Chapter 3.1 Neoplasia Flashcards
Define neoplasia. Describe its defining characteristics. Compare neoplasia and hyperplasia.
Neo=new
plasia=growth
=new tissue growth
unregulated, irreversible, monoclonal
distinct from hyperplasia and repair (hyperplasia occurred when increase in stress on organ like uterus during pregnancy, but hyperplasia is regulated and reversible, polyclonal in that multiple cells produce daughter cells that result in hyperplasia)
What does it mean that tumor cells are monoclonal?
all tumor cells arise from one single mother or father cell, one progenitor cell
Neoplastic cells are derived from a single mother cell
How can clonality be determined?
Describe the mechanism.
G6PD isoforms (or androgen receptor isoforms)
If looking at uterus, G6PD is important X linked enzyme (multiple isoforms exist across population; G6PDa, b etc… any single female has inherited only one isoform of G6PD from mother and one form from father; she has 2 forms, so each cell in female express both forms; G6PDa and G6PDb …in female one X chromosome is inactivated so there will only be one active copy of G6PD but X chromosome inactivation is random; so if you look at all cells present in uterus the ratio of G6PDa and G6PDb will be 1:1
pregnant, uterus undergoes hyperplasia, increase in number of cells… the daughter cells will show exact same isoform of G6PD as their mother cell …so in hyperplasia (polyclonal proliferation) cells are derived from multiple individual cells and 1:1 ratio of G6PD will be maintained
neoplasia- all cells derived from ONE mother cell and that one cell produces ALL the tumor cells so ALL the tumor cells will express the same isoform of G6PD.
so in female prove monoclonality by looking at G6PD isoforms (if 1:1 ratio its polyclonal) in male use androgen receptor isoforms which are on the X chromosome
Are there some forms of neoplasia that are not monoclonal? (Benign, malignant, etc)
ALL NEOPLASIA benign or malignant are monoclonal
Neoplasia benign or malignant are monoclonal
How is clonality of B cells determined? Describe the mechanism.
Ig light chain phenotype
looking at lymph node of individual, B cells present in lymph node express Ig composed of heavy and light chain. Light chain is kappa or lambda
Ratio of kappa to lambda is 3:1
Patient gets an infection and they will get hyperplasia of cells of lymph node because response to infection and B cells proliferate, lymph node becomes bigger, what type of proliferation? If hyperplasia would expect the ratio now to be 6:2 … still a 3:1 ratio
(Bc proliferation in hyperplasia is polyclonal)
Lymph node 3:1 ratio K:L neoplastic proliferation (lymphoma) then ONE cell makes all the malignant cells and get massive excess of kappa or lambda; now the K:L ratio will be 20:1
Patient has enlarged lymph node; what is differential diagnosis?
Biopsy shows proliferation of lymphocytes with light chain ratio of 20:1.
- metastatic cancer (spreads to lymph node)
- reactive hyperplasia (from infection)
- lymphoma
proliferation of lymphocytes= lymphoma or hyperplasia (20:1 ratio tells you monoclonal proliferation and must be lymphoma)
Neoplastic tumors are benign or malignant. Describe the difference between a benign or malignant tumor.
Benign tumors remain localized and do not metastize
malignant tumors (cancer) invade locally and have potential to metastasize
if patient has breast cancer and is localized to breast, if that cancer has propensity to metastasize we still call it cancer even though it hasn’t metastasized in this patient yet
What are 4 major tissues in body and where are they found?
epithelium (line skin, esophagus, urogenital tract)
mesenchyme (fat blood vessels, bone, cartilage, soft tissue..
lymphocytes
melanocytes
What is a benign tumor of epithelium, when produces glands, called? When creates papillary finger-like structures?
What is a malignant tumor of epithelium, when produces glands called? When creates papillary finger-like structures?
benign glands- adenoma
malignant glands- adenocarcinoma
benign papillary fingers- papilloma
malignant papillary fingers- papillary carcinoma
What is papillary growth?
(papillary growth= growth of epithelial cells and they overlie a connective tissue core with a blood vessel in the center)
What is a benign/malignant tumor of mesenchyme called?
lipoma
liposarcomma
osteoma
ostosarcomma
angiooma
angiosarcomma
What is a benign/malignant tumor of lymphocytes called?
there is no benign tumor of lymphocytes; anytime there is a tumor of lymphocytes it is called lymphoma/leukemia (malignant/cancer)
What is a benign/malignant tumor of melanocytes?
benign-nevus (mole)
melanoma
What kind of cancer is a nevus (mole)?
benign cancer of melanocyte
Is cancer the 1st or 2nd leading cause of death in adults and children?
2nd
What are the 3 top causes of death in adults?
- CV disease
- cancer
- cerebrovascular disease (or chronic respiratory)
What are the 3 top causes of death in children?
- accidents
- cancer
- congenital defects
What are the most common cancers in adults by incidence?
What are the most common cancers in adults by mortality?
(excluding skin bc they rarely metastasize, quickly reveal themselves and not common cause of death)
By incidence:
- breast/prostate
- lung
- colorectal
By mortality:
- lung
- breast/prostate
- colorectal
Breast and prostate are common but they are not the most common killers
Early detection is KEY
Why is lung cancer the 1st cause of mortality but 2nd in incidence?
Can screen for breast or prostate or colorectal so these cancers can be caught relatively early and so we can do a better job at reducing mortality
no way to screen for lung cancer,
5 year survival for lung cancer has been about 15% for the past 30 years despite drugs and understanding of microbiology, underlying principle is we can’t screen, we can’t pick it up early
About how many divisions occur before earliest clinical symptoms arise in cancer?
Cancer begins as single mutated cell; one cell becomes mutated, replicates, until you produce cancer in which clinical symptoms arise
approx. 30 divisions occur before earliest symptoms arise
Which cancers are more likely to have a poor prognosis? Why?
with every division, there are increased mutations, growing out of control, check systems can’t control cell; so with every division are increased mutations
so cancers that do not produce symptoms until late in disease will have undergone additional divisions and mutations
cancers that are detected late tend to have a poor prognosis (ex cancers that have large space to grow before clinical symptoms arise like ovarian and pancreatic; ovarian carcinoma - tumors can grow and extend far beyond 30 divisions and each time picking up more mutations; same for pancreas - space to grow before symptoms arise, large reserve before tissue damage reveals, same for lungs
What is the goal of screening for cancer? Explain why.
with each division, increase in mutations so screening hopes to:
catch dysplasia before it becomes carcinoma (Pap smear looking for CINI, II, III CIN is dysplasia not cancer; risk for developing, when have CIN, remove CIN before it can become cancer
dysplasia has mutations but is reversible, cancer has mutations and is irreversible)
detect carcinoma before clinical symptoms arise
if we catch before clinical symptoms we catch before additional mutations (w additional mutations cancer becomes more severe)
What is the role of pap smear?
Pap smear looking for CINI, II, III CIN is dysplasia not cancer; risk for developing, when have CIN, remove CIN before it can become cancer
dysplasia has mutations but is reversible, cancer has mutations and is irreversible)
eliminate possibility of carcinoma by eliminating dysplastic cells
Describe specifically what mammography screens for in breast cancer.
pick up ductal carcinoma in situ (malignant proliferation of ductal cells that grows in duct; goal to pick those up in situ before tumor cells invade to vessels and lymphatic spaces) more tumor spreads the worse patients do…
ductal carcinoma in situ calcifies (so mammograms look for calcifications which can indicate DCIS)
average size detected is 2 cm but in mammography is 1 cm… detects tumor half size (larger tumor the increased risk of mutations)
