Chapter 3.1 Neoplasia

Question 1

Define neoplasia. Describe its defining characteristics. Compare neoplasia and hyperplasia.

Answer 1

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)

Question 2

What does it mean that tumor cells are monoclonal?

Answer 2

all tumor cells arise from one single mother or father cell, one progenitor cell

Neoplastic cells are derived from a single mother cell

Question 3

How can clonality be determined?

Describe the mechanism.

Answer 3

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

Question 4

Are there some forms of neoplasia that are not monoclonal? (Benign, malignant, etc)

Answer 4

ALL NEOPLASIA benign or malignant are monoclonal

Neoplasia benign or malignant are monoclonal

Question 5

How is clonality of B cells determined? Describe the mechanism.

Answer 5

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

Question 6

Patient has enlarged lymph node; what is differential diagnosis?

Biopsy shows proliferation of lymphocytes with light chain ratio of 20:1.

Answer 6

• 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)

Question 7

Neoplastic tumors are benign or malignant. Describe the difference between a benign or malignant tumor.

Answer 7

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

Question 8

What are 4 major tissues in body and where are they found?

Answer 8

epithelium (line skin, esophagus, urogenital tract)

mesenchyme (fat blood vessels, bone, cartilage, soft tissue..

lymphocytes

melanocytes

Question 9

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?

Answer 9

benign glands- adenoma

malignant glands- adenocarcinoma

benign papillary fingers- papilloma

malignant papillary fingers- papillary carcinoma

Question 10

What is papillary growth?

Answer 10

(papillary growth= growth of epithelial cells and they overlie a connective tissue core with a blood vessel in the center)

Question 11

What is a benign/malignant tumor of mesenchyme called?

Answer 11

lipoma
liposarcomma

osteoma
ostosarcomma

angiooma
angiosarcomma

Question 12

What is a benign/malignant tumor of lymphocytes called?

Answer 12

there is no benign tumor of lymphocytes; anytime there is a tumor of lymphocytes it is called lymphoma/leukemia (malignant/cancer)

Question 13

What is a benign/malignant tumor of melanocytes?

Answer 13

benign-nevus (mole)

melanoma

Question 14

What kind of cancer is a nevus (mole)?

Answer 14

benign cancer of melanocyte

Question 15

Is cancer the 1st or 2nd leading cause of death in adults and children?

Answer 15

2nd

Question 16

What are the 3 top causes of death in adults?

Answer 16

1. CV disease
2. cancer
3. cerebrovascular disease (or chronic respiratory)

Question 17

What are the 3 top causes of death in children?

Answer 17

1. accidents
2. cancer
3. congenital defects

Question 18

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)

Answer 18

By incidence:

1. breast/prostate
2. lung
3. colorectal

By mortality:

1. lung
2. breast/prostate
3. colorectal

Breast and prostate are common but they are not the most common killers

Early detection is KEY

Question 19

Why is lung cancer the 1st cause of mortality but 2nd in incidence?

Answer 19

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

Question 20

About how many divisions occur before earliest clinical symptoms arise in cancer?

Answer 20

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

Question 21

Which cancers are more likely to have a poor prognosis? Why?

Answer 21

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

Question 22

What is the goal of screening for cancer? Explain why.

Answer 22

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)

Question 23

What is the role of pap smear?

Answer 23

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

Question 24

Describe specifically what mammography screens for in breast cancer.

Answer 24

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)

Question 25

Describe why screening for prostate cancer is important. What tests are used to screen?

Answer 25

PSA and DRE

running through center of prostate is urethra; cancer tends to grow in posterior peripheral aspect of prostate; so relatively silent disease bc doesnt produce urinary symptoms…

(BPH involves center of prostate which compresses urethra and prod. urinary symptoms)

prostate cancer doesn’t compress the urethra until late in disease so its a clinically silent disease.

so screen using increase in PSA or digital rectal exam (DRE)
running along the posterior periphery of prostate is rectum, palpate posterior periphery of prostate where prostate cancer most commonly develops

Question 26

Describe the role of hemooccult test and colonoscopy.

Answer 26

colonic adenomas and carcinomas

adenocarcinoma of colon develops from adenomas
A to C sequence

colonoscopy goal is to remove adenomas; if patient has cancer we hope to catch before cancer is found

hemoccult test- test occult blood within stool which could be indicative of adenocarcinoma or carcinoma

Question 27

What would a kappa to lambda ratio of 1:3 indicate?

Answer 27

Normal ratio is Kappa to Lambda 3:1 so a 1:3 ratio would indicate lymphoma

(ratio could also increase to greater than 6:1 which would also indicate this)