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116 Cards in this Set

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Leukemia Overview
Alkylating agents side effects

treat with?
neutropenia, also a risk factor for Acute Myeloid Leukemia arising from myelodysplastic dysplasia

GM-CSF and G-CSF
Gram negative sepsis can cause what in neutrophil count?
decrease due to mobilization to tissues
High cortisol state
Causes apoptosis of lymphocytes

Mobilization of marginal pool of leukocytes leading to release of neutrophils into bloodstream.
What cell line is most sensitive to whole body radiation?
Lymphocytes
Fc Receptors?
CD16
What distinguishes immature neutrophils?
Low expression of Fc receptors(CD16)
How does bacterial infection cause leukocytosis
mobilization of marginal pool
Monocytosis is seen in
chronic inflammatory state and malignancy
Eosinophilia is seen in
Allergic hypersensitivity, parasitic infection and Hodgkin's Lymphoma
Mechanism of Eosinophilia in Hodgkin's lymphoma...
increased IL-5 production
Basophilia
Chronic Myelogenous Leukemia(CML)
Lymphocytic Leukocytosis is seen in...
increased circulating lymphocytes caused by:
viral infection and Bordetella Pertussis
Lymphocytic leukocytosis is a/w what BACTERIAL infection? MOA
Bordetella Pertussis
-- produces lymphocytosis-promoting factor which blocks circulating lymphocytes from leaving the blood to enter lymph nodes. As such the lymphocytes are trapped in the blood
EBV infects?
-- Oropharynx,
--liver(hepatitis and hepatomegaly, elevated liver enzymes)
-- B cells
atypical lymphocytes(which look like monocytes). They are reactive CD8+ T-cells that look like monocytes is characteristic of?
viral infection

EBV

T-cell hyperplasia causes:
--Lymphadenopathy - paracortex(where T-cells reside)
--Splenomegaly - Peri-arteriolar lymphatic sheath(PALS, where T-cells reside)
Monospot test. Interpretation?
Detects IgM heterophil antibodies that agglutinate RBCs from another animal.

+ means EBV. Confirm with viral capsid antigen.
- with classic signs of mononucleosis could be infected with CMV
Splenic rupture?
infectious mononucleosis with EBV.

Avoid contact sports for a year
Rash after penicillin
EBV
EBV risks
increase the risk of B-cell lymphoma, especially if immunocompromised
Characteristic marker for ALL?
TdT which is a DNA polymerase exclusive to lymphoblastic precursors
Characteristic marker for AML? Exceptions?
MPO and Auer Rods(crystallized MPO) are exclusive to AML

Acute Monocytic Leukemia and Acute Megakaryoblastic Leukemia usually lack MPO
Children over 5 with Down's syndrome a/w
ALL
Most common type of ALL? Classic markers?
B-ALL

CD10, CD19, CD20
What prophylaxis do you need to administer in a case of B-ALL?
CSF and scrotum since they have a blood-brain blood-testis barrier that prevents medication from getting to them

B-ALL responds well to chemotherapy
T-ALL markers?
CD2 to CD8
(CD2, CD3, CD4, CD7, CD8)

NOTABLY NO CD10
B-ALL chromosomal abnormalities?
t(12;21) translocation - good prognosis
t(9;22) translocation(Philadelphia chromosome) - poor prognosis

t(9;22) normally associated with CML but can also be seen with a poor prognosis form of B-ALL
Common presentation of T-ALL
mediastinal(thymic) mass in a teenager.
Think T's - Thymic Teenager T-ALL

Acute Lymphoblastic LymphOMA since it is a mass.
What subtype of AML is associated with a chromosomal abnormality?
Acute Promyelocytic Leukemia has t(15;17) which involves translocation of retinoic acid receptor(RAR) on chromosome 17 to chromosome 15; RAR disruption blocks maturation and promyelocytes(blasts) accumulate. Since these blasts contain lots of Auer Rods which can activated coagulation, there is a risk for DIC.
APL puts you at risk for? How do you prevent this?
DIC due to Auer rods in blasts.

all-trans-retinoic acid(ATRA, a vit A derivative). Binds altered receptors and causes the blasts to mature(and eventually die).
Acute Myeloid Leukemia arises predominantly in what demographic?
Older population, 50-60 yrs
leukemia with infiltration of gums. Notable lab feature?
Acute monocytic leukemia(AML subclassification)

usally lack MPO
leukemia that lack MPO
Acute megakaryoblastic leukemia(don't need/use MPO)
also, Acute monocytic leukemia
Children under 5 with Down's syndrome a/w
Acute megakaryoblastic leukemia

lacks MPO
Hematopoietic Stem Cell expresses what receptor
CD34+
Chronic Leukemia is characteristic of what cell line?
Mature lymphocytes(B and T cells)
Chronic Lymphocytic Leukemia has what cells? What receptors are expressed?
b-cells. CD5 and CD20

CD5 normally expressed on T-cells. Here it is aberrantly expressed
Smudge Cells seen in CLL
Small Lymphocytic Lymphoma
involvement of lymph nodes in CLL
Complications of CLL
-- Hypogammaglobulinemia: neoplastic B-cells won't make Ig's. If they do, the Ig's suck and agglutinate self-RBCs causing...
--Autoimmune Hemolytic Anemia
--Possibility to transform to large B-cell lymphoma
What is a risk factor for large B-cell lymphoma
CLL(Richter Transformation)
marked clinically by a NEW ONSET enlarging lymph node or spleen with a history of stable enlarged lymph nodes.

Also, follicular lymphoma
Most common cause of death in CLL
infection due to defective Ig production
tartrate resistant acid phosphatase
TRAP...a/w Hairy Cell Leukemia


splenomegaly - notably, expansion of RED PULP.
Dry Tap - bone marrow is fibrosed
NOTABLY lymphadenopathy is ABSENT because they are trapped in red pulp.
hairy cytoplasmic processes a/w what disease? clinical features?
Tartrate resistant acid phosphatase(Hairy Cell leukemia)

splenomegaly - notably, expansion of RED PULP.
Dry Tap - bone marrow is fibrosed
NOTABLY lymphadenopathy is ABSENT because they are trapped in red pulp.
treatment of hairy cell leukemia?
2-CDA(cladribine) which is an adenosine deaminase inhibitor.

Causes adenosine to accumulate to toxic levels in neoplastic B-cells
ATLL
Adult T-cell Leukemia\Lymphoma
neoplastic proliferation of CD4+ T cells

Strongly associated with HTLV-1(retrovirus)
geographic associations with ATLL
Japan and the Caribbean

Neoplastic proliferation of CD4+
Clinical features of ATLL
rash, lytic(punched out) bone lesions with hypercalcemia and lymphadenopathy with hepatosplenomegaly.

DO NOT CONFUSED WITH multiple myeloma(frequently associated with lytic bone lesion). Rash is a good distinguishing feature.
Mycosis Fungoides - clinical symptoms?
Neoplastic proliferation of CD4+ T-cells.

Aggregates of neoplastic cells in the epidermis are called Pautrier microabscesses.
Cells can spread to involve blood producing "Sezary syndrome" with characteristic lymphocytes with "cerebriform nuclei"(Sezary Cells) seen on blood smear.
Sezary Cell, Cerebriform nuclei, mycosis Fungoides, CD4+ leukemia with skin infiltration(Pautrier Abscesses)
Demographic of Myeloproliferative Disorders
Brief description of common symptoms?
late adulthood
neoplastic proliferation of mature cells of myeloid lineage.
Common symptoms:
-- Hyperuricemia and gout
-- marrow fibrosis
-- transformation to acute leukemia
MOA of myeloproliferative symptom of hyperuricemia and gout
Hyperuricemia and gout -- increased turnover of cells result in activation of purine degradation pathway whose end metabolite is uric acid.
Chronic Myeloid Leukemia. Characteristic chromosome abnormality? What cell type is characteristically increase?
Neoplastic proliferation of granulocytes. Predominant cell that is increased is basophils
t(9;22) - philadelphia chromosome -- generates BCR-ABL protein that increases tyrosine kinase activity
First line treatment for CML? MOA?
Imatinib which blocks the tyrosine kinase
Worst complication of CML? Preceded by?
Acute Leukemia heralded by new onset enlargement of spleen.

NOTABLY, transformation can turn into AML OR ALL since the mutation is in the HSC(CD34+).
Distinguish between a leukemoid reaction(infection) and CML
CML will have the following findings:
1.) Negative leukocyte alkaline phosphatase(LAP) stain
2.) Increased basophils
3.) t(9;22)

LAP is an enzyme present in the secondary granules during inflammation. Therefore leukemoid reactions would be positive for this.
JAK2 Kinase associations
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
Classic a/w Polycythemia Vera
most common cause of Budd-Chiari syndrome-- blockage of hepatic vein
itching after bathing
Polycythemia Vera due to excessive mast cells
treatment for polycythemia vera
1.) Phlebotomy
2.) Hydroxyurea
reactive polycythemia vs polycythemia vera
Reactive Polycythemia due to lung disease
--> Decreased SaO2, increased EPO

Polycythemia secondary to Renal Cell Carcinoma secreting EPO
--> SaO2 normal, EPO high

Polycythemia Vera
--> SaO2 normal, EPO low
What is associated with excessive platelets?
Iron deficiency anemia
Essential Thrombocythemia
Notable difference with Essential Thrombocythemia compared to other myelodysplastic syndromes?
No risk for hyperuricemia, gout or progression to acute leukemia. This is due to the fact there is not an increase in turnover of nuclear material since platelets are just pieces of megakaryocyte cytoplasm pinched off.
JAK2 associated disorder associated with marrow fibrosis
myelofibrosis
Clinical features of myelofibrosis. Mutation in? What cell predominates?
JAK2 Kinase mutation leading to proliferation of mature myeloid cells(esp. megakaryocytes)
Splenomegaly due to extramedullary hematopoiesis
tear-drop RBC's, nucleated RBC's(Howell Jowelly bodies), immature granulocytes)
tear drop RBC's a/w
myelofibrosis
follicular lymphadenopathy
Rheumatoid arthritis and early HIV(due to dendritic cells expressing CD4+ receptors and hanging out in follicles)

follicles are habitated by B-cells
Paracortex lymphadenopathy
viral infections
Deep in medulla lymphadenopathy
LN draining tissue with cancer

(hyperplasia of sinus histiocytes)
Small B cell lymphoma's
Follicular lymphoma
Mantle Cell Lymphoma
Marginal Cell lymphoma
Small Lymphocytic Lymphoma(CLL associated)
Intermediate sized b cells lymphoma
Burkitt lymphoma
Most common form of non-hodgkin's lymphoma
Diffuse large b cell lymphoma
What receptor do small b-cells express
CD20+
key marker for B-cells
Chromosomal abnormality with follicular lymphoma
t(14;18) -- IgH, BCL2 translocation.

overstabilization of mitochondria causes failure to for some b-cells to die during somatic hypermutation
Treatment for follicular lymphoma
only for symptomatic peoples - use rituximab(anti-CD20 antibody) with low dose chemotherapy
demographic of small b cell lymphomas
mostly late adulthood
Important complication of follicular lymphoma. What else can progress to this?
progression to diffuse large b-cell lymphoma.
Generally have lots of lymphomas, but if one spontaneously starts GROWING get worried for large b-cell.

Similar to Chronic Lymphocytic Leukemia
Distinguish follicular hyperplasia with follicular lymphoma
1.) disruption of architecture(follicles stay near cortex in normal tissue)
2.) lack of tangible body macrophages(somatic hypermutation leads to some apoptotic cells with macrophage consumption in normal tissue)
3.) Bcl2 expression(NOT expresses in reactive hyperplasia)
4.) Monoclonality - test with kappa:gamma ration being not 3:1(normal is 3:1)
Mantle Cell lymphoma chromosomal abnormality. gene product?
t(11;14) which switches cyclin D gene with IgG. Cyclin D regulates progression from G1 --> S
Marginal Zone Lymphoma a/w?
Associated with chronic inflammatory states such as Hashimoto Thyroiditis, Sjogren Syndrome, and H. Pylori gastritis.

MALToma is a marginal zone lymphoma...
Marginal zone is only formed through activation of zone through germinal centers
"Neoplastic proliferation of cells immediately adjacent to follicle"
Mantle Cell Lymphoma
H. pylori gastritis can lead to
Gastric MALToma, which is a marginal zone lymphoma
Burkitt Lymphoma presents in what demographic?
Presents in child/young adult as an extra nodal mass.
Burkitt Lymphoma geographical associations?
African form a/w jaw
Sporadic form a/w abdomen
Burkitt's lymphoma chromosomal abnormality?
t(8;14) results in translocation of c-myc to the IgH leading to overexpression of c-myc.

c-myc is an oncogene and promotes cell growth.
"starry sky" sky is rapidly growing cells, stars are dead cells cause they grow so fast
Burkitt's Lymphoma is a/w what infection?
EBV
most common form of non-hodgkins lymphoma?
Diffuse large b-cell lymphoma
demographic of diffuse large b-cell lymphoma
late adulthood as an enlarging lymph node. Arises sporadically or as a transformation(follicular lymphoma)
lacunar cells

special kind of reed-sternberg cell present in nodular sclerosis type of hodgkin's lymphoma
owls eye nuclei
reed-sternberg cell
hodgkin's lymphoma
Mixed cellularity hodgkin's lymphoma is a/w?
eosinophilia and abundant eosinophils in tissue due to the production of IL-5 by reed-steinberg cells
Multiple proliferation of plasma cells? What etiology?
Multiple Myeloma
-- production of high IL-6 which is a stimulator of plasma cell growth and immunoglobulin production
Multiple Myeloma clinical features?
1.) production of osteoclast activating factor causes lytic bone lesions(Remember ATLL) especially in vertebrae and skull

2.) M protein spike on electrophoresis due to neoplastic production of immunoglobulin.

3.) Primary AL amyloidosis occurs due to excess production of light chain which gets secreted into blood as AL amyloid, into the urine as Bence-Jones protein and causes renal failure in the kidneys.
What types of Ig is produced by multiple myeloma?
IgG and IgA
Increased serum protein decreases charge between RBCs causing them to stick together...
Rouleaux formation of RBCs due to multiple myeloma
Most common cause of death in multiple myeloma?
increased risk for infection due to overproduction of useless Ig(lacks antigenic diversity)
What is diagnostic of Monoclonal Gammopathy of undetermined significance?
A finding of M-protein spike in electrophoresis but lacking any other feature of multiple myeloma...
NO AL amyloid in blood
NO bence-jones protein in urine
NO hypercalcemia or lytic bone lesions

Common in elderly
Waldenstrom's Macroglobulinemia
B-cell lymphoma that produces monoclonal IgM(it's a BIG Ig)

patients present with generalized lymphadenopathy. There will be M-spike due to IgM. No lytic bone lesions. Causes serum viscosity leading to defective platelet aggregation

Treat with plasmaphoresis
What receptors on Hodgkin's lymphoma?
It is a B-cell lymphoma but NOTABLY does not have CD20 receptor. It has CD15 and CD30 and contains Reed-Sternberg cells which are associated with "owl's eye"
classic presentation of nodular sclerosis hodgkins?
young adult female with cervical or mediastinal lymph node
What are langherhan's cells?
specialized dendritic cells that are found predominantly in the skin that derive from bone marrow monocytes.
What is characteristic of langherhan's cells? What receptors are they positive for?
Birbeck granules on electron microscopy.

CD1a+ and S100+
Chronic leukocytic leukemias
B-cell Leukemia's
Chronic Lymphocytic Leukemia(CLL)
Hairy Cell Leukemia

T-Cell Leukemia's(CD4+)
Adult T-Cell Leukemia/Lymphoma(ATLL)
Mycosis Fungoides
Myeloproliferative Disorders
Chronic Myeloid Leukemia(CML)
Polycythemia Vera(PV)
Essential Thrombocythemia
Myelofibrosis
Lymphadenopathy
Can be chronic(painLESS) or acute(painFUL)
Name all the important Lymphomas
Non-hodgkins
--Follicular Lymphoma
--Mantle Cell Lymphoma
--Marginal Zone Lymphoma
--Small Lymphocytic Lymphoma
--Burkitt Lymphoma
-- Diffuse Large B-cell lymphoma

Hodgkin's Lymphoma
Small Lymphoma(s)
--Follicular Lymphoma
--Mantle Cell Lymphoma
--Marginal Zone Lymphoma
Large Lymphoma(s)
--Diffuse Large B cell lymphoma
Intermediate Lymphoma(s)
-- Burkitt's Lymphoma
someone with CLL that has an acutely enlarging lymph node/spleen
Richter transformation -- progression of CLL to Diffuse large B-cell lymphoma
skin rash with lytic bone lesions
ATLL
lytic bone lesions
multiple myeloma
"starry sky"
burkitt's lymphoma
most common PRIMARY malignancy of bone?
multiple myeloma - malignant proliferation of plasma cells in the bone marrow
These diseases will have M spikes on serum protein elecrophoresis...
Multiple Myeloma
Waldenstroms Macroglobulinemia
Monoclonal Gammopathy of undetermined significance
Most common subtype of hodgkin's lymphoma?

What are other subtypes?
Nodular Sclerosis

Lymphocyte-rich
Mixed cellularity
Lymphocyte-depleted