15 - Acute Leukemias

Question 1

Definition of Acute Leukemia

Answer 1

• Clinical Definition: A life-threatening event caused by the accumulation of immature white bloods cells in the bone marrow requiring immediate therapeutic intervention.
• Pathologic Definition: Maturation arrest at the level ofhematopoietic precursor cells (myeloblasts or lymphoblasts) defined by the presence of at least 20% blasts in the bone marrow.

Question 2

Clinical Presentation of

Acute Leukemia

Answer 2

• Symptoms result from displacement of normal hematopoietic elements in the bone marrow
  – Displacement of myelopoietic cells => infections
  – Displacement of megakaryopoiesis => bleeding
  – Displacement of erythropoiesis => anemia

Question 3

How to diagnose Acute Leukemia?

Answer 3

• Morphology (bone marrow, peripheral blood)
• Immunophenotyping (mainly flow cytometry)
• Cytogenetics
• FISH
• Molecular Studies (Next Generation Sequencing, PCR etc.)

Question 4

Comparison between Acute Leukemia
and Myeloproliferative Disease and Myelodysplasia

Answer 4

• Blasts in bone marrow
  and peripheral blood
• Effective abnormal
  hematopoiesis,
  hypercellular marrow and
  peripheral leukocytosis
• Ineffective abnormal
  hematopoiesis,
  hypercellular marrow,
  peripheral cytopenia(s)

Question 5

Two Major Types of Acute Leukemia

Answer 5

• Acute Lymphoid Leukemia (ALL)
• Acute Myeloid Leukemia (AML)

Question 6

Myeloid and lymphoid
maturation and differentiation

Answer 6

Question 7

Acute Lymphoblastic Leukemia/Lymphoma of B-Cell Type

Answer 7

• Most common cancer in children (peaks at age 3)
• Childhood ALL is a therapeutic success story (95% go into full remission, 85% permanently cured)
• CNS involvement more common in ALL than in AML
• 90% have structural and numerical chromosomal changes
• Presents as leukemia and not as tumor
• Positive for TdT, CD19, CD10, CD22 etc. Negative for surface Ig by definition

Question 8

Acute Lymphoblastic Leukemia of B-Cell Type

Answer 8

Question 9

Acute Lymphoblastic Leukemia/Lymphoma of T-Cell Type

Answer 9

• Can arise from bone marrow or thymus
• Most common in adolescent males
• Aggressive malignancy
• Thymic masses common
• Presents as leukemia and/or tumor
• Positive for TdT

Question 10

Normal peripheral blood

Answer 10

Question 11

Acute Lymphoblastic Leukemia/Lymphoma of T-Cell Type

Answer 11

Question 12

classification of acute lymphoblastic leukemias

Answer 12

Question 13

Acute Myeloid Leukemia

Answer 13

• As in ALL, symptoms are caused by
  displacement of normal bone marrow cells.
• Tumor formation is possible
  (myeloid/monocytic sarcoma, extramedullary
  myeloid tumor), e.g. leukemia cutis, gingiva
  involvement
• CNS involvement less common than in ALL
• Tumor cells positive for myeloperoxidase
• Some AMLs may have Auer Rods

Question 14

acute myeloid leukemia with definining genetic abnormalities and differentiation

Answer 14

Question 15

Acute Myeloid Leukemia M1

Answer 15

Question 16

Acute Promyelocytic Leukemia

Answer 16

• Patient presents with DIC (symptoms caused
  by clotting and bleeding)
• Normally positive for t(15;17) involving PML-
  RARA
• Excellent prognosis, treatable with all-trans
  retinoic acid (85% curable)

Question 17

Acute Myeloid Leukemia with
Monocytic Differentiation – M5

Answer 17