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.