(MDS/MPN) - Overlap syndromes + Acute Myeloid Leukemia Flashcards by Katherine E Nordstrom

Are there any detectable genetic abnormalities for MDS/MPN?

yes
but none specific for MDS/MPN

(-)BCR-ABL-1

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What are the general features seen in MDS/MPN?

usually leukocytosis

hypercellular bone marrow

normal/slightly increased blast (<20%)

maturation is present but hematopoiesis effectiveness is variable

organomegaly is common

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What are the diagnostic criteria for Chronic myelomonocytic leukemia (CMML)?

persistent monocytosis at least 6 months
leukocytosis (common)
dyspoiesis present in 1 or more cell lineage
<20% blasts in blood & bone marrow
No Ph Chromosome or BCR-ABL1 fusion gene
No rearrangement of PDGFRA (platelet derived growth factor A), PDGRFAB, FGFR1, or PCM1-JAK2

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If a patient has all the diagnostic criteria for CMML except that they have >20% blasts, what condition do they have?

AML

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What are the risk factors for developing CMML?

older age

male

environmental toxins

radiation

previous chemotherapy

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What is the clinical presentation of patients with CMML?

splenomegaly & hepatomegaly are common

tissue-based leukemic infiltrates may occur

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What would you expect to seen a peripheral blood smear from a patient with CMML?

absolute monocytosis
+/- absolute leukocytosis, anemia, thrombocytopenia
dysplasia (esp. granulocytes)
- hypolobated neutrophils & hypogranular

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What is a major differentiating factor between CML & CMML?

CML = (+) BCR-ABL1

CMML = (-) BCR-ABL1

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What would you expect to seen a bone marrow sample from a patient with CMML?

dyspoiesis in the aspirate (megakaryocytes)

biopsy with mild/moderate reticulin fibrosis

typically hypercellular (less than CML)

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What is the prognosis of CMML?

may progress to AML

wide spectrum of survival times

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What is AML & what is the cause?

clonal proliferation of immature myeloid cells, usually blasts

caused by acquired mutations of hemopoietic stem cells that impede differentiation & block maturation

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What tissue is rarely involved with AML?

lymph node

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Is AML more common in adults of children?

accounts for 80% of acute leukemias in adults

only 20% in children - except it IS the most common acute leukemia in neonates

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Does primary or secondary AML have a worse prognosis?

AML arising secondary to myelodysplasia or therapy has worse prognosis

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What type of AML tend to arise de novo?

AML with recurrent genetic abnormalities

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What risk factors are associated with AML?

down syndrome

fanconi anemia

bloom syndrome

benzene

alkylating agents

topoisomerase inhibitors

ionizing radiation

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De novo AML typically has what type of genetic factors associated with it?

What about AML that arises from myelodysplasia or from DNA-damaging drugs?

primary (de novo)
- balanced chromosomal translocations
secondary
- deletions or monosomies involving chromosomes 5 & 7

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What clinical signs are often seen in patients with AML?

nonspecific symptoms
- anemia, weakness, pallor, malaise, fever, fatigue, bone pain
gingival hyperplasia
- monocytic lineage
Disseminated intravascular coagulation (DIC) with acute promyelocytic leukemia
organomegaly is uncommon

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In AML, blasts must comprise >20% of marrow cells except in what cases?

AML with specific cytogenetic abnormalities

some erythroleukemias

What do the myeloblasts look like in AML?

delicate nuclear chromatin

2-4 nucleoli

abundant cytoplasm

fine, azurophilic, peroxidase (+) granules or distinctive peroxidase (+) Auer rods

What do the monoblast look like in AML?

folded or lobulated nuclei

lack Auer rods

usually express non-specific esterase

usually do not express peroxidase

What are the general peripheral blood & marrow features of AML?

peripheral counts vary (usually anemia + thrombocytopenia)

marrow cellularity usually increased

blast maturation varies

dysplasia in one or more lineage is common (not required)

What is the most common type of childhood AML?

AML with t(8;21)(q22;q22); RUNX-1-RUNX1-T1

What is the genetic cause of AML with t(8;21)(q22;q22)?

Fusion gene of RUNX1 (core binding factor alpha) and RUNX1T1 to form RUNX1-RUNX1T1

What are the clinical features of AML with t(8;21)(q22;q22)?

predominantly in younger patients generally some maturation of neutrophil lineage large & small blasts - **frequent Auer rods** good response to chemotherapy

What is the genetic cause of AML with inv(16)(p13.1q22)?

**CBFB-MYH11** fusion gene (core binding factor beta - smooth muscle myosin heavy chain)

What are the clinical features of AML with inv(16)(p13.1q22)?

* mostly younger age groups * monocytic & granulocytic differnetiation * abnormal eosinophil component * immature eosinophilic granules are abnormally large - purple & numerous * blasts have Auer rods * high rate survival

What is the genetic mutation associated with Acute Promyelocytic Leukemia with PML-RARA?

* balanced t(15;17)(q22;q22) * results in formation PML-RARa fusion gene * drives proliferation of promyelocytes

What are the two type of Acute Promyelocytic Leukemia with PML-RARA? How are they different?

* microgranular * high peripheral blood WBC count - resemble monocytes * fine pink granules in cytoplasm * usually no discernable Auer rods * procoagulants in granules → DIC * hypergranular * **many Auer rods within each cell**

Why is rapid diagnosis of Acute Promyelocytic Leukemia with PML-RARA so important?

patients commonly develop DIC, which is one of the few hematologic emergencies

What are the clinical features seen in Acute Promyelocytic Leukemia with PML-RARA?

* typically middle aged adults * abnormal promyelocytes predominate * **strongly myeloperoxidase positive** * patients commonly develop DIC

How is Acute Promyelocytic Leukemia with PML-RARA treated? Prognosis?

**all-trans retinoic acid (ATRA) & arsenic trioxide** they induce differentiation and maturation of the malignant promyelocytes Good prognosis

What are the clinical features of AML with Myelodysplasia-Related Changes?

generally the elderly severe pancytopenia & multilineage dysplasia generally poor prognosis

What are the criteria for a diagnosis of AML with myelodysplasia-related changes (AML-MRC)?

* AML \>20% blasts in blood/BM * prior history of MDS or MDS/MPN * cytogenic/molecular abnormalities associated with MDS * Should NOT have genetic abnormalities that place it into AML with recurrent genetic abnormalities

How long after treatment do therapy-related myeloid neoplasms usually develop? How do they present? Prognosis?

5-10 yrs marrow failure & cytopenias (some will present as overt AML 1-5 yrs after treatment with topoisomerase II inhibitors) multilineage dysplasia poor prognosis

What is the criteria for a diagnosis of AML, not other wise specified?

lack defined genetic abnormality for a specific category neither therapy-related nor myelodysplasia-related classification based largely on morphology & cytochemistry

Which of the following blood smears is from an acute leukemia & which is from a chronic leukemia?

* Left * acute - mainly blasts * Right * chronic - fewer blasts, mainly more mature cells

What is the most common type of leukemia in adults?

AML

Which cell type, indicative in Acute Promyelocytic Leukemia with PML-RARA, is shown in each of the provided images?

What type of AML, not otherwise specified is seen in the provided image?

AML with minimal differentiation no myeloid differentiation by morphology or cytochemistry flow cytometry shows myeloid markers lasts sometimes resemble lymphoblasts no granules or Auer rods

What type of AML, not otherwise specified is seen in the provided image?

**Acute myelomonocytic leukemia** proliferation of both neutrophilic and monocytic precursors large cells with abundant cytoplasm

What type of AML, not otherwise specified is seen in the provided image?

**AML with maturation** similar in morphology to AML Auer rods & granules often present - some maturation

What type of AML, not otherwise specified is seen in the provided image?

AML without maturation high percentage of blasts without evidence maturation cytochemical stains (myeloperoxidase or sudan black B) are + flow cytometry shows myeloid markers blasts with granules +/- Auer rods

What type of AML, not otherwise specified is seen in the provided images?

**Acute/monocytic/monoblastic leukemia** * 80% or more of bone marrow cells are monocytic lineage * acute monoblastic leukemia (\>80% monoblasts) * acute monocytic leukemia (\<80% monoblasts)

What clinical symptom is commonly seen in patients with acute monocytic/monoblastic leukemia?

extramedullary lesions are common

What type of AML, not otherwise specified is seen in the provided image?

**Acute Erythroid leukemia** extremely rare leukemia at least 80% of marrow cells are erythroid erythroblasts often with PAS-positive vacuoles

What type of AML, not otherwise specified is seen in the provided image?

\>50% of blasts are of megakaryocytic lineage look close, may see some platelets that are pinching off the side association with mediastinal germ cell tumors observed in young males