MDS and AML Flashcards by Meghan May

Cytopenias, dysplasia (one or more
myeloid cell lineages), ineffective
hematopoiesis, and increased risk of
development of AML

Myelodysplastic syndromes

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Myelodysplastic syndromes are what kind of disorders?

Clonal hematopoietic stem cell disorders

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Myelodysplastic Syndromes

Enhanced degree of apoptosis contributes to_________
Myeloblasts :

cytopenias

Myeloblasts < 20% (PB or BM)

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What chromosomal abnormalities do we see in myelodysplastic syndromes in 50% of the cases

-5 or del5q, +8, -7 or del7q

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What lab findings do we see associated with MDS?

 Cytopenias (uni-, bi-, or pancytopenia)
 Leukoerythroblastic reaction
 Dysplastic features
 Hypercellular BM
 Ring sideroblasts
 Increased myeloblasts

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What do we see on a blood smear in a patient with MDS?

Hypolobulated and hypogranular neutrophils

GIANT platelets and large hypogranular platelets

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What do we see on bone marrow aspirate in a patient with Myleodysplastic syndrome

dysplastic megakaryocyte (in picture)

dysplastic erythroid precursors

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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)

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what is wrong in this G banding and what disease is it characteristic of?

Monosomy 7

Seen in MDS

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How do patients with MDS usually present and what age group?

Weaknes, infections, hemorrhage or asymptomatic

In the elderly (50s-80s)

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In MDS, what is the median survival?

9-29 months

t-MDS is only 4-8 months

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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

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Therapy for MDS (Three different categories)

Supportive: blood products, antibiotics, GFs

Hypomethylating agents: not curative

-Decitabine or Azacitidine

Allogenic stem cell transplant

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Define Acute leukemia

Neoplastic proliferation of immature
cells (blasts) recapitulating progenitor
cells of the hematopoietic system

(AML or ALL)

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What is the difference between Acute and Chronic leukemias

Acute = weeks to months with IMMATURE cells

Chronic = months to years with MATURE cells

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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

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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

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How do we differentiate ALL and AML besides age and why is it important?

Different Tx regimens

baesd on:

 Morphology
 Cytochemistry
 Immunophenotyping
 Genetics

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Auer rods and myelodysplasia are present in AML or ALL

Auer rods = AML!

myelodyspalisa also seen in AML

Neither present in ALL

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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

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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

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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

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HE of ALL

Small to medium blasts with coarse chromatin. Absent or indistince nucleoli with scant cytoplasma and no granules in cytoplasm.

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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

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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

MDS and AML Flashcards

(63 cards)