Precursor Neoplasms: T and B-ALL/LBL

Question 1

What is the immunophenotype of

blasts of Precursor B-ALL/LBL, NOS?

Answer 1

• Positive for:
  
  • CD19
  • CD10
  • PAX5
  • CD34
  • CD99, HLA-DR
  • Nuclear Tdt

Question 2

How does the Burkitt Lymphoma

IHC panel compare to precursor B-ALL/LBL?

Answer 2

• CD19 +
• CD20 +
• CD10 +
• HLA-DR and CD99 +
• TDT (-)
• surface immunoglobulin (+)

Question 3

What is the immunophenotype of

precursor T-ALL/LBL?

Answer 3

• CD19 (-)
• CD20 (-)
• CD10 (-)
• HLA-DR (-)
• surface immunoglobulin (-)
• CD7 and TdT (+)

Question 4

What is the prognosis for patients with B-ALL/LBL

in children and adults?

Answer 4

• Children: CR >95%
• Adults: CR 80%

This is with therapy. Adults have a slightly worse prognosis.

Question 5

What are the key prognostic variables for

B-ALL/LBL patients?

Answer 5

• Favorable:
  
  • age: 1-9 years old
  • WBC: <50,000
  • good response to initial treatment

Question 6

What genetic finding is associated with

a poor prognosis in B-ALL/LBL?

Answer 6

• hypodiploidy (46 chromosomes)

Question 7

What are general characteristics of

Lymphoblastic lymphoma and lymphoblastic leukemia?

Answer 7

• LBL: lesions involve the tissue and spare the peripheral blood
• ALL: lesions heavily involve the marrow and peripheral blood

Question 8

When does ALL peak and

what are the characteristics of ALL?

Answer 8

• peaks: at age 3
• most childhood ALL = B-ALL
  
  • 10% are T-ALL
• T-ALL is more common in males and teens
  
  • <15%
  • most are LBL 85-90%

Question 9

What are risk factors for the development of

ALL/LBL?

Answer 9

• Down Syndrome
• Fanconi Anemia
• Li-Fraumeni Syndrome
• Ataxia-Telangiectasia
• Bloom Syndrome

Question 10

What is the characteristic clinical presentation

of T-LBL?

Answer 10

• anterior mediastinal mass
• may be associated with hypercalcemia

Question 11

What is the characteristic clinical presentation of

B-LBL?

Answer 11

• involves the lymph nodes, CNS, liver, spleen and testes
• does not involve the mediastinum

Note: both present with fatigue and cytopenis with or without bone pain

Question 12

What is the characteristic morphology of

T or B-ALL/LBL?

Answer 12

• monotonous proliferation of undifferentiated blasts
• T-LBL may be associated with infiltrating eosinophils
• PAS-positive in block pattern
  
  • negative for MPO
  • negative for Sudan black B

Question 13

What is the most common molecular finding

in B-ALL/LBL that has a poor prognosis?

Answer 13

• t(9;22)
• BCR-ABL
  
  • minor breakpoint 190 kd chimeric protein
  • different than the CML breakpoint which is 210
• distinctly unfavorable finding

Question 14

What are the translocation proteins, morphology, prognosis and age group of

B-ALL/LBL with t(9;22)?

Answer 14

• genetics: BCR/ABL
• age group:
  
  • adults: 25% (p210, p190)
  • children: 3% (p190)
• poor prognosis
• usual morphology

Question 15

What are the IHC findings of

t(9;22) B-ALL/LBL?

Answer 15

• CD19 +
• CD10 +
• Tdt +
• CD34 +
• CD13/33 + (weak)
• CD25 +

Question 16

What are the translocation proteins, morphology, prognosis and age group of

B-ALL/LBL with t(4;11)?

Answer 16

• second translocation: t(v;11q23)
• genetics: KMT2A (MLL)
• seen in infants ( <1 year)
  
  • CNS involved
  • can start in utero
  • associated with Topoisomerase II inhibitors
• poor prognosis
• usual morphology

Question 17

What is the IHC of the t(4;11) B-ALL/LBL?

Answer 17

• CD19 +
• CD10 (-)
• CD15 +
• express FLT3

Question 18

What are the translocation proteins, morphology, prognosis and age group of

B-ALL/LBL with t(12;21)?

Answer 18

• genetics: TEL-AML1 (ETV6-RUNX1)
• 25% of children
• good prognosis
• usual morphology

Question 19

What is the IHC of B-ALL/LBL with

t(12;21) or TEL-AML1 (ETV6-RUNX1)?

Answer 19

• CD10 +
• CD19 +
• CD9 (-)
• CD13/33 + (weak)
• CD34 +

Question 20

What are the translocation proteins, morphology, prognosis and age group of

B-ALL/LBL that are hyperdiploid ?

Answer 20

• genetics: > 50 chromosomes
  
  • extra copies of esp 21, 4, 14, and X
• seen in 25% of children
• good prognosis
• usual morphology

Question 21

What are the IHC findings for the

hyperdiploid B-ALL/LBL?

Answer 21

• CD19 +
• CD10 +
• Tdt +
• CD34 +

Question 22

What are the translocation proteins, morphology, prognosis and age group of

B-ALL/LBL with hypodiploid genetics ?

Answer 22

• genetics: <46 chromosomes
• < 5% of children and adults
• poor prognosis
• usual morphology

Question 23

What are the IHC findings for

B-ALL/LBL that are hypodiploid?

Answer 23

• CD19 +
• Tdt +
• CD10 +
• CD34 +

Question 24

What are the translocation proteins, morphology, prognosis and age group of

B-ALL/LBL with t(1;19)?

Answer 24

• genetics: E2A-PBX1
• pre-B-ALL phenotype
• 5% of children
• poor prognosis
• usual morphology

Question 25

What are the IHC findings for B-ALL/LBL with t(1;19)?

Answer 25

* pre-B-ALL phenotype * CD10 + * CD19 + * CD34 (-) * CD9 (+)

Question 26

What are the translocation proteins, morphology, prognosis and age group of B-ALL/LBL with t(5;14)?

Answer 26

* genetics: IL3-IGH * seen in \< 1% of children and adults * usual prognosis * associated with significant eosinophilia * not malignant eos

Question 27

What are the IHC findings for B-ALL/LBL with t(5;14) (IL3-IGH)?

Answer 27

* CD19 + * CD10 + * CD34 + * Tdt +

Question 28

What are the translocation proteins, morphology, prognosis and age group of B-ALL/LBL with BCR-ABL like phenotype?

Answer 28

* genetics: lack BCR-ABL translocation * similar expression profile * seen in high risk children, adults * poor prognosis * usual morphology

Question 29

What is the IHC profile seen in BCR-ABL like B-ALL/LBL?

Answer 29

* CD19 + * CD10 + * Tdt + * CD34 +

Question 30

What are the translocation proteins, morphology, prognosis and age group of B-ALL/LBL with iAMP21 ?

Answer 30

* genetics: RUNX1 * seen in 2% of children * poor prognosis * usual morphology IHC: * CD19 + * CD10 + * Tdt and CD34 +

Question 31

What is the typical presentation of T-ALL-LBL?

Answer 31

* commonly presents in adolescents * rapid growth with sparing of the bone marrow * most important is the initial response to treatment * difficult to distinguish from a thymoma in the anterior medistinum (refer to IHC)

Question 32

What are the IHC findings for T-ALL/LBL?

Answer 32

* Positive: * CD99, Tdt (cytoplasmic and nuclear) * CD2, CD3, CD5, * CD7 * CD34 (variable) * HLA-DR negative * IMP: CD4 and CD8 are either both positive or both negative * TCR genes are rearranged, 20% have IGH arrangements

Question 33

What are the IHC findings of a thymoma to help differentiate it from a T-LBL?

Answer 33

* Thymic T cells coexpress: CD4 and CD8 * Epithelial cells present in thymomas and stain with EMA

Question 34

What translocation and gene are seen in T-LBL with eosinophilia and myeloid hyperplasia?

Answer 34

* 8p11.2 syndrome * invovles the FGFR1 gene

Question 35

What are the criteria from the WHO to assign Acute leukemia with mixed lineage?

Answer 35

* must have following criteria to assign blast populatino \> 1 lineage * Myeloid * MPO or monocytic differentiation (at least 2) * NSE, CD14, CD64, CD11b, Lysozyme * B lineage * need strong CD19 and 1 of the following: * CD79a, cytoplasmic CD22, and CD10 * or weak CD19 and 2 of the following: * CD79a, cytoplasmic CD22, and CD10 * T lineage * cytoplasmic CD3 by Flow * surface CD3 (rare)