Pathology of the Cervix, Vulva and Vagina Flashcards
Describe the cells of a normal endocervix.
Single layer of ciliated mucin-secreting epithelium, sitting on a basement membrane with stroma underneath
List the 6 different cell layers of a normal ectocervix (out to in).
- Exfoliating cells
- Superficial cells
- Intermediate cells
- Parabasal cells
- Basal cells
- Basement membrane
Where is the ‘transformation zone’?
Cervix
Describe the transformation zone.
Squamo-columnar junction between ectocervical (squamous) and endocervical (columnar) epithelia
In what stages of a woman life does the transformation zone alter?
- Menarche
- Pregnancy
- Menopause
What is cervical erosion?
Exposure of delicate endocervical epithelium to acid environment of vagina leads to physiological squamous metaplasia
What is the characteristic sign of cervical erosion?
** Nabothian follicles **
What is metaplasia?
One type of epithelium transforms into another type of epithelium
Can squamous metaplasia be physiological?
Yes
Cervicitis can be ____________
Asymptomatic
What is cervicitis?
Inflammation of the cervix
What complication can cervicitis lead to?
Infertility, due to simultaneous silent fallopian tube damage
What can the inflammation in cervicitis be?
Non-specific acute/chronic
In follicular cervicitis, what can be seen on the cervix?
Sub-epithelial reactive lymphoid follicles
Name 2 infections which can lead to cervicitis.
- Chlamydia trachomatis (sexually transmitted).
* Herpes Simplex Viral infection.
What is a cervical polyp?
A localised inflammatory outgrowth in the cervix
Can a polyp cause bleeding?
Yes, if it is ulcerated
Is a polyp premalignant?
NO
What 2 neoplastic changes can occur in the cervix?
- Cervical Intraepithelial Neoplasia (CIN).
* Cervical Cancer:
What are the 2 main types of cervical cancer?
- Squamous carcinoma.
* Adenocarcinoma
What type of virus is HPV?
A DNA virus
What strains of HPV are responsible for 70% of all cervical cancers?
16 and 18
Between 10-30 years after being infected with HPV, a small proportion of women will go on to develop cancer
T
What HPV strains are high risk?
16, 18, 31, 33, 35, 45, 48
What increases your risk of getting HPV?
Multiple sexual partners
When is the ( squamocolumnar)SC junction of the vagina vulnerable?
In early reproductive life
What factors make the SC junction more vulnerable?
- Age at first intercourse.
- Long term use of oral contraceptives.
- Non-use of barrier contraception.
Does smoking increase the risk of cervical cancer?
Yes, it increases risk by 3x
HPV causes _________ warts
Genital
What HPV types cause genital warts?
6 and 11
Is HPV 6 and 11 low or high risk?
Low
What is Condyloma Acuminatum?
Thickened ‘papillomatous’ squamous epithelium with cytoplasmic vacuolation (‘koilocytosis’)
What type of HPV causes CIN?
High risk HPV – types 16 and 18
Describe the typical histological appearance of CIN.
Infected epithelium remains flat, but may show koilocytosis, which can be detected in cervical smears.
What type of cervical cancer does HPV cause?
Invasive squamous carcinoma.
What does virus integrate into?
Host DNA
What is the usual time frame in which HPV infection becomes high grade CIN?
6 months - 3 years
How long does it take for high grade CIN to develop into invasive cancer?
5-20 years
What is the cumulative prevalence of HPV in a lifetime?
80%
Most people develop immunity for HPV
T
What increases the risk of HPV disease?
PERSISTENCE !!!
What is dyskaryosis?
Abnormal cells with multiple nuclei seen in the cervix of someone with HPV
What is CIN?
A pre-invasive stage of cervical cancer
Where does CIN occur?
At the transformation zone
CIN can involve a large area of the cervix
T
Histologically, what is seen in CIN?
Dysplasia of squamous cells.
How does CIN usually present?
Asymptomatic – detected by cervical screening.
Describe the 3 KEY histological features of CIN.
- Delay in maturation/differentiation
- Nuclear abnormalities
- Excess mitotic activity
Describe the excess mitotic activity seen in CIN.
- Situated above basal layers
* Abnormal mitotic forms
Describe the nuclear abnormalities seen in CIN.
- Hyperchromasia (very black nuclei)
- Nucleocytoplasmic ratio (high)
- Pleomorphism (marked variation in cell size and shape)
Describe the delay in maturation seen in CIN.
- Immature basal cells occupying more of epithelium
What is Koilocytosis indicative of?
HPV
When is Koilocytosis seen?
CIN
How is CIN graded?
I-III, depending on the severity of the above 3 factors (delay in maturation/differentiation, nuclear abnormalities, excess activity).
CIN I can be diagnosed if …
Basal 1/3rd of epithelium occupied by abnormal cells.
- Raised number of mitotic figures in lower 1/3rd.
- Surface cells quite mature, but nuclei slightly abnormal.
CIN II can be diagnosed if …
Abnormal cells extending to the middle 1/3rd.
- Mitoses in middle 1/3rd.
- Abnormal mitotic figures.
CIN III can be diagnosed if …
Abnormal cells occupy full thickness of epithelium.
- Mitoses, often abnormal in upper 1/3rd.
Full thickness atypia, general lack of cytoplasm, very high nucleus to cytoplasmic dysplasia.
Would show severe dyskaryosis on smear.
What does this describe?
CIN III
Invasive squamous carcinoma accounts for 75-95% of all malignant cervical tumours
T
Invasive squamous carcinoma is the __nd most common female cancer worldwide
2nd
Who are invasive squamous carcinomas usually detected in?
Young women
What does invasive squamous carcinoma develop from?
CIN
The fact that ISC is developed from CIN is good because it means lots of cases are preventable, why?
CIN can be picked up on smears
Why is the staging of ISC important?
Treatment and prognosis is different for every stage
Outline the staging of ISC.
- Stage 1A1 - depth up to 3mm, width up to 7mm.
- Stage 1A2 - depth up to 5mm, width up to 7mm.
(low risk of lymph node metastases)
- Stage 1B - confined to the cervix.
- Stage 2 - spread to adjacent organs (vagina, uterus, etc.).
- Stage 3 - involvement of pelvic wall.
- Stage 4 - distant metastases or involvement of rectum or bladder.
When is there usually no symptoms of invasive carcinoma?
At microinvasive and early invasive stages (detected at screening).
What symptoms may invasive carcinoma present with?
ABNORMAL BLEEDING !!!
- Pelvic pain.
- Haematuria/urinary infections.
- Ureteric obstruction/renal failure.
In what situations, might someone with invasive carcinoma notice abnormal bleeding?
- Post-coital.
- Post-menopausal.
- Brownish or blood-stained vaginal discharge.
- Contact bleeding – friable epithelium.
Locally, where can squamous carcinoma spread to?
- Uterine body
- Vagina
- Bladder
- Ureters
- Rectum
Other than local spread, how else can squamous carcinoma spread?
Lymphatic - early - pelvic, para-aortic nodes.
Haematogenous - late - liver, lungs, bone.
Name a glandular lesion seen in the cervix.
Cervical Glandular Intraepithelial Neoplasia (CGIN)
A CGIN is an adenocarcinoma
T
Where does CGIN arise from?
Endocervical epithelium
What is CGIN?
A preinvasive phase of endocervial adenocarcinoma
What is more difficult to diagnose on smear?
A. CGIN
B. CIN
CGIN
If something is not easy to detect on smear, what does this mean?
Screening is less effective
Describe the histological appearance of high grade CGIN.
Cells lose polarity – nuclei are no longer found along the base only
What % of cervical cancers is endocervical adenocarcinoma responsible for?
5-25%.
Compared with the prognosis of squamous carcinoma, adenocarcinoma is …..
WORSE
List 3 risk factors for the development of endocervical adenocarcinoma.
- Higher socioeconomic class.
- Later onset of sexual activity.
- Smoking.
HPV __ causes endocervical adenocarcinoma
HPV 18
Give 3 examples of other HPV driven diseases.
- Vulvar Intraepithelial Neoplasia, VIN.
- Vaginal Intraepithelial Neoplasia, VaIN.
- Anal Intraepithelial Neoplasia, AIN.
What is Paget’s disease?
Vulvar intraepithelial neoplasia (VIN).
VIN is described as ‘bimodal’ - describe this.
Can affect both YOUNG women and OLDER women
VIN is ________
Bimodal
Describe VIN affecting young women.
Often multifocal, recurrent or persistent, causing treatment problems.
Describe the main concern associated with VIN affecting older women.
Greater risk of progression to invasive squamous carcinoma.
What can VIN progress into?
Invasive squamous carcinoma
What is VIN often, but not always associated with?
HPV
What is VIN often synchronous with?
Cervical and vaginal neoplasia (CIN and VaIN).
Who does Vulvar Invasive Squamous Carcinoma usually affect?
Elderly women
What does Vulvar Invasive Squamous Carcinoma usually present as?
Ulcer or exophytic mass
What can Vulvar Invasive Squamous Carcinoma arise from?
Normal epithelium or VIN
Where does VISC usually spread to?
Inguinal lymph nodes
What is the most important prognostic factor of VISC?
Spread to inguinal lymph nodes
How is VISC treated?
Surgery – radical vulvectomy and inguinal lymphadenectomy
How does Vulvar Paget’s Disease present?
As a crusting rash
Where are tumour cells found in vulvar Paget’s?
Epidermis
What do tumour cells found in the epidermis of vulvar paget’s contain?
Mucin
What do the tumours of vulvar pagets arise from?
Sweat gland on the skin
Give examples of infections which can affect the vulva.
- Candida (esp in diabetics).
- Vulvar wards (HPV 6 + 11).
- Bartholin’s gland abscess (blockage of gland duct).
Give examples of non-neoplastic epithelial disorders affecting the vulva.
- Lichen sclerosis.
* Other dermatoses – lichen planus, psoriasis.
When may vulval atrophy occur?
Post-menopause