Exam 4 Flashcards
What kind of genetic issue is there with the Philadelphia chromosome
translocation on chromosome 9 and 22 (t9,22)
What is the difference between a leukemia and a lymphoma
leukemia- originate in the BM, cells get into peripheral blood, lymphoid tissues and other organs
Lymphoma- originate in the lymphatic system, cells can circulate in peripheral blood
Describe the differences between acute and chronic leukemias
acute- sudden, onset, rapid, quicker death, variable counts, excess blasts
chronic- insidious/ slow, longer survival, usually high WBC count, too many mature cells
What are the 3 hematologic neoplasms
leukemias
lymphomas and
myelodysplastic syndromes (MDS)
What leukemia is more common in children
ALL- Acute lymphoblastic leukemia
What leukemia is more common in adults
CLL- Chronic lymphocytic leukemia
Describe FAB vs WHO classifications of leukemias
FAB- based on morphology
WGO- more precise, based on clinical features, genetics, morphology
What are epigenetic mechanisms
mechanics that control how genes are expressed and silenced
What are protooncogenes
encode for proteins that are essential for normal cell function.
What is an oncogene
a mutation of a protooncogene with leukemogenic potential
if activated could become malignant
What is a qualitative mutation
structural change to the protooncogene and production of an abnormal protein product
What is a quantitative mutation
overexpression of a normal protooncogene in a HSC
What are tumor suppressor genes
proteins that protect cells from malignant transformation
How can tumor suppressor genes promote malignant transformation
if they are inactivated or deleted
Which is dominant and which is recessesive
tumor suppressor genes and oncogenes
tumor suppressor- recessive
oncogene- dominant
What are the 2 classification of chemotherapies
Phase specific- affects cell cycle only in specific phases, or phase non specific
Mechanism of action- what agent is used to kill cancer cells, alkylating agents … etc
What are the 3 types of remission
hematologic- normal BM, blood cells are recovered, no evidence of leukemic cells
cytogenetic- karyotyping used to determine no leukemic cells
molecular- no leukemic cell nucleic acids are present
What is targeted therapy
act on specific malignant cells leaving normal ones untouched.
What is Gleevac
a molecular targeted therapy for chronic phase CML
tyrosine kinase inhibitor induces apoptosis of CML cells
What is ATRA
all trans retinoic acid
treatment for pts with APL with PML RARA gene
What is Rituximab
monoclonal ab treatment for lymphoid neoplasms
anti-CD20
What are the 3 types of HSC donors
syngeneic- from an identical twin
allogeneic-from an HLA-identical sibling or unrelated donor
autologous- donating to yourself
What are the WHO and FAB requirements to consider a diagnosis of acute leukemias
FAB- 30% blasts in BM or peripheral blood
WHO- 20% blasts in BM or peripheral blood
A pt with 21% blasts in their peripheral blood. Do they have acute leukemia based on the FAB an WHO standards?
FAB- not acute leukemia
WHO- acute leukemia
List out the characteristics of ALL
what age group tends to get it
What does it stand for
What determines the prognosis
Acute lymphoblastic leukemia
mostly in 2-5 year olds
prognosis is worse on adults
What are the unique signs and symptoms for B cell ALL and T cell ALL
B cell- bone pain caused by intramedullary growth of leukemic cells, can infiltrate meninges
T cell- mass in mediastinum/ chest lump in X ray, also bone pain
What are the common symptoms for both B cell ALL and T cell ALL
anemia, thrombocytopenia, organomegaly like splenomegaly, hepatomegaly,
Describe the morphology of a blast
1-2.5 x the size of a normal lymph
scant blue cytoplasm
indistinct nucleoli
or could be large- 2-3x normal
prominent nucleoli
membrane irregularities
What are the 4 main things that a prognosis depends on
lymphoblast load- tumor burden
immunophenotype- flow cytometry results
age- children especially toddlers have better prognosis
genetic abnormalities- chromosomal translocations depending on which kind can have good or bad prognosis
What genetic abnormality indicates a more favorable prognosis in ALL
hyperploidy- more than 46 chromosomes
Both B and T cells are derived from ____ progenitors
lymphoid
Where do CD34 present? T or B cells, or both
both
Where do TdT present? T or B or both
immature lymphs only B and T
terminal deoxy… transferase
Where do HLA-DR present
on all lymphoid cells
What is the worst prognosis among all ALLs
Philadelphia chromosome
12-year-old presents with complaints of easy bruising and fatigue. X-ray shows presence of a mediastinal mass. BM biopsy shows 45% blasts. Immunophenotyping shows blasts are CD2+, CD3+, CD4+, CD8+, CD34+, and TdT+.
Acute leukemia T Cell ALL
What are the signs and symptoms of AML
acute myeloid leukemia
palor, fatigue, bruising, bleeding, splenomegaly
What is the CBC count in AML
WBC 5-30 x 10^9/L
decreased of all cells
anemia, thrombocytopenia, neutropenia
>20% of cells are blasts
What is the most notable differential finding in AML
myeloblasts in peripheral blood
What is tumor lysis syndrome
seen in AML
metabolic complications that are caused by the breakdown of dying cancer cells
causes renal failure, hyper Ca, K, Uric acid, glucose
Explain what this means
t(8;21)(q22;q22.1); RUNX1/RUNX1T1
translocation between chromosome 8 and 21
translocation was on the q arm- long arm-
Gene from chromosome has created an abnormal protein
What is an inversion vs translocation
translocation- one chromosome breaks off and is attached to another
inversion- chromosome is rearranged, single chromosome rearranged with itself
AML with
Put into FAB nomenclature
What age group tends to get it
what morphology help ID it
What is the prognosis
How rare is it
M2
children and young adults
auer rods
favorable prognosis
5% of AML cases
T 8 21
AML with INV 16 or T 16:16
Put into FAB nomenclature
What age group tends to get it
what morphology help ID it
What is the prognosis
How rare is it
M4
all ages, mostly younger
myeloblasts, monoblasts and promyelocytes
50% cure rate
5-8% of cases
APL with PML RARA t 15:17
Put into FAB nomenclature
What age group tends to get it
what morphology help ID it
What is the prognosis
How rare is it
acute promyelocytic leukemia M3
all ages, mostly young adults
hypergranular pro, with auer rods
no prognosis listed
5-10% of AML cases
What disease state is associate with APL PML-RARA, how is it diagnosed
DIC- release of primary granules causes procoagulant activity
t 15:17
Microgranular APL
what morphology help ID it
What is the prognosis
How rare is it
cells with no granules, butterfly or coin on coin nucleus
better than any other type of AML
30-40% of APL cases
What treatment is used on microgranular APL
ATRA
AML
Put into FAB nomenclature
What age group tends to get it
what morphology help ID it
What disease is it associated with
How rare is it
M5 t 9:11
children
monoblasts and immature monocytes- granules and vacuoles in blasts
gingival and skin
6% of AML cases
AML with myelodysplasia
how many blasts
prognosis
poor prognosis
at least 20% blasts
Patient is experiencing DIC
Differential shows 34% blasts in peripheral blood
Many Auer rods- only in myeloid
Cytogenetic testing shows presence of t(15;17)
ATRA
Acute myeloid leukemia not otherwise specified
what is required for diagnosis
at least 20% blasts in peripheral blood
List out the FAB leukemias
M0
M1
M2
M3
M4
M4eo
M5a
M5b
M6
M7
M0- acute myeloid leukemia, minimally differentiated
M1-acute myeloid leukemia, without maturation
M2- Acute myeloid leukemia with maturation
M3 -Acute promyeloid leukemia
M4- acute myelomonocytic leukemia
M4eo Acute myelomonocytic leukemia with eosinophilia
M5a- Acute monocytic leukemia, poorly differenciated
M5b- Acute monocytic leukemia, well differenciated
M6- Acute erythroleukemia
M7 Acute megakaryocytic Leukemia
M0
BM findings
Staining
M0- Acute myeloid leukemia with minimal differenciation
no evidence of cellular maturation in BM
All stains are negative
M1
BM findings
staining
Acute Myelocytic leukemia without maturation
blasts are non erythroid cells <10% maturation in WBCs
positive MPO or SBB stains
M2
age group
BM findings
staining
middle aged adults
clear evidence of maturation, auer rods, hypercellular,
MPO, SBB and CAE pos
M3
BM findings
What translocation is it
What treatment
Acute promyelocytic leukemia
blasts and pros have heavy granulation, auer rod bundles
DIC
T 15:17- ATRA treatment
promyelocytes with a bund of auer rods in it, looks like a bunch of sticks
M3- APL
M4
BM findings
Antigen testing results
staining
acute myelomonocytic leukemia
monocytic blasts and myeloid in peripheral and BM
pos myeloid and monocytic antigens
MPO, SBB and NSE pos
M5
BM findings
staining
related disease states
Acute monoblastic and monocytic leukemia
most Cells are monocytic
MPO NSE pos
extramedullary involvement- gingival bleeding
M6
BM findings
80% erythroids, abnormal multinucelic, nucleus more immature than cytoplasm, vacuolization
many NRBCs in peripheral blood
M7
BM findings
staining
dry tap common, dysplastic in all cell lines,
immunostaining- antigen testing
What is the associated with trisomy 21 and AML
down syndrome more likely to have AML
Practice chart on Ch 31 slide 52
practice
Match to stain
-enzyme in primary granules of granulocytic cells, does not stain lymphs
-stains the cellular lipids, staining is more intense as cells mature, does not stain lymphs
-only stains granulocytes, stains esters
-stains esters in all cells not just granulocytes
-stains primary granules in neutrophils
MPO myeloperoxidase
SBB sudan black
SE specific esterase
NSE non specific esterases
CAE chloroacetate esterase
What testing is used to differentiate lymphoma from leukemia
flow cytometry and immunohistochemistry
What are b symptoms
the physical exam, the first step in accurate diagnosis
fever, drenching night sweats, loss of 10% body weight over 6 months
What disease is specific to alcohol intolerance, rash upon taking ampicillin
Hodgkin lymphoma
What disease is specific to skin issues
T cell disorders
What are the Ann Arbor and Lugano systems
Ann Arbor- classifies lymphomas by presence or absence of B symptoms, nodes above diaphragm, stages 1 and 2, nodes on both halves- stages 3 or 4
Lugano- classifies into stages I and II- limited, III and IV- advanced
What are the 5 parameters of IPI
age
serum LDH
performance status
stage
extranodal involvement
What leukemia is the most common in adults in western countried
CLL
CLL
B or T cell
age group
diagnosis
B cell
older adults
asymptomatic, at least 5x 10^9 B lymphs for more than 3 months
What leukemia shows soccer ball cells and lots of smudged cells
lymphs- CLL
How is CLL treated
targeted inhibitor
How is the prognosis of CLL determines
with Fai and Binet staging
How is the prognosis of CLL determines
with Fai and Binet staging
PLL
age group
how bad is it
clinical symptoms
elderly
aggressive
massive splenomegaly, very high lymph count
skin can get infiltrated
Cells with cerebriform appearance
PLL- T cell
How to distinguish T cell PLL and B cell PLL
B cell- bigger cells, more open chromatin, more prominent nucleus
T cell- smaller cells, irregular contour, cerebriform appearance
Treatment for PLL
Akemtuzumab- anti CD52
possible hematopoietic stem cell transplant
HCL
age group
clinical symptoms
how bad is it
about 50 years
splenomegaly, cytopenias
indolent
What cancer is associated with hairy cells lymphs with round/ oval nuceli, no nucleus and ragged projections around the cell
HCL hairy cell leukemia
Leukemia with dry tap, and shows anti-CD20
HCL hairy cell leukemia
Treatment for HCL
BRAFV600E vermurafenib
inhibitor for a specific mutation
LGL
age group
clinical symptoms
Large granular lymphocytis leukemia
rare- older adults
asymptomatic
Cancer where there are many pale blue cytoplasmic cells with azurophilic granules
LGL
Treatment for LGL
myeloid growth factors
What is ATLL
Adult T cell leukemia/ lymphoma
T cell disorder
What leukemia is associated with HTLV-I
ATLL
What leukemia is assocaited with flower cells
ATLL
What is BL
Burkitt lymphoma/ leukemia
B cell
What leukemia is associated with HIV
BL
What leukemia has deeply basophilic cytoplasm with vacuoles looks like a starry sky
BL
What is FL
Folicular lymphoma germinal B cell disorder
What leukemia is associated with cleft nuclei, look like hoof prints
FL
What is MCL
Mantle cell lymphoma
What leukemia is associated with GI tract issues
MCL
What is DLBCL
diffuse large B cell lymphoma
What is the most common form of NHL
DLBCL
What leukemia is associated with large cells with a diffuse pattern in lymph node samples
DLBCL
What is MZL
marginal zone lymphoma- B cells
What leukemia is associated with MALT
MZL
What cancer is associated with polar distribution or villanous lymphs
SMZL splenic MZL
What cancer is associated with Hep C
NMZL
What is MF/ SS
Mycosis fungoides/ sezary syndrome
T cell lymphoma
MF mostly skin
SS systemic with peripheral blood- worse prognosis
What cancer is associated with cerebriform folded nuelus and sezary cells
MF/SS
Is ALCL a T cell or B cell issue
T cell- anaplastic large cell lymphoma
What is a plasma cell neoplasm?
disorder of differenciated B cells
plasma cell secrete monoclonal immunoglobulins, becomes decreased
What is an M-spike
immunofixation electrophoresis, shows too many gamma globulins, spike at the end of the chart
What is the order of incidence of heavy chain involvement
GAMDE
What is associated with increase in IgG
Multiple myeloma
What is MM
BM plasma cell neoplasm with extension to bone or soft tissue
What is associated with osteolytic lesions (moth bitten X rays) and reauloux
MM
What treatment for MM
anti CD38 daratumumab
What is WM
waldenstroms macroglobulinemia
lymphoplasmacytic lymphoma
associated with secretion of IgM
What is associated with the MYD88 mutation
WM
What is hogdkin lymphoma
lymph node disease, rare, in young adults
Classic vs LPHL
classic- continuous movement through lymphs
LPHL-lymphocytic predominant non contagious nodal movement- no pattern
How is Hodgkins lyphoma diagnosed?
lymph node biopsy
What is the best way to differentiate non hodgkins from hodgkins
presence of RS cells in HL
absence in NHL
What cancer is associated with popcorn cells
Lymphocytic predominant hodkins lymphoma
LPHL
Cancer with RS reed sternberg cells, look like owl eyes
HL
