Cancer Flashcards
1
Q
Trusseau sign
- what is it
- location
- associated w
- LE
- UE
A
- superficial migratory thromboflibitis -> inflammation of blood vessel secondary to clot
- superficial v
- pancreatic CA
- long (mid shin) and short saphenous v (on top calf)
- Cephalic v and basilic v
2
Q
Cachexia
- what is it
- sxs
- caused by
- how
- when else can this occur, sxs
A
- failure to thrive in adult
- anorexia, muscle wasting, fatigue, malaise
- TNF alpha -> from macrophages and neoplastic cells
- stimulates hypothal to decrease appetite
- septic shock -> tachycardia, hypotensive, fever
3
Q
Resistance to chemo
- caused by
- codes for
- presentation
A
- human mutli-drug resistance gene
- p -glycoprotein which is transmembrane ATP efflux pump protein to flush away chemo
- tumor won’t shrink
4
Q
Tumor lysis syndrome
- what is it
- when
- labs
- sxs
- tx and MOA
A
- lots of cancer cells killed at exact same time and lysing realing all intracellular ions at once
- high grade lymphoma or high sensitvity to chemo
- hyperkalemia, hyperphasphatemia, hypo Ca bc binding to phophorus, uric acid from DNA and RNA causing acidic env
- cardiac arrythmia, muscle weakness, phophate crystals, calcium stones, tetany, seizure, myopathy
- racburicase -> washes out excess uric acid
5
Q
Most Common CA
- men
- men causing death
- women
- women causing death
A
- prostes, lung, colon
- lung, prostate, colon
- lung, breast, colon
- lung, breast, colon
6
Q
Most Common CA overall
- 1
- 2
- 3
- 4
A
- breast
- lung
- prostate
- skin
7
Q
Types of Cell changes
- metaplasia: what is it, ex
- dysplasia: what is it
A
- one cell type replaced by different cell type -> barrets (strat squamous -> columnar -> adenocarcinoma)
- abnormal cell growth that is conficed to epi -> does not violate basement membrane
8
Q
Grade
- low
- high
- invasive
A
- not entire epithelium
- entire epithelium but not into BM (carcinoma in situ)
- invades into BM
9
Q
Histo of Dysplasia
- pleomorphic
- staining
- mitoses
A
- cells and nuclei differ in shape and size
- stain intensely because all nuc and little cytoplasm
- increase significantly
10
Q
how dysplastic cells violate BM to become invasive carcinoma
- step 1
- step 2
- step 3
A
- decrease in e-cadherin -> no longer attached to neighboring cells
- increase in laminin -> so it can attach to BM
- secretion proteolytic enzyme by tumor (metalloproteinase and cathepsin D protease) in order to break down BM and ECM
11
Q
Why does CA met? Most common mets
- breast
- colon
- lung
- melanoma
- prostate
A
- bc it outgrows local blood supply
- bone, brain, liver, lungs
- liver, lung, bone, brain
- bone, brain, liver, adrenal
- bone, brain, liver lung
- bone
12
Q
Mech of CA
- pre initiation
- initiation
- promotion
- progression
- malignancy
A
- no CA
- exposed to carcinogen which interacts with DNA
- carcinogen causes mutation in DNA -> usually a transcription regulator -> will start replicating faster than cells around it
- continue to have exposure to carcinogens -> mutations in DNA accumulate -> dysplasia is occurring so benign tumor is growing
- cancer begins to violate BM
13
Q
Tumor suppressor genes
- what are they
- mutations
- ways
- two hit hypothesis
- kinds of mutations
A
- anti-oncogene protecting cell from CA
- loss or reduction of function allowing cell to progress to CA
- gene repression, apoptosis, cell adhesion, block loss of contact inhibition, inhibit mets, DNA repair, stop cell cycle
- both alleles have to be mutated in order to have increased susceptibility to CA
- point mutation -> causing truncated protein OR large deletion -> loss of protein function
14
Q
Oncogenes
- what are they
- proto; code for
- activation
A
- genes that can cause CA
- normal gene that can become oncogene if mutated; cell growth and differentiation
- mutation in proto oncogene or its regulatory region
15
Q
Classifying Oncogenes
- Growth Factors
- Receptor Tyr Kinase
- Reg GTPase
- Transcription factors
- cytoplasmic kinase
- cytoplasmic tyrosine kinase
A
- induce cell proliferation
- transduce signal for cell growth and differentiation
- signal pathway that leads to cell proliferation
- reg transcription of genes that induce proliferation
- cell cycle regulation, proliferation, differetiation, survival
- mediates response to and activation of receptors for cell proliferation
16
Q
Oncogenes Altered in CA
- AKT1 *
- BRAF *
- FOS *
- ERB2 *
- C-MYC *
- N- MYC *
- HRAS
- KRAS
- NRAS *
- RET *
- WNT1 *
A
- hepatoblastoma, wilms, lung, ovarian, colon, beckwidth weeman syndrome
- breast CA, lung, colon, rectum, ovary, thyroid, Gastro-intestinal stromal tumors
- osteosarcoma, endometrial, cervical
- breast, lung, gastric, ovarian, glioma **
- murkitts, ovarian, breast, colorectal, pancreas, uterus
- neuroblastoma
- neuroblastoma
- MEN2a, 2b, medullary CA of thyroid
- basal, colorectal, breast
17
Q
Important translocation
- 9:22
- 8:14
- 14:18
- 11:22
- 15:17
A
- phil chromosome -> CML
- burkitts
- follicular
- ewings osteosarcoma
- AML -> promyeloblastic
18
Q
Viruses and CA
- how
- HPV
- EBV
- Hep B, C
- Retrovirus
A
- activate growth promoting pathways or inhibit tumor suppressor
- E6 -> p53, E7 -> RB; throat cancer, vulvar CA, penile CA, rectal CA
- HCC
- T cell leukemia
19
Q
Staging
- what is it
- T
- N
- M
A
- extent or severity of CA
- extent of tumor; 0= only marker, TIS = in situ, 1-3: size or extenet of tumor
- Lymph nodes; regional LN, n=0 none, N1-3: # LN or extenet of spread
- Mets; 0= no mets, 1: distant mets
20
Q
Grading
- what is it
- in situ
- localized
- regional
- distant
- unknown
- 1
- 2
- 3
- 4
A
- classifies CA cells in terms of how abnormal the cells look microscopically and how quickly they are to grow and spread
- abnrml cells present only in layer of cells in which they devleop
- cancer limited to organ where it began
- CA spread beyond primary sight to nearby LN or organs
- CA spread from primary sight to distant organ of LN
- not enough info to determine stage
- well differentiated (low) -> similar to histo of tissue of origin
- moderately diff (intermediate)
- poorly diff (high) -> lack majority of characteristi features of normal cells
- undiff (high) -> do not look anything like a normal cell
21
Q
Benign
- looks
- mobile
- encapsulated
- mets
A
- well circumcribed
- freely
- yes, and does not grow outside capsule
- no, will not grow
22
Q
Malignant
- looks
- mobile
- encapsulated
- mets
A
- not circumscribed
- adehent to surrounding tissue
- no, outgorwn
- yes, outgrows blood supply
23
Q
Anaplastic tumors
- architesture
- mitoses
- nuceli
- look like
A
- loss of cell polarity, variation in sixe and shape
- lots
- large, deep staining
- giant, multi nucleated tumor cells
24
Q
2 factors for malignant neoplasia success
- angiogenein
- endostatin
A
- help CA produce own vessels
- anti-angiogenic: interferes with activity of certain growth factors
25
Tx for CA
- target
- chemo
- radiation
- normal cells affected
- destroy rapid dividing cells
- kill cancer cells
- induce new mutations and cease cell division
- RBC -> anemia, Hematopoetic stem cells -> WBC, GI tract -> ulcer, Hair follicles -> allopecia, Mucous membranes -> mucositis
26
Cancer Meds that affect S
- 5FU
- 6MP
- 6 thioguanine
- MTX (oral ulcers and hepatotoxic)
- azathioprine
- cladribine
- cytarabine
- cant turn UMP to TMP to make thymine for DNA
- purine analog -> PRPP aminotransferase -> no purine synthesis
- gets turned into 6thio- GMP and provides negative feedback to rate limiting enzyme
- dihyrdofolate reductase -> no tetra hydro folate -> prevents uracil from becoming thiamine
- purine analog that will get turned into 6 mercaptopurine -> inhibits purine synthesis
- purine analog works the same as azathioprine
- damages DNA
27
Cancer Meds that affect G2
- Etoposide and doxarubicin (heart tox)
- bleomycin (pulm fibrosis)
- topoisomerase 2 inhibitor stops taking down of supercoil
| - DNA strand breaker
28
Cancer Meds that affect M
- Paclitaxel
- vincristine and vindlastine
- Vinca Alkaloid
- prevent MT disassembly; chromosomes will not separate
- bind to tubulin and block spindle assembly
- add alkyl group to guanine which forms DNA cross links
29
Leukemia Nomenclature
- acute
- chronic
- second letter
- abnormal proliferation of precursor cells
- abnormal proliferation of mature cells
- tells you where its from, lymphoblasts (T or B cells) or myeloblast (PMNS, marco, eosinophil, basophil)
30
Types
- ALL
- AML
- CLL
- CML
- acute lymph
- acute myelo
- chronic lymph
- chronic myelo
31
ALL
- what is it
- effects on myeloid line
- effects on RBC
- mutation
- diff B from T
- stain w/
- Common ALL antigen
- physical sxs
- tx
- lymphoblasts proliferating and taking up all room in BM; greater than 20% lymphoblasts
- myeloid cells will be squeezed out and can no longer be produced -> thrombocytopenia
- RBCs can be made but will be pushed put quickly and pinched making teardrop cells
- chromosomal abnormality leads to abnormal transcription factors affecting B and T cells
- children
- with immuno typing; B- 10, 19; T - 2, 3, 4, 5, 7, 8
- TdT
- marker w/ good prognosis bc indicates that CA will respond well to therapy and is seen in 80% pts
- ant mediastinal mass -> can cause SVC syndrome, dyshpagia or dyspnea and stridor
- MTX and prednisone (kills T cells)
32
AML
- what is it
- effects on myeloid line
- effects on RBC
- caused by
- cell morphology
- sxs
- epi
- stain w/
- acute promyeloblastic: translocation, causes
- stain w/
- why is it worse than ALL
- tx
- myeloblasts proliferating and taking up all room in BM; not maturing into normal cells -> so still no platelets
- RBCs can be made but will be pushed put quickly and pinched making teardrop cells
- oncogene mutation disrupting differentiation leading to accumulation of myeloid blasts
- auer rods, myeloblasts
- anemia, neutropenia, thrombocytopenia
- adults, 67 yrs old
- black w/ sudan black stain
- cannot generate PMN or macrophages and since crowding out lymphoblasts you have no immune sxs
- chemo and bone marrow transplant
33
SXS of leukemia
- weight loss, fever, SOB, weakness, LN swelling, night sweats, easy bleeding and bruising
34
CLL
- what is it
- cell morphology
- CBC
- epi
- tx
- prognosis
- abnormal proliferation of mature lymphocytes
- smudge cells
- lymphocytosis
- male adults (avg age of dx is 70)
- alkylating agents -> only when white count elevated
- best
35
CML
- what is it
- caused by
- cell morph
- sxs
- epi
- terminal phase
- elevated levels of WBC
- phili chromosome; 9:22
- hypercellular marrow, elevated eosinophils and basophils
- only have sxs when WBC greater than 200K
- 20-50 yrs old
- blast phase, final phase, nehaves similar to acute leukemia
36
Hairy Cell Leukemia
- what is it
- sub-type of
- look like
- confirmed with
- tx
- T cell leukemia, 75% B cell and 25% t cell, whil most other lymphoblastic leukemias are 99% B cell
- CLL
- have hair like projections
- tartrate resistant acid phosphatase
- cladribine -> purine analog -> shuts down ribonuc reductase -> no purine synthesis
37
Leukemia Age Group
- ALL
- CML
- AML
- CLL
- 0 - 15 yr
- 50 -60 yr
- 67 yrs
- 70 yrs
38
Lymphoma
- what is it
- look for
- then
- CA in LN
- enlarge LB
- biopsy -> reed sternburg clles
39
Nodes at Suspicious Site
- suprcalvicular
- inguinal
- epitrochlear
- what about cervical
- lymphoma or gastric
- no hx of STD then likely lymphoma
- at elbow, very rare, need biopsy
- usually viral infection, just watch, only biopsy after 4-6 weeks
40
Reed sternburg
- indicates
- looks like
- positive for
- negative for
- indicative of hodgkin lymphoma
- multi nucleated
- CD 15 and 30
- CD 20 and 45
41
Hodgkins
- distribution
- prognosis
- nodular
- lymph depleted
- lymphocyte predominate
- mixed
- bimodal, 20-40 or elderly
- relatively good, 70-90% survival
- most common, female, least # RS, scarring LN, intermediate prognosis
- least # lymphocytes, worst prognosis, rare, associated with HIV
- rare, many lymph, best prognosis
- many RS w/ inflamm cells, associated with EBV and HIV, intermediate prognosis, older pts
42
Non- Hodgkins
- seen in
- present w
- most common
- follicular: sxs, architecture, translocation, prognosis
- Burkitts: translocation, associated w/, variations, histo
- immuno compromised -> get HIV test
- abdominal or jaw mass
- follicular
- painless LN enlargement or abd discomfort; tumors arranged in follicles; 14;18 translocation w/ over expression BCL2 (anti-apoptosis); very slow growing tumor w/ avg survival being 10 yrs
- 8:14(c-myc and ig H); associated with EBV; endemic (africa, kids w/ chronic malaria), sporadic( non- african, imapired immunity leaves susciptble to EBV, involves ileocecal region), immuno defficient (HIV); starry sky made up of macrophages that contain apoptotic tumor cells
43
Staging Lymphoma
- 1
- 2
- 3
- 4
- 1 group LN
- 2 group LNs on same side diaphragm
- 2 or more groups LN on both sides diaphragm
- mets throughout body
44
Lymphoma Tx Side effects
- cyclophosphamide
- adriamycin
- bleomycin
- hemm cysittis
- cardiac fiboris
- pulm fibrosis
45
Polycythemia Rubra Vera
- what is it
- HCT
- primary
- secondary
- sxs
- tx
- caused by
- all cell lines from BM are increase, but RBC more increase
- more than 60%
- Bone marrow
- chronic hypoxia
- headahce, vertigo, itchy after hot shower (bs increase of mast cells and hot shower causes degranulation causing pruritis)
- phlebotomy
- mutation in jak 2 (tyr kinase) enabling cells sensitive to EPO -> increase RBC
46
Essential Thrombocytopenia
- what is it
- sequelae
- therapy
- prognosis
- increase in all cell lines but greatest is platelets
- MI or stroke
- anti- platelet and hydroxy urea to lower platelet count
- slowl progressing, usually asymptomatic
47
Aplastic Anemia
- what is it
- most common cause
- tx
- bone marrow
- viruses
- drugs
- all cell lines depleted
- viral or drug related, but check BM to identify if bone marrow is cause
- remove cause
- replaced by fatty tissue
- parvo virus, hep E, hep C
- AZT, vinblastine, chloramphenicol
48
Myelo fibrosis
- what is it
- sxs
- tx
- sequalae
- bone marrow cancer that burns out bone marrow and makes it scar up
- bone pain, anemia, panyctopenia, petechial bleeding, tear drop cells
- stem cell replacement
- need transfusions bc panctopenia
49
Multiple Myeloma
- what is it
- epi
- histo
- sxs
- M protein
- IL-6
- kidneys
- rouleau formation
- plasma cell CA
- 40-60 yrs old
- basophilic cytoplasm, with wagon wheel distribution of chromatin, and plasma cell in BM
- bone pain, pathologic fx w/ punched out lesions, anemia, hyper Ca
- monoclonal Ig in serum; usually IgG
- secreted by neopplastic cells causing osteoclastic activity
- bence jones protein (light chain from antibody depositing), toxic to tubules
- stacked RBC
50
Cancer Antigen
- what do they do
- how
- examples
- only hows association
- if pt has tumor, then measure them before, resect tumor, measure after to ensure decrease, then continue checking to look for reoccurence
- PSA- prostate; HER2, BRCA- breast; Rb - retino blastoma or ewing
