Lecture 8 Acute Lymphoblastic Leukemias Flashcards
(41 cards)
What is Acute Lymphocytic Leukemia?
ALL is a hematological malignancy characterized by uncontrolled proliferation and accumulation of poorly differentiated (immature) lymphoid cells.
ALL starts with a lymphoid stem cell, immature T or B cell, and/or pluripotent cell mutation that transforms it to a malignant cell which does not respond to normal cytokine regulation and proliferates first in the bone marrow and then often spills into the peripheral blood.
What are the general symptoms of Acute Lymphocytic Leukemia?
Symptoms usually occur quite suddenly.
1. Malaise, fatigue, SOB, and pallor due to anemia.
2. Thrombocytopenia causing bruising and bleeding can be present.
3. Frequent infections due to granulocytopenia demonstrated by fevers and chills.
4. Bone pain, sternal tenderness, swelling and tenderness of large joints due to leukemic cell infiltration.
5. Meningeal infiltration by leukemic cells can result in cranial nerve paralysis, increased intracranial pressure, eye hemorrhage.
6. Lymph node enlargement, splenomegaly and hepatomegaly.
What is the number one cause of death for those with ALL?
Infection (neutropenia),
Risk is proportional to degree of granulocytopenia from either the marrow replacement by leukemic cells or chemotherapy (during treatment).
What are the other causes of death for those with ALL after infection?
- Bleeding (from thrombocytopenia)
- Infiltration of liver by leukemic cells can decrease synthesis of Vitamin K dependent clotting factors causing increased risk of bleeding.
What kind of anemia can occur in a small number of ALL cases? What is the characteristic of the problem?
DIC (a MAHA)
Results in patient first going into a thrombotic state producing clots which if not controlled exhausts the coagulation factors and platelets to the point where the patient is at risk of spontaneous bleeding (hemorrhagic). This is called a thrombotic/hemorrhagic state.
DIC is where fibers are laydown in the blood vessels and uses up clotting factors.
What can the WBC count be in ALL?
In ALL the WBC count can be low, normal or high.
60% of cases, WBC>10
15% of cases, WBC>100
25% of cases, WBC <4.0
What is the predominant cell circulating in the peripheral blood? What is the exception to this?
Lymphoid blast cell.
Except in aleukemic leukemia where the malignant cells stay in the marrow and few to none go into the peripheral blood.
What are laboratory findings in the bone marrow for ALL?
- Bone marrow almost always hypercellular and infiltrated by lymphoid blast cells.
- Fibrosis (10-15% of cases)
- Thrombocytopenia and anemia almost always present due to reduced normal marrow elements.
What other diseases can cause lymphocytosis in the peripheral blood similar to ALL?
Pertussis
Infectious mononucleosis
Other viral illnesses.
Can produce lymphocytosis with fever, enlarged nodes and splenomegaly with marrow only minimally affected whereas in ALL the marrow is majorly affected.
What is the difference between Adult ALL and cases that occur in children?
Adult ALL has
1. Higher WBC Count
2. Higher incidence of Philadelphia chromosome.
3. Type 2 morphology.
What are the cytologic features for L1 ALL Lymphoblasts (cell size, chromatin, nuclear shape, nucleoli, amount of cytoplasm, basophilia of cytoplasm and cytoplasm vacuolation)?
Cell size: Small cells predominate (still 2X size of small lymphocyte)
Chromatin: Homogeneous in any one case
Nuclear shape: Regular, occasional clefting or indentation
Nucleoli: Not visible or small and inconspicuous (usually only 1)
Amount of cytoplasm: Scanty
Basophilia of cytoplasm: Slight or moderate, rarely intense
Cytoplasmic vacuolation: Variable.
What are the cytologic features for L2 ALL Lymphoblasts (cell size, chromatin, nuclear shape, nucleoli, amount of cytoplasm, basophilia of cytoplasm and cytoplasm vacuolation)?
Cell size: Large, heterogeneous
Chromatin: Variable; heterogeneous in any one case
Nuclear shape: Irregular, clefting and indentation common
Nucleoli: One or more present, often large
Amount of cytoplasm: Variable; often moderately abundant
Basophilia of cytoplasm: Variable; deep in some
Cytoplasmic vacuolation: Variable.
What are the cytologic features for L3 ALL Lymphoblasts (cell size, chromatin, nuclear shape, nucleoli, amount of cytoplasm, basophilia of cytoplasm and cytoplasm vacuolation)?
Cell size: Large and homogeneous
Chromatin: Finely stippled and homogeneous
Nuclear shape: Regular, oval to round
Nucleoli: Prominent; one or more; vesicular
Amount of cytoplasm: Moderately abundant
Basophilia of cytoplasm: Very deep
Cytoplasmic vacuolation: Often prominent
Which type of ALL has the best prognosis and which one has the worst?
ALL-L1 has the best prognosis, whereas ALL-L3 has a poor prognosis.
How are L2 and L1 type cell’s nucleus outline/shape different between each other?
L1 has a very homogeneous presenting nucleus/chromatin. L1’s nucleus is usually round and regular with only occasional clefting and indentation whereas L2 has nuclear with clefting, folding and indentation as common with gross irregularities present in some cases.
How are L2 and L1 type cell’s different in size in ALL?
L1 is small (only 2x’s size of small lymphocyte) whereas L2 is a large cell.
Which type of lymphoblast only has a scant cytoplasm in ALL and which one has a variable often moderately abundant cytoplasm?
ALL-L1 has a scant cytoplasm
ALL-L2 has a variable, often moderately abundant cytoplasm
Which type of lymphoblast may have vesicular (rectangular) nucleoli in ALL?
ALL-L3
How does L1 and L2 nucleoli differ from each other in ALL?
L1 has none nucleoli visible or are small and inconspicuous and then usually only 1.
L2 will have one or more nucleoli present that are often large.
What are the key differentiating features of ALL-L3?
ALL-L3:
Basophilic cytoplasm with vacuolation of the cytoplasm and nucleus.
What really are the vacuoles seen in L3 and why do they appear? Can they be seen in the nucleus?
The vacuoles are not really vacuoles in ALL-L3 lymphoblast cells but are lipid containing deposits demonstrated by Wright’s stain as clear spots.
Yes they can also be present in the nucleus - called nuclear vacuolation. Result of lipid deposits overlying the nucleus and appearing as vacuoles with Wright’s stain.
What is Periodic Acid Schiff not helpful in differentiating L1 and L2? Why would it be used?
L1 and L2 are both strongly positive with PAS and therefore cannot be used to differentiate L1 from L2.
However L3 is PAS negative.
What are the staining results for ALL with Sudan Black B (SBB) and Myeloperoxidase (MPO)?
SBB and MPO are generally negative in ALL however some ALL’s are weakly positive for SBB and some immature AML’s (M0) are negative for MPO .
What is acid phosphotase used for? And its limitations?
Acid phosphotase is useful for differentiating T-Cell from B-Cell ALL (but not B-Cells from Myeloid Cells).
T-Cell shows stronger positivity with a localized pattern in the golgi region of the cell. However, B-Cell shows diffuse pattern which can also be present in Myeloid cells therefore not helpful for separating these two.
