Pathology of Cervical Dysplasia and Malignancy

Question 1

What is the histological grading of precancerous cervical squamous lesions?

Answer 1

HPV infection
Cervical intraepithelial neoplasia 1 (CIN1)
CIN 2
CIN 3

Question 2

Cervical intraepithelial neoplasia 3/CIN 3 is equivalent to

Answer 2

carcinoma in situ

Question 3

Carcinoma in situ refers to

Answer 3

When dysplastic changes are marked and involve the full thickness of the epithelium, but the lesion does not penetrate the basement membrane, it is considered a pre-invasive neoplasm and is referred to as carcinoma in situ

Question 4

Cervical intraepithelial neoplasia is a malignant/premalignant lesion?

Answer 4

premalignant

Question 5

What is the cytological grading of precancerous cervical squamous lesions?

Answer 5

Low-grade squamous intraepithelial lesion

High-grade squamous intraepithelial lesion

Question 6

What is the nuclear structure of HPV?

Answer 6

dsDNA

Question 7

HPV specifically infects

Answer 7

squamous epithelium because it can only complete its infectious cycle in differentiated squamous epithelium

Question 8

HPV types ______ are more common in skin infections

Answer 8

1, 2, 4

Question 9

Which HPV subtypes/genotype are associated with pathology in the female genital tract?

Answer 9

HPV 16 and 18

Question 10

DNA of HPV consists of

Answer 10

early and late genes

Question 11

Late HPV genes encode for

Answer 11

capsid proteins

Question 12

Early HPV genes encode for

Answer 12

replication, proliferation, viral release

Question 13

For HPV to infect squamous epithelium, it must gain contact with

Answer 13

the basement membrane or the basal keratinocyte - there has to be pre-existing damage to the epithelium so they can enter and make contact

Question 14

What is the pathogenesis of HPV?

Answer 14

capsid gains contact with BM or basal keratinocytes; enters cells and propagates through various stages of differentiation to the most superficial/terminally differentiated keratinocytes where it is packaged and released as these keratinocytes are sloughed off

Question 15

In HPV infection, early genes are expressed in

Answer 15

E1-E7 in middle and basal keratinocyte layers

Question 16

In HPV infection, late genes are expressed in

Answer 16

terminally differentiated keratinocytes (top layer) such that proteins encoding the capsid are expressed on the outermost cell layer for packaging and release of the HPV

Question 17

In keratinocytes, what happens to HPV DNA?

Answer 17

can be integrated into cellular host DNA or be episomal

Question 18

Episomal HPV DNA is associated with

Answer 18

latent disease prior to significant dysplasia in the epithelium

Question 19

HPV E2 gene encodes for

Answer 19

a transcription factor that suppresses genes E6 and E7

Question 20

Disruption in the E2 gene occurs when

Answer 20

a break point occurs in replication of the genome at some point as it amplifies through keratinocyte differentiation

Question 21

Disruption of the E2 gene leads to

Answer 21

disruption of the gene and the HPV genome is able to integrate into the host chromosomal DNA

Question 22

When HPV DNA is incorporated into the host cell genome, what happens relative to the E2 gene?

Answer 22

regulation of E6 and E7 is lost and they become significantly increased in number inside the cell

Question 23

E6 binds to

Answer 23

p53

Question 24

E7 binds to

Answer 24

Rb

Question 25

p53

Answer 25

tumour suppressor gene that regulates the cell cycle by initiating apoptosis in cells with damaged DNA

Question 26

Rb

Answer 26

retinoblastoma protein; tumour suppressor protein that prevents excessive cell growth by inhibiting cell cycle progression until a cell is ready to diide

Question 27

Binding of HPV E6 to p53 results in

Answer 27

promotion of p53 destruction which prevents p53-triggered apoptosis in cells with damaged DNA

Question 28

Binding of HPV E7 to Rb results in

Answer 28

disruption of its ability to halt cells at restriction point between G1 and S phase of the cell cycle; allows neoplastic cells to proliferate

Question 29

The transformation zone marks

Answer 29

junction between cervical squamous epithelium of external cervix with glandular epithelium of the endocervical canal

Question 30

If no squamous dysplasia is seen but koilocytic change is seen in nuclei on histopathology, the diagnosis is

Answer 30

cervical or flat condyloma; koilocytosis reflects changes in the nuclei consistent with HPV infection of the cell

Question 31

When dysplasia is present in epithelium in histopathology, the diagnosis is

Answer 31

cervical intraepithelial neoplasia, graded 1-3 (3 = carcinoma in situ)

Question 32

CIN 3 can progress to

Answer 32

squamous cell carcinoma

Question 33

HPV-related glandular lesions include

Answer 33

adenocarcinoma in situ and adenocarcinoma (no 1-3 grading)

Question 34

What is the histological appearance of a cervical condyloma?

Answer 34

squamous epithelium is significantly thickened with papillomatous appearance; parakeratosis (dead keratinocytes with nuclei) and koilocytosis

Question 35

What is the histological appearance of a flat condyloma?

Answer 35

Koilocytes

Question 36

Koilocytes appear as

Answer 36

Atypical keratinocytes (HPV infected); have enlarged, darker/hyperchromatic nuclei with irregular nuclear outlines in a hap-hazard non-layered arrangement with nuclei throughout all layers instead of waning off towards superficial layers as in normal keratinocytes

Question 37

What is the histological appearance of CIN 1?

Answer 37

atypical changes (nuclear pleomorphism, overlapping nuclei, disordered nuclear architecture, nuclear enlargement, nuclear hyperchromasia) occurring at the lower 1/3 of the squamous epithelium

Question 38

What is the histological appearance of CIN 2?

Answer 38

Atypical changes involving the middle 1/3 of the squamous epithelium

Question 39

What is the histological appearance of CIN 3?

Answer 39

Atypical changes involving the full thickness of the squamous epithelium (anywhere above 2/3rds)

Question 40

CIN 2 and CIN 3 are ______ lesions with a high chance of progressing to

Answer 40

high-grade; invasive squamous cell carcinoma

Question 41

Normal squamous mucosa epithelium shows

Answer 41

squamous epithelium at the top with endocervical glands in the stroma

Question 42

What is the histological appearance of invasive squamous cell carcinoma?

Answer 42

irregular nests of glands arranged haphazardly within the stroma with infiltrative margins

Question 43

What is the histological appearance of normal glandular epithelium?

Answer 43

Basal nuclei with abundant cytoplasm, no mitoses

Question 44

What is the histological appearance of adenocarcinoma in situ?

Answer 44

haphazard, atypical nuclei, loss of cell polarity, numerous mitoses, some apoptotic debris amongst epithelial cells, nuclear pleomorphism

Question 45

What is the histological appearance of adenocarcinoma on low power?

Answer 45

Extensive glandular proliferation with stromal reactivation around invasive glands; infiltrative and destructive pattern of invasion

Question 46

What is the histological appearance of adenocarcinoma on high power?

Answer 46

atypical cells with enlarged nuclei and decreased cytoplasm; coalescence of glands into cribiform structures or micro-papillary formations

Question 47

In cytology, low-grade squamous intraepithelial lesions encompass

Answer 47

HPV, CN1, or both

Question 48

What is seen on cytology of low-grade squamous intraepithelial lesions?

Answer 48

koilocytes with binucleation, cytoplasmic clearing, and irregular hyperchromatic nuclei

Question 49

In cytology, high-grade intraepithelial lesions encompass

Answer 49

CN2 and CN3

Question 50

What is seen on cytology of high-grade squamous intraepithelial lesions?

Answer 50

Worse cytological atypia: markedly enlarged nuclei with minimal cytoplasm, significant hyperchromacy, significant pleomorphism

Question 51

What would be seen on cytology of a high-grade lesion that would suggest squamous cell carcinoma?

Answer 51

cytology resembles HSIL; presence of necrotic debris in background sways dx to invasive squamous cell carcinoma

Question 52

What is the cytological appearance of adenocarcinoma and adenocarcinoma in situ?

Answer 52

trying to retain glandular structure but nuclear atypia is significant with hyperchromasia and feathering of nuclei at edges

Question 53

What is the normal cytological appearance of glandular epithelium?

Answer 53

picket fence of glandular structures with visible columnar outlines

Question 54

HPV vaccine is designed against which proteins?

Answer 54

late proteins for the capsid - without them the HPV cannot gain access into the cell

Question 55

Unsatisfactory smears are recommended to be repeated

Answer 55

after 6-12 weeks

Question 56

Diagnosis of a definite or possible LSIL on smear is repeated

Answer 56

12 mo; if negative, in another 12 mo then back to routine (2 yrs); if LSIL again or HSIL refer to gynaecology for colposcopy

Question 57

Lesions that mimic cervical dysplasia include

Answer 57

squamous metaplasia or reactive changes in squamous epithelial cells that appear with nuclear enlargement, prominent nucleoli, irregular nuclear outlines