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Clinical Pathology > Lecture 34 - Cervical and vulval pathology > Flashcards

Lecture 34 - Cervical and vulval pathology Flashcards

1
Q

VIN

A

Vulval intraepithelial neoplasia

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2
Q

CIN

A

Cervical intraepithelial neoplasia

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3
Q

CGIN

A

Cervical glandular intraepithelial neoplasia

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4
Q

VaIN

A

Vaginal intraepithelial neoplasia

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5
Q

AIN

A

Anal Intraepithelial neoplasia

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6
Q

Dysplasia

A

Earliest morphological manifestation of multistage process of neoplasia
In-situ disease ; non-invasive
Shows cytological features of malignancy, but no invasion
No invasion = no metastasis = curable
If left, significant chance of developing invasive malignancy

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7
Q

Human Papillomaviruses (HPVs)

A
  • Double standard DNA viruses
  • 7.9kb circular genome, 7 ‘early genes’, 2 ‘late’ genes
  • > 100 subtypes, based on DNA sequence
  • Different types affect different tissues
  • Lifecycle linked to epithelial differentiation
  • Genital HPVs grouped into low and high oncogenic rislk
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8
Q

HPV risk groups - Low risk

A

Associated with genital warts and other low-grade cytological abnormalities: 6, 11, 40, 42, 43, 44, 53, 54, 61, 72, 73 and 81
6, 11 - linked with genital warts - most common

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9
Q

High risk HPV groups

A

High-risk subtypes associated with high-grade pre-invasive and invasive disease are 16, 18, 31, 33, 35, 39, 45, 51, 52

99,7% of cervical cancers contain HPV DNA
Types 16, 18 associated with - 70% OF CERVICAL CANCERS

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10
Q

Low risk HPV

A

6, 11 - lower genital tract warts (condylomas= benign squamous neoplasms), low grade ‘IN’s’

Very rare in malignant lesions

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11
Q

High risk HPV

A

16, 18, 31, 33

High grade Intraepithelial Neoplasia’s and Invasive carcinomas

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12
Q

Human Papilloma Virus vaccinations

A

2 vaccines
Gardasil (Merck) HPV - 6,11,16,18

cervarix (MSK) HPV - 16,18

uk vaccinations started in sep 2008 - cervarix
Age 12 -13 with catch-up to 18

Switch to Gardasil Sep 2012

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13
Q

Mode of action of High risk HPV

A

early genes expressed at onset of infection which
control viral replication
oncogenic viruses - involved in cell transformation
Late genes code capsid proteins

High risk HPV’s integrate into host chromosomes
Upregulates E6, E7 expression

E6 binds to and inactivates p53
E7 binds to RB1 gene product

p53 mediates apoptosis in response to DNA damage - accumulation of genetic damage

RB1 is tumour suppressor gene
Controls G1/S checkpoint in cell cycle - dysregulation of cell proliferation

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14
Q

What does E6 expression do

A

E6 binds to and inactivates p53

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15
Q

What does E7 binds to RB1 gene product

A

E7 binds to RB1 gene product

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16
Q

What does p53 do and what does inactivation do?

A

Mediates apoptosis in response to DNA damage - accumulation of genetic damage

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17
Q

What does RB1 do and what does inactivation do?

A

is a tumour suppressor gene

controls G1/S checkpoint in cell cycle - dysregulation of cell proliferation

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18
Q

Classical/ warty/ baseloid VIN

A

graded VIN 1-3
Related to HPV
Younger people

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19
Q

Differentiated VPN

A

not graded
not HPV related
Occurs in chronic dermatoses esp. lichen sclerosis
Older people

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20
Q

Behaviour of VIN

A

35-50% recur
Positive margins predict recurrence
Progression to invasive carcinoma in 4-7% treated women and up to 87% of those untreated

21
Q

When is invasion more likely to occur in VIN?

A

In postmenopausal/immunocompromised

Spontaneous regression may occur particularly in young postpartum women (after childbirth)

22
Q

Squamous cell carcinoma

A

most common vulval cancer - 90%

23
Q

What can squamous cell carcinoma be associated with

A

Associated with VIN AND INFLAMMATORY DERMATOSES

24
Q

Squamous cell carcinoma associated with VIN

A

Age less than 60
Assoc lower genital tract neoplasia - CIN
HPV +ve

25
Q

Squamous cell carcinoma associated with inflammatory dermatoses

A

age more than 70
licen sclerosis
Lichen planus

26
Q

what is the risk of malignancy for symptomatic lichen sclerosus

A

15% risk of malignancy

27
Q

Vulval squamous cell carcinoma

A

Associated with VIN
associated with inflammatory dermatoses
eroded plaque or ulcer

28
Q

how does Vulval squamous cell carcinoma spread

A

locally to involve vagina and distal urethra

to ipsilateral inguinal LNs
to contralateral inguinal LNs,
deep iliofemoral LNs (25% if inguinal nodes +ve)

29
Q

Risk of lymph node mets for vulval squamous cell carcinoma

A

Depth of invasion LN Mets
< 1 mm Very rare
1 - 3 mm 10% - wide local excision
> 4 mm 40 % - Lymph node sampling groin node dissection or sentinel node biopsy

30
Q

Prognosis of Vulval squamous cell carcinoma

A 
stage 1 - 95%
stage 2- 90%
stage 3 - 70%
stage 4a - 20%
stage 4b - <10%

overall prognosis 70%

FIGO staging system

31
Q

vulval tumours - malignant melanomas

A

5% of vulval cancers
Mean age 50 - 60
Local recurrence in 1/3, spread to urethra frequent
Lymph node/ haematogenous spread common
Depth of invasion correlates with LN involvement

32
Q

Paget’s disease

A

Extramammary

  • 5% Vulval cancers, mean age 80
  • pruritic/burning/eczematous patch
  • In-situ adenocarcinoma of squamous mucosa
  • Tend to recur following excision
  • Can develop invasive adenocarcinoma
33
Q

Paget’s disease location

A

bladder
cervix
exclude primary rectal ca
wherever there is a prominent perianal component

34
Q

what is a transformation zone

A

Physiological area of squamous metaplasia

TZ is vulnerable to oncogenic effects of HPV - site of development of CIN

35
Q

Cervical intraepithelial neoplasia (CIN)

A

pre-invasive stage of cervical SCC
Detection is aim of cervical screening programme
graded according to increasing abnormality

36
Q

CIN 1

A

Regression 60%
Persistence 30 %
Progression to CIN III 10%
Progression to invasion 1%

37
Q

CIN 2

A

Regression 40%
Persistence 40 %
Progression to CIN III 20%
Progression to invasion 5%

38
Q

CIN 3

A

Regression 33%
Persistence ~56%
Progression to invasion 20% - 70%

39
Q

Cervical screening programme

A 
Available test has high sensitivity and specificity
Test is not harmful
Defined pre-invasive stage
Long enough to allow intervention
Simple, successful treatment

Is not a test for cancer

40
Q

Cervical screening programme schedule

A

Agegroup(years) Frequency of screening
25 First invitation
25 – 49 3 yearly
50 – 64 5 yearly
65+ Only screen those who have not
been screened since age 50 or
have had recent abnormal tests

Uses liquid based cytology and focused high risk HPV testing

41
Q

Why there is no screening under 25

A

Evidence does not support its use

High HPV carriage rate, incl high risk types – 70-80% will be eliminated

Reactive changes produce confusing cytology
Unnecessary LLETZ procedures can have obstetric consequences

42
Q

What is dyskaryosis?

A

Abnormal cytologic changes of squamous epithelial cells characterized by hyperchromatic nuclei and/or irregular nuclear chromatin

43
Q

what do you do we with a borderline nuclear change/ low grade dyskaryosis

A

HPV testing
if +ve - refer for colposcopy + Rx
if -ve = normal recall

44
Q

What do you do with high grade dyskaryosis or similar ?

A

Refer for a colposcopy + Rx

45
Q

Colposcopy and treatment of CIN

A

Large Loop Excision of the Transformation Zone (LLETZ)

46
Q

Cervical squamous cell carcinoma causes

A 
High risk HPV is most important causative factor
Multiple sexual partners
Male partner with multiple partners
Young age at first intercourse
High parity
Low socioeconomic group
SMOKING
Immunosuppression
47
Q

Cervical adenocarcinoma

A

Presentation/spread same as SCC
Related to high risk HPV
Precursor is Cervical Glandular Intraepithelial Neoplasia (CGIN)
Treated same as CIN/SCC

Stage for stage worse prognosis that SCC ?due to radioresistance

48
Q

what is a precursor of cervical adenocarcinoma

A

Cervical Glandular Intraepithelial Neoplasia

49
Q

Spread and prognosis of cervical carcinoma - FIGO staging

A

Simplified FIGO staging

I Confined to cervix
II Invades beyond uterus, not to pelvic side wall
III Extends to pelvic wall, lower 1/3 vagina, hydronephrosis
IV Invades bladder or rectum or outside pelvis

Metastasis
Predictably to pelvic and para-aortic lymph nodes
Via blood to lungs, bone etc

Clinical Pathology (16 decks)

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