Imported: Pathoma Chapter 6

Front 1

Leukemia Overview

Front 2

Alkylating agents side effects

treat with?

Back 2

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

GM-CSF and G-CSF

Front 3

Gram negative sepsis can cause what in neutrophil count?

Back 3

decrease due to mobilization to tissues

Front 4

High cortisol state

Back 4

Causes apoptosis of lymphocytes

Mobilization of marginal pool of leukocytes leading to release of neutrophils into bloodstream.

Front 5

What cell line is most sensitive to whole body radiation?

Back 5

Lymphocytes

Front 6

Fc Receptors?

Back 6

CD16

Front 7

What distinguishes immature neutrophils?

Back 7

Low expression of Fc receptors(CD16)

Front 8

How does bacterial infection cause leukocytosis

Back 8

mobilization of marginal pool

Front 9

Monocytosis is seen in

Back 9

chronic inflammatory state and malignancy

Front 10

Eosinophilia is seen in

Back 10

Allergic hypersensitivity, parasitic infection and Hodgkin's Lymphoma

Front 11

Mechanism of Eosinophilia in Hodgkin's lymphoma...

Back 11

increased IL-5 production

Front 12

Basophilia

Back 12

Chronic Myelogenous Leukemia(CML)

Front 13

Lymphocytic Leukocytosis is seen in...

Back 13

increased circulating lymphocytes caused by:
viral infection and Bordetella Pertussis

Front 14

Lymphocytic leukocytosis is a/w what BACTERIAL infection? MOA

Back 14

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

Front 15

EBV infects?

Back 15

-- Oropharynx,
--liver(hepatitis and hepatomegaly, elevated liver enzymes)
-- B cells

Front 16

atypical lymphocytes(which look like monocytes). They are reactive CD8+ T-cells that look like monocytes is characteristic of?

Back 16

viral infection

EBV

T-cell hyperplasia causes:
--Lymphadenopathy - paracortex(where T-cells reside)
--Splenomegaly - Peri-arteriolar lymphatic sheath(PALS, where T-cells reside)

Front 17

Monospot test. Interpretation?

Back 17

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

Front 18

Splenic rupture?

Back 18

infectious mononucleosis with EBV.

Avoid contact sports for a year

Front 19

Rash after penicillin

Back 19

EBV

Front 20

EBV risks

Back 20

increase the risk of B-cell lymphoma, especially if immunocompromised

Front 21

Characteristic marker for ALL?

Back 21

TdT which is a DNA polymerase exclusive to lymphoblastic precursors

Front 22

Characteristic marker for AML? Exceptions?

Back 22

MPO and Auer Rods(crystallized MPO) are exclusive to AML

Acute Monocytic Leukemia and Acute Megakaryoblastic Leukemia usually lack MPO

Front 23

Children over 5 with Down's syndrome a/w

Back 23

ALL

Front 24

Most common type of ALL? Classic markers?

Back 24

B-ALL

CD10, CD19, CD20

Front 25

What prophylaxis do you need to administer in a case of B-ALL?

Back 25

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

Front 26

T-ALL markers?

Back 26

CD2 to CD8
(CD2, CD3, CD4, CD7, CD8)

NOTABLY NO CD10

Front 27

B-ALL chromosomal abnormalities?

Back 27

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

Front 28

Common presentation of T-ALL

Back 28

mediastinal(thymic) mass in a teenager.
Think T's - Thymic Teenager T-ALL

Acute Lymphoblastic LymphOMA since it is a mass.

Front 29

What subtype of AML is associated with a chromosomal abnormality?

Back 29

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.

Front 30

APL puts you at risk for? How do you prevent this?

Back 30

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).

Front 31

Acute Myeloid Leukemia arises predominantly in what demographic?

Back 31

Older population, 50-60 yrs

Front 32

leukemia with infiltration of gums. Notable lab feature?

Back 32

Acute monocytic leukemia(AML subclassification)

usally lack MPO

Front 33

leukemia that lack MPO

Back 33

Acute megakaryoblastic leukemia(don't need/use MPO)
also, Acute monocytic leukemia

Front 34

Children under 5 with Down's syndrome a/w

Back 34

Acute megakaryoblastic leukemia

lacks MPO

Front 35

Hematopoietic Stem Cell expresses what receptor

Back 35

CD34+

Front 36

Chronic Leukemia is characteristic of what cell line?

Back 36

Mature lymphocytes(B and T cells)

Front 37

Chronic Lymphocytic Leukemia has what cells? What receptors are expressed?

Back 37

b-cells. CD5 and CD20

CD5 normally expressed on T-cells. Here it is aberrantly expressed

Back 38

Smudge Cells seen in CLL

Front 39

Small Lymphocytic Lymphoma

Back 39

involvement of lymph nodes in CLL

Front 40

Complications of CLL

Back 40

-- 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

Front 41

What is a risk factor for large B-cell lymphoma

Back 41

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

Front 42

Most common cause of death in CLL

Back 42

infection due to defective Ig production

Front 43

tartrate resistant acid phosphatase

Back 43

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.

Front 44

hairy cytoplasmic processes a/w what disease? clinical features?

Back 44

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.

Front 45

treatment of hairy cell leukemia?

Back 45

2-CDA(cladribine) which is an adenosine deaminase inhibitor.

Causes adenosine to accumulate to toxic levels in neoplastic B-cells

Front 46

ATLL

Back 46

Adult T-cell Leukemia\Lymphoma
neoplastic proliferation of CD4+ T cells

Strongly associated with HTLV-1(retrovirus)

Front 47

geographic associations with ATLL

Back 47

Japan and the Caribbean

Neoplastic proliferation of CD4+

Front 48

Clinical features of ATLL

Back 48

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.

Front 49

Mycosis Fungoides - clinical symptoms?

Back 49

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.

Back 50

Sezary Cell, Cerebriform nuclei, mycosis Fungoides, CD4+ leukemia with skin infiltration(Pautrier Abscesses)

Front 51

Demographic of Myeloproliferative Disorders
Brief description of common symptoms?

Back 51

late adulthood
neoplastic proliferation of mature cells of myeloid lineage.
Common symptoms:
-- Hyperuricemia and gout
-- marrow fibrosis
-- transformation to acute leukemia

Front 52

MOA of myeloproliferative symptom of hyperuricemia and gout

Back 52

Hyperuricemia and gout -- increased turnover of cells result in activation of purine degradation pathway whose end metabolite is uric acid.

Front 53

Chronic Myeloid Leukemia. Characteristic chromosome abnormality? What cell type is characteristically increase?

Back 53

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

Front 54

First line treatment for CML? MOA?

Back 54

Imatinib which blocks the tyrosine kinase

Front 55

Worst complication of CML? Preceded by?

Back 55

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+).

Front 56

Distinguish between a leukemoid reaction(infection) and CML

Back 56

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.

Front 57

JAK2 Kinase associations

Back 57

Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis

Front 58

Classic a/w Polycythemia Vera

Back 58

most common cause of Budd-Chiari syndrome-- blockage of hepatic vein

Front 59

itching after bathing

Back 59

Polycythemia Vera due to excessive mast cells

Front 60

treatment for polycythemia vera

Back 60

1.) Phlebotomy
2.) Hydroxyurea

Front 61

reactive polycythemia vs polycythemia vera

Back 61

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

Front 62

What is associated with excessive platelets?

Back 62

Iron deficiency anemia
Essential Thrombocythemia

Front 63

Notable difference with Essential Thrombocythemia compared to other myelodysplastic syndromes?

Back 63

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.

Front 64

JAK2 associated disorder associated with marrow fibrosis

Back 64

myelofibrosis

Front 65

Clinical features of myelofibrosis. Mutation in? What cell predominates?

Back 65

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)

Front 66

tear drop RBC's a/w

Back 66

myelofibrosis

Front 67

follicular lymphadenopathy

Back 67

Rheumatoid arthritis and early HIV(due to dendritic cells expressing CD4+ receptors and hanging out in follicles)

follicles are habitated by B-cells

Front 68

Paracortex lymphadenopathy

Back 68

viral infections

Front 69

Deep in medulla lymphadenopathy

Back 69

LN draining tissue with cancer

(hyperplasia of sinus histiocytes)

Front 70

Small B cell lymphoma's

Back 70

Follicular lymphoma
Mantle Cell Lymphoma
Marginal Cell lymphoma
Small Lymphocytic Lymphoma(CLL associated)

Front 71

Intermediate sized b cells lymphoma

Back 71

Burkitt lymphoma

Front 72

Most common form of non-hodgkin's lymphoma

Back 72

Diffuse large b cell lymphoma

Front 73

What receptor do small b-cells express

Back 73

CD20+
key marker for B-cells

Front 74

Chromosomal abnormality with follicular lymphoma

Back 74

t(14;18) -- IgH, BCL2 translocation.

overstabilization of mitochondria causes failure to for some b-cells to die during somatic hypermutation

Front 75

Treatment for follicular lymphoma

Back 75

only for symptomatic peoples - use rituximab(anti-CD20 antibody) with low dose chemotherapy

Front 76

demographic of small b cell lymphomas

Back 76

mostly late adulthood

Front 77

Important complication of follicular lymphoma. What else can progress to this?

Back 77

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

Front 78

Distinguish follicular hyperplasia with follicular lymphoma

Back 78

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)

Front 79

Mantle Cell lymphoma chromosomal abnormality. gene product?

Back 79

t(11;14) which switches cyclin D gene with IgG. Cyclin D regulates progression from G1 --> S

Front 80

Marginal Zone Lymphoma a/w?

Back 80

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

Front 81

"Neoplastic proliferation of cells immediately adjacent to follicle"

Back 81

Mantle Cell Lymphoma

Front 82

H. pylori gastritis can lead to

Back 82

Gastric MALToma, which is a marginal zone lymphoma

Front 83

Burkitt Lymphoma presents in what demographic?

Back 83

Presents in child/young adult as an extra nodal mass.

Front 84

Burkitt Lymphoma geographical associations?

Back 84

African form a/w jaw
Sporadic form a/w abdomen

Front 85

Burkitt's lymphoma chromosomal abnormality?

Back 85

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

Front 86

Burkitt's Lymphoma is a/w what infection?

Back 86

EBV

Front 87

most common form of non-hodgkins lymphoma?

Back 87

Diffuse large b-cell lymphoma

Front 88

demographic of diffuse large b-cell lymphoma

Back 88

late adulthood as an enlarging lymph node. Arises sporadically or as a transformation(follicular lymphoma)

Back 89

lacunar cells

special kind of reed-sternberg cell present in nodular sclerosis type of hodgkin's lymphoma

Front 90

owls eye nuclei

Back 90

reed-sternberg cell
hodgkin's lymphoma

Front 91

Mixed cellularity hodgkin's lymphoma is a/w?

Back 91

eosinophilia and abundant eosinophils in tissue due to the production of IL-5 by reed-steinberg cells

Front 92

Multiple proliferation of plasma cells? What etiology?

Back 92

Multiple Myeloma
-- production of high IL-6 which is a stimulator of plasma cell growth and immunoglobulin production

Front 93

Multiple Myeloma clinical features?

Back 93

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.

Front 94

What types of Ig is produced by multiple myeloma?

Back 94

IgG and IgA

Front 95

Increased serum protein decreases charge between RBCs causing them to stick together...

Back 95

Rouleaux formation of RBCs due to multiple myeloma

Front 96

Most common cause of death in multiple myeloma?

Back 96

increased risk for infection due to overproduction of useless Ig(lacks antigenic diversity)

Front 97

What is diagnostic of Monoclonal Gammopathy of undetermined significance?

Back 97

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

Front 98

Waldenstrom's Macroglobulinemia

Back 98

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

Front 99

What receptors on Hodgkin's lymphoma?

Back 99

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"

Front 100

classic presentation of nodular sclerosis hodgkins?

Back 100

young adult female with cervical or mediastinal lymph node

Front 101

What are langherhan's cells?

Back 101

specialized dendritic cells that are found predominantly in the skin that derive from bone marrow monocytes.

Front 102

What is characteristic of langherhan's cells? What receptors are they positive for?

Back 102

Birbeck granules on electron microscopy.

CD1a+ and S100+