Leukocyte Disorders Flashcards
Pelger-Huet Anomaly presentation
hypo-lobated nucleus in neutrophils
what causes Pelger-Huet Anomaly
a mutation causing decreased expression of the lamin-beta receptor
what is the lamin-beta receptor
a protein in the inner nuclear membrane
what does a decrease in expression of the lamin-beta receptor do
affects chromatin distribution and nuclear shape
how is Pelger-Huet anomaly inherited
autosomal dominant
does Pelger-Huet anomoly effect cell function
no
in what conditions can you see pseudo Pelger-Huet
MDS, AML, CML multiple myeloma, drugs and chronic infections
Alder-Reilly anomaly presentation
large pink granules in neutrophils and lymphocytes
what is the cause of Alder-Reilly anomaly
cells are unable to breakdown mucopolysaccharides due to a lack of enzymes
what does Alder-Reilly anomaly cause
altered WBC function, severe mental retardation, dwarism, organomegaly and skeletal deformities
what is the inheritance of alder-reilly
recessive
what is the inheritance of Chediak-Higashi
autosomal recessive with a LYST gene mutation
what does Chediak-Higashi cause
aggregation of primary and secondary granules forming large abnormal lysosomes with defective degranulation and diminished delivery of enzymes to phagosomes
what is treatment for Chediak-Higashi
antibiotics and high doses of ascorbic acid
what other types of cells are effected by Chediak-Higashi
platelets and melanocytes
presentation of May-Hegglin anomaly
large blue inclusions in all granulocytes that resembled dohle bodies
what is the inheritance of May-Hegglin anomaly
autosomal dominant
what do you typically see in May-Hegglin anomaly
thrombocytopenia and giant platelets
what causes the May-Hegglin anomaly
a mutation in MYH9 gene that encodes cytoskeletal proteins in platelets
what does the May-Hegglin anomaly effect
usually asymptomatic but sometimes have bleeding issues
what is chronic granulomatous disease
a neutrophil disorder that is unable to initiate respiratory burst and produce superoxides
what is the inheritance of CGD
usually x-linked but also autosomal recessive
what is the cause of CGD
mutations in genes responsible for producing NADPH oxidase complex
what does CGD cause
reoccuring fungal and bacterial infections in lungs, deep tissues, skin, lymph nodes and liver
how id CGD diagnosed
testing of neutrophils using nitro-blue-tetrazolium reduction tests or glow cytometry
what causes infectious mononucleosis
epstein-barr virus
how does infectious mononucleosis present
elevated WBC, absolute lymphocytosis, reactive lymph
what can infectious mononucleosis lead to
cold agglutin syndrome
what are possible causes of leukemia
radiation, chemotherapy drugs, chemicals and drugs, viruses
what conditions can leukemia occur secondary to
hematological diseases, genetic predispositions, immunodeficiencies
what characterizes an acute leukemia
sudden onset of symptoms, >20% blasts in PBS
what are the general lab findings in the PBS of acute leukemia
anemia, thrombocytopenia, neutropenia, >20% blasts
what are the general lab findings in the BM of acute leukemia
high M:E ratio, infiltration of blasts
what are the characteristics of myeloid blasts
large with moderate dark blue/grey cytoplasm, azurophilic granules, chromatin is fine and lacy, numerous round or oval nucleoli, may contain auer rods
what are the characteristics of lymphoid blasts
smaller than myeloblasts but larger than mature lymphs, scant cytoplasm, chromatin is denser, scant nucleoli, usually no granules
what does myeloperoxidase stain
primary granules of granulocytes and monocytes
what does sudan black stain
cellular lipids (more sensitive for early myeloids)
what does NSE stain
monocytes and megakaryocytes
what does PAS stain
glycogen inside the cytoplasm of the cell (lymphoblasts will be strongly positive)
what is TdT
a DNA polymerase present in stem cells and early lymphoid cells
what are the CD markers in B cell lymphoblastic leukemia
34, 10, 19, 20, 22, 24, 79a, TdT
what are the CD markers in T cell lymphoblastic leukemia
1, 2, 3, 4, 5, 7, 8, TdT
What are the general conditions for AML
blasts of myeloid lineage with >20% blasts, neutropenia, thrombocytopenia and anemia
What are the lab findings for ALL
blasts
increased WBC
decreased PLT
normo/normo anemia
neutropenia
What are confirmatory tests for ALL
MPO negative
PAS block positive
What are lab findings for AML
blasts with auer rods
increased WBC
decreased PLT
normo/normo anemia
neutropenia
What are confirmation tests for AML
MPO positive
SBB positive
NSE positive
What are lab findings for APL
hypergranulated promyelocytes
faggot cells
bilobed nucleus
What are confirmatory tests for APL
MPO positive
SBB positive
What are lab findings for AMML
neutrophils and monocytes
20%+ blasts
decreased PLT
neutropenia
normo/normo anemia
increased monocytes in PBS
What are confirmatory tests for AMML
MPO positive
SBB positive
NSE positive
What are lab findings for AMonoL
monoblasts
monocytic precursors
auer rods in monocytic leukemia
What are confirmatory tests for AMonoL
NSE positive
What are lab findings for AEL
> /= 50% normoblasts in BM
/= 20% myeloblasts in BM
nRBC in PBS
dysplastic precursors
What are confirmatory tests for AEL
PAS positive
NSE positive
What are lab findings for AMegL
> /= 50% megakaryocytes
large-medium in size
can be agranular
circulating megakaryocytes in PBS
hypogranular neutrophils
giant PLT
What are confirmatory tests for AMegL
PAS positive
NSE positive
What can CLL progress into
autoimmune hemolytic anemia
What are lab findings for CLL
normo/normo anemia
increased WBC
lymphocytosis
neutropenia
normal/decreased PLT
smudge cells
What are confirmatory tests for CLL
CBC/smear
immunophenotyping
cytogenetics
What are lab findings for hairy cell leukemia
small lymphs with hair like fibriae
normo/normo anemia
decreased PLT
What are confirmatory tests for CLL
trephine biopsies (fibrosis)
CBC/smear
TRAP stain
immunophenotyping
annexin I positive
What are lab findings for plasma cell myeloma
normo/normo anemia
plasma cells in PBS/BM
IgG/IgA increased
normal/decreased WBC
neutropenia
normal/decreaed PLT
rouleaux
decreased retics
flame cells in BM
mott cells in BM
ostolytic lesions
What are confirmatory test for plasma cell myeloma
increased ESR
PT/PTT abnormal
bence jones proteins in urine
M protein on immunofixation
increased serum Ca
What are lab findings for walderstrom macroglobinemia
increased IgM
normo/normo anemia
neutropenia
decreased PLT
rouleaux
plasmacytoid lymphs
What are confirmatory test for walderstrom macroglobinemia
decreased serum calcium
increased ESR
PT/PTT abnormal
bence jones proteins in urine
What are lab findings for CML
normo/normo anemia
increased WBC
normal/increased PLT
left shift with blasts
nRBC
increased eos/basos
increased M:E
What causes CML
BCR-ABL-fusion gene of the philidelphia chromosome
What are confirmatory tests for CML
CBC/smear
LAP stain negative
cytogenetics
molecular genetics
immunophenotyping
What causes PV
a mutation of the Jak 2 gene V617F
What are lab findings for PV
all cell lines proliferate uncontrollably (independent of EPO)
normo/normo anemia that can turn hypo/micro
increased HT
increased HGB
marrow fibrosis
splenomegaly
What can PV progress to
acute leukemia
What causes secondary PV
increased EPO due to tumor, chemical exposure, or drug abuse
only effects RBC lineage
What causes relative PV
decreased plasma due to dehydration or smoking
What are lab findings for primary myelofibrosis
increased prolifereation of granulocytes and megakaryocytes
fibrosis in the BM
tears, eliptos, myeloid precursors
hypercellular BM in stage 1
normo/normo anemia
What can primary myelofibrosis progress to
AML
What are confirmatory tests for primary myelofibrosis
trephine biopsy
genetic testing
molecular testing
What are lab findings for ET
larg/hypogranular/clumping PLT
decreased HGB
increased PLT (600-1000+)
megakaryocyte fragments
normo/normo anemia
mild leukocytosis with left shift
What are confirmatory tests for ET
iron stores in BM decrease over time
genetic testing
molecular testing
What are lab findings for MDS of granulocytes
hypogranulation
hypersegmentation
hyposegmentation
karyorrhexis
megaloblastic changes
mitotic figures
decreased WBC
What are lab findings for MDS of Erythroid
tears
macro/macroovalocytes
micro
hypo
schisto
acantho
spheros
elipto
HJ/BS
normo/normo anemia
dimorphic picture
nRBC
What are lab findings for MDS of megakaryocytesB-lymphocytes
agranular or hypogranular
giant PLT
micromegakaryocytes
PLT clumps
decreased PLT
increased blasts
nRBC
What are the main cells effected by CLL
B-lymphocytes
What is hairy cell leukemia a subclass of
CLL
What CD markers are unique for hairy cell leukemia
103, 11c
What is monoclonal gammopathy of undetermined significance
when M protein is detectable but too low for diagnosis of other B-cell neoplasms
What are the four subclasses of plasma cell myeloma
asymptomatic, non-secretory, symptomatic, plasma cell leukemia
What is hodgkins lymphoma
a rare disorder of the lymph nodes of the upper body
reed-sternberg cells (owl-eyes) are found in lymph node biopsies
What is non-hodgkins lymphoma
originates anywhere in the body with lymphatic tissue
does not have reed-sternberg cells
What are the three phases of CML
chronic, accelerated, blast
What are treatments for CML
tyrosine kinase inhibitors
inteferon-alpha
bone marrow/stem cell transplants
synthetic proteins that inhibit BCR-ABL protein
immunotherapy
What is treatment for PV
therapeutic phlebotomy to reduce blood viscosity
myelosuppressive therapy
tyrosine kinase inhibitors
targeted molecular therapy
What are the three phases of primary myelofibrosis
initial, fibrotic, blast
What is the treatment for primary myelofibrosis
chemotherapy
drugs to improve cytopenia and anemia
blood transfusions
splenectomy
stem cell transplant
targeted molecular therapy
What is the pathophysiology of primary myelofibrosis
an overproduction of hematopoetic stem cells leads to increased proliferation of granulocytes and megakaryocytes
malignant or neoplastic megakaryocytes will release fibroblastic growth factors which activates the fibroblasts which causes an uncontrolled assembly of collagen that brings fibrosis
What can ET progress to
AML
What is the treatment for ET
anticoagulant therapy
phlebotomy
plateletpheresis
targeted molecular therapy
drugs which suppress production of platelets
What can cause myelodysplastic syndromes
exposure to chemicals
smoking
predisposition due to family history
