Exam #2: Neoplasia II Flashcards
What are the four criteria used differentiate between a benign and malignant neoplasm?
1) Rate of growth
2) Differentiation and anaplasia
3) Local invasion
4) Metastasis
When does growth occur in normal tissues? How does this compare to malignant tissues?
In normal tissue, growth occurs in response to damaged tissues & is limited
In neoplasms, growth is not damage induced & it is limitless and there is:
1) Evasion of host control over growth
2) Limitless replication potential
3) Loss of contact inhibition
What is the difference between normal cells, benign tumors, and malignant cells that are in s-phase?
Generally, there is an increase in cells in s-phase.
>1%= Normal
1-10%= Benign
20-80%= Malignant
What are the factors that determine increased growth rate?
1) Doubling time
2) Faction of tumor cells in proliferative pool i.e. % of cells in s-phase
3) Cell production vs. cell loss
What is double time? What are the important clinical aspects of doubling time?
Doubling time= the time that it takes a cell population to divide and become twice its original size
- Takes roughly 30x to become a detectable mass ~1g
- 10x more doubling times= 1kg, maximum size compatible with life
What is the difference between the submicroscopic stage and later stages in terms of growth?
- Submicroscopic stage= early stage & higher growth fraction
- Later stages= low growth faction
How do growth rates of benign tumors compare to malignant tumors?
Benign= slow Malignant= rapid
Microscopically, what are the indications of cell proliferation?
- Mitotic cells= i.e. mitotic figures are indicative of proliferation
- Atypical mitotic figures= proliferation & malignant
*****Mitotic figures= loose and expanded nuclei
What are Ki-67 & PCNA? How are they used?
PCNA= Proliferating cell nuclear antigen–a marker of proliferation
Ki-67= a second marker for proliferation
*****Increased amounts of these indicate cell proliferation and are used to calculate the Proliferating Cell Nuclear Antigen Score
What is the clinical significance of different growth rates in tumors?
Cells within the cell cycle are susceptible to chemo and/or radiation therapy
*Slow growth= surgery
What is differentiation?
Cells or tissue resemble their normal progenitors, both morphologically and functionally
How does differentiation compare between benign & malignant tumors?
Benign= low proliferating activity but cells & tissues are differentiated
Malignant= many cells/ tissues do NOT resemble the cells or tissue of origin
What is the difference between a well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated/ anaplasic tumor?
Anaplastic or undifferentiated= complete lack of differentiation & HIGHLY MALIGNANT
The other terms describe the spectrum of differentiation. The more differentiated, the better.
How do the cells of the normal thyroid gland & thyroid adenoma?
Normal= well formed follicles & colloid
Thyroid adenoma= resembles normal thyroid but has an encapsulated thyroid mass
How do a well differentiated, poorly differentated, and anaplastic carcinoma of the thyroid gland compare?
Well-differentiated= resembles normal thyroid gland but shows invasion
Poorly-differentiated= little resemblance to normal thyroid w/ few follicles & scant colloid–>has metastatic potential
Anaplastic= no resemblance to normal thyroid tissue–>high metastatic potential
How are poorly differentiated and anaplastic neoplasms differentiated?
1) Expression of cell markers
2) Cytological findings
What is the term “loss of polarity” referring to?
- Normally, cells are well organized and have an inherent polarity
- A loss of this inherent organization & polarity is a marker of malignancy
What is cellular atypia?
Generally, cells within the same tissue with different morphology
- Cellular pleomorphism= cells that vary in size & shape
- Nuclear pleomorphism= different sizes & shapes of nuclei
- Nuclear hyperchromiticity i.e. increased DNA content indicated by darker stanining
- Nucleolar pleomorphism
- Increased nucleus to cytoplasm ratio
What is cellular atypia indicative of?
Pre-malignancy & malignancy
What is the difference between nuclear pleomorphism & hyerchromasia?
Pleomorphism= variation in size & shape of cells/ nuclei
Hyperchromasia= abundant DNA that is extremely dark staining
What is the normal N/C ratio? What N/C ratio is indicative of malignancy?
1: 5 is normal
1: 1= malignancy
What are the cytologic features of anaplasia?
1) Nuclear & cellular pleomorphism
2) Hyperchromatic nucleus
3) Increased N/C ratio
4) Prominent nuclei
5) Abundant + atypical mitoses
6) Bizarre tumor giant cells
What are tumor giant cells? What is the significance of tumor giant cells?
- Single huge polymorphic nucleus or more than 2 nuclei; hyperchromatic nuceli
- Represent anaplasia
What is the clinical significance of recognizing anaplasia?
- Indication of poorly differentiated
- More aggressive & poorer prognosis
What are the most prominent features of neoplasms at high magnification?
Atypical mitoses
What is desmoplasia?
Hyperplasia of activated fibroblasts that leads to an abundance of collagenous stroma
*****This makes the tissue hard & is seen in female breast cancer & “cholangiocarcinoma”
What color does collagen stain with trichrome staining?
Blue i.e. blue stroma= collagen & “desmoplasia”
What does a tumor cell require to grow in size?
Angiogenesis & adequate blood supply
What are the two most important factors in tumor angiogenesis?
VEGF
FGF
List three pro-angiogenic factors?
VEGF
bFGF
HIF
List the anti-angiogenic factors.
Thrombospondin-1
Angiostatain
Endostatin
Tumstatin
Why do malignant tumors show central necrosis?
Tumors outgrow its blood supply & areas of ischemic necrosis appear
