(MDS/MPN) - Overlap syndromes + Acute Myeloid Leukemia Flashcards
Are there any detectable genetic abnormalities for MDS/MPN?
yes
but none specific for MDS/MPN
(-)BCR-ABL-1
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
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
If a patient has all the diagnostic criteria for CMML except that they have >20% blasts, what condition do they have?
AML
What are the risk factors for developing CMML?
older age
male
environmental toxins
radiation
previous chemotherapy
What is the clinical presentation of patients with CMML?
splenomegaly & hepatomegaly are common
tissue-based leukemic infiltrates may occur
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
What is a major differentiating factor between CML & CMML?
CML = (+) BCR-ABL1
CMML = (-) BCR-ABL1
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)
What is the prognosis of CMML?
may progress to AML
wide spectrum of survival times
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
What tissue is rarely involved with AML?
lymph node
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
Does primary or secondary AML have a worse prognosis?
AML arising secondary to myelodysplasia or therapy has worse prognosis
What type of AML tend to arise de novo?
AML with recurrent genetic abnormalities
What risk factors are associated with AML?
down syndrome
fanconi anemia
bloom syndrome
benzene
alkylating agents
topoisomerase inhibitors
ionizing radiation
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
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
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
