MDS, CMML, aCML, JMML Flashcards
Myelodysplastic Syndromes (MDS) - General Features:
- Signs/Symptoms (3)
- Splenomegaly (+/-)
- Fatigue, Infection, and/or Bleeding
- Splenomegaly ABSENT
Myelodysplastic Syndromes (MDS) - Primary vs. Secondary: -Population
Primary MDS (Most Common): -Older adults
Secondary MDS:
-Young adults
Secondary Myelodysplastic Syndrome (MDS):
-Causes (4)
- Chemotherapy (Alkylating Agents)
- Radiation
- Benzenes
- Fanconi Anemia
In Secondary MDS, Alkylating agents (chemotherapy) is often associated with genetic anomalies involving what chromosomes?
5q/7q
Myelodysplastic Syndromes (MDS) - Morphology:
- BM cellularity
- BM finding (2)
- Blast %
- Hypercellular BM
- Abnormal localization of immature precursors
- Dyspoiesis present in 1 or more cell lines
- Blasts <20%
MDS - Erythroid Dyspoiesis:
-Peripheral Blood (4)
- Anemia
- Basophilic stippling
- Poikilocytosis
- Macrocytosis
MDS - Erythroid Dyspoiesis:
-Bone Marrow (7)
- Megaloblastoid change/Nuclear Lobation
- Internuclear Bridging
- Multinuclearity
- Karyorrhexis
- Ringed-Sideroblasts
- Cytoplasmic PAS+
- Cytoplasmic Vacuolization
MDS - Erythroid Dyspoiesis:
-Functional (5)
- Increased susceptibility to complement mediated lysis
- Increased HbF
- Abnormal RBC Ag expression
- Enzyme defects (eg, PKD)
- Thalassemia (acquired)
MDS - Granulocytic (Myeloid) Dyspoiesis:
-Peripheral Blood (3)
- Neutropenia
- Abnormal Granulation
- Nuclear Segmentation (psuedo-Pelger-Huet anomaly)
MDS - Granulocytic (Myeloid) Dyspoiesis:
-Bone Marrow (2)
- Megaloblastoid Maturation
- Abnormal Granulation
MDS - Granulocytic (Myeloid) Dyspoiesis:
-Functional (1)
-Increased susceptibility to Bacterial Infections
MDS - Megakaryocytic Dyspoiesis:
-Peripheral Blood (3)
- Thrombocytopenia
- Variable size
- Variable granulation
MDS - Megakaryocytic Dyspoiesis:
-Bone Marrow (3)
- Micromegakaryocytes
- “Pawn Ball” (Multinucleated)
- Hypolobated
MDS - Megakaryocytic Dyspoiesis:
-Functional (1)
-Abnormal Platelet Aggregometry
In MDS, dyspoeisis must be present in what percentage of a cell line for a diagnosis of dysplasia?
> 10%
*NOTE: Healthy marrow contains dyspoietic cells (<5%)
MDS - Molecular and Cytogenetics:
- Most Common
- 2nd
- 3rd
MDS - Molecular and Cytogenetics:
- Complex Karyotype - 2 or more clonal abnormalities (MC)
- Isolated monosomy 7 or 7q- (2nd)
- Isolated 5q (3rd)
Which MDS Cytogenic abnormalities are associated with a Favorable prognosis? (4)
-Normal Karyotype Isolated loss of: -Y -5q- -20q-
Which MDS Cytogenic abnormalities are associated with a UNfavorable prognosis? (2)
- Complex Karyotype (3 or more anomalies)
- Chr7 anomalies
MDS - 5q- syndrome:
- Population
- Clinical course
- Findings (3)
-Elderly Females
-Indolent clinical course
Findings:
-Anemia
-Normal/Elevated Platelets
-Micromegs in BM
Myelodysplastic/Myeloproliferative Neoplasms (MD/MPN):
-Common features (2)
- Dyspoiesis
- Increased production of Mature cells
Myelodysplastic/Myeloproliferative Neoplasms (MD/MPN):
-Types (3)
- Chronic Myelomonocytic Leukemia (CMML)
- Atypical CML (aCML)
- Juvenile Myelomonocytic Leukemia (JMML)
Chronic Myelomonocytic Leukemia (CMML):
-Diagnostic criteria (4)
- Persistent Absolute Monocytosis (>1x10^9/L)
- Marrow dysplasia (Dysgranulopoiesis MC)
- <20% blasts (includes Promonocytes)
- Absence of Philadelphia Chromosome (9;22)
Chronic Myelomonocytic Leukemia (CMML):
-Other Frequent findings (4)
- Hepatosplenomegaly
- Anemia
- Thrombocytopenia
- Abnormal Monocyte morphology
Chronic Myelomonocytic Leukemia (CMML) Type 1 (CMML-1) - Blasts/Promonocytes:
- Blood
- Bone Marrow
<5% in Blood
<10% in BM
Chronic Myelomonocytic Leukemia (CMML) Type 2 (CMML-2) - Blasts/Promonocytes:
- Blood
- Bone Marrow
5-19% in Blood
10-19% in BM
Chronic Myelomonocytic Leukemia (CMML) - Molecular and Cytogenetics:
- JAK2 mutation
- If Eosinophilia is present
JAK2 mutation present in SMALL proportion of cases
Eosinophilia present:
-Rearrangement of PDGFRA and PDGFRB should be Excluded
Atypical Chronic Myelogenous Leukemia (aCML):
-Diagnostic criteria (4)
- Neutrophilia (Spectrum of Neuts/Metas/Myelos/Pros)
- Marrow Dysplasia
- <20% Blasts
- Absence of Phila Chr (9:22)
Most Atypical Chronic Myelogenous Leukemias (aCML) have cytogenetic anomalies, which are most common? (2)
- Chr8+
- del(20q)
*Some cases have JAK2 mutation
Juvenile Myelomonocytic Leukemia (JMML):
-Findings (6)
- Monocytosis/Granulocytosis
- Hepatosplenomegaly
- Constitutional Sxs
- Anemia
- Thrombocytopenia
- Increased HbF
Juvenile Myelomonocytic Leukemia (JMML):
-MC chromosomal abnormality
Monosomy 7 (25%)
What is the confirmatory finding in Juvenile Myelomonocytic Leukemia (JMML)?
Spontaneous formation of granulocyte macrophage colonies (in vitro) that are hypersensitive to GM-CSF.
Juvenile Myelomonocytic Leukemia (JMML):
-Nearly 10% of cases are associated with what?
Neurofibromatosis type 1 (NF1)
