Acute leukimia Flashcards
What is Acute leukemia
Rapid clonal proliferation in BM of LYMPHOID or MYELOID progenitor cells
Lymphs and Myelos
What is the FAB classification of acute leukemia
-based on morph and cytochemical staining to diff lymphs from myeloblasts
need to have more than 20% blasts when diagnosing acute leukemias as per WHO
What is tumor lysis syndrome
-complication in patients with malignancy - lymphoma and leukemia with or without treatment
-causes breakdown products of dying cells that cause acute uric acid nephropathy and renal failure
What is tumor lysis syndrome characterized by
HyperKalemia - high K = fatal
hypokalemia - low K
Hyperuricemia - excess uric acid due to cell turnover
Hyperphosphatemia - increased PHO4 due to cell lysis and bone destruction
Hypocalcemia - low calcium due to bone destruction
Laboratory Findings of Acute Leukemia
What we see in BM :
how does it manifest
-Anemia low RBC
Thrombocytopenia
granulocytopenia
expanding leukimic cells
-Fatigue malaise, pallor
bruising , bleeding
fever, infections
bone or joint pain
check slide 7
What are required tests for leukemia as per FAB and WHO
FAB
CBC & hem tests
BM
Flow
WHO
Cytogenetics
Molecular Diagnostics
What will a general CBC/PBS show in Acute Leukemia
CBC
Anemia - N/N
decreased platelets
WBCS variable
PBS
Blasts
NRBCs
Dysplastic features
The BM aspirate for AL should show
% Blasts in all ANC
>20% for acute leukemia
- variable M:E ratio
-look at megakaryocytes
%blasts in non myeloid cells (NEC)
-used for FAB classification
What do you look for in a BM biopsy
Cellularity - hyper cellular not too much fibrosis
Overall structure
What are some reflex hematology tests included in a BM panel
Retic - RBC destruction . BM production or release is response to the anemia
ESR - increased in inflammation and infection but in leukemia its just slightly increased
exception in multiple myloma as it increases IgG in plasma and increasing ESR due to cell stacking
What are the types of cytochemical cells we can use
-help diff between acute myeloid and acute lymphoid
Myeloperoxidase (MPO/MPX) - enzyme stain - granulocytes , primary granules of myeloid cells
Sudan Black B (SBB) - lipid stains (1 and 2 myeloid) and lysosome stain in monocyte
Esterases - Specific(primary granular like myeloblast) stain & Non-specific (positive in monocytes) enyzme stain
Periodic Acid Schiff (PAS)- glycogen stain - abnormal RBC precursors and lymphs
NBE - enzyme stain - alpha napth but esterase monocyte marker
if positive diff between all and aml
What is flow cytometery good for
- produces scatter plot like diff
-addition of monoclonal AB to detect Cluster of differentiation antigens
-CD markers associated with lineage and maturity
34- immature myeloblast and Lymp progenitors
33 - pan myeloid marker
What does cytogenetics help with
-detects chromosomal abnormalities
-Numerical - Trisomy
Structural - deletions, inversions, translocations
Karyotypes and FISH - uses a probe that binds to a chromosome
how does molecular diagnostics help detect residual disease after treatment
- looks at DNA at molecular level - not just chromosome form
-PCR amplifies DNA to detect DNA sequence
What does real time PCR do
- detects single malignant cell amongst millions with labeled probes
- to detect how much residual disease is left
-detects 1(15, 17) to measure minimal residual disease after treatment
What are ALL
- disease of childhood and adolescence
-25% of childhood cancers
-peak between 2-5 years
-rare in adults
-risk increases with age , adults who get are older than 50
-subtype of ALL is important indicator for survival
-Adults have poorer outlook
What are the WBC counts in ALL
WBC increased
Extreme leuocytosis in <15% ALL
Leukopenia in 25%
counts vary
Clonal proliferation in B cell lymphoid progenitors results in =
what do the patients present with
B cell ALL - most common type of ALL
Pts present with
Fatigue due to anemia
Fever - due to neutropenia and infection
Muconutaneous bleeding due to thrombocytopenia
enlarged lymphs
splenomegaly
haptomegaly
bone pain (intramedullary growth of leukemic cells)
-BLASTS WILL BE SEEN IN CSF
What is T cell ALL
symptoms
- when pts have mass in mediastinum
Fatigue from anemia
Fever from neutropenia and infection
Mucocutaneous bleeding and thrombocytopenia
Organomegaly
Bone pain
leukopenia is less severe than B cell ALL
What does the prognosis of ALL depend on
- age at time of diagnosis
-lymphoblast load
-immunophenotype (T cell and Mature B cell have a worse outcome than immature B cell)
-genetic abnormalities
-genetic translocation associated with poorer prognosis
lymphoblast >20-30 X 10^9/L, hepatosplenomegaly , and lymphadenopathy are associated with worse outcome
What are the two morphologic types of lymphs
Small lymphs
large lymphoblast
Small lymph - most common
1-2 times the size of a normal one
-scant blue cytoplasm
indistinct nucleoli
Larger lymphoblast (looks like a MYELOBLAST)
2-3 times the size of lymph (larger ones can be confused with blasts of AML)
PROMINENT nucleoli
nuclear membrane irregularities
What do BM myeloblasts look like
3-5x larger then lymph
moderate blue/grey cyto
-uniform chromatin
2-3 PROMINENT nucleoli maybe AUER RODS
What are the 4 types of immunologically classifed ALL
how are they sorted by genetic abnormality
done through CD markers
Early B ALL - pro B or Pre Pre B
Intermediate B ALL - Common B
Precursor or Pre B ALL
T- ALL
B-ALL 9 types of specific genetic abnormalities t(9, 22)
T ALL no specific genetic abnormalities
Where is T cell ALL seen
- seen in teenage males with:
-mediastinal mass - increased peripheral blast counts
-causes of neurological problems with the meninges of the brain being invovled
-infiltration of extra marrow sites
t cell markers are CD2, CD3, CD4, CD5, CD7, CD8
What type of gene does T ALL have
- gain of function mutation
-NOTCH1 gene alternation that is a signalling pathway responsible for normal T cell development
What type of ALL has the worst prognosis
B cell LL
with t(9,22) translocation , BCR-ALB1 mutation Philadelphia Chromosome - Positive ALL
-most common in adults than in children
B cell vs T cell
B cell
Most childhood ALL
-better prognosis
-many levels of B cell markers
-genetic abnormalities 9 diff classification
T cell
1% of childhood ALL
-poor prognosis
-not specific genetic abnormalities
-less correlation with treatment outcome
What are the 3 groups that the FAB system separates ALL
L1
l2
l3
but this is no longer valid most places rely on immunophenotypic, cytogenetic and molecular findings
What does the L1 classficiation have
-uniform population of blasts
-scant cytoplasm
homogenous pattern
inconspicuous nucleoli
-regular nuclear shape and occasional clefting
What does the L2 classification have
-cellular hetergeneity
- some blasts look like L1 some are larger with abundant cytoplasm
loose chromatin pattern
prominent nuceoli
-nuclear clefting and indentation seen
What does the L3 classification seen as
- large blast with deeply vacuolated basophilic cytoplasm
-Round - Oval nucleus
-known as Burkett type because its similar to what we see in Burkitt’s leukemia
What is AML
symptoms
- most common type of Leukemia
-Peak at 40
-less common in children
fatigue, pallor, bruising , bleeding, fever
Splenomegaly
Bone, joint pain
What does AML present as clinically
non specific decreased production of BM element
CBC with PBA
BM aspirate and biopsy
WBC count can be normal, increased, or decreased
Myeloblasts in PB in 90% of cases
-treatment and prognosis depends on exact diagnosis
anemia, thrombocytopenia, neutropenia, hypercellular BM >20% blast (depending if aberrations are present)
DIC, malignant cells into gums and mucosal sites, splenomegaly, Tumor Lysis Syndrome
Abberation
T(8, 21)
-mutation in 5% of AML
-children and young adults
-myeloblasts with dysplastic, granular cytoplasm, Auer rods
-similar to Fab M2
-see Pseudo Pelger Huet and hypo granulation
-eosinophilia
t(16,16)
5-8 of AML
chromosomal INVERSION
increase in myeloid and monocytic lines
-PB- myeloblasts, monoblasts and promyelocytes
BM- eosinophilia
-central system is site of relapse
mostly younger pts
What is t (15, 17) or APL
- found in younger patients 5-10 of AML cases
-hyper granular promyleocytes - can have AUER rods
-when promylos release their primary granule contents DIC is initiated - sometimes in APL granules are so small that cells look like they have no granules
What is the microgranular variant present in some APL cases
can be confused with other presentation of AML
-presence of Auer rods , butterfly or coin on coin nucleus,
t(9, 11)
rare in AML
-in children
-associated with gingival, skin involvement and DIC
-increase in monoblast and immature monocyte iwth pseudopodia
-blasts are large with lots of cytoplasm and fine chromatin
Acute MYELOID Leukemia -FAB classification grouped on
morph
flow cytometery phenotyping
limited cytochemical reactions
-needs a blast percentage of 20% for peripheral blood
-this category has 25 % of all AML
As per FAB classification
what are we looking for in the BM
% blasts and % mature cells
Early myeloblasts - NO auer rods
Myeloblasts (AUER RODS) alone or with maturation (pros, myelo, and meta)
-promye and blasts
-combo of myelo and mono
-monos only
-RBC mainly
-megakaryocyte
What is AML - FAB MO
Acute myeloid leukemia with minimal differentiation
Mostly Large Agranular Blasts in PB with thrombocytopenia
-Blasts in AML with minimal differentiation
- CD13+, CD33+, CD34+, and CD117+
-AUER RODS absent
-no evidence of cellular maturation
Myeloperoxidase - Negative
Sudan black B - Negative
report ABCL unless you see Auer rods then you would say AML
AML fab m1
Acute myeloid leukemia without maturation
Mostly Blasts and Thrombocytopenia in PB
Blasts in AML without maturation are
CD13+, CD33+, and CD117+ (CD34
-90% nonerythroid cells in BM
- have Auer Rods
-less than 10% of leukocytes show maturation to promyelocyte stage
Myeloperoxidase - Positive
Sudan black B - Positive
report this as an ABCL or as an AML if you see Auer rods in the blasts.
AML - FAB M2
Acute myeloid leukemia with maturation
Blasts with some maturation and thrombocytopenia in PB
Blasts in AML with maturation
>20% blasts in BM
10% maturing cells in neutrophil line = promyelo and metamyelo
<20% precursors with monocytic lineage
-Auer Rods present
Myeloperoxidase - Positive
Sudan black B - Positive
we would report it as either an ABCL or an AML if we see Auer rods.
AML - FAB M3
Acute promyelocytic leukemia
Mostly Hypergranular promyelocytes in PB
-nuclei is bilobed or kidney shaped
- Auer rods in blasts and promyleo can be in bundles
-severe thrombocytopenia
Diagnostic mutation: t(15;17)
Same as WHO
Myeloperoxidase - Strongly Positive
Sudan black B - Strongly Positive
report this as either an acute promyelocytic leukemia (APL) or M3.
What do monoblasts look like
- large with ltos of cytoplasm, small granules, pseudopodia
-large nuc, immature with many nucleoli
AML - FAB M4
Acute myelomonocytic leukemia
significantly increased WBC with thrombocytopenia
-presence of myeloid and monocytoid cells in PB and BM
-left shift with monocytosis in PB
Blasts, Pros, Myelocytes, Monoblasts, Promonocytes, Monocytosis (both 20%)
positive for the myeloid antigens CD13 and CD33 and the monocytic antigens CD14, CD4, CD11b, CD11c, and CD64.
myeloblast can have auer rods
MPO/MPX positive
NBE positive
report it as an acute myelomonocytic leukemia or an M4.
AML - FAB M4 Eo
Acute myelomonocytic leukemia with Eosinophilia
-Same as AML FAB M4, but with >5% eosinophils
-left shift with myeloblasts
-monocytoid cells
-thrombocytopenia
AML - FAB M5 (M5a and M5b)
Acute monocytic leukemias – poorly & well differentiated
Divided into monoblastic and monocytic based on how mature the monocytic cells in PB or BM are
-more than 80% of cells in Marrow will be monocytic
CD14+, CD4+, CD11b+, CD11c+, and CD64+.
Nonspecific esterase – Positive
MPO/MPX - Positive
NBE - Positive
AML - FAB M5a
Acute monocytic leukemia – poorly differentiated
Mostly Blasts with thrombocytopenia in PB
Monoblasts are
large
abundant basophilic cytoplasm
-1 or more prominent nucleoli
-fold cleft nuc
- if there is maturation the cells are called promonocytes
M5a is suspected, report as an ABCL.
AML - FAB M5b
Acute monocytic leukemia – well differentiated
Mostly monocytes and promonocytes with thrombocytopenia in PB
- can look like a monocytosis
>20% blasts in BM
Promonocytes
Large
Abundant Basophilic Cytoplasm
Irregular Nucleus
Granules
Vacuoles
report this as a M5b.
AML - FAB M6
What are the two types
Acute Erythroleukemia (Erythroid/Myeloid)
Pure Erythroid Leukemia
Dimorphic RBCs and RBC precursors with thrombocytopenia in PB
Acute Erythroleukemia (Erythroid/Myeloid)
type of M6
50% normoblasts - all RBC stages
>20% myeloblast in BM
NRBC and myeloid precursor
Pure Erythroid Leukemia
50% Pronormoblasts with >30% basophilic normoblasts
80% of the BM is made up of very immature erythroid cells
- precursors will have multinucleation , megaloblastic asynchrony, NRBC in high numbers in PB
AML - FAB M7
Acute megakaryoblastic leukemia
Micromegakaryocytes, pleomorphic blasts with agranular cytoplasm
- giant plts or normal ones
-delicate chromatin with prominent nucleoli - immature MK can have light blue cytoplasmic blebs
-CD42b positive
