Cell Growth and Neoplasia (complete)

Question 1

Discuss the key concepts of normal cell growth and differentiation control

Answer 1

• Overall, highly orchestrated and regulated process
• Results in formation of specialized tissues, organs, etc.

For multicellular organism — Dramatic changes in cell…

1) proliferation
2) death
3) differentiation
4) migration
5) also, cell-cell interactions

Humans = more static

Question 2

Normal homeostasis is different in different tissues. What are 3 types of “normal” homeostasis

Answer 2

1) Continuously dividing
2) Quiescent tissues/cells
3) Non-dividing tissue/cells

Question 3

Which areas are continuously dividing? Describe this.(homeostasis)

Answer 3

• Skin
• Gut epithelium
• Hematopoietic system

Constant turnover — commonly causes cancer b/c of high freq of division

Increased likelihood of error

Question 4

Which areas are quiescent tissues/cells? Describe this. (homeostasis)

Answer 4

• Liver — hepatocytes (can regrow w/ damage)

Normally little turn over

Capacity for proliferation if needed

Question 5

Which areas are non-dividing tissues/cells? Describe this. (homeostasis)

Answer 5

• CNS neurons
• the heart!

Little to no capacity for proliferation — terminally differentiated

Question 6

Define hypertrophy. Give examples.

Answer 6

• Increase in cell size
• May be reversible
• Physiologic: e.g. pregnant uterus!!
• Pathologic: e.g. hypertensive cardiac hypertrophy… oh boy

Question 7

Define hyperplasia. Give examples.

Answer 7

• Increase in cell #
• Drive by hormones/GFs
• May be reversible
• May predispose neoplasia
• Physiologic: e.g. breast when preggers/puberty
• Pathologic: e.g. endometrium

Question 8

Define metaplasia. Give examples.

Answer 8

• Change from one benign, differentiated cell type to another
• Usually b/c of injury/inflammation
• May predispose neoplasia

Examples:

1) Bronchus (columnar to squamous — b/c of smoking)
2) Esophagus (squamous to columnar — b/c of acid reflux)

Question 9

Define dysplasia. Give examples.

Answer 9

• Disordered growth
• Signifies early premalignant neoplasia in epithelia
• GIVEN A GRADE!

Characteristic histo features:

1) loss of cytologic uniformity
2) loss of normal histologic maturation
3) loss of architectural orientation

Couldn’t find examples

Question 10

Define neoplasia. Give examples.

Answer 10

Think tumor

• New formation
• Progressive, unchecked ^ in cell #
• Has a clonal process
• Pathologic and irreversible :(
• Inherited or acquired

Question 11

Define tumor. Give examples.

Answer 11

• Generally synonymous w/ neoplasm

Do you really need examples??

Question 12

Define and describe malignant neoplasms

Answer 12

• Invade and metastasize
• CANCER!!!
• Causes injury to both local and distant tissues
• Invasive to adj tissues
• Necrosis!

GO LOOK AT A HISTO SLIDE! know what it looks like

Question 13

Define and describe benign neoplasms

Answer 13

• Don’t invade or metastasize
• Cause injury by compression/interference w/ surrounding tissue function
• Circumscribes/encapsulated
• Necrosis is uncommon

GO LOOK AT A HISTO SLIDE! know what it looks like

Question 14

What is the etiology of malignant neoplasia? List non-genetic factors

Answer 14

1) Age
2) Lifestyle/environment (tobacco/alcohol)
3) Occupational hazards (chemicals)
4) Radiation (UV!)
5) Infection (HPV - get vaccinated)
6) Inflammation (IBD)

Question 15

What is the epidemiology of malignant neoplasia?

Answer 15

Almost 1 in 2 American get cancer

1 in 5 will die from it

wow…

Probably related to extended longevity due to healthcare advances

Question 16

What is the pathobiology of malignant neoplasia?

Answer 16

Think of the two-hit hypothesis w/ genetic causes

1) self-sufficiency in growth signals
2) doesn’t respond to anti-growth signals
3) tissue invasion/metastasis
4) continue to grow w/ checks
5) evade apoptosis
6) Makes its own blood vessels

Question 17

Discuss TNM classification, stage and relationship to clinical outcome

Answer 17

T: Tumor (Tis -» T4, not so bad -» bad)

N: Regional lymph nodes (N0 -» N2, none -» metastasis in 4+ nodes)

M: Distant metastasis (MX -» M1, can’t be assessed -» yup there is some)

These help calculate which stage of cancer plus survival rate

SEE “Tumor stage and clinical outcome” SLIDE FOR MORE INFO

Question 18

What is the etiology of malignant neoplasia? List genetic factors

Answer 18

well shit… back to M2M

1) Autosomal dominant (Retinoblastoma, Li-Fraumeni, ya I’m done)
2) Autosomal recessive (xeroderma pigmentosum)
3) Familial (breast, ovarian, pancreatic)

Question 19

What are 2 mechanisms by which neoplasia develops b/c of disruption of normal homeostasis?

Answer 19

1) Altered cell-autonomous mechanisms

2) Cell-nonautonomous mechanisms

Question 20

Describe how neoplasia begins through altered cell-autonomous mechanisms

Answer 20

• Activation of oncogenes

- Inactivation of tumor suppressors

Question 21

Describe how neoplasia begins through cell-nonautonomous mechanisms

Answer 21

• Altered microenvironment — surrounding tissues (stroma, blood vessels, immune cells)
• Altered macroenvironment — circulating cells (e.g. immune cells) and other hormones, GFs

Question 22

Describe the multi-step pathway of carcinoma development

Answer 22

Injury/infection/other homeostatic disturbance
---->>>
Metaplasia/hyperplasia
---->>>
Dysplasia/carcinoma-in-situ
---->>>
Invasive carcinoma
---->>>
Metastatic carcinoma