ALL (Exam III) Flashcards
Lymphocyte Ontogeny
Starts with a hematopoietic stem cell
- specific growth factor determines if it’s a B or T lymph
Antigen dependent matuaration
- B lymphocytic cells develop in BM
- T lymphocytic cells develop in the thymus (committed cells that migrated there from the BM)
Migrate to secondary lymphoid organs (lymph nodes, spleen and other)
- wait for antigen presentation
Antigen dependent maturation
Lymph node structure
Going from outside in:
Cortex
- B lymphocytes populate outermost region for growth and development
Paracortex
- T lymphocytes
Medulla
- B lymphocytes and plasma cells
Cases of ALL occur in
75% in children
Children have a higher rate of remission (85%) than adults
WBC count in ALL
> 100,000 / ul
More often in T-ALL
ALL symptoms
- Splenomegaly
- hepatomegaly
- thrombocytopenia
- bleeding
- nosebleeds
- bruises
- CNS Involvement
ALL classification depends on
- Molecular and cytogenetics
- Immunophenotype
- Cytochemistry
- Morphology
Most common ALL type
B cell ALL
WHO ALL and Lymphoma classification
ALL
- >25% lymphoblasts in BM (out of all nucleated cells)
Lymphoma (LBL)
- equal or less than 25% lymphoblasts in BM
- Lymphoblastic leukemia process mass lesion elsewhere in the body
Most common Lymphoma
T cell Lymphoma
B cell ALL
- B cell lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
- B cell lymphoblastic leukemia/lymphoma, not otherwise specified
ALL in children, what age is affected a lot?
1-4 years of age
T cell Lymphoma
- Ealry T cell precursor lymphoblastic leukemia
- Natural killer cell (NK) cell lymphoblastic leukemia / lymphoma
T cell Lymphoma
- Ealry T cell precursor lymphoblastic leukemia
- Natural killer cell (NK) cell lymphoblastic leukemia / lymphoma
CALLA
common acute lymphoblastic leukemia antigen
CD10
CD10 =
CALLA
B lymphocyte development review
CHECK POWERPOINT
Plasma cells
secrete antibodies
memory B cell
Contains antibodies on cell surface
CD19 and CD20, CD10(CALLA)
indicates B cell lineage. (ALL)
present when the cell is young
TdT
cytochemistry is used to detect TdT
CD19 + CD20
indicates immature stafes
NOS (not otherwise specified group) of ALL
Lymphoblast morphology
- 2x size of resting mature lymphocyte
- condensed nuclear chromatin
- small scanty cytoplasm
OR/AND
- larger blasts
- dispersed nuclear chromatin
- Moderate Basophilic cytoplasm
Immunophenotype in NOS ALL
- HLA-DR, CD10, CD19, CD20, CD34, cytoplasmic CD22, CD79a
Cytochemistry NOS ALL
MPO neg, SBB Neg, TdT+
Cytochemistry - Terminal deoxynucleotidyl transferase (TdT)
Stains terminal deoxynucleotidyl transferase (TdT) activity
- positive staining = Fluorescence
- Present in PreB and preT lymphoblasts, but not in mature lymphocytes
TdT +
indicates ALL
TdT -
indicates AML
B cell ALL/LBL
t(9;22)(q34;q11)
BCR-ABL1
B cell ALL/LBL
t(v;11q23)
KMT2A rearranges
B cell ALL/LBL
t(12;21)(p13;q22)
ETV6-RUNX1
B cell ALL/LBL
Hyperdiploidy
50-66 chromosomes in lymphoblasts
B cell ALL/LBL
Hypoploidy
<45 chromosomes in lymphoblasts
B cell ALL/LBL
t(5;14)(q31;q32)
IL3-IGH
Eosinophilia
B cell ALL/LBL
t(1;19)(q23;p13)
TCF3-PBX1
Additional immunophenotype marker; cytoplasmic mu
Similar to FAB L3 or Burkitt’s classification
B cell ALL/LBL
BCR-ABL1-like
gene expression present but BCR-ALB1 fusion lacking
B cell ALL/LBL
intrachromosomal amplificaiton of chromosome 21 (iAMP21)
RUNX1 gene on chromosome 21 amplified, more or equal to 5 times
T Lymphocyte development
REVIEW PPT
T cell can become
CD4 = helper ce
CD8 = cytolytic killer cell
CD3 in T cells
mature T cells
CD8 in T cells
suppressor cells
CD4T cells
helper cells
CD7 T cells
Pan T, immature
T lymphoblastic leukemia/lymphoma
cases:
More prevalent in adolescents than children
Males>females
Lymphoblast morphology
T Lymphoblastic Leukemia
- medium size
- prominent nucleoli; occasional nuclear clefting
- moderate cytoplasm
OR/AND
- small size
- HIGH N:C ratio
- Scanty, indistinct cytoplasm
Immunophenotype
T lymphoblastic Leukemia/Lymphoma
Cytoplasmic CD3, CD7 and variable CD1, CD2, CD4, CD5, CD8, CD10
- most identified as Prothymocyte
Possible myeloid CD expression (CD13 and CD34)
Cytochemistry
T cell Lymphoblastic Leukemia/Lymphoma
MPO neg, SBB neg, TdT+
Cytochemistry - Acid phosphatase
stains “acid phosphatase” activity
- has 7 isoenzymes classified
- positive staning - orange/red precipitate
- Present in all hematopoietic cells - T lymphocytes stain stronger than B lymophocytes
Used to differentiate lymphoblasts in suspected acute T cell lymphocytic leukemia
NK Lymphoblastic Leukemia / lymphoma
Little is known about this disease
Immunophenotype
- CD56 (NK cell marker)
- Immature T cell markers present (CD2 and Cd7)
- Myeloid markers absent
- B lymphoid markers absent
Need to exclude Blastic Plasmacytoid Dendritic cell
Leukemia prior to diagnosis
TdT present in
(B cell)
- stem cell
- early pre B cell
- Pre B cell
CD10 and CD19 present in
(B cell)
- early pre B cell
- Pre B cell
- B cell
CD20 present in
(B cell)
- pre B cell
- B cell
TdT present in (T cell)
- prothymocyte
- cortical thymocyte
CD7 presen in (T cell)
- prothymocyte
- cortical thymocyte
- medullary thymocyte
- Mature T cell (peripheral)
CD3 present in (T cell)
- cortical thymocyte
- medullary thymocyte
- mature T cell (peripheral)