Module 4 Path

Question 1

What are the cellular adaptations to stress?

Answer 1

Atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia

Question 2

A neoplasm can be classified as what two things?

Answer 2

Benign

Malignant: sarcoma, carcinoma. other (mixed, teratoma, etc)

Question 3

What are some general characteristics of tumors?

Answer 3

Differentiation 
Anaplasia
Rate of Growth 
Invasion 
Metastasis

Question 4

The phases of malignant tumor growth, each card will go into details of these phases. 1st phase is transformation

Answer 4

1. Transformation: monoclonal proliferation

- additional mutations over time can lead to subclones –> increases resistance to chemo

Question 5

The next phase is tumor growth, explain some characteristics

Answer 5

2. Tumor Growth- requires 30 doubling times for clinical significance
   - Angiogenesis via FGF,PDGF,VEGF to maintain blood supply

Question 6

The third phase of malignant tumor growth is local invasion, explain some characteristics

Answer 6

3. Local Invasion -resistant tissues -mature cartilage and elastic tissue in arteries

Question 7

What are the steps to local invasion

Answer 7

1. Detachment of tumor by downregulating E-cadherin and mutation of catenins
2. Attachment of ECM proteins - laminins, integrins, fibronectin
3. ECM protein degradation -type IV collagenase
4. Generation of new sites -MMP2 and MMP9 secreted by the tumor
5. Movement through ECM proteins -autocrine motility factors

Question 8

The fourth and final step in malignant tumor growth is distant metastasis, what are some features?

Answer 8

via lymphatics, hematogenously or seeding

Question 9

what is atrophy?

Answer 9

Decrease in size and function of cell; decreased size of whole organ
if persistent: cell death

Question 10

What is hypertrophy?

Answer 10

Increase in size and augmented function of cell

Question 11

What is hyperplasia?

Answer 11

Increase in number of cells

Question 12

What is metaplasia?

Answer 12

Conversion of one differentiated cell type to another

both types of cells are normal

Question 13

What is dysplasia?

Answer 13

Alteration in size, shape, organization of cells

Question 14

What is aplasia, hypoplasia and agenesis?

Answer 14

Aplasia: absence of an organ (only rudiment present)
Hypoplasia: decrease size due to incomplete development
Agenesis: complete lack of organ

Question 15

What is a neoplasm?

Answer 15

Abnormal mass of tissue
growth exceeds and is uncoordinated with that of normal tissue
persists in the same excessive manner after cessation of the stimulus which evoked the change

Question 16

How are neoplasms named?

Answer 16

1. type of neoplastic cells:indicate tissue of origin

2. nature of tumor (Whether benign or malignant)

Question 17

In regards to classifying tumors there are two ways in which this is done, grading and stage. How are tumors graded?

Answer 17

Level of differentiation (well, moderately, or poorly differentiated), mitoses and character of tumor
Grade based on I-IV on histological appearance
Problems with variation of histology of various areas and observer variation

Question 18

How are tumors staged?

Answer 18

Extent of spread (more important then grade)

• clinical staging: based on evidence acquired before treatment
• Pathological staging- obtained at surgery via examination tissues

Question 19

In regards to staging, what does T,M and N stand for?

Answer 19

Size of the primary tumor = T
Extent of spread to regional lymph nodes (N)
Presence or absence of metastases (M)

Question 20

What are the two major systems of categorization?

Answer 20

TNM: Union Internationale Contre Cancer
-clinical staging:based on evidence acquired prior to decision of definitive trust
-pathological staging: includes info obtained at surgery and from examination of tissue by pathologists
American Joint Committee (AJCC): divides tumors into stages 0-IV-factors similar to TMN

Question 21

What is cervical intraepithelial neoplasia (CIN) aka Cervical dysplasia?

Answer 21

-Potentially pre-malignant transformation and abnormal growth (dysplasia) of squamous cells on surface of cervix

Question 22

What is the etiology of CIN?

Answer 22

HPV infection

Question 23

What is the pathogenesis for CIN?

Answer 23

Squamous dysplasia from HPV 16 and 18 strains incorporating in host genomes –> express E6 and E7; E6 inactivates p53 and E7 inactivates Rb

Question 24

There are three stages of CIN –all of which are asymptomatic. Each card will go through one. First –>

Answer 24

CIN I (mild/flat condyloma) -lower 1/3 of epithelium is dysplastic and upper 2/3 has koilocytic change
-Koilocytic change=perinuclear halo and nuclear hyperchromasia

Question 25

What is the second stage of CIN ?

Answer 25

CIN II (moderate) -lower 2/3 is dysplastic and upper 1/3 has koilocytic change

Question 26

What is the third stage of CIN?

Answer 26

CIN III (severe dysplasia/carcinoma in situ) - entire epithelium is dysplastic --> no koilocytic change, basement membrane is intact ( not carcinoma yet)

Question 27

For screening it is recommended to do a yearly pap smear, what does a normal pap smear look like?

Answer 27

- Superficial cells located at the top of the stratified squamous epithelium; very small nucleus --> non-mitotically active; mature cells - Intermediate cells: are in b/t the parabasal and superficial layers - Parabasal cells: near the BM; will show expanded nucleus --mitotically active

Question 28

What does an abnormal pap smear look like?

Answer 28

- Increased nuclear/cytoplasmic ratio; disproportionately large nuclei (not round); deep basophilic nuclei (mitotically active), disorganized cellular arrangement - occurs at squamo-column junction (transformation zone)

Question 29

What is Schillers Test?

Answer 29

test for non-glycogen containing areas of the cervix, which may be a site of early carcinoma; uses iodine - Mitotic cells = glycogen absent (Being used) =fails to stain - Non-mitotic cells=glycogen =stains brown

Question 30

What are the 5 features of dysplasia/atypica?

Answer 30

1. Increased nucleus to cytoplasmic ratio 2. Nuclear hyperchromasia (blue/basophilic) 3. Nuclear Pleomorphism (different sizes and shapes) 4. Cellular pleomorphism 5. Enlargement, irregularity and loss of polarity (orientation of cells doesnt make sense)

Question 31

Naturally in the cervix, squamous cells mature from bottom to top as they accumulate what?

Answer 31

glycogen

Question 32

What cells do you want to do a pap smear on?

Answer 32

Superficial cells

Question 33

What two HPV strains do not incorporate in the host genome --> do not cause dysplasia or carcinoma

Answer 33

6 and 11

Question 34

What do HPV 6 and 11 strains lead to?

Answer 34

Genital Warts (totally benign) -> but can still do koilocytic change (indicates the presence of HPV)

Question 35

When does CIN become cancer?

Answer 35

Invades the BM

Question 36

What is the most important predisposing factor for cervical cancer?

Answer 36

History of multiple sexual partners

Question 37

What is the most common symptom of cervical carcinoma?

Answer 37

Post-coital bleeding (also have dyspyrunia which is painful intercourse), white vaginal discharge (leukorrhea)

Question 38

How do the malignant cells present on histological slide?

Answer 38

Malignant squamous cells with keratin pearls = well differentiated in function b/c making keratin pearls

Question 39

What is Anaplasia?

Answer 39

De-differentiated or lack of differentiation in structure and function Rapid cell growth and hallmark of malignancy

Question 40

How does Anaplasia appear on histological image?

Answer 40

Epithelial Origin -Carcinoma- cytokeratin stain (disseminate via lymphatics) Mesenchymal origin-sarcoma-vimentin stain (disseminate hematogenously via venous drainage) (liver and lungs frequent sties) Muscle Origin - desmin stain

Question 41

What are the black areas of anaplasia on histological image?

Answer 41

Tumor giant cells (multinucleated) b/c anaplastic tumors divide at a very fast rate -K167 is the stain for rapidly dividing tumor cells

Question 42

What age do women start getting pap smears?

Answer 42

21

Question 43

A pap smear is a screening test for cervical cancer, what are other screening tests commonly used?

Answer 43

Mammogram (breast cancer) Digital Rectal Exam (prostate cancer) Colonoscopy (colon cancer)

Question 44

PSH is considered a tumor marker, what is the role of a tumor marker enzyme?

Answer 44

To monitor response to treatment not | to diagnosis

Question 45

If a patient has an abnormal pap smear, what is the next recommended investigation?

Answer 45

Colposcopy and then biopsy (these will allow you to see the basement membrane)