Oncology Dan Cushman. No presence detected by any currently available studies Cancer What is...
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Transcript of Oncology Dan Cushman. No presence detected by any currently available studies Cancer What is...
Oncology
Dan Cushman
No presence detected by any currently available studies
Cancer
What is “complete remission?” Decrease in tumor size by 50%What is “partial remission?”
Obtain a piece of the tumor (not the whole thing)What is an incisional biopsy? Lung, breast, colonWhat are the main three
cancers in terms of mortality?
AgeMain risk factor for cancer? Smoking#2 risk factor?
Breast, bone, thyroidThree most sensitive tissues to oncogenic exposure? TissueWhat is the issue?
1.5 million
Epidemiology of CancerHow many incidences of cancer
in the US annually? 1:3What is the lifetime risk of developing cancer?
They’re both decreasingAre incidences and mortality rates of cancer increasing or
decreasing?MenWho has a higher mortality rate
– men or women?
Prostate, Lung, ColorectalTop three male cancers? Breast, lung, uterusTop three female cancers?
Lung, prostate, colorectalTop three male cancers in terms of mortality? Lung, breast, colorectalTop three female cancers in
terms of mortality?
Leukemia, CNS, lymphoma
Epidemiology of CancerMain three pediatric cancer
sites? Tobacco, diet, infectious processesTop three environmental risk factors for cancer?
Mammogram, PSA, sigmoidoscopy, PAP smear
Four main screening programs for cancer? 30%What percentage of cancer
deaths are caused by smoking?
Lung, oropharyngeal, esophageal, pancreatic, bladder, laryngeal,
renal, cervical, colorectal, …
Which cancers are caused by smoking?
Smoking isn’t cool
The inactive trimer dissociates into an α- and a β/γ subunit; the α
subunit binds GTP
Molecular BiologyWhat happens to a G-protein
upon activation?
The GTP of the active α subunit is hydrolyzed upon binding to a
target proteinHow are G proteins inactivated?
G-protein-coupled reaction increase in cAMP
What does a β-adrenergic receptor do after a ligand binds
(step 1) ?Activates PKAThe increased cAMP does what?
Enters the nucleus and promotes cell cycle progress & DNA
replication by using the CREB protein
What does PKA then do?A receptor tyrosine kinase (RTK) allows Ras to trade its GDP for a
GTPHow is Ras activated?
Activates the kinase cascadeWhat does the activated Ras protein do next?
Activates transcription factors, resulting in the stimulation of DNA
synthesis and cell division (e.g. myc)
What does the kinase cascade eventually do?
Joke of the dayQ: What does the molecular biologist do
for fun?
A1: They go cAMPing.
A2: Let’s be realistic, molecular biologists are never fun.
G-proteins, RTK, PIP3
Molecular Biology
How is PLC activated? PIP2What molecule does PLC work
on?
Diacylglycerol (DAG) + Inositol triphosphate (IP3)
What is created when PLC cleaves PIP2?
IP3 IP3-gated Calcium channels increase in intracellular [Ca]
activates PKC + Calmodulin Kinase
What does the IP3 end up doing?
DAG directly activates PKCWhat does the DAG lead to?PKC enters the nucleus and
promotes cell cycle progression. It also activates the kinase cascade.
What does PKC do?
PI 3-kinaseWhat is an alternate enzyme
that works on PIP2?Both RTKs and G-protein-linked
receptorsHow is PI 3-kinase activated?
PIP3
Molecular BiologyWhat does PI 3-kinase create
from PIP2?
It activates other cell division and metabolism pathways (e.g. PLC-γ,
PKB, PKC)…and what does PIP3 do?
It inhibits apoptosisWhat does PKB ultimately do? PKB BCL-2 inhibits apoptosisWhat intermediate molecule accomplishes this?
PKB mTORThrough what other mechanism can PKB affect cell growth?
Rapamycin (mTOR = “mammalian Target of Rapamycin”)What drug can block mTOR?
Promotion of the cell cycleWhat does WNT ultimately cause?
WNT Blocks APC frees β-catenin transcriptionWhat is the pathway for WNT?
APC generally “mops up” excess β-catenin in the cell, preventing cell
cycle progression
Molecular BiologyWhat is the relationship
between APC and β-catenin?
Metastasis (↑ Wnt ↓ e-cadherins cell migration) and
invasion (↑ metalloproteinases)
What other aspect of cancer is Wnt responsible for?
Transforming growth factorWhat does TGF stand for? Epithelial cells = tumor suppressor, mesenchymal = stimulatory
How does TGF behave for mesenchymal and epithelial
cells?
SmadWhat intermediate molecule is part of the TGF-β pathway in
epithelial cells?Chronic myelogenous leukemiaWhat is Gleevec used for?
It replaces ATP in the bcr-abl proteinHow does Gleevec work? PTEN phosphataseWhat inhibits PI 3-kinase
activity?
Molecular BiologyMolecule Cell Growth Promotion or Inhibition
PKA PromotionPKB PromotionPKC Promotion
TGF-β InhibitionRas PromotionWnt PromotionAPC Inhibition
Calmodulin kinase PromotionCell-matrix junction Promotion
Cell-cell junction InhibitionCytokine receptors Promotion
β-catenin Promotion
Molecule Previous step(s) Next step(s)PKA ↑ cAMP Transcription factors (TF)PKB PIP3 BCL-2, mTOR
PKC DAG, ↑Ca2+ TF, Kinase cascadeTGF-β (it’s a ligand) Receptor Smad
Ras RTK, FAK/SRC, JAK Kinase cascadeWnt (it’s a ligand) Receptor blocks APCAPC Wnt intermediaries β-catenin, Cyclin B
Calmodulin kinase ↑Ca2+ TFDAG PIP2 PKC
Kinase cascade Ras, PKC TF (e.g. myc)STAT IL-2 Cytokine receptor TF
β-catenin Cell-cell junctions APC, TF
Steps…
E2F Cyclin D : CDK4/6Cyclin E: CDK2
Cyclin D : CDK4/6, plus the positive feedback loop created by CDK2 :
Cyclin Ep21 (p53) and p27
DNA damage Activates p53
Mdm2 (which binds p53) is blocked by ATM
Upregulates DNA repair enzymes (BRCA, chk)
To which molecule is Rb normally bound? What activates Rb?
What is required for E2F to initiate DNA replication factors? What inhibits CDK2 : Cyclin E?
What activates ATM? Activated ATM does what?
How is p53 activated by ATM? What else does ATM do?
Molecular Biology
Tip of the dayNo matter how cool you think you are, never say “Cyclin-dependent kinase” at
a dinner party.
Never.
It ubiquitinates p53
Molecular Biology
What is the purpose of Mdm2? Multiple stagesAt which point of the cell cycle can ATM be activated?
Both – oncogenic in response to growth factors, suppressive in high
levels
Is myc oncogenic or tumor suppressing? myc p14ARF p53How does myc relate to p53?
It is a powerful transcription factor for multiple genes (cyclin D, E2F,
p27 degradation)How can myc be oncogenic? TGF-β p16INK4; TGF-β p27
inhibits CDK2 : Cyclin EHow does TGF-β inhibit the cell
cycle?
It is inhibitory to p16How else can myc be oncogenic?
Fas ligand Fas protein caspase cascade apoptosis
What is the extrinsic pathway of apoptosis activation?
Deep thought of the day
If you were a Fas ligand, would you be proud of your job?
Mitochondria
Molecular BiologyWhat is the main cell organelle
involved in the intrinsic pathway of apoptosis activation?
Cytochrome CWhat is released from the
mitochondria to trigger apoptosis?
Bax (from p53)What protein initiates the
release of cytochrome C from the mitochondria?
BCL-2What protein inhibits cytochrome C release?
They overexpress BCL-2What is the probable relation between breast tumors and
BCL-2?
The ends become sticky chromosome fusion and breakage
What happens to chromosomes that lack telomerases?
Usually not, unless there is a concurrent loss of p53
Will a lack of telomeres result in the breakage-fusion-breakage
cycle?
It ubiquinates proteins for degradation in proteosomes
What is the main (general) function of APC?
CDK4/6 : Cyclin D, followed by CDK2 : Cyclin E
Molecular BiologyWhat cyclins and CDKs are
involved in progressing a cell from the G1 phase to the S?
CDK2 : Cyclin AWhat cyclins and CDKs are
involved in progressing a cell from the S phase to the G2?
CDK1 : Cyclin BWhat cyclins and CDKs are
involved in progressing a cell up to the mitosis phase?
MetaphaseUp to which phase of mitosis
does the CDK1 : Cyclin B combination work?
The destruction of cyclin B (and inactivation of CDK1) by APC
What event allows for the initiation of anaphase? APC (Adenomatous Polyposis Coli)
Which protein is often responsible for starting the
transition to cancer in patients with Familial Polyposis Coli?
TGF-β is knocked out
Which protein is often responsible for starting the
transition to cancer in patients with HNPCC?
DNA repair enzymes, helped by p53
What are the functions of the BRCA1 & 2 genes (associated
with breast cancer)?
Ras, but myc + Ras is far more oncogenic
Molecular BiologyWhich induces more tumors –
myc or Ras? DominantAre oncogenes dominant or recessive?
RecessiveAre tumor suppressors dominant or recessive?
Single point mutation hyperactive protein made in
normal amounts
What is the usual mechanism for the development of a
mutation in the Ras protein?
Gene amplification normal protein greatly overproduced
What is the usual mechanism for the development of a
mutation in the N-myc protein?Chromosomal rearrangementWhat is the usual mechanism
for the development of a mutation in the abl protein?
It is a key feature of the ability of a cell to metastasize
What is important about the ability of a cell to undergo epithelial-to-mesenchymal
transition?
It is resistant to chemotherapy (due to its quiescence) and it is able
to reseed new tumors after treatment
If a stem cell gives rise to and perpetuates a tumor, why is this
dangerous?
Loss of responsiveness to normal growth controls
Pathology
What characterizes a neoplasm? SarcomaWhat is the term given to a
malignant tumor of mesenchymal origin?
CarcinomasWhich is more common – carcinomas or sarcomas? HTLV-1, EBV, HBV, HPVName four oncogenic viruses
16 & 18Which strains of HPV are oncogenic?
It refers to the level of cytologic differentiationWhat is “grading?”
It takes into account the lesion size, extent of spread, and presence of
metastasesWhat is “staging?” Tumor suppressors
Which are related to the “two-hit” hypothesis – tumor
suppressors or oncogenes?
After resecting a tumor from a mouse, injection of tumor cells
back into the “cured” mouse resulted in no tumor
Immune SystemWhat animal-based experiment showed a role of the immune
system in tumor control?
Mutation new protein new Ag; Overexpression of normal self-
protein increased density of Ag
What are the two ways in which a tumor can be recognized by
the immune system?
Dendritic cells, macrophages, and B cells
What are the three types of professional antigen-presenting
cells?Both
Which is involved in tumor detection and destruction – the innate or the humoral immune
system?
Both (immunoediting)Does the immune system help limit or facilitate tumor growth?
Elimination, equilibrium, and escape
What are the three elements of immunoediting?
Low immunogenicity, antigenic modulation, and tumor-induced
immune suppression
What are three mechanisms in which tumors escape immune
recognition?
Incubation of tumor-based lymphocytes with IL-2 injection
back into patient
How can IL-2 be used to fight cancer?
Cdk4-cyclin DCdk6-cyclin D
Cdk1-cyclinB
Cdk2-cyclin A
Cdk2-cyclin E
CDK?:Cyclin?
CDK?:Cyclin?
CDK?:Cyclin?
CDK?:Cyclin?
1
2
3
4
Cell Cycle
Cell CycleWhich portion of the cycle involves the replication of
the DNA genome?
Which portion of the cycle involves nuclear and cytoplasmic division?
Which portion of the cycle involves the synthesis of cellular components for
mitosis?
Which portion of the cycle involves the synthesis of cellular components for
DNA synthesis?
Resectability refers to the ability to remove the tumor, while
operability refers to the overall condition of the patient
Oncological SurgeryWhat is the difference between “operable” and “resectable?” Colon
Which type of cancer can metastasize and still be treated
surgically?
Liver > LungWhere does colon cancer generally metastasize?
Don’t cut into the tumor, as it can seed other tissues
During surgery, where should the surgeon avoid cutting?
After; neoadjuvant is given beforeIs adjuvant chemotherapy given before or after surgery? YesIs surgery appropriate for
palliation?
ReconstructiveApart from palliation, when
else would surgery be used for non-curative oncologic means?
Radiosensitivity refers to ability of the cell to respond to radiotherapy,
not necessarily its ability to be completely eliminated
Radiation OncologyWhat is the difference between
“radiocurability” and “radiosensitivity?”
An implantable device that gives localized radiationWhat is brachytherapy?
Acute < 3 monthsSubacute 3-6 months
Chronic >6 months
What length of time signifies acute radiation damage?
Subacute? Chronic?
Highly-active cells (high growth rate)
What type of cells are most susceptible to X-ray-induced
damage?
S phase (G0 phase too?)Which stage of the cell cycle is
least susceptible to DNA damage from X-rays?
Rapidly-dividing tissue (hair, bone marrow, GI tract, gonads, etc.)
ChemotherapyWhich normal tissues are most
often affected by chemotherapy?
No; they differentiate between rapidly-dividing and slow- or non-
dividing cells
Can chemotherapeutics differentiate between normal
and cancerous cells?
A percentage of cells is killed with each treatment; starting with a
smaller tumor has a better chance of being completely eliminated
What’s the “Log Kill Hypothesis?”
Cells in G1, S, G2, & M------------------------------------
Cells in G0, G1, S, G2, & M
What is the equation for the growth fraction?
Lower, because less cells are cycling
Which is more difficult to treat – a higher or lower growth
fraction?
Neither; non-phase-specific agents kill cells in G1, G2, S, or M
Which kills cells in G0… phase-specific or non-phase-specific
agents?
Transporters, block apoptosis, slow-growing cells (hypoxia)
Name the three methods of resistance-development for
tumors
Hypoxic cells have less ability to generate ATP from oxidative
processes and depend more on glycloysis
How can inhibiting glycolysis kill tumor cells?
Tip of the day
Don’t try to make a joke about chemotherapy. You can’t win that one.
Yes
Antimetabolites
Phase-specific? S-phaseWhich phase?
Mercaptopurine, methotrexate, ARA-C
Name three main drugs in the class
Block synthesis of replication metabolites – mostly DNA or RNA
building blocksMechanism of action?
Binds Dihydrofolate Reductase inhibits formation of purinesHow does methotrexate work? It’s a purine analogHow does mercaptopurine
work?
Decreased polyglutamate (which traps methotrexate in the cell)How can cells become resistant
to methotrexate?
Mercaptopurine (it’s usually inactivated by xanthine oxidase, which is blocked by allopurinol)
Which antimetabolite has a dangerous interaction with
allopurinol?
Tip of the dayCan’t remember how mercaptopurine
works?
Just remember that “mercapto” is Latin for “wanna-be”
For example, you could say some people are “mercaptosexy” or “mercaptoblack”
No
Alkylating Agents
Phase-specific? They are metabolized by the liver, which activates them
What is important about their metabolism?
Mustards, Cyclophosphamide, Chlorambucil
Name three main drugs in the class Alkylate DNA DNA damageMechanism of action?
Aldehyde Dehydrogenase (low levels in tumor cells higher
potency)
Which enzyme helps degrade cyclophosphamide?
Brain tumors (they’re highly lipophilic and can cross the BBB)
Where are nitrosoureas (chlorambucil, melphalan)
useful?
No
Anthracyclines
Phase-specific? CardiacMain toxicity?
Adriamycin, doxorubicinName two main drugs in the class
Intercalate into DNA block transcriptionMechanism of action?
It is cumulativeWhat is special about the cardiac toxicity?
Yes
Tubulin-Binding Agents
Phase-specific? M-phaseWhich phase?
Taxol, vinca alkaloidsName the main drugs in the class
Impairs proper microtubule formationMechanism of action?
Neurotoxicity (remember that synaptic vesicles are carried on
microtubules)
What is the main form of toxicity for these agents?
Drug ToxicityAnthracyclines Cardiac
Cisplatinum KidneyBleomycin Pulmonary fibrosis
Vinca alkaloids NeurologicalCyclophosphamide Cystitis
Chemotherapy Toxicities
Using two drugs with different mechanisms that function
additively
ChemotherapyWhat is “therapeutic
synergism?”
It can shrink the tumor, making it easier to resect; the patient is
healthier pre-surgery; sensitivity to a specific drug can be monitored
What are the advantages of using a neoadjuvant?
Bind ligandBind receptor
Inhibit kinase activityInhibit secondary messengers
What are the four ways with which signal transduction can
be interfered?
Tumor cells often create excess proteins, which can overwhelm cell
if they are not degraded
How can a proteosome inhibitor be useful for tumor cells?
CMLFor which type of cancer is Gleevec used?
A RTK that receives epidermal growth factor (EGF)What is the HER receptor?
Non-Hodgkin Lymphoma
Monoclonal antibodies
What is Rituximab used for? CD20 on B-lymphocytes…what does it target?
80%, but tend to improve after first infusion
How common are side effects with Rituximab? Metastatic breast cancerWhat is Trastuzumab
(Herceptin) used for?
HER2 membrane protein…what does it target? 25% of patients express amplified amounts of HER2 proteinIs it useful in all breast cancers?
Fever/chills, pain at the tumor site, GI, cardiac dysfunctionWhat are the side effects?
Factoid of the DayMonoclonal antibodies are named after
their founder.
Guess who developed Rituximab?
Hint: her last name is Gupta.
Immune-mediated, hormone-mediated, thrombophilia
Paraneoplastic SyndromesWhat are the three general
types of paraneoplastic syndromes?
Antibodies against voltage-gated Calcium channels at the NMJ
What is the pathophysiology of Lambert-Eaton Syndrome?
Small-cell cancer of the lungTo which type of cancer is LES classically related?
Proximal muscles of the lower extremities
Where does LES usually present itself?
It is cytokine-mediated and caused by a malignancy
Why is cachexia considered a paraneoplastic syndrome?
Involuntary loss of >5% of body weight
What is the definition of cachexia?
Cachexia is a hypermetabolic state that can not be overcome by eating
more
What is the difference between anorexia and cachexia? GI and lung cancers
Which two general types of cancer are most commonly associated with cachexia?
Increased lipolysis, proteolysis skeletal muscle loss, neurologic
symptoms
Paraneoplastic SyndromesWhat is affected in states of
cachexia? TNF-α, IL-1, IL-6, PTHrPWhat are the main cytokines associated with cachexia (4)?
Steroids, dronabinol, marijuanaHow can cachexia be treated? DermatomyositisWhich type of paraneoplastic syndrome gives fever, fatigue,
proximal weakness, and a rash?
Creatine kinaseWhat lab is elevated in dermatomyositis? Treat cancer; steroidsHow do you treat
dermatomyositis?
HypercalcemiaWhat is the most common paraneoplastic electrolyte
imbalance?
Humoral (PTHrP or calcitriol production), Osteolytic
What causes the hypercalcemia (2)?
Fatigue, weakness, constipation, altered mental status, polyuria,
decreased QT interval
Paraneoplastic SyndromesWhat are the main symptoms of
hypercalcemia?Neuroendocrine tumors (carcinoid,
pancreatic NE tumor)
Which types of cancer are associated with Cushing’s
Syndrome?
↓[Na] due to ↑ADH production (from tumor)
What causes paraneoplastic hyponatremia? Poor
If a clotting disorder is the first sign of a cancer, what is the
prognosis?
HypercoagulableCancer – hyper- or hypocoagulable? Fluids and bisphosphonatesHow is hypercalcemia treated?
Heparin, not coumadin
What drug should be used for avoiding complications of
hypercoagulability associated with a malignancy?
Breast, lung, prostate, kidney
Oncologic EmergenciesWhich tumors most commonly
cause spinal cord compressions?Yes, it occurs in 20% of vertebral
column mets
Is spinal cord compression a common paraneoplastic
syndrome?
Most of those who walk in will walk out, regardless of the cancer
Can patients recover after surgery for spinal cord damage?
Prompt application of high-dose corticosteroids
What’s the treatment for spinal cord compression?
Melanoma, lung, breastWhat types of metastatic
tumors are most commonly found in the brain?
Solitary = neurosurgery;Multiple = irradiation, steroids
How are metastatic brain tumors treated?
Lung, breast, melanomaWhat are the three most
common tumors to metastasize to the pleura?
The tumor compresses the SVCWhat is the pathophysiology of SVC syndrome?
Lung cancer > lymphoma > benign
Oncologic EmergenciesWhat cancer is the most
common cause of the SVC syndrome?
The diagnosis is more important than urgent therapy; the tumor is
treated appropriatelyHow is SVC syndrome treated?
<500What is the neutrophil count in a neutropenic patient? 7-10 days post-chemo
At what stage of chemotherapy is a patient most at risk of developing neutropenia?
Bacteria from intestinal flora (E. coli or Pseudomonas)
What type of bacteria is a febrile neutropenic patient most
likely infected with?
Elevated potassium, phosphate, & uric acid; Decreased [Ca]
What are the electrolyte imbalances of a patient with
tumor lysis syndrome?
Allopurinol, hydrationWhat is the treatment for tumor lysis syndrome?
Cardiac arrest, electrolyte imbalances, acute renal failure,
arrhythmias, hypotension
What are the clinical features of tumor lysis syndrome?
Breast Cancer
Invasive Non-InvasiveMain two types?
Ductal Carcinoma
Lobular Carcinoma
High-gradeLow-grade
Ductal Carcinoma In-Situ
Lobular Carcinoma In-Situ
High-gradeLow-grade
90% benign
Breast CancerAre most breast tumors benign
or malignant? Yes, most typesIs fibrocystic change known to progress to malignancy?
Atypical intraductal hyperplasia > intraductal hyperplasia, ductal
papillomatosis
Which type of fibrocystic change is most likely to progress to
malignancy?
Fibroadenomas; they can be sarcomatous
What are phyllodes tumors similar to?
Phyllodes tumors have increased stromal cellularity
What separates a phyllodes tumor from a fibroadenoma,
histologically?Bloody discharge from the nippleWhat is the main presenting sign of a intraductal papilloma?
Well-differentiatedAre low-grade tumors well- or poorly-differentiated?
Hyperplasia looks very similar to and can progress to CIS
What is the relationship between hyperplasia and
carcinoma in-situ?
Cancerous cells pass through ducts all the way to the skin
Breast CancerWhat is the pathophysiology of
Paget’s disease?Usually a non-invasive cancer
(often DCIS)Is Paget’s disease an invasive or
a non-invasive cancer?
60-70% of breast carcinomas express them
Is it more common to have a tumor with or without extra
estrogen receptors?
Tubular, colloid, papillary, and lobular
Which tumor types are always ER+?
WorseDoes overexpression of HER2
give a better or worse prognosis?
Herceptin (Anti-HER2 monoclonal antibody)
What is the treatment for tumors that overexpress HER2?
Smoking metaplasia of bronchial epithelium dysplasia of
squamous epithelium SCC
Lung CancerWhat is the progression in the development of squamous cell
carcinoma?79% non-small cell
Which are more common – small cell or non-small cell
carcinomas?
Adenocarcinoma, squamous cell > large cell, adenosquamous
What are the two most common non-small cell
carcinomas?Small Cell Carcinoma
Which lung tumors are treated by chemotherapy as the first-
line treatment?
They contain mucin in the cytoplasm
How can adenocarcinomas be identified by histology? PeripheralAre adenocarcinomas found
centrally or peripherally?
The normal alveolar tissue is lined with malignant cells
What is indicative of bronchioalveolar carcinoma,
histologically?
Typical carcinoid > atypical carcinoid > small cell/large cell
Which type of neuroendocrine tumor of the lung carries the
best prognosis?
Endobronchial growth pattern, abundant blood vessels
Lung CancerBronchoscopically, what do carcinoid tumors look like? <45 years oldWhat age group is affected by
carcinoid tumors?
MetastaticWhich is more common in the lung – primary or metastatic
tumors?Metastatic
Which is more common in the pleura – primary or metastatic
tumors?
Calretinin (+), Membranous EMA (+)
What tumor markers can be found from malignant
mesothelioma?
Only 1% of all GI malignancies
GI TumorsHow common are malignancies
of the small intestine? Near the ampulla of VaterWhere do most small intestinal adenocarcinomas occur?
Epithelial cells in the cryptsFrom what type of tissue are
carcinoids of the small intestine derived?
Carcinoid of the appendix (it rarely metastasizes, even with local
spread)
If you had to have one type of GI cancer, what would it be?
SerotoninWhat substance is responsible for the carcinoid syndrome? Interstitial cells of Cajal
From what type of cell do gastrointestinal stromal tumors
originate?
Anywhere in the digestive tractWhere do GISTs occur? GleevecHow is GIST treated?
Oh yeah – 40-50% of all people over 60yo have them
GI TumorsAre adenomas of the colon
common? Tubular > TV > Villous, flatWhat is the most common type of adenoma?
10 yearsHow long does it take for an adenoma to double in size?
Villous > tubular (especially large ones)
Which types of adenomas carry a malignant risk?
Adenomas progress into carcinomas over time
What is the relationship between adenomas and carcinomas of the colon?
SporadicWhat is the most common cause of colorectal carcinoma?
60-79yo (<20% are under 50)What age group is most
commonly affected by sporadic colorectal carcinoma?
Ascending, sigmoidWhich sections of the colon are
most commonly affected by sporadic CC?
Lung, liver, bone
GI TumorsTo where do colorectal
carcinomas usually metastasize?Mucosal/cutaneous pigmentation,
hamartomatous polyps
What are the main characteristics of Peutz-Jeger
syndrome?
Autosomal dominantIs Peutz-Jeger a dominant or recessive condition? Loss of APC geneWhat causes Familial
Adenomatous Polyposis?
Tubular adenomas in patients who are in their teens and twenties
What is the main clinical feature of Familial Adenomatous
Polyposis?
Classic, Attenuated, Gardner Syndrome, Turcot Syndrome
What are the four subtypes of Familial Adenomatous
Polyposis?
They do not arise from preexisting polyps
From which type of polyp does the carcinoma from HNPCC
arise?Proximal colon
In which region does HNPCC usually manifest itself in the
colon?
Intercalated cells
Urologic TumorsFrom what type of cell do oncocytomas originate? Tuberous sclerosis
With what disease are angiomyolipomas of the kidney
associated?
Convential Renal Cell CarcinomaWith what kind of tumor is the VHL gene associated with? Renal vein
Where is a common site of metastasis of renal cell
carcinomas?
Medulla or cortex (peripherally)Where are renal cell carcinomas usually located in the kidney? They rarely metastasizeHow quickly do chromophobe
carcinomas metastasize?
Collecting Duct CarcinomaWhich type of renal carcinoma is predominantly located in the
pelvis of the kidney?Poor
What is the prognosis of a sarcomatoid carcinoma of the
kidney?
Transitional Cells
Urologic TumorsFrom what type of cells do
urothelial carcinomas derive? Urothelial carcinomaWhat is the most common type of bladder cancer?
Papilloma Grades I-IIIWhat are the four grades of urothelial neoplasms? Adenocarcinoma, squamous cellWhat are the 2 other major
types of bladder cancer?
SchistosomiasisWhat causes squamous cell carcinoma of the bladder?
0-10 (the two most common patterns, scaled 0-5); 7+ suggests
action is surely required
What is the range of scores on the Gleason scale?
Chemotherapy – it is quite chemosensitive
How is testicular cancer treated? Osteoblastic activity
What is the general pattern of prostate cancer metastasis to
the bone?
Biopsy – it could be a sign of malignancy
Gynecologic TumorsWhat should be done with
leukoplakia? HPV (16 & 18, of course)What is the main cause of vulvar
and vaginal squamous carcinomas?
NoIs Paget’s disease invasive? DES exposure to the mother of the affected patient
What is the main cause of vaginal adenocarcinoma?
Strains 16 & 18 affect Rb and p53How does HPV cause cancer? The T-zoneWhere does most cervical cancer occur?
EndometrialWhat is the most common type of female GU cancer? It’s asymptomaticWhat is the main symptom of
CIN?
Excess estrogen without progesterone
Gynecologic TumorsWhat is the pathophysiology of
endometrial cancerExcess estrogen production in the
fat cellsHow is obesity related to
endometrial cancer?
It can be pre-cancerousIs there a relationship between
endometrial hyperplasia and endometrial carcinoma?
Abnormal uterine bleeding (especially post-menopausal)
What is the main presenting symptom of endometrial
carcinoma?
AdenocarcinomaWhat type of cancer is endometrial carcinoma, usually? Often bilateralIs ovarian cancer uni- or
bilateral?
CA125 – it is nonspecificWhat marker can be used with ovarian cancer? Is it specific? Surface epitheliumFrom which tissue do ovarian
tumors generally derive?