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Reproduction > Pathology of Cervical Dysplasia and Malignancy > Flashcards

Pathology of Cervical Dysplasia and Malignancy Flashcards

1
Q

What is the histological grading of precancerous cervical squamous lesions?

A

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

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2
Q

Cervical intraepithelial neoplasia 3/CIN 3 is equivalent to

A

carcinoma in situ

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3
Q

Carcinoma in situ refers to

A

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

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4
Q

Cervical intraepithelial neoplasia is a malignant/premalignant lesion?

A

premalignant

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5
Q

What is the cytological grading of precancerous cervical squamous lesions?

A

Low-grade squamous intraepithelial lesion

High-grade squamous intraepithelial lesion

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6
Q

What is the nuclear structure of HPV?

A

dsDNA

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7
Q

HPV specifically infects

A

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

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8
Q

HPV types ______ are more common in skin infections

A

1, 2, 4

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9
Q

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

A

HPV 16 and 18

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10
Q

DNA of HPV consists of

A

early and late genes

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11
Q

Late HPV genes encode for

A

capsid proteins

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12
Q

Early HPV genes encode for

A

replication, proliferation, viral release

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13
Q

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

A

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

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14
Q

What is the pathogenesis of HPV?

A

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

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15
Q

In HPV infection, early genes are expressed in

A

E1-E7 in middle and basal keratinocyte layers

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16
Q

In HPV infection, late genes are expressed in

A

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

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17
Q

In keratinocytes, what happens to HPV DNA?

A

can be integrated into cellular host DNA or be episomal

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18
Q

Episomal HPV DNA is associated with

A

latent disease prior to significant dysplasia in the epithelium

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19
Q

HPV E2 gene encodes for

A

a transcription factor that suppresses genes E6 and E7

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20
Q

Disruption in the E2 gene occurs when

A

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

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21
Q

Disruption of the E2 gene leads to

A

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

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22
Q

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

A

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

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23
Q

E6 binds to

A

p53

24
Q

E7 binds to

A

Rb

25
Q

p53

A

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

26
Q

Rb

A

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

27
Q

Binding of HPV E6 to p53 results in

A

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

28
Q

Binding of HPV E7 to Rb results in

A

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

29
Q

The transformation zone marks

A

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

30
Q

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

A

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

31
Q

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

A

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

32
Q

CIN 3 can progress to

A

squamous cell carcinoma

33
Q

HPV-related glandular lesions include

A

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

34
Q

What is the histological appearance of a cervical condyloma?

A

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

35
Q

What is the histological appearance of a flat condyloma?

A

Koilocytes

36
Q

Koilocytes appear as

A

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

37
Q

What is the histological appearance of CIN 1?

A

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

38
Q

What is the histological appearance of CIN 2?

A

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

39
Q

What is the histological appearance of CIN 3?

A

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

40
Q

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

A

high-grade; invasive squamous cell carcinoma

41
Q

Normal squamous mucosa epithelium shows

A

squamous epithelium at the top with endocervical glands in the stroma

42
Q

What is the histological appearance of invasive squamous cell carcinoma?

A

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

43
Q

What is the histological appearance of normal glandular epithelium?

A

Basal nuclei with abundant cytoplasm, no mitoses

44
Q

What is the histological appearance of adenocarcinoma in situ?

A

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

45
Q

What is the histological appearance of adenocarcinoma on low power?

A

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

46
Q

What is the histological appearance of adenocarcinoma on high power?

A

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

47
Q

In cytology, low-grade squamous intraepithelial lesions encompass

A

HPV, CN1, or both

48
Q

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

A

koilocytes with binucleation, cytoplasmic clearing, and irregular hyperchromatic nuclei

49
Q

In cytology, high-grade intraepithelial lesions encompass

A

CN2 and CN3

50
Q

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

A

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

51
Q

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

A

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

52
Q

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

A

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

53
Q

What is the normal cytological appearance of glandular epithelium?

A

picket fence of glandular structures with visible columnar outlines

54
Q

HPV vaccine is designed against which proteins?

A

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

55
Q

Unsatisfactory smears are recommended to be repeated

A

after 6-12 weeks

56
Q

Diagnosis of a definite or possible LSIL on smear is repeated

A

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

57
Q

Lesions that mimic cervical dysplasia include

A

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

Reproduction (11 decks)

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