Chapter 3 Flashcards
Place the following cancers in order of most fatal to lease :Skin cancer, breast cancer, colorectal cancer, prostate cancer, Pulmonary cancer
Pulmonary
breast/prostate
colorectal
malignant melanomy
what is melanoma?
a tumor resuolting from the malignant transformation of the cells that produce the pugment melanin.
Why is melanoma a current concerning cancer?
Its prevelance is growing exponentially. More and more cases are being diagnosed.
List the risk factors associated to malignant melanoma
Race/Gencer age sun exposure ORgan transplant and previous hx of cancer benign nevi dysplastic nevi
What is the most at risk race for developing melanoma? What is the at most gender?
caucasians, Celtic ancestery.
Males (head and neck) > females (torso)
people under 49 (females)
What is the most common age for developing melanoma
Adults (uncommon before puberty)
What are some sun exposure risk factors for developing melanoma?
Intermitten, intense, recreational expisure.
Sun burns ^^ probability
Fair skin + freckles ^^ proibability.
What radiation is the principal culprit in producing tumors?
UV radiation, split between UVA and UVB —- > carcinogenic.
The risk of developing malignant melation increases by how many folds after receiving an organ transplant?
3-4 x
What is congenital nevi?
present at bith, increases risk based on size of primary lesion
How does the present of benign nevi increase your risk to developing malignant melatoma
risk related to number and seize of the lesions.
What is the significance of dysplastic nevi?
marker for a higher risk of developing melanoma. The risk increases with the number and is up to 10x higher with those who have 5+ lesions
Dysplastic Nevi are characterized by size (>5mm) and what 3 additional characteristics?
- variable pigmentation
- irregular outline
- indistinct borders
Does family history of dysplastic nevi increase your risk of developing MM?
yes
How is melanoma dx?
skin biopsy and microscopic examination.
Clinically suspecious skin lesions can be identified using the ABCDE criteria. Define this.
A= asymmetry of the lesion B= border irregularity C= color variation d=diameter greater or equal to 6mm E= evolving with changes over time
What is amelanotic melanoma?
melanoma lesions that lack pigment
What are the 4 major histologic subtypes of melanoma?
- superficial spreeding melanoma
- nodular melanoma
- lentigo melanoma
- acral lentiginous melanoma
What is superficial spreding melanoma?
most common
can occur in both sun and non-sun exposed areas of the body.
Chracterized by irregular margins and pigment variation.
What is nodular melanoma?
Characterized by a dark blue-black or blueish-red uniformly colored lesions
- rapid onset
- common in males on trunk of the body
What is lentigo maligma>
- common in older individuals
- sun exposed skin
- arises from pre-existing benign pigmented lesion known as a hutchinson freckel
- slowly progressive
What is Acral Lentiginous Melanoma?
- occur on the palm, sole or under nale
- black and dark complexioned individuals
- difficult to dx
What is the most important prognostic factor for mortality in melanoma?
depth of the invasion (breslow level)
Thicker = ^ risk
What is the second most important prognostic factor for mortality in melanoma?
ulceration
- ie pathologically there are no skin surface cells or epidermis overlying the tumor.
What is the differential point in terms of scaling risk?
presence of at least one mitosis per square millimeter.
What are the prognostic factors of important for mortality of melanoma?
- age of onset. young > mortality
- lesion location
- presence of lymph node metastasis
- # +ve nodes
- extent of involvement within node
- presence of ulceration - clark level
Define Clark level
an indication of the level of skin to which the tumor has invaded.
1. level 1- epidermis only
2. level 2- upper portion of the papillary dermis
3 level-3. fills the papillary dermis
4. level 4. reticular dermis
5. level 5. subcutaneous fat
What is the significance of a high mitotic rate?
the number of actively dividing cells detected on pathologic examination is a marker for worsend outcome
What is Angiogensis?
new blood vessel formation- its associated with increased mortality
What is microsatellites?
nest of tumor cells separated from the main body of the lesion, being a marker for the ability of the tumor cells to implant and survive- associated with a greater depth of invasion and predictive of an increased rick of relapse and reduced survival
What do tumor infiltrating lymphocuytes represent?
an inflammatory immune response to the lesion and a greater response is associated with thinner tumors and a better outcome.
What AJCC American Joint Committee on Cancer follows the TNM system. This system evaluates tumors based on what? (3)
- local extent of, depth of the lesion - T
- presence of lymph node metastasis, N
- Existence of metastasis, <
Define the 4 different T levels from the Tis system
T1 <1.0mm
T2 1.01-2 ,,
T3 2.01-4.0mm
T4 >4mm
Ta- no ulcerations
Tb- ulcerations
How does the Sloan-Kettering Nomogram for predicting lymph node metastasis work?
uses age, site of involvement and clark level in addition to thickness and ulceration.
A prognosis system for the identification of high risk thin melanomas has been found to be more accurate than AJCC staging and uses four key factors. Name them
Mitotic rate,
growth pattern (radical or along the surface vs vertical)
gender
Clark level
What is the effective tx for melanoma?
complete surgical resection.
usually resistant to radiation and responses poorly to chemo.
Can also try immunotherapy, using monoclonal antibodies, vaccines and other approaches to attack the tumor. »_space; Still new, and being studied
Try genetic-based understanding of cellular signalling pathways. And create inhibitors of BRAF and NRAS pathway.
Name two drugs that inhibit the BRAF pathway and are FDA approved for tx of melanoma
Vemurafenid
Dabrafenib
The occurrence of more than one melanoma in a given individual suggest what?
either genetic predisposition exist or individual has > exposure to risk factors.
What are some conditions that clearly predispose to the development of melanoma?
familial dysplastic nevus syndrome and the presence of a large congenital nevi-
What is melanoma insitu?
malignant cellular changes without invasion.
Incidence rates for prostate cancer has dramatically increased since 1990’s. Why?
corresponds to the advent of widespread PSA screening.
However death rates have decrease
What race has the highest incident rate for prostate cancer
Black males 2x white males, and asians the lease
What are some risk factors in developing Prostate-ca?
Age Fx Genetic disposition- Hormonal factors- less male pattern bladness diets Reduced sexual activity metabolic syndrome
What are two genes that are associated with increase risk of prostate cacner?
BRCA1 BRCA2. - presence = aggresive
Also increased chances with Lynch Syndome hx
HOXB13 also linked.
What is the etiology of prostate cancer
A cascade of genetic alterations, primarily somatic that gradually transform normal tissue into an invasive tumor
Define the transitional sequence of the prostate-cancer etiology
Normal prostatic eputhelium progresses to proliferative inflammatory atrophy (PIA) to prostatic intraepithelial neoplasia (PIN) to invasice cancer.
What are some screening methods used for detecting prostate cancer
- digital rectal Exam- (DRE)
2. Blood testing for PSA levels
What is detected through DRA
glandular induration
discrete nodules
asymmertry of the gland as the hallmarks of cncer presence
What is PSA?
a serine protease glycoprotein that is produced almost exclusively by the epithelial tissue of the prostate gland.
How is PSA related to cancer detection
PSA is produced more per unit volume in malignant tissue than benign tissue.
What other factors can produce high levels of PSA besides prostate-ca?
- BPH
- Prostatitis
- prostatic massage
- surgery
- instrumentation (biopsy or resection of the gland)
What drugs can affect PSA levels?
PRoscar and Avodart used to tx BPH, decrease PSA levels by a half.
What are the upper limits of PSA normal ? (for caucasians?)
- 5 ages 40-49
- 5 ages 50-59
- 5 ages 60-69
- 5 ages 70-79
What is PSA velocity?
the rate of rise of the PSA level. Anything >0.75 per year is highly suggestive of malignancy and is useful even if the total PSA level is normal.
3 readings over 18 mo is good for accuracy
What is Percentage free PSA (fPSA %)
PSA circulates in blood in two forms:
1. bound to protein
2. unbound- “Free”
prostate cancer disproportionetaly produces more bound PSA and reduces # of Free %.
What is PSA density (PSAD)
Calculate by: PSA level/ prostate volume per g - as calculated by ultrasound.
Idea of PSA per volume being produced.
f-PSA is comprised of 3 isoforms… what are they?
- pro-PSA
- BPH- associated PSA
- Intact free PSA
Subfractions of pro-PSA have been found to mark cancer
What is the Prostate Health Index (PHI)?
a new FDA approved formula that combines the result of total PSA, free PSA and p2PSA.
This index has shown a better marker for the presence of prostate-ca and presence of cancer with high Gleason score.
What are the most promising biomarkers used for diagnosis currently on the market…. for prostate-ca?
human Kallikrein 2 or hK2 (enzyme similar to PSA) and two urine tests- prostate -ca antigen 3 or PCA 3 and transmembrane protease serine 2 (TPMRSS2) are all overexpressed in prosta-ca
What is the pursepo of a Transrectal Ultrasound,? In terms of prostate-ca?
used to evaluate the gland when the suspicion of a malignancy is increased.
- presence of cancer is hypioechoic or low density area.
What is the purpose of MRI and CT scanning, in terms of cancer diagnosis?
to evaluate for spread of prostate tumor outside the gland to surrounding pelvic structures/lymphs.
MRI also used to guide prostate biopsy.
How many biopsies are typically retrieved?
traditionally sextant biopsies (6).
but now 10-12.
What details are given from a prostate biopsy?
- presence of the invasive cancer
- extent of the tumor
- grade or defree of malignancy of the cells.
What grading system is used to classify prostate cancer?
Gleason system. Looks at the two most common cellular patterns on tissue sample and classifies each on a scale.
1= normal 5= most deranged . They are then added to find the final scor
Name the different levels of the Gleason scores
- 2-4 are considered well differentiated
- 5-6 moderately differentiated
- 8-10 are poorly differentiated.
- Gleason 7 lesions are in a gray zone- behaviors depends on how the score is derived.
What is prostatic intraepithelial neoplasia (PIN)?
can be found on the biopsy,
- has malignant changes in the ductal cells, but there is no invasion
- High grade PIN is considered a precursor to prostate cancer and is found in associated with invasive tumors
What are Atypical small acinar proliferations (ASAP)
small glands that are precursors for prostate cancer. Repeat biopsy usually recommended.
What staging system is used for prostate-ca?
TNM system
What is the purpose if the small letters c or p that are placed in front of the staging categories?
To designate is the staging was clinically or pathologically derived.
Define the differences between T1-T3 staging
T1- incidental dindings, Ta,b, are patholgical and Tc is clinical
T2- lesions confined to prostate, in one lobe (Ta/b) or both lobes (c)
T3- LEsions indicated extension outside of prostatic capsule without (a) or with (b) seminal vesicle invasion
What is the T score for tumors that are located in the apex or that invade the prostatic capsule wihtout penetration thorugh the capsule?
T2, not T3.
What are the 3 most important prognostic factors in prostate-ca?
- extent or stage of tumor
- Gleason grade
- pre-treatment PSA level
What are the two major forms of treatment for presumed organ-confined prostate cancer?
- surgery *better long-term
2. radiation therapy.
Are males that are frail and have significant comorbid medical conditions likely to be tx’ed with radiation or surgery?
radiation.
What is radical prostatectomy?
the removal of the entire prostate gland and is primarily reserved for males who are otherwise resonably health and good progected life expectancy.
What are the major complications of a prostatectomy?
impotence
urinary impotence
Radiation therapy can be applied in two forms. What are they?
- external beam radiation
2. radioactive seed implants.
What is external beam radiaction?
uses a conventional radiation beam to irradiate the prostatic tissue.
How does external beam radiation with conformational therapy work?
uses information from CT or MRI to precisely locate the prostate gland within the pelvis for delivery of the radiation beam
How does external beam radiation with intensity modulated therapy work?
provides high doses ot the prostatic bed than the surrounding normal tissue. Both modifications have allowed substantially higher doses or radiation to be delivered to the tumor
How does external beam radiation combined with adjuvant hormonal therapy work?
its given in a shot course to shrink the tumor prior to the delivery of definitive tx in order to improve response rates.
Why does tx with radiation take longer?
it doesnt destroy tumor cells, it damages the cells to lead to their death. PSA can take yrs to drop.
IF PSA rises again (ie 3x in a row) this is a sign of tx failure.
When would someone use External Beam radiation therapy?
in individuals who have been tx’ed with a radical prostatectomy but who have then have a rising PSA level.
What is Radioactive Seek implantation (Branchytherapy)
Another form of radiation therapy. seeks of iodine-125 or palladium-103 are implanted directly into the prostate gland in order to deliver radiation doses directly to the tumor.
When would someone use Radioactive Seek implantation?
For smaller, low risk lesion.
But it can be combined with external beam irradiation for larger or more extensive tumors.
Are the complications with brachytherapy lower or higher than those for surgery or external beam therapy?
lower
Prostate cancer is very sensitive to hormonal stimulation with what feature?
Androgrens (testosterone and its analogues)
How can someone remove androgens?
surgically via castration or medically using drugs like gonatropin releasing hormone analogues that eliminate the production of testosterone.
What is Cryotherapy?
A cooling process that kills tymor cells directly, as well as via vascular damage.
- used for individuals that have been previously irradiated.
- small lesions
- high risk of impotence
When would someone use a watchful waiting or active surveillance approach to prostate cancer?
for older males with limited life span. Aim is to acoid morbidity of therapy in an individual with non-aggressive disease
What is the Key risk factor driving mortality?
Extent of diease or stage and the Gleason grade.
Also pathologically dx vs clinically dx cancer. Resulting in surgery tx vs radiotherapy tx.
What factors are used to predict a more rapid profession of prostate cancer?
- shorter time from tx to PSA recurrences
- high Gleason Score
- A shot PSA doubling time
The majority (80%) of the breast-cancers that are diagnosed are what kind? What are the remaining 20%
invasive lesions.
In situ lesions, and have cells that show malignant changes but are not invaded through basement membrane.
There has been a decrease in death rates d/t breast-cancer. Why?
improved screening with mammography , and improvements with therapy.
What are some risk-factors associated to breast-cancer?
- age
- estrogen exposure
- family history
- benign breast disease
- environmental factors
- prior hx of breast-ca
What are some causes for prolonged estrogen exposure?
- early menarche
- older age at first pregnancy
- delayed menopause.
- current use Oral contreceptives.
- hormone replacement therapy
In terms of family history, what are some predispositions that may increase the risk for breast cancer?
- number of family members
- Age (premenopausal vs post)
- bilateral disease.
4.
What are the two identified genes that are associated with increased risks of breast-cancer?
BRCA1 and BRCA2, on chromosomes 17, 13
What causes an increase risk of developing breast cancer, in terms of benign breast disease?
- presence of proligeration
- increase cell turover
- alterations of the normal cellular structure, or atypica on the biopsy specimen
Determine whether the following environmental risk factors would increase or decrease the risk of developing breast-ca
- radiation
- prior hx of breast-ca
- alcohol
- smoking
- obesity
- high levels of physical activity
- dietary fat intake
- SERM drugs
- increases, commonly results from tx of radiation for hodgkins
- increases
- increased
- increase
- increases in post menopausal, but not pre
- decrease,
- no association
- decrease
What are the two types of in situ carcinomas?
ductal (DCIS) - most common
lobular (LCIS)
Define how DCIS is dx
mammogram
clustered microcalcifications
low mortality
True precursor lesion
Define how LCIS is dx
incidental finding
young females,
diffuse involvement in both breasts
-no precursor, does not progress. marker for development of invasive cancer (15 yrs to come)
What is the most common invasive breast-cancer tumors in order?
adenocarcinomas > invasive ductal carcinoma > invasive lobular carcinoma. > papillary > colloid > musinous tumors and tubular carcinomas
How is breast-cancer typically diagnosed?
- no sxs, usually indicated through self-exam as a lump or node, new skin or nipple changes.
- primary dx is mammogram, new dx with mamm + breast tomosynthesis
- ultrasounds second steps
- MRI if needed.
What would show up on a mammogram when checking for breast-ca?
what reduces visability?
microcalcifications,
nodules
massess
surgery, dense breast, implants
what is typically observed with an ultrasound when dx breast-ca?
cysts from solid lesions, lymph nodes from nodules
guides biopsies and cyst drainage
Why would you use an MRI during the dx of breast-ca?
dense breast individuals
people with mutation carriers (high risk)
— has a high false +Ve
What staging system is used for breast-ca
TNM
T is size and local extend of the tumor
N is the nodal status and is evaluated clinically or pathologically
M distant metatasis absent (M0) or present (M1)
Name the T staging of breast-cancers
Tis- carcinoma in Situ T1- <2cm T1mi <1mm ta1 >1mm <5mm t1b >5mm <10mm t1c >10mm <20mm T2 >2cm <5cm t3 >5cm t4- any size with extensions or inflammatory changes
Name the N staging of breast-cancers
N0- no nodes N1- 1-3 nodes N2 4-9 nodes N4 10+ nodes additional N subcategories used for the extent of involvement of lymph nodes/locations.
What is meant by “the grade of degree of differentiation of the cancer” , in relation to breast-cancer
reflects how different the cancer cells look from normal cells and provides an estimate of how malignant the tumor is. the less differentiated the greater the risk.
Does lymphatic or vascular invasion on the pathologic specimen increase of degrease the risk of local and distant spread
increased.
In view of estrogen and progesterone receptors, what is the disadvantage and advantages of having -ve vs positive receptors?
receptor -ve: higher early recurrence rates
receptor +ve: higher later recurrence rates.
long term survival out-comes are the same.
A new prognostic indicator is using specific gene markers for tumors to assess risk. Name a gene that is an example of a single gene type assay.
test for HER-2/neu proto-oncogene
its over expressed with increase tumor aggressiveness and increased mortality in individuals with lymph node +ve disease.
What is a tripple -ve tumor?
an estrogen-receptor negative, progesterone-receptor -ve, and HER-2/neu -ve.
- common in females <40
- agressive with poorer prognosis, ^ metastasis
- limited tx options
How is DCIS treated?
lumpectomy, with local radiation or mastectomy.
How is LCIS treated?
prevent development of other invasive cancers.
- prophylactic bilateral mastectomy, chemoprevention using hormone replacement therapy (SERM) or aromatase inhibitor drugs
How are invasive breast-cancer tumors treated?
- lumpectomy/Mastectomy with or without radiation.
- lymph node dissection (dosnt improve survival but increases morbidity)
- use of adjuvant chemotherapy and/or hormone therapy employed after surgery.
What does aromatase inhibitor drugs do?
In post-menopausal setting: block the enzymes that converts androgens to estrogens in adipose tissue, the adrenal glans, and the breast-tumor themselves- cutting off the supply of this hormone to the cancer
- new and may be superior to SERMS
What are the 3 major prognostic factors that affect breast-cancer mortality?
- lymph node status
- tumor size
- grade
The recurrence pattern with breast cancer tends to be bimodal. When are the peaks of recurrence?
2 yrs and 5-8 yrs after dx.
those with metastatic disease show increased mortality out to 25 yrs or more after dx
second primary tumor risk is increased in those with dx of breast-ca- constant over time.
Why do males tend to do worse with this disease
because the cancer is further advances prior to its dx. the clinical suspension is lower and dx is delayed.
Death rates for colon-cancer have decreased significantly, why?
Increased screening and improvements in diet
80% of colon cancer cases are sporadic. What are some risk factors?
- age
- Family hx
- Diets (high in fat and low in fiber) / Geo related
- Build
- IBS (crohns and UC)
- smoking/ETOH
What is the etiology of colon-cancer. List the cause of which cancers arise in order (ie how do they develop)
colonic polyps
sessile (flat)- serrated adenomas
Mucosa – > invasive cancer by adenomatous polyp > frank carcinoma >metastasize
Does the risk of cancer increase as the size of the polyp increases?
yes.
Polyps can be hyperplastic or adenomatous. What does this mean?
- hyperplastic polyps- small and little risk for cancer, unles large in #
- adenomas breaks into
a) tubular - most common lease risk
b) tubulovillous adenoma- 4x the risk
c) villous adenomas- 5x risk
About 1/3 colonic polyps and 1/2 of cancers develop proximal to what flexure?
splenic.
How long does it typically take for a polyp to develop to the onset of carcinoma
10-15 yrs,
depends on location, more quick in proximal lesions.
Name inherited colon cancers that are characterized by an increased number of polyps?
- familial adenomatous poluposis syndrome (FAP)
- juvenile polyposis
- gardner’s syndrome
- tyrcots syndrome
- cowden syndrome
- peutz-jeghers syndrome
What is a hereditary colon cancer syndrome that does not increase the number of polyps?
hereditary nonpolyposis colon-cancer (HNPCC)
What is FAP?
an autosomal dominant condition associated with the mutation in the APC gene on chromosome 5.
- +^1000 polyps
- cancer inevitable
- age dx 35-43
- devleop extracolonic polyps or adenomas in small intestine and stomach
- extrecolonic malignancies can develop as well
What is HNPCC (lynch syndrome) - define its characteristics
- autosomal dominant
- 3-5% of colon-ca
- 70-80% chance of developing cancer
- early age and multiple tumors
- precursor lesion is an adenoma that is flat
- risk for endometrial and ovarian-ca
Name the basis screening mechanisms for colon-ca in order of sensitivity (better detection abilities)
purpose: remove colonic polyps in the premalignant phase
- DRE (digital rectal exam)
- fecal occult blood testing (FOBT)
- Barium enema
- Flexible sigmoidscopy
- colonoscopy
- CT, capsule endoscopy, stool examination for genetic alterations** unproven
Why is the colonoscopy the gold screening standard?
allows for screening of entire colon, removal of lpolyps, and biopsies
Colon cancer can be clinically presented in what ways?
- exophytic or polypod lesions
ulcerative masses
annual lesions
infiltrative tumors extending over a length of a bowel wall
How do polypoid vs transverse colon cancers vs. left sided tumors present in terms of bleeding
- polypod lesions- cecum- manifest as occult bleeding
- transverse- occult bleeding or obstruction of bowel
- tumors of the L side/descending/rectum- gross blood in the stool and sxs related to obstruction, change in bowel habits
What are the two specific subtypes of colon cancers that are considered to be variants of undifferentiated tumors?
Mucinous carcinoma and signet cell carcinoma
What are 3 items of importance that are included on colon-cancer pathology reports
- extent of invasion of bowel wall
- , degree of differentiation
- presence of lymph node invasion
What staging system is used to classify colon-cancer?
TNM- and looks at the extent of local tumor, lymph node presence and distant metastasis.
What are the different T stagings for colon cancer?
Tis- carinoma in sity (Tis) T1- invasion of the submucosa T2- invasion of the muscularis propria T3- invasion through the bowel wall T4- direct invasion of other organs of structures
Define the different N stages of colon-cancer
N0- none
N1- 1-3 +Ve
N2- 4+ nodes
Define the M staging of colon-cancer
M0 -absent
M1- present
a- one organ
b- more than one organ
What are the prognostic markers that suggest a worst outcome?
- poorly-differentiated or undifferentiated lesions
- tumor with abN DNA content
- gross tumor perforation of the bowel wall
- direct invasion of adjacent organs
- venous invasion
- high preoperative carcinoembryonic antigen (CEA) levels
What is meant by microsatellite instability in terms of colon-cancer genetic factors
- mutation within repetitive DNA sequences
- 15% of these tumors occur in R colon, good prognosis
- 85% are L and bad prognosis
- dx with microarray
What is the tx for colon-cancer?
Surgery, to remove primary lesion and all the draining lymphatic areas.
- hemicolectomy and permanent diverting colostomy for low rectal cancers.
chemo and radiation used as adjuvant therapy
What is the tx option for polyps?
excision/resection through c-scope
however if too aggressive - surgery
What is the choice of therapy for an individual with
- stage one
- stage two
- stage 3
- stage 4
1- surgery
2- surgery + chemo for high risk stage 2- ie poor differentiation, invaions, obstructions, T4 stage or <12 lymphs
3- Chemo (5GU) combined with leucovorin and surgery,
4- chemo, biological agents, surgery can be employed with palliative or sxs but no curative
What is (carcinoembryonic antigen) CEA?
protein typically found in the fetal or development period, can be detected in the blood of an individual with colon-ca.
- not specific to the disease
can be elevated in smoker, and some normal individuals
Are late recurrences in colorectal cancer common?
no, most recurrences happen within the first 2-3 yrs after tx.
Where does colon-cancer typically metastasize to?
lungs and liver.
What are the major risks for mortality following colon-ca?
the extent of the disease
grade of the tumor
presence of lymph node metastasis
highest mortality risk is in the firs 5 yrs after dx.
