Gynae Pathology

Question 1

Cervical cytology

Answer 1

• study of cells from the cervix.
• used to reduce incidence of cervical cancer by detecting pre-invasive lesions.
• Early detection has proved to decrease mortality from cervical cancer.

Question 2

Introduction of Organised Screening

Answer 2

• In 1988 it was found that women who were at greatest risk of cervical cancer weren’t attending regular screenings
• DOH insisted that all health authorities set up computerised call and recall system.
• All women aged 25-64 invited for screening at 3 to 5 yearly intervals depending on their age

Question 3

Achieving attendance of screenings

Answer 3

• Financial incentives were set up for GP surgeries in order to obtain high population coverage. GP’s were effectively paid for taking cervical smears.
• Despite this coverage is still approximately only 80% of the target age population and often below – reducing effectiveness.

Question 4

Role of cytology

Answer 4

• study of cells and is used to detect abnormalities in cells from the cervix that are dyskaryotic/pre-cancerous.
• changes are graded from borderline-severe dyskaryosis and depending on both persistence of abnormality or severity, women will be referred into colposcopy for further treatment

Question 5

Role of colposcopy

Answer 5

• used to obtain tissue samples of abnormal cells on cytology
• Cervical Intraepithelial Neoplasia and grades range from 1 to 3 depending on severity
• Any major discrepancies between cytology and histology result are discussed at a Multidisciplinary meeting where follow up and treatment are decided

Question 6

Introduction of Liquid Based Cytology

Answer 6

• trials at 6 hospitals in 2004 across the UK, LBC received a recommendation from the National Institute of Clinical Excellence (NICE)
• decided that LBC would be the preferred method of sample collection, fixation, preparation and screening in cervical cytology.

Question 7

Sample taking for LBC

Answer 7

• Cells are removed from the cervix using the “cervex”™ brush and a 360° rotation of the cervical os and ectocervix
• repeated 5 times
• Previously was done using the aylesbury spatula

Question 8

Sample fixation

Answer 8

• cells collected on the brush are placed immediately into pot of alcohol based preservative fluid
• prevents “drying out” of the sample which can cause diagnostic problems when screening

Question 9

Sample processing

Answer 9

• Hologic T5000™ fully automated processing machine prepares samples producing a circular preparation of the cells onto a slide
• then stained with Papanicolaou staining technique on a fully automated platform

Question 10

The request card (HMR101 form/ICE)

Answer 10

• HMR101 form or electronic ICE request is completed with patient details which must match those on sample pot and both are sent to the laboratory for processing.
• any discrepancies between the form and the pot they will not be accepted by the laboratory.

Question 11

Screening

Answer 11

• Slides once prepared are matched with their request cards and screened.
• Each slide takes approx. 5-12 minutes to screen depending on the difficulty of the case

Question 12

What are the screening staff looking for?

Answer 12

• Normal samples make up the majority of our workload.

- Therefore we need to know what features are “normal” to know what are “abnormal”.

Question 13

Indicators of abnormality in screening

Answer 13

• increased nuclear/cytoplasmic ratio
• irregular nuclear outline
• hyperchromasia (darkening) of nuclear chromatin
• bi/multi nucleation of cells.

Question 14

Cervical epithelium

Answer 14

• structurally the same as any other skin surface on the body but is the only one that responds to changes in oestrogen levels during the menstrual cycle.
• At day 14 of menstrual cycle oestrogen levels peak and achieves full thickness.
• offers protection against infection and therefore “optimal” time to take the sample
• oestrogen levels are high the cervix “bulks” up and cause cells from endocervical canal to evert out over the ectocervix and form a reddened area.
• known as an ECTROPIAN and is a normal condition.

Question 15

Endocervicals

Answer 15

• ectocervix is exposed to the acidity of the vaginal canal.
• fragile endocervical cells, when exposed to this acid environment the cells undergo transformation into squamous cells to offer protection
• This process is continuous, it is “normal” and is known as squamous metaplasia

Question 16

How is squamous metaplasia recognised?

Answer 16

• by dense opaque blue cytoplasm and bizarre shapes/forms

Question 17

Endometrial cells

Answer 17

• glandular cells higher in the uterine body
• seen “normally” at days 1- 14 and 26-27 of menstrual cycle, therefore important for the patient to know the 1st day of her last menstrual period
• if LMP is unknown, the patient is >40, and these cells are present they will be treated as suspicious and the patient will be referred for further treatment in gynaecology

Question 18

Infections in cervical samples

Answer 18

• All infections produce excess of WBCs (usually polymorphs) which can be troublesome when screening
• can obscure the cells and make the sample inadequate for interpretation and a repeat test will be requested by the laboratory

Question 19

Infections

Answer 19

• mainly sexually transmitted.

- Some are more easily treated than others

Question 20

Trichomonas Vaginalis

Answer 20

• Can infect both men and women
• yellow/green foul smelling discharge
• its a parasite and has no link to cervical cancer

Question 21

Candida Albicans (thrush)

Answer 21

• yeast infection
• occurs mainly in 16-35 year old women
• Hyphae and spores can be observed which stain red
• Inflammatory changes often occur alongside infection
• Treatable with drugs or cream (canesten)

Question 22

Actinomyces like organisms/ ALO’s

Answer 22

• related to true bacteria
• found in women using Intra Uterine Contraceptive Devices (IUCD).
• usually appear as dark dense clusters with a central core and filaments protruding from the structure
• filaments aid in their identification
• not linked to cervical cancer

Question 23

Herpes Simplex Virus (HSV)

Answer 23

• 2 types of the virus
• Type 1 - found on lips and nose
• Type 2 - found on genitalia.
• sexually transmitted and incurable.
• Appears cytologically as large multinucleated cells with dense central cores.

Question 24

Human Papilloma Virus (HPV)

Answer 24

• One of the most common infections
• viral particle that has 100’s of variants, some causatives of cervical cancer.
• Viral strains 6, and 11 are found in low grade lesions and don’t usually progress to cervical cancer
• strains 16 and 18, have been found to be present in almost all cervical cancers

Question 25

HPV and cervical cancer

Answer 25

• found that repeated and/or prolonged infection with High Risk HPV can lead to cervical cancer
• virus can invade and interrupt the normal cell cycle leading to the “turning on” of uninhibited cell growth with the involvement of oncogenes E6 and E7

Question 26

HPV screening

Answer 26

• March 2012: HPV testing for women with first occurrence of low grade abnormality on cytology commenced.
• March 2013: any woman with a low grade abnormality or involved in annual follow up after treatment in Colposcopy were given an HPV test (Test of Cure)
• For both of these tests HPV was done as a triage test to routine screening.

Question 27

HPV as Test of Cure

Answer 27

• March 2013: women who had previous treatment in
  Colposcopy and had follow ups in 12 monthly intervals (for 10 years) were given an HPV test.
• If this was positive following an abnormal cytology patients were referred back to Colposcopy for further treatment
• if negative they were given a 3 year recall then a normal recall of either 3/5 years depending on their age.

Question 28

Advantages of HPV primary screening

Answer 28

• A negative HRHPV result offers more protection for women than a negative cytology sample
• The call recall will be longer reducing stress and anxiety for women
• HRHPV testing with cytology triage has been found to be much more effective for disease detection in a vaccinated population

Question 29

HPV vaccine

Answer 29

• offers protection against viral strains 6,11, 16 & 18
• introduced in 2006 to all 12-13 year old children
• decrease in incidence of cervical cancer due to the high uptake of the vaccine by school children in Scotland
• some third world countries use of the vaccine has almost eradicated cervical cancer

Question 30

2 less common infections

Answer 30

• Gonorrhoea

- Chlamydia

Question 31

Mild Dyskaryosis

Answer 31

• slight irregularity in the nuclear membrane
• slightly raised nuclear/ cytoplasmic ratio,
• chromatin is slightly clumped and hyperchromatic in the nucleus
• nucleus occupies 1/3 of total cell area corresponds to the histological grade CIN 1.

Question 32

Moderate Dyskaryosis

Answer 32

• more marked irregularity of the nuclear membrane
• nuclear /cytoplasmic ratio becomes higher
• chromatin clumping is much more pronounced.
• chromatin very hyperchromatic (dark)
• nucleus occupies 2/3rds of the total cell area

Question 33

Severe/invasive dyskaryosis

Answer 33

• more likely to progress to cancer and treatment of such lesions should be carried out within 2 weeks of the cytology report being issued
• Severely dyskaryotic cells which haven’t invaded through epithelial basement membrane are still classed as pre-cancerous

Question 34

Adenocarcinoma

Answer 34

• “glandular abnormality” present in either endocervical / endometrial cells

Question 35

Abnormalities in glandular cells in the cervix

Answer 35

• Pseudostratification (layering) of cells
• Loss of regularity / organisation /cohesion
• Excessively clumped chromatin/hyperchromasia
• Feathering of groups
• Elongation of nuclei to form oval shapes
• Rosette formation

Question 36

Advantages of screening and vaccination

Answer 36

• Regular testing with cervical cytology triage saves lives.
• screening programme is constantly changing and vaccination is available for all girls and boys aged 13
• catch up vax programme is available for girls aged 18.
• primary screening will now determine patient treatment and follow up.
• molecular testing has now been rolled out for use as a primary screening test with cytology triage
• Women will need to be informed prior to test what the test involves and what the results mean
• In fully vaxxed population cervical cancer could be eradicated

Question 37

The future of HPV testing

Answer 37

• now been rolled out across England a primary screening tool (full conversion by 2020).
• service has become automated w/ fewer samples (approx. 10-15% requiring cytology screening).
• Fewer screening staff will be required and merging of labs has been started to reduce costs and realise savings from economies of scale
• HPV is a molecular test which has changed cervical cytology from a screening to a diagnostic test