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?