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Year 2 Clinical Pathology > Diseases of the female genital system 1 > Flashcards

Diseases of the female genital system 1 Flashcards

1
Q

What is meant by VIN?

A

Vulval intraepithelial neoplasia

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2
Q

What is meant by CIN?

A

Cervical intraepithelial neoplasia

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3
Q

Intraepithelial neoplasia refer to what kind of growth?

A

Dysplasia

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4
Q

What is meant by CGIN?

A

Cervical glandular intraepithelial neoplasia

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5
Q

What is meant by VaIN?

A

Vaginal intraepithelial neoplasia

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6
Q

What is meant by AIN?

A

Anal intraepithelial neoplasia

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7
Q

Intraepithelial neoplasia of the female genital system can be caused by which virus?

A

HPV virus

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8
Q

What is dysplasia?

A

Earliest morphological manifestation of multistage process of neoplasia, its in situ disease (ie. non-invasive), shows the cytological features of malignancy without invasion

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9
Q

Is dysplasia treatable?

A

Yes as it is not invasive

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10
Q

Does HPV infection always cause harm?

A

No, in most women HPV will not cause long term harm and will be cleared by the immune system

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11
Q

The lifecycle of HPV is linked to what?

A

Epithelial differentiation

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12
Q

How many subtypes of HPV are there?

A

> 100, based on DNA sequence - different types infect different tissues

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13
Q

Genital HPVs are grouped into what 2 categories?

A

1) Low risk

2) High oncogenic risk

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14
Q

Low risk HPVs are associated with what?

A

Lower genital tract warts (condylomas = benign squamous neoplasms) and low grade intraepithelial neoplasms

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15
Q

High risk HPVs are associated with what?

A

Hihg grade intraepithelial neoplasma and invasive carcinomas

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16
Q

Which are the 2 most common low risk HPVs?

A

6 and 11

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17
Q

Which are the 2 most common high risk HPVs?

A

16 and 18

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18
Q

What percentage of cervical cancers contain HPV?

A

99.7% (types 16 and 18 associated with 70% of all cervical cancers)

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19
Q

Why is all cervical cancer not prevented by HPV vaccine?

A

Current HPV vaccine only vaccinates against the 2 low risk types (6 and 11) and the 2 most common high risk types (16 and 18) - other types can cause cervical cancer

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20
Q

What 2 types of genes are possessed by HPVs and what is the role of each?

A

Early genes - expressed at onset of infection, control viral replication and in oncogenic viruses are involved in cell transformation
Late genes - encode capsid proteins

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21
Q

High risk HPVs intergrate into the host chromosomes, which 2 proteins does it upregulate the expression of?

A

E6 and E7

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22
Q

What does the protein E6 do in cells infected by high risk HPV, what effect does this have?

A

Binds to and inactivates P53
P53 normally mediated apoptosis in response to DNA damage so as a result of its inactivation get accumulation of genetic damage

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23
Q

What does the protein E7 do in cells infected by high risk HPV, what effect does this have?

A

Binds to an inactivates RB1 which is a tumour suppressor gene which controls G1/S checkpoint in cell cycle thus through its inactivation you have dysregulation of cell proliferation

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24
Q

What are the 2 molecular pathways for the development of VIN?

A

1) Classical/ warty/ baseloid

2) Differentiated VIN

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25
Q

The classical/ warty/ baseloid VIN is related to what and most common in which group?

A

Most common in younger people

Related to HPV infection

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26
Q

Is the classical VIN graded?

A

Yes Graded 1-3

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27
Q

The differentiated VIN is related to what and occurs in which group?

A

Occurs in older people

NOT related to HPV - occurs in chronic dermatoses (inflammatory skin conditions) especially Lichen Sclerosus

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28
Q

Is differentiated VIN graded?

A

No

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29
Q

What percentage of cases of VIN recur and what is a predictor of recurrence?

A 
35-50% recur
Positive margins (ie. neoplastic cells extend beyond the edge of the tissue resected) predicts recurrence
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30
Q

What is the difference in rates of progression to invasive Ca in untreated and treated VIN?

A 
Treated VIN (surgery) - 4-7%
Untreated VIN - 87%
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31
Q

In which group is spontaneous regression of VIN most likely to occur?

A

Young, post partum women

32
Q

Progression to invasive Ca is most likely to occur in which group?

A

Post menopausal or immunocompromised

33
Q

What is the most common type of vulval cancer, accounting for 90% of vulval cancer?

A

Squamous cell carcinoma

34
Q

Squamous cell carcinoma of the vulva is associated with what 2 conditions?

A 
VIN (in people under 60)
Inflammatory dermatoses (in people over 70, particularly Lichen sclerosis)
35
Q

What percentage of women with symptomatic Lichen Sclerosus go on to develop squamous cell carcinoma of the vulva?

A

15%

36
Q

How does a vulval squamous cell carcinoma appear macroscopically?

A

Eroded plaque or ulcer

37
Q

Vulval squamous cell carcinoma spreads very predictably, to what 3 places does it spread?

A

1) Locally to involve vagina and distal urethra
2) To ipsilateral inguinal LNs
3) To contralateral inguinal LNs, deep iliofemoral LNs

38
Q

What is a sentinel lymph node?

A

The first lymph node to which a cancer metastasises - can be identified by injecting tumour with a radioactive tracer

39
Q

The risk of lymph node mets can be related to what factor relating to the tumour?

A

Depth of invasion - lymph node mets for a tumour with

40
Q

What staging system is used to stage vulval squamous cell carcinoma and what 5 stages does it involve?

A

FIGO staging system, stages 1,2,3,4A,4B

41
Q

What is the overall 5 years survival for vulval squamous cell carcinoma?

A

around 70%

42
Q

Name 2 other common vulval tumours?

A

1) Malignant melanoma

2) Extramammary Paget’s disease

43
Q

Malignant melanoma accounts for what percentage of vulval cancers?

A

5%

44
Q

What is the mean age of incidence vulval malignant melanoma?

A

50-60

45
Q

Where is a common sight of spread of vulval malignant melanoma and how does it spread?

A

Commonly spreads to urethra

Lymph node and haematogenous spread are both common

46
Q

Lymph node involvement correlates with what factors in vulval malignant melanoma?

A

Depth of invasion

47
Q

What is Paget’s disease?

A

An in situ adenocarcinoma of the squamous mucosa

48
Q

What is the recurrence rate of Paget’s disease?

A

Tend to recur following excision

49
Q

How does Paget’s disease appear macroscopically?

A

Pruritic/ burning/ eczematous patch

50
Q

What can Paget’s disease develop into?

A

Invasive adenocarcinoma

51
Q

What percentage of vulval cancers does Paget’s disease account for, what is the mean age of incidence?

A

5% of vulval cancers

Mean age = 80

52
Q

In Paget’s disease of the vulva is there usually an underlying tumour?

A

No - in only 5% is there regional malignant disease (Bladder, cervix, anus)

53
Q

How does the epithelium of the cervix change with menarche and what develops?

A

Ectocervix is lined by squamous epithelium
Cervical canal is lined by simple columnar epithelium
At menarche there is a physiological bulking of the cervix (increase in connective tissue component) and this causes a mechanical eversion of the squamocolumnar junction
The columnar epithelium now on the ectocervix cannot withstand the acidic environment of the vagina and undergoes squamous metaplasia
This area undergoing metaplasia is known as the transition zone - this area is vulnerable and is often where CIN develops

54
Q

What happens to the transition zone of the cervix post menopause, why does this create a problem for cervical cancer screening?

A

Cervix shrinks and some of transition zone retracts up the cervical canal
This transition zone is a high risk area for development of CIN thus is the area screened - CIN may be missed if it occurs in the area contained within the cervical canal

55
Q

What is CIN, is it graded?

A

Pre-invasive stage of cervical SCC (thing we are trying to catch on screening) - it is graded according to increasing abnormality

56
Q

There are 3 grades of CIN, why is grade 1 not treated?

A

It has a regression rate of 60% - standard treatment is thus to watch and wait and see if it goes away by itself

57
Q

What is the treatment for grade 2 and 3 CIN?

A

Surgery

58
Q

For what 5 reasons is the cervical screening programme a good screening programme?

A

1) The available test has high sensitivity and specificity
2) Test is not harmful
3) Defined pre-invasive stage which can be identified
4) Long enough to allow intervention
5) Simple, successful treatment

59
Q

Is the cervical screening programme a test for cancer?

A

No!

60
Q

What testing does the cervical screening programme use?

A

Liquid based cytology and focused high risk HPV testing

61
Q

What are the 4 main reasons for not screening people under 25?

A

1) Evidence doesn’t support its use
2) High HPV carriage rate, including high risk types - 70-80% will be eliminated
3) Reactive changes produce confusing cytology
4) Unnecessary LLETZ procedures can have obstetric consequences

62
Q

What is meant by dyskaryosis?

A

abnormal nuclei

63
Q

In the cervical screening programme what test is undertake if no dyskaryosis is found?

A

No further testing - normal recall

64
Q

If low grade dyskaryosis is identified, what test is undertake?

A

HPV testing - if positive then refer for colposcopy and Rx

If negative then no further testing and normal recall

65
Q

If high grade dyskaryosis is identified, what test is undertake?

A

Referred for colposcopy

66
Q

What is the treatment for CIN?

A

LLETZ - Large Loop Excision of the Transformation Zone

67
Q

What is the most important causative factor in the development of cervical squamous cell carcinoma?

A

HPV infection

68
Q

What are the 7 other risk factors for cervical squamous cell carcinoma?

A

1) Multiple sexual partners
2) Male partner with multiple partners
3) Young age at first intercourse
4) High parity (lots of babies)
5) Low socioeconomic group
6) Smoking
7) Immunosuppression

69
Q

In addition to cervical squamous cell carcinoma, what other type of cervical cancer exists?

A

Cervical adenocarcinoma

70
Q

How does cervical squamous carcinoma present and spread?

A

The same as SCC

71
Q

Is cervical adenocarcinoma related to HPV?

A

Yes

72
Q

What is the precursor to cervical adenocarcinoma?

A

Cervical Glandular Intraepithelial neoplasia (CGIN)

73
Q

How is cervical adenocarcinoma/ CGIN treated?

A

The same as CIN/SCC - LLETZ

74
Q

Why is cervical adenocarcinoma thought to have a worse prognosis than cervical SCC?

A

Thought to be due to radioresistance

75
Q

What staging system is used for cervical carcinoma, how many stages does it describe?

A

FIGO staging system - describes stages 1, 2, 3, 4

76
Q

What is the predictable pattern of metastasis of cervical carcinoma?

A

Predictably to pelvic and para-aortic lymph nodes and via blood to lungs, bone etc.

Year 2 Clinical Pathology (64 decks)

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