Homogeneous proliferation of immature cells with high nuclear-cytoplasmic ratio, fine chromatin pattern and visible nucleoli. Sometimes have Auer rods
Acute myeloid leukemia (20% blasts required for Dx)
3. Flow cytometry:
Above: Normal bone marrow
Acute leukemia
CD45 is an antibody that stains hematopoietic cells. In normal bone marrow, see many cell types – high granulocytes, low lymphocytes. In acute leukemia, normal hematopoietic cells (granulocytes, lymphocytes, etc.) are displaced by blasts.
AML: Dx based on flow cytometric evaluation. o low density CD45 o CD33 o CD13 o HLA-DR o CD34 o CD117 o CD7 o CD11b o negative for CD15 Test q: Flow cytometry cell markers consistent w/AML are: CD33, CD13.
4. Cytogenetics and molecular studies: • Normal male karyotype: 46,XY [20] • Molecular testing negative for NPM1 and CEBPA mutations • Final diagnosis: AML, without maturation Correlation of morphology, flow cytometry and cytogenetics Example: Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA Test q: A 23F presents w/mucosal bleeding and fatigue. CBC shows a microangiopathic, hemolytic anemia and numerous myeloblasts w/Auer rods. You suspect: AML (M3).
Above: AML (M3) aka Acute Promyelocytic Leukemia. Promyelocytes with numerous azurophilic granules and frequent Auer rods (myeloperoxidase+).
Acute promyelocytic leukemia [AML with t(15;17)]:
O High CD33 – not normal.
Above: Normal bone marrow
AML with t(15;17) See granulocytes.
Highly proliferative.
Myeloperoxidase+
O
Above: CD117 – marker for immature myeloid cell.
Acute promyelocytic leukemia [AML with t(15;17)]: Characteristic morphology and immunophenotype o CD33 bright + o HLA-DR – o CD34 – (Note: HLA-DR and CD34 – immature.) o CD15 – And presence of t(15;17) by cytogenetics or RARα/PML fusion gene by molecular studies Acute Myeloid Leukemia Summary: o Most common in adults o Abrupt presentation with pancytopenia and its complications o Bone marrow and peripheral blood show proliferation of blasts (several types of blasts may be present) and lack of normal maturing hematopoietic elements o Subclassified by stage of differentiation and genetic lesions, which correspond to prognostic groups o Only a proportion of patients can be cured with currently available treatments
Leukemias: – Myeloid neoplasms: – Acute myeloid leukemia – Chronic: – Myelodysplastic syndromes – Myeloproliferative neoplasms – Lymphoid leukemias: – Acute – Chronic Myelodysplastic syndromes: – Clonal stem cell disorder characterized by actively proliferating hematopoietic cells with maturation defect (=ineffective hematopoiesis=cytopenias) – Bone marrow is hypercellular, however patient presents with pancytopenia (BM not efficient) – Morphology is heterogeneous; all lineages are represented in the bone marrow and show dysplastic features – – –
Primary (idiopathic) – Develops insidiously usually in older patients (mean age 70) Secondary (therapy-related) – Complication of chemotherapy or radiation therapy Clinical course: – Pancytopenia and its complications – Transformation to acute leukemia (10-40% of cases)
Approach to diagnosis of myelodysplastic syndrome: Integration of morphology, clinical history, ancillary techniques, cytogenetic and molecular features.
MDS Morphology: Milestone Features • Hypercellular BM (Pic #1: only a few fatty cells)
• Dysplastic features (Pic #2: yellow circle around normal cells, green circles around irregular cells – do not have round nuclei.)
Dysplasia: • Number of blasts Higher number = more aggressive disease and higher risk of transformation to acute leukemia (e.g. disease is less aggressive in a patient with 1% of blasts as compared to a patient with 15% blasts) MDS = ALWAYS LESS THAN 20% BLASTS
1
2
O O
3
O
• Ring sideroblasts (Pic #3: atypical nucleated erythrocytes with granules of iron accumulated in perinuclear mitochondria) Above: Granulocytic lineage. See improper segmentation – only two lobes. Above: Megakaryocytes. See loss of lobation – only one nucleus. Test q: Acute leukemia is most reliably distinguished from chronic leukemia on the basis of: number of blast cells in peripheral blood and/or bone marrow. REPEATED x2
Classification of myelodysplastic syndromes: Disease
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