Blood and BM Path Chapter 19 - Acute Lymphoblastic Leukemia/Lymphoma

Question 1

How many patients with ALL are under the age of 15?

Answer 1

85%

Question 2

At what leukocyte count are patients at risk for leukostasis?

Answer 2

>100 x 10⁹/L

Question 3

ALL morphologic types

Answer 3

aka FAB L1, L2, and L3

Question 4

Recurrent genetic anomalies observed in B lymphoblastic leukemia/lymphoma

Answer 4

• t(9:22)
• t(1:19)
• t(various;11q23 rearranged)
• hyperdiploid ALL
• hypodiploid ALL
• B-LBL NOS

Question 5

Co-expression of myeloid antigens on B-ALL

Answer 5

Poor prognostic marker

Suggests association with t(9:22)

Useful for monitoring in minimal residual disease state (MRD)

Question 6

Frequency of anomalies in B-ALL

Answer 6

Question 7

Frequency of anomalies in T-ALL

Answer 7

Question 8

Classifying B-ALLs

Answer 8

• Classified by state of B cell differentiation, as characterized by:
  
  • cytosolic CD79a expression
  • CD10 expression
  • cytosolic μ expression
  • sIg expression
• Thus, the classes are as follows:
  
  • CD79a+ only: B-I / Early-B
  • CD79a+CD10+: B-II / Common-B
  • CD79a+CD10+cμ+: B-III / Pre-B
  • CD79a+CD10+cμ+ and either sIg+ or surface μ+: B-IV / Mature B
  • CD79a+sIg+: B-IV - Burkitt-type

Question 9

Classifying T-ALLs

Answer 9

• Earliest T cell changes: cCD3+
• Pro T cell / T-I: cCD3+ cCD7+
• Early T cell / T-II: cCD3+ CD7+ CD5+ OR CD2+
• Corticothymocyte-like cell / T-III: cCD3+CD7+CD5+CD2+ CD1a+ (may or may not have surface CD3)
• Mature T cell / T-IV: CD3+CD7+CD5+CD2+ CD1a-

Note that Pro T cells and early T cells may coexpress myeloid antigens in a healthy individual.

Question 10

B-ALL with t(4;11) or MLL anomalies

Answer 10

• Morphology:
  
  • Lymphoblastic
• Genetics:
  
  • t(4;11) MLL/AF4 fusion protein
  • Anomalies of the MLL gene
• Immunophenotype:
  
  • TdT+
  • B-I expression profile: CD79a+CD10-
  • Aberrant CD15+, CD65+

Question 11

B-ALL with t(9;22)

Answer 11

• Morphology:
  
  • Lymphoblastic
• Genetics:
  
  • t(9;22) Bcr-Abl (Philidelphia chromosome)
• Immunophenotype:
  
  • TdT+
  • CD34+
  • B-II expression profile: CD79a+CD10+
  • Aberrant CD13+, CD33+, low CD38
  • Differentiating from t(12;21): CD66c+

Question 12

B-ALL with t(12;21)

Answer 12

• Morphology:
  
  • Lymphoblastic
• Genetics:
  
  • t(12;21) TEL/AML1, aka ETV6-RUNX1
• Immunophenotype:
  
  • TdT+
  • CD34+
  • B-II expression profile: CD79a+CD10+
  • Aberrant CD13+, CD33+, low CD38
  • Differentiating from t(9;22): CD66c-

Question 13

Hyperdiploid B-ALL

Answer 13

• Morphology:
  
  • Lymphoblastic
• Genetics:
  
  • ~51-65 chromosomal karyotype
• Immunophenotype:
  
  • TdT+
  • CD34+Aberrant CD123 overexpression (IL-3R)

Question 14

Ploidy in B-ALL

Answer 14

Hypodiploidy: Poor prognosis

Hyperdiploidy: Good pronosis

The same does NOT hold for T-ALL.

Question 15

Assessing ploidy by flow cytometry

Answer 15

Propidium iodide intercalation of cells pre-treated with RNAse

Question 16

In B-LBL, molecular changes often affect. . .

Answer 16

. . . B-cell lineage transcription factors:

PAX5 (chr9), IKAROS (chr7), E2A (chr19), and EBF1 (chr5)

Question 17

Minimal residual disease

Answer 17

• Defined as the tumor mass still remaining after chemotherapy or HSC transplant.
  
  • Important prognositc marker
• Gold standard: qRT-PCR

Question 18

Features of B-ALL detectable to quantify MRD

Answer 18

Typically differential expression of CD20, CD34, CD10, and CD38 is sufficient.

CD123 (IL-3R) may be utilized if all else fails

Question 19

Features of T-ALL detectable to quantify MRD

Answer 19

Combination of cCD3 and nTdT is effective, but unfortunately requires permeabilization which may destroy cells.

Aberrant over-expression of CD99 in combination with immature T cell markers is a useful tool. CD1a is very useful if working with a T-III ALL.

Question 20

What is a mixed phenotype acute leukemia?

Answer 20

An acute leukemia of ambiguous lineage with no clear evidence of differentiation towards any particular phenotype.

May express antigens associated with multiple lineages.

Two specific genetic rearrangements are recognized for particular clinical features: MPAL with t(9;22) BCR-ABL1, and MPAL with t(v;11q23) MLL rearrangements.

Question 21

Algorithm for diagnosis of mixed lineage acute leukemia

Answer 21

Question 22

Classification of MPAL NOS

Answer 22

B/myeloid, T/myeloid, or rare type

B lineage is suggested if: CD19 is bright and one of CD10, cCD79a, CD20, and cCD20 is present OR if CD19 is dim and two of those markers are present.

T lineage is suggested if: cCD3 is present.

Myeloid lineage is suggested if: cMPO is present OR if there are signs of monocytic maturation such as nonspecific esterase, intracytoplasmic lysozyme, CD14, CD11c, CD36, or C64.

Question 23

What is this morphology?

Answer 23

FAB L3

Question 24

What is this morphology?

Answer 24

FAB L2

Question 25

What is this morphology?

Answer 25

FAB L1

Question 26

PAS stain on lymphoblasts

Answer 26

Classically, PAS stains “clumps” in the cytoplasm of lymphoblasts

Question 27

Three “classical” cytologic blast stains to aid in differnetiation

Answer 27

Myeloperoxidase (granular stain in myeloblasts)

Sudan Black B (granular stain in myeloblasts)

Periodic Acid Schiff (clumpy stain in lymphoblasts)