Neoplasia continued: Differentiation
In Situ basically means....
"situated inside the boundaries"
Anaplasia
(poor cell differentiation)
Cancer Grading and Staging M
*Metastases* M: extent of distant metastases M0: no metastases M1: demonstrable metastases (can see in scan) M2: no longer used (used to be suspected metastases)
Cancer Grading and Staging N
*Nodes* N: lymph node involvement; a higher number means more nods are involved N0: no nodes involved N1: adjacent nodes N2: distant nodes (eg other body parts)
Cancer grading and staging T
*Tumor* T: primary tumor; the number equals the size of tumor and its local extent T0: free of tumor T1: lesion <2cm T2: lesion 2-5cm T3: beyond organ
endocarditis
*inflammation of the endocardium* semilunar and atrioventricular valves-clumps smack against valves, leads to inflammation
rapidly growing cancers often contain central areas of ________ ___________ because the tumor's blood supply fails to keep pace
*ischemic necrosis*
Benign tumors grow slowly and malignant tumors grow much faster. There are exceptions to this rule. Name two causes of an exception.
- benign tumors influenced by circulating hormone levels -pressure constraints
Lymphatic Spread
-*"skip metastasis"* -skipped a lymph node -more typical of carcinomas (epithelial origin) -depends on the primary site and the natural lymphatic drainage of the site
Why are the liver and lungs the most frequently involved secondary sites in hematogenous spread?
-IVC->heart->pulm a. (get smaller)->lung -liver: portal system->(veins get smaller)
local invasion by cancers
-cancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue
tumor cells require less oxygen. What does this mean about their structure? Function?
-fewer mitochondria -better tolerance to lactic acid by-products
name two characteristics of local invasion by cancers
-force sheets or finger-like projections along lines of least resistance -pressure from the growing mass leads to local tissue death (which further aids the spread)
List three characteristics of Carcinoma in Situ
-have not *yet* broken through the basement membrane -may be erroneously confused with benign tumors -may be non-invasive for *variable periods* of time before progressing to invasive carcinomas...but will eventually become invasive
Name three paraneoplastic syndromes (group of symptoms that run together)
-hypercalcemia -Cushing's syndrome -endocarditis
Clinical Importance of tumor angiogenesis
-intratumor microvascular density is a prognostic factor in breast cancer -angiogenesis inhibitors have potential for use in treatment in the future
What are the three main effects of tumors on the host?
-location/size -hormone production -ulceration
Name at least three characteristics of dysplasia
-loss of uniformity (pleomorphic) -loss of architectural orientation -mitotic figures more abundant and in abnormal locations
What are at least three characteristics of a malignant tumor?
-non-differentiated -no specialization -lots of potential -HOT
Two characteristics of nuclei
-nuclei are very hyperchromic (anemic) and large -nuclei are variable and bizarre in size and shape
Seeding
-occurs in natural body cavities -characteristic of ovarian cancers -enhanced by lack of intracellular adhesion *basically clumps of cancer cells all over*
What are the main characteristics of benign tumors?
-remain localized at site of origin -expand slowly -do *not* have ability to infiltrate, invade, or metastasize
Growth Properties in Cell Culture: (cells grown in lab) what are some differences between tumor cells and normal cells? -nutritional needs -lifespan -arrangement -growth requirements
-tumor cells have less stringent nutritional requirements -malignant cells tend to pile up to form nodules -cancer cells can float suspended in clumps (anchorage independent) -normal cells have a finite lifespan -normal cells exhibit contact inhibition -normal cells require support for growth
Hematogenous Spread
-typical of sarcomas -arteries are less readily penetrated than veins -liver & lungs most frequent secondary sites -tissue-specific homing of some tumor cells (ex: prostatic cancer likes lumbar vertebrae)
Clinical Manifestation of Cancer: *Pain*
-usually little/no pain in early stages -pain occurs in 60-80% terminally ill patients
What are at least three characteristics of a benign tumor?
-well differentiated -more specialization -they have less potential
chemotherapy
-work by killing *any cell* in the cell growth cycle
why can't tumors enlarge beyond 1-2 mm in diameter *unless they are vascularized*?
1-2 mm is how far oxygen can diffuse away from a capillary
The three steps of metastasis
1. invasion & penetration into blood vessels, lymphatic vessels, or body cavities 2. transport to a second site 3. arrest, adherence, and proliferation at the secondary site (stop, stick, start to grow)
Malignant neoplasms disseminate by one of three pathways. Name them.
1. seeding 2. lymphatic spread 3. hematogenous spread
Benign vs Malignant local *invasion*
Benign: No Malignant: Yes
Benign vs. Malignant metastasis
Benign: no Malignant: varies (some fast to metastasis & some little, or do a lot of destruction where they are)
Benign vs Malignant rate of growth**
Benign: slow Malignant: varies (usually faster than B)
Benign vs Malignant *differentiation*
Benign: well-differentiated Malignant: well to poorly differentiated
True or False Malignant tumors are undifferentiated (anaplastic)
FALSE Malignant tumors range from well-differentiated to totally undifferentiated (anaplastic) ie. a spectrum
True or False In anaplasia, cells have a relatively similar structure
FALSE in anaplasia, cells have no recognizable patter of orientation to eachother
True or False Tumor cells contain all enzymes and proteins that normal cells do.
FALSE tumor cells don't contain all enzymes or produce all the proteins that normal cells do
True or False Carcinoma in Suti is benign.
FALSE!! its super malignant
Cell growth cycle
G0- "non-pregnant", resting G1 S G2 M-Mitoses
pre-invasive is.....
NOT pre-cancerous, *they ARE cancer*
TRUE OR FALSE genes that are normally "turned off" during differentiation can be mutated or reactivated by carcinogenic agents
True
True or False Malignant tumors NEVER have capsules
True
True or False benign tumors may produce functional hormones
True!
True or False rate of growth of malignant tumors correlates with their level of differentiation
True!
True or False normal cells have contact inhibition.
True, malignant cells go where they want, they don't have contact inhibition
True or False biochemical differences in tumor cells are seen compared to normal cells. For example, the metabolism of a tumor cell would be much simpler than that of a normal cell.
True...
Dysplasia
a *disorderly* but *non-neoplastic* proliferation of (usually epithelial) cells.
cancer cachexia
a wasting syndrome -progressive loss of body fat, profound weakness, anorexia, and anemia -cancer patients have an increased basal metabolic rate (takes ATP from host)
Cushing's Syndrome (excessive glucocorticoids)
abnormal production by the cancer of ACTH or ACTH-like peptides (adrenocortico tropic hormone)
Highest rate of cancer incidence in women
breast 31% lung 13%
dysplastic changes are often found adjacent to __________ ____
cancerous foci "pre-cancerous"
Tumor Angiogenesis
cancers which "outgrow" their vascular supply and develop necrotic centers
ulceration leads to
causes bleeding and secondary infection
doubling time of tumor cell growth
cells may be triggered to cycle *more often*, but do NOT completed the cycle more rapidly
pleomorphism
cells show marked variation in size and shape, many sizes & many shapes *when you look at anaplastic cell under microscope = pleomorphism)
anaplasia
cells show the most extreme disturbances in cell growth (no differentiation, *top* of range)
Fatigue is the most frequently reported symptom of cancer. Why?
decrease in supply of ATP combined with an increased need for ATP
malignant tumor cells have: __________ cell-to-cell adhesion ____________ cell motility (pseudopodia)
decreased adhesion increased motility
What is the only difference between dysplasia and neoplasia?
dysplasia can be reversible if mild to moderate
If dysplasia is irreversible, what happens?
dysplasia will continue to become neoplasia
location and size of a tumor
ex: a benign tumor could be deadly depending on size and location -pituitary gland, just above sphenoid bone, and right above that is the optic chiasm--could go blind before tumor is even found
differentiation of a tumor cell
extent to which the tumor cells resemble their normal forebears, both morphologically and functionally
less differentiation=
faster growth (top of spectrum)
most, but not all, benign tumors develop an enclosing ______ _________ that separates them from the normal tissue.
fibrous capsule
Benign vs Malignant anaplasia
found only in the worst of malignant tumors -poorly differentated
if the number of new cells > number of cells lost,
growth gets bigger
if the number of new cells<number cells lost,
growth shrinks
if the number of new cells = number of cells lost,
growth stays the same
debulking the tumor by surgery or using radiation can cause the surviving cells to go into active growth, which means what?
it makes the cells more susceptible to chemotherapy
the more anaplastic a tumor, the _____ likely it is to have specialized functional activity.
less
Highest rate of cancer mortality in women
lung 25% (breast 17%)
Highest rate of cancer mortality in men
lung 32% (prostate 14%)
malignant tumors have high levels of ______ _________, which break down and destroy things.
lytic enzymes -cause significant damage to the extracellular matrix
larger neoplasms are _______ likely to metastasize. Anaplastic neoplasms are ______ likely to metastasize.
more more
Lowest cancer incidence by site (or one of the lowest in men and women)
mouth cancer 2-3% *(mortality 1-2%)* melanoma of skin 3% *(mortality 1-2%)*
Mitoses in anaplastic cells are ________ and _________.
numerous and abnormal
Pain can also be caused by psychological phenomenon. Explain.
pain is influenced by fear, anxiety, sleep loss, fatigue and physical deterioration
Carcinoma in Situ
pre-invasive epithelial tumors *malignant*
What causes pain in cancer patients? (name a few reasons)
pressure, obstruction, invasion of a sensitive structure, stretching of visceral surfaces, tissue destruction, and inflammation can all contribute to pain
Highest rate of cancer incidence in men
prostate 41% lung 13%
Malignant tumors show wide variation in their
rate of growth -may grow slowly for years, then suddenly grow more rapidly
As cells become more differentiated, they may lose their ability to __________.
replicate
greater differentiation=
slower growth (bottom of spectrum)
normal cells become irreversibly more __________.
specialized
Metastasis
spread of cancer cells from a primary site of origin to a distant site
hypercalcemia
synthesis of a protein related to parathyroid hormone by tumor cells (as well as other factors)
the degree of cachexia usually correllates to
the cancer's size and aggressiveness
metastasis
the development of secondary malignant growths at a distance from a primary site of cancer.
Differentiation
the process by which cells become different from eachother
growth fraction
the proportion of cells within the tumor that are replicating
Cells of benign tumors most closely resemble what other cells?
their normal counterparts
Benign and malignant tumors differ on the basis of _________ _____
their type
Anaplastic Cells
total loss of differentiation
_______ cells are adapted to survive under unfavorable conditions
tumor
Central Necrosis is typically found where
typically found only in very rapidly growing, very dangerous cancers.
Why does cancer cause a wasteful usage of glucose?
uses glycolysis (2ATP) instead of Kreb's (36ATP) -they don't need oxygen, so they put their glucose through glycolysis
Why are arteries less readily penetrated than veins?
veins have less pressure, thinner wall, and a continuous flow -path of least resistance