myeloid, WBC III, Putthoff, lec Flashcards
myeloid neoplasms come from what
hematopoietic progenitor cells
how do you Dx a myeloid neoplasm
bone marrow, at least 20% blasts
3 categories of myeloid neoplasms
acute myeloid leukemia
myelodysplastic syndromes
myeloproliferative disorders
what type of cancer is from immature blasts in bone marrow that suppress normal hematopoiesis
acute myeloid leukemia
defective maturation of myeloid progenitors leading to ineffective hematopoiesis and cytopenia
myelodysplastic syndrome
what is characteristic of myeloproliferative disorders
increase production in 1+ types of blood cells
what is CD34 on
multipotent stem cell
what is CD64 indicative of
mature myeloid cell
what is CD33
immature myeloid cell
what genes are commonly affected in AML
RUNX1 and CBFB genes that are needed for hemtopoiesis
what are the WHO categories of AML
I AML with genetic changes
II AML with MDS-like features
III AML therapy related
IV AML not otherwise specified
what are the AML not otherwise specificed classifications
M0 minimally differentiated M1 AML w/o maturation M2 AML w/ myelocytic maturation M3 Acute promyelocytic leukemia M4 AML w/ myelomonocytic maturation M5 AML w/ monocytic maturation M6 AML w/ erythroid maturation M7 AML w/ megakaryocyte maturation
what are the common genetic mutations of AML
t 8;21
t 15;17
t 11q23;V
inv (16)
majority of AML is what stage and what is assoc genetic mutation
M2 AML with myelocytic maturation
t8;21
which AML is associated with DIC? stage? age of occurrence?
Acute promyelocytic leukemia stage M3
age 35-40
What AML is peroxidase + and non specific esterase +
AML with myelomonocytic maturation class M4
nonspecific esterase + in AML means what
from monoblast
if auer rods are seen in AML then can tell arised from what lineage
myeloblast
which AML has platelet specific Ag to vWF or GpIIb/IIIa
the megakaryocyte M7
clincal features o fAML
anemia, neutropenia, thrombocytopenia, fatigue, infecitonm bleeding, mucosal bleeding and opportunistic infections
what is leukemia cutis and when is it seen
skin infiltration of tumor on cutaneous skin
seen in monocytic AML
what should you do is suspect AML
karyotyping because 90% associ with abberations
Myelodysplastic syndrome patients are at high risk in develping what
AML
what are types of myelodysplastic syndromes
primary idiotpathic and secondary genotoxic
what are Sx of idiopathic myelodysplastic syndrome
weakness, infections, hemorrhages
how do you Dx myelodysplastic syndromes
bloos mear
bone marrow and cytologic studies
what type of myelodysplastic syndrome is more aggressive and what is onset timing and survival
genotoxic
2-8 yrs post exposure
4-8 mo survival
age onset myelodysplastic syndrome
around 70
what will histo look like in myelodysplastic syndromes
multilobated nuclei of RBC progenitors
ringed sideroblasts, iron laden macrophages
pseudo pelger huet cells (neutrophils with 2 lobes)
megakaryocytes with multiple nuclei
what will you see in peripheral blood in myelodysplastic syndromes
pancytopenia
what is Tx for young patient with myelodysplastic syndrome? older?
young: hematopoietic stem cell transplant
older: suppportive, thalidomide like drugs for 5q variants and DNa methylation inhibitors
what are mutations associated with myelodysplastic syndromes
monosomies 5 and 7
deletions: 5q 7q 20q
trisomy 8– MYC
what mutations occur in myeloproliferative disorders
mutated constitutively activates tyrosine kinase
What is mutation in CML
chimeric BCR-ABL, 9;22
how to Dx CML
fluorescence in situ hybridization or PCR based
leukocytosis >100,000, low LAP
CML preferentially drives what cell lines
granulocytic, megakaryocytic progenitors
what is distribution of CML
50 y.o M>F
clnical features CML
insidious onset: fatigue, weakness, weight loos, anorexia, abdmonial fullness or pain
massive splenomegaly
what shoul dyou suspect in CML patient with severe LUQ pain
splenic infarct
histo of CML looks how
hypercellularity
Macrophages are wrinkled with blue/green cytoplasm “sea blue” histiocytes
what is prognosis CML
3 yr w/o Tx
What occurs within first year of CML
blast crisis and accelerated phase
what is Tx CML
BCR-ABL inhibitors
young- stem cell transplant 75% curable
If LAP measured and is high what do you suspect
reactive (infection
how come myeloproliferative disorders lead to cytopenias
the bone marrow is exhausted and gives up
What occurs in Polycythemia vera
JAK2 point mutation that is activated
dec need for erythropoeitin
increase RBC, granulocytes and platelets
what is the point mutation in PCV
JAK2 valine- phenlyalanine 600
what age group affected PCV and Sx
late middle age
insidious: plethora, cyanosis, intense pruritis, HA, HTN, GI ulceration, splenomegaly, hyperuricemia
What will CBC show for PCV
increase Hct increase RBC increase platelets
basophilia
what accounts for pruritis in PCV
basophilia
what is Tx for PCV
phlebotomy inc surivval 10 yrs
what is first sign of PCV in many patients
DVt or MI or stroke
what is spent stage of PCV
marrow fibrosis and splenomegaly because bone marrow exhausted
What is Essential thrombocytosis
thrombocytosis without PCV
mutaiton in ET
JAK2 or MPL increasing platelet count and megakaryocytes
how Dx ET
bone marrow biopsy and Dx of exclusion
what must you rule out for ET
reactive procress (inflammation or infeciton)
what are Sx and age onset ET
adults>60
insidious
erthromelalgia
what is erythromelalgia
throbbing and burning of hands and feet from occlusion of small arterioles by platelet aggregates
What is Tx for ET
chemo
survival 12-15 yr
What markers are on Langerhans cell histiocytosis
S100+ CD1a+ HLA-DR+
histo of Langerhans cell histiocytosis
vesicular nuclei with linear grooves or folds & vacuolated cytoplasm
birbeck granules in cytoplasm (langerin in granules)
what is mutation in Langerhans cell histiocytosis
valine to glutamate at 600 BRAF
also have TP53 RAS and MET
what are the categories of Langerhans cell histiocytosis
multifocal/multisystemic Langerhans cell histiocytosis
unifocal and multifocal unisystem Langerhans cell histiocytosis
pulmonary Langerhans cell histiocytosis
what are Sx of mutlifocal multisystemic Langerhans cell histiocytosis
cutaneous lesions like seborrheic eruption
HSM, lymphadenopathy, pulm lesions, bones lesions, anemia, throbocytopenia and recurrent infecitons
age Dx multifocal multisystem Langerhans cell histiocytosis
before 2 y.o
sometimes adult
what is Tx for multifocal mulisystemic Langerhans cell histiocytosis
50% survive 5 yrs
what do you see in blood fo unifocal and multifocal unisystem Langerhans cell histiocytosis
langerhans + eos+ plasma cells + lymphocytes + neutrophils
how does unifocal Langerhans cell histiocytosis present
skel system in older children like ribs, skull and femur
how does multifocal Langerhans cell histiocytosis present
multiple erosive bony masses in young children, 50% have DI because involvement of posterior pituitary stlak
What is Hans Schuller christian triad and assoc with?
calvarial defects + DI + exopthalmus
assoc with multifocal unisystem Langerhans cell histiocytosis
Tx for unisystem Langerhans cell histiocytosis
unifocal is resection or irradiation
multifocal is chemo
what is pulmonary Langerhans cell histiocytosis
b/l interstitial lung disease in middle and upper zones
smoking
What are normal markers on langerhans cells
CCR6
neoplastic markers on Langerhans cells
CCR6 AND CCR7!
