White Blood Cell Disorders Flashcards
Chediak Higashi Syndrome
CHS1 (LYST) gene mutation
Lysosome defect in WBCs and other cells (platelets, neurons, etc.)
Very large inclusions
Poor phagocytosis
Related to albinism
MYH9 Related Disorders
May Hegglin (and Sebastion, fletcher,epstein… now all included)
Large Platelets, thrombocytopenia, hearing loss, cataracts, glomerulonephritis
Dohle bodies (endoplasmic reticulum, RNA)
NORMAL FUNCTION
Alder Reilly Anomaly
no lysosomes to break down mucopolysaccharides. (Hurler’s, Hunters)
Dense Metachromatic granules
in all WBCs
PAS+
Autosomal Recessive
NORMAL NEUTROPHILS
Can get some of these in MDS, but would not be all the cells
Pelger-Huet anomaly
Bi-lobed nucleus neutrophils
neutrophils NORMAL
No clinical significance
Autosomal dominant, with laminin B receptor mutation
AML 15:17 translocation
15 : 17 Translocation
Acute Promyelocytic Leukemia
Severe DIC association
Creates fusion protein: PML-RAR alpha blocks maturation beyond promyelocyte
Therapy: Al-trans retenoic acid
Die in 90% cases if not treated. 90% survive with treatment
BI-lobed nucleus
variants:
hyper granular - can have auer rods
micro granular -granules too small my light microscopy (may have auer rods too)
CD13, 33, 117 (typically lack blast markers 34 and DR)
CD2 in micro granular
AML 8:21
good prognosis
core binding factor brings core binding factor to eto
associated with M2
CD19, PAX5, CD56
may have less than 20% blasts but still counts
AML Inversion 16
good prognosis
core bind factor beta with smooth muscle myosin heavy chain
AML M4 (myelomonocytic with eosinophils)
increase eosinophils (may have basophil granules too)
AML 9:11
mixed lineage
monocytes differentiation
seen with trisomy 8
most commonly in kids
AML 6:9
dec and muc214
basophilia
multilineage dysplasia
pancytopenia
FLT3
poor prognosis
AML Inversion 3
increase bone marrow megakaryocytles hyperlobated
poor prognosis
AML 1:22
m7
organomegaly
hepatosplenomegaly
associated with down syndrome
transient abnormal myelopoiesis early in life (does not progress)
ALL 4:11
negative for CD10
coexpressions of myeloid antigens
ALL hyper diploid or 12:21
children
25% of kids with ALL
good prognosis
ALL 9:22
adults (25%)
philadelphia chromosome
poor prognosis
T cell ALL :
mutations in T cell receptors
notch1 activating in 50% of pediatric cases - good prognosis
CML 9:22
philadelphia chromosome
JAK2 activation
tyrosine kinase that intracellular mediates intracellular signaling
ErythroPoietin, Thrombopoietin
polycythemia vera (90%) and others around 50% (ET, PMF)
usually V617F mutation, but a few are exon12 or exon13
not a prognostic marker
CD56
Natural Killer Cells
CD3+ , CD4-, CD8-
Gamma/Delta T cells
CD 117
highly specific for myeloid leukemias
Myeloblasts
typically positive for MPO, CD13, CD33, and CD117
Hairy Cell Leukemia
Strong CD20+, CD25+, annexing A1 +
bone marrow fibrosis common
monocytosis common
usually no adenopathy
spleen, peripheral blood, bone marrow, and the liver
The phenotype of HCL is CD20 +, CD25 +, CD103 +, and tartrate-resistant acid phosphatase (TRAP) +
Follicular Lymphoma
BCL2 rearrangement, CD10 +
t14:18
Burkets Lymphoma
MYC rearrangment
Mantle Cell Lymphoma
t(11:14)(q13;q32) in CCND1-IGH
DLBCL
t(3;14)(q27:q32) BCL6-IGH
CD10- (germinal center)
fast grow, necrosis
CLL
CD5+ , CD23, CD20 dim, low or undetectable Ig light changes
13q- favorable (other changes unfavorable)
commonly transforms to DLBCL (Richter transformation)
NK Cells
CD 4+ , CD8 - , CD3- , CD56!
Gamma Delta Cells
CD3+, CD4-, CD8-
Mixed Lineage Lymphoma
CD10-, CD15+
Mycosis fungicides and Sezary syndrom
CD2+, CD5+, cd3+, cd4+, loss of CD7
MF - indolent
SS - poor prognosis, depends on PB skin, lymphoma node involved
CD45
positive on all cells except erythrocytes, so used to do initial gate for white cells
mature express brightly, immature dim
blast gate is low side scatter and dim 45
HLH
soluble cd25
Systemic mastocytocis
CD2 or CD25 positive mast cells
Activating mutations of KIT
Elevated serum tryptase
Gaucher Disease
Tissue paper cytoplasm with striations
Glucoceroroside accumulation
Glucocerorosidase deficiency
Niemann-Pick Dz.
Foamy macrophages
vacuolated cytoplasm
Sphingomyelin accumulation
Sphingomyelinase deficiency
Hematogones
Benign B cell Precusors in Bone marrow
recovering marrows, pediatric patients
“Blastlike”
Flow - look for maturation of CD20 (some have it, more get it as they get older)
Versus B-ALL - no loss of CD10
Cytochemistry PAS
- PAS for lymphoblasts with block positivity.
- weakly and diffusely for myeloblasts
Cytochemistry Myeloid
- MPO
- myeloid only
- enzyme degrades with time
- Sudan Black B
- stains lipids for myeloid
- Non-specific esterase
- Alpha-naphl butyrate and acetate
- Monocytes
AML with Recurrent cytogenetic abnormalities
- exception to rule of needing 20% blasts
- t(15:17) PML-RARA
- RUNX1-RUNX1T1
- Inv 16
- AML w/BRC-ABL fusions
Acute Myelomonocytic
- both myeloid and monocyte
- > 20% blasts includes promonocytes
- > 20% neutrophils and myeloid precussors
- > 20% monocytes and promonocytles
- CD4, CD16
- some cells folded (monocytes), some myeloid
- Gingival hypertrophy
Acute Monoblastic and Monocytic Leukemia
- > 80% of cells are monocytic
- M5a - > 80% of these are blasts
- M5b - < 80% of these are blasts
- Myelomonocytics antigens expressed
Pure Erythroid Leukemia
- cytoplasmic vacuoles
- dark blue cytoplasm
- positive e-cadhedrin, glycophorin, CD71
- >80% cells are erythroid
- >30% erytroblasts
- No myeloblastic component
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Acute Megakaryoblastic Leukemia
- 20% blasts, 50% are megakaryoblasts
- small cytoplasm, blebbing
- reticulin fibrosis
- lots of megakaryocytles
- CD41, CD42, CD 61
B-lymphoblastic leukemia lymphoma
- Mostly children < 6 y.o.
- good prognosis children
- poor prognosis adults
- usually presents in PB and BM
- overall better survival than t-cell
B-ALL Phenotype
- Blasts, TdT, CD34
- B-cell markers (CD19, CD20 may be negative)
- CD10 +/- , CD45 usually negative
- Surface Immunoglobulins usually negative
- Aberrant co-expressions of myeloid markers (CD13, CD15, CD 33 is common and should not be confused with AML)
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T-lyphoblastic lymphoma/leukemia
- Children or adults
- mediastinal mass presenting often
- TdT+
- Variable expression: CD1a, CD99, CD2, CD3, CD4, CD5, CD7, CD8
- CD4+ CD8+, CD4- CD8-
- CD7 and cCD3 are most often +
- CD13 and CD33 often present (myeloid)
- Rare CD117 (myeloid) CD79a (b-cell)
T-ALL Genetics
- 30% have translocations involving T-cell receptor on chromosomes 7 and 15
- Partner genes of fusions: Myc, TAL, etc.)
- Notch mutations t(7:9)
Essential Thrombocythemia
- MPN with proliferation of megakaryocytles and sustained thrombocytosis
- > 450,000 platelets
- hemorrhage or thrombosis
- good prognosis
Polycythemia Vera
- Hgb > 16.5M 16.0W
- Jak2 Mutation
- Hypercellular bone marrow
- 3 phases
- prepolycythemic
- overt polycythemic
- spent phase
- cytopenias, fibrosis
- Lab tests:
- Low EPO
- Endogenous erythroid colony formation
Primary Myelofibrosis
- A BAD myeloproliferative disorder! (worse than ET, PV)
- Megakaryocyte and granuloctyle proliferation leads to fibrosis
- Mutations JAK2 V617F 50%, 25% CALR, 5% MPL
- Peripheral Blood
- Leukoerythroblastic reaction (leukoblasts and nucleated red cells)
- Teardrop cells (dacrocytes)
- Bone marrow usually fibrotic
- atypical megas
- osteosclerocis
- There is a pro-fibrotic phase
CML BCR-ABL+
- Defined by BCR-ABL t(9:22) Philadelphia chromosome
- FISH or RT-PCR must be performed if cytogenetics is negative
- Presentation
- median age 50 yo
- splenomegaly (70%), anemia, fatigue, weight loss
- LAP Score decreased (increased in leukomoid and other MPNs)
- CML is Peripheral blood diagnosis
- leukocytosis >50,000
- myeloid cells at all stages of development
- myeloid bulge
- basophilia
- Do a bone marrow to establish phase of disease
- Chronic <10% blasts
- Accelerated 10-19%
- Blast phase > 20% blasts OR extrameduallary blasts
- 70% myeloid
- 30% lymphoid
- Hypercellular, myeloid hyperplasia, left shift, small megas, clustered
- Molecular:
- constitutional tyrosine kinase activity
- use inhibitors for tx:
- imatinib, nolotinib, dasatinib
- RT-PCR used for minimal residual disease
- ABL1 Kinase mutations may decrase effectiveness of tx
- Major Breakpoint 210 kD (minor 190 kD seen in ALL and CNL)
Myelodysplastic Syndrome
- Ineffective hematopoiesis, cytopenias, dysplasia in one or more myeloid lineages
- <20% blasts
- dysplasia >10% of cells
- ringed sideroblasts (iron in mitochondria)
- can go on to AML
- increased infection and bleeding from low platelets
- can have hypercellular marrow
- CD 34 shows increased blasts (but less than 20%)
- tend to see numeric gains and losses in chromosome segments (-5, -5q, -7, -8, etc..)
- if more than 3 abnormalities, poor prognosis
- isolated -5q, -Y, -20 good prognosis, others bad
- translocations rare
- chromosome 7 abnormalities poor prognosis
- Flow not used for diagnosis
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Juvenile Myelomonocytic leukemia
- Childhood proliferation of myelomonocytic cells
- RAS, MAPK, NRAS, KRAS, NF1 , CBL, PTPNF11
- Monosomy 7 most common
- increased in patients with neurofibromatosis (noonans syndrome)
- poor prognosis
- Dx:
- Monocytes > 1000
- <20% blasts
- no BCR-ABL
- splenomegaly
- increase HgF
t(11;14)(q13;q32)
Mantle Cell Lymphoma
t(11;18)(q21;q21)
MALT
t(14;20)
Multiple Myeloma
other mutations as well t(11;14) is good prognosis
14q32 (IGH) rearrangements seems in 50%\
addition of 1q deletion is poor prognosis
also trisomies of odd numbered chromosomes
t(x;18)
Synovial sarcoma
Anaplastic Large Cell Lymphoma, ALK+
t(2;5)
best prognosis in children
t(3;14)
DLBCL
