Gynae Pathology Flashcards
Cervical cytology
- 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.
Introduction of Organised Screening
- 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
Achieving attendance of screenings
- 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.
Role of cytology
- 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
Role of colposcopy
- 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
Introduction of Liquid Based Cytology
- 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.
Sample taking for LBC
- 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
Sample fixation
- 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
Sample processing
- 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
The request card (HMR101 form/ICE)
- 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.
Screening
- 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
What are the screening staff looking for?
- Normal samples make up the majority of our workload.
- Therefore we need to know what features are “normal” to know what are “abnormal”.
Indicators of abnormality in screening
- increased nuclear/cytoplasmic ratio
- irregular nuclear outline
- hyperchromasia (darkening) of nuclear chromatin
- bi/multi nucleation of cells.
Cervical epithelium
- 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.
Endocervicals
- 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
How is squamous metaplasia recognised?
- by dense opaque blue cytoplasm and bizarre shapes/forms
Endometrial cells
- 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
Infections in cervical samples
- 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
Infections
- mainly sexually transmitted.
- Some are more easily treated than others
Trichomonas Vaginalis
- Can infect both men and women
- yellow/green foul smelling discharge
- its a parasite and has no link to cervical cancer
Candida Albicans (thrush)
- 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)
Actinomyces like organisms/ ALO’s
- 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
Herpes Simplex Virus (HSV)
- 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.
Human Papilloma Virus (HPV)
- 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
HPV and cervical cancer
- 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
HPV screening
- 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.
HPV as Test of Cure
- 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.
Advantages of HPV primary screening
- 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
HPV vaccine
- 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
2 less common infections
- Gonorrhoea
- Chlamydia
Mild Dyskaryosis
- 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.
Moderate Dyskaryosis
- 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
Severe/invasive dyskaryosis
- 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
Adenocarcinoma
- “glandular abnormality” present in either endocervical / endometrial cells
Abnormalities in glandular cells in the cervix
- 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
Advantages of screening and vaccination
- 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
The future of HPV testing
- 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