promyelocyte stage
How does ATRA work for patients with APL?
Pharmacologic doses of all-trans retinoic acid
(ATRA) overcome block and essentially mature
the cells; also quickly corrects the coagulopathy
Responsiveness to ATRA unique to this AML
variant
typical markers for Langerhans cell histiocytosis
CD1a, langerin
What type of disesase do we see these cells in?
Birbeck granules (tennis racket apperance)
seen in Langerhan cell histiocytosis
What type of mutations are seen with Langerhan cell histocytosis
BRAF mutations
In Hemophagocytic lymphohistiocytosis /
hemophagocytic syndrome there is very high ___
What primary genetic defect is this associated with?
What about secondary?
ferritin
Primary = HLH; defects in perforin gene
Secondary HLH: EVB and lyphomas
Hypertrigliceridemia, hypofibrinogenemia,
hemophagocytosis is seen in what condition
Hemophagocytic lymphohistiocytosis/hemophgocytic syndrome
