White Cell Disorders Flashcards
What is the cell finding in Chediak Higashi?
Defect in?
Associated with?
What makes this disease worse?
White cells/PMN with large granules
CHS1 (LYST) gene and lysozyme function; microtubule issues
Occulocutaneous albinism, neuropathy, plt dysfunction
EBV common to start accelerated phase
MYH9 diseases has what findings?
Inheritance pattern?
Finding in WBCs?
Large plts, thrombocytopenia, hearing loss, cataracts, and glomerulonpehritis
Auto dom
Dohle bodies: small purple cytoplasmic inclusions; Normal neutorphil function
What is Alder Reilly anomaly?
What do you seein WBCs/special stain?
Neutrophil function?
Auto recessive disease; lysosomal enzyme don’t break down muopolysacchardies
Dense metachromatic azurophilic granules in ALL WBCs; PAS+
Normal neutrophil function
What is Pelger-Huet anomaly/micro finding?
Clinical significance?
Hypolobated neutrophil; Auto dom disorder lamin B receptor
No significance
DDx: Peudo Pelger Huet cells in MDS (only some hypolobated)
Gaucher disease machophages look like?
Issues with?
Tissue paper (folded blue cytoplasm)
Glucorerebroside accumulation and glucocerbrosidase deficency
Niemann-Pick macrophage morphology?
Issue with?
Foamy, vacuolated cytoplasm
Sphringomyelin accumulation/ sphingomyelinase deficiency
Atypical lymphocytes associated with?
Cell type?
Morphology?
LGL’s are what kind of cell?
NK/T LGL leukemia (months and cell count)?
Infection, EBV, HIV, etc
CD8+ T-cells reacting to infected B-cells
Cytoplasm with edge that is darker and scallops RBCs
LDL: Cyto T and NK with granules (CD3, CD16, CD56+)
>6 months, >2000 cells, cytopenias
Hematogones look like?
Flow markers?
How to seperate from B ALL?
Blasts
Cd20, CD10, CD34, TdT+
B ALL has CD10-
Myeloblasts have?
Monoblasts have?
Promyelocyte features?
Auer rods (primary granules fused); or granuloles
Mono: Very fine granules, blue gray cytoplasm
Single or bilobed nuclei, hypo or hyper granular cyto with Auer rods
ALL has what PAS staining pattern?
AML staining with Sudan black?
AML nonspecific esterates/ if 2 colors?
Lymphoblasts: BLOCK POSITIVITY
Myeloid cells: Weak
Sudan black: Myeloid marker marks lipid
Alpha napthy acetate, alpha napthyl butyrate–NSE
IF 2 COLORS THEN MYELOMONOCYTIC LEUKEMIA
Acute myelomonocytic leukemia definition?
Flow?
What classic clinical finding?
>20% blasts (promonocytes count); >20% neutorphils and myeloid precursor, >20% monocytes and promonocytes
Gingival hyperplasia
CD4 +, CD 16+
Acute monoblastic and monocytic leukemia definition?
>80% monocytic cells
M5a: 80% >Monocytic cells and monoblasts
M6b: <80% monocytic cells are monoblasts
Pure erythroid leukemia definition, cytoplasmic finding?
Postive stains?
Erytholeukemia requirements?
>80% erythroid, >30% erythroblasts, blue cytoplasm with possible vacuoles
E-cadherin, glyophorin, CD71
Trick question:
Now called AML with MDS related changes (>20% BLASTS); or MDS with Excessive blsts (<20% blasts)
Acute megakaryoblastic leukemia definition?
Genes excluded?
Markers?
>20% blasts; 50% of blasts must be megakaryoblasts!; BM fibrosis common
t(1;22), inv (3), t(3;3); and Downs syndrome related
EM (platelet preroxidase), CD41, CD61, CD42 +
Good prognosis AML recurrent genetics (3 of them)?
t(15;17), t(8;21); inv16
APL has what transolation/genes, cyto findings?
Reason we need to dx quickly?
Phenotype?
Tx?
t(15;17)(q22;q12) PML-RARA; see Auer Rods
>20% blasts
DIC
Myeloid +, CD34-, HLA-DR -, CD15-; DO NOT DX ON FLOW ONLY!
All trans retinooic acid and conventional chemo
APL ATRA resistant translocations?
Is there a microglandular variant of APL, what to lok for?
t(5;17)(q23;q12); 5-nucleophosmin gene
t(11;17)(q13;q21): 11 nculear matrix associated
t(11;17)(q23;q21); ZBTB16 (PLZF)
YES: bilobed BUTTERFLY CELLS!; same ATRA response
AML t(9;11)(p22q23) is what genes?
What differentiation?
Risk?
Population?
MLLT3-KMT2A
MONOCYTIC diff
Intermediate risk
More common in kids
AML t(6;9)(p23q34) genes?
Common finding?
Prognosis?
DEK-NUP214
INCREASED BASOPHILS
POOR
AML inv(3) or t(3;3) genes?
Classic finding?
Prognosis?
GATA2-MECOM (EVI1)
Dysplastic hypolobated megas
Poor
AML t(1;22) genes?
Cell type?
Population of patients?
DDx?
RBM15-MLK1
Megakaryoblasts
Kids under 3
Myeloid leukemia of Downs or Transient abnormal myeloporesis
Prognosis of therapy related AML from akylating agents?
Of topoisomerase II inhibitors?
Poor!; MDS associated; 3-5 years after
Better; not associated with MDS; Monocytic; better prognosis
AML normal karyotype:
NPM1 prognosis?
CEBPA prognosis?
FLT3-IDT?
FLT3 TKD?
NPM1; good pronosis IF NO FLT3-IDT
CEBPA: Favorable
FLT3 ITD: Poor and resistance to chemo
FLT3-TKD: Pronosis controversal
Who gets BLL?
Where does it present vs TLL?
Prognosis vs TLL?
Kids <6 (good prognosis); adults rare and bad
BM and Peripheral blood; TLL as mediastinal mass in kids
Better than TLL
B ALL flow markers?
What about CD20?
What about Pax5?
TdT+, CD34+, CD10+/-. CD45-, Surface immuno -, Aberrant myeloid markers (eg CD13, CD15, CD33)
Expressed later as Pre B (earlier pro B’s are negative)
Pax5 is positive in B lymphoblastic leukemia
B-LBL good prognosis genes, age?
B-LBL poor prognosis, genes and age?
t(12;21) ETV6-RUNX6
Hyperploid>50
Age 1-10
Poor: Hypodiploid, t(9;22) BCR-ABL, 11q23 MLL; t(4;11) MLL/AF4, RUNX1 amplification and complex abnormalities
t(4;11)
t(12;21)
t(9;22)
In ALL what age group (infant, kids, adult) are the translocations in?
t(4;11) infant
t(12;21) kid
t(9;22) adult
TLL occurs where?
Immunophenotype?
Medistinal mass commonly
TdT+
Variable T-cell marks: Cd1a, CD2, CD3, CD4, CD5, CD7, CD8
CD7 and cCD3+ commonly
CD10+
CD13, 33+
RARE CD117 and CD79a
What chr has Alpha and delta TCR?
B TCR?
Gamma?
What genetic finding is rare but commonly seen?
A/Delta: 14q11.2
Beta: 7q35
Gamma 7p14
t(7;9) NOTC1 (<1% however)
Myeloid neoplasms with eosinophils have what mutations?
Mastocytosis mutation?
PDGFRA, PDGFRB, FGFR1
Masto: KIT D816V
JAK2 most common mutation?
Associated with?
V617F; 5% exon 12 adn 13 issues
PV 95%, ET 50%, PMF 50%
Essential thrombocythemia, definition?
Survival?
Mutations?
BM findings?
MPN in megakaryocytes, >450e9 platelts/L
Good >80% 5 yr
JAk2 V617F, CLAR 30%, MPL W515L (<5%)
BM: Normocellular, large cluster, hyperlobated megas, NO FIBROSIS
PCV criteria?
3 phases?
Hemagloblin >16.5 g/dL in med or 16.0 g/dL women, elevated hematocrit >49% men, >48% women or incread RBC mass
Increased BM cellularity with trilineage group but prom erythroids
JAK2 V617F or exon 12 mutation
Phases: Pre, Overt, Spent (decreased RBCs, fibrosis, spleen enlargement)
Primary myelofibrosis is important becasue?
Peripheral blood has?
Mutations?
BM?
BAD PROGNOSIS
Leukoerythoblastic reaction (blastic immature white and red cells) and tear drop cells
50% JAK2 V617F, CALR 25%, 5% MPL
Pre: Manmyelosis with megakaryocytes with dysplasic >>other MPNs
Fibrotic: Reticulin/collagen fibrosis/ 10-19% blasts=accelerated phase, OSTEOSCLEROSIS
ET vs prefibrotic PMF?
PMF has more panmyelosis, more dysplastic megs, AND leukoeyrthroblastosis
CML has what gene?
Clinical presentaiton?
LAP score in CML?
PB shows?
Do you need BM?
t(9;22) BCR-ABL1 fusion; turns on TK
Splenomegaly, anemia, weakness
CML: decreased, LAP increased in other MPNs (old test)
WBC >50,000 with myelocytic cells at all stages of development
Molecular testing needed, BM not needed to dx but to stage (BLASTS)
CML chronic phase, accelerated, blast?
Blast has what additional cytogenetic changes?
BM findings?
Chronic: <10%
Accelerated 10-19%
Blasts >20% myeloblasts or lymphoblasts with addition changes +Ph, i(17q), +8, +19
BM: Hypercellular, meyloid hyperplasia, Left shift, small clustered hypolobated megs, Pseudo-Gaucher cells (sea blue histeocytes)
ABL1 kinase mutations cause?
Is BCR-ABL1 specific for CML?
Major
Minor
u?
Resistance to TKI therapy
No seen in ALL and CNL (chronic neutrophilic leukemia?)
Major: 210kd CML
Minor: p190 seen in B-ALL
u: p230 CNL
CMML lacks?
What is atypical CML; gene associated?
BCR-ABL1 but has peripheral blood monocytosis
Looks like CML but is BCL-ABL1 negative; Dysplasia, SEPBP1
MDS needs dysplasia in what %?
BM; hyper/hypocellular in MDS?
Good MDS genetics?
Intermediate?
Poor?
At least 10% in one lineage!
Mostly hyper but can be hypo!
Side not: lots of gains and losses of chromosomes
Good: Normal, -Y, del(5q), del (20q)
Interemdiate: other
Poor; >3 abnormalities (complex), Chr7 abnormalities
MDS isolated deletion of 5q progonsis?
PB?
BM finding?
Genes that are lost?
Tx?
Good!
PB: Macrocytosis and thrombocytosis
BM: Small hypolobated mega
RPS14, SPARC, TN1P1
Lenalidomide
MDS in kids:
Findings vs adults?
What cells tend to be dysplastic?
Hyper or hypocellular?
More neutropenia, thrombocytopenia than anemia
More neutrophil and megakaryocyte dysplasia
Hypocellular
Myelodysplastic/Myeloproliferative neoplasms:
CMML definition?
Mutations?
Blood monocytosis >1e9 /L
CD123+ (plasmacytoid dendridic cell); CD13, CD14, CD68, CD64 and CD33 +
ASXL1, TET2, SRSF2, KRAS, NRAS, SETBP1
Juvenile myelomonocytic leukemia?
Patient population?
Genes?
Most common cytogenetic?
Hb lab finding?
Associated with?
Drug?
Prognosis?
Childhood proliferation of myelonocytic cells
RAS, MAPK, NRAS, KRAS, NF1, CBL, PTPN11
Mono 7 most common
Increased HbF
NF1 or Noonan
Increased sensitivity to GM-CSF
Poor
