Pathology of the Cervix, Vulva and Vagina

Question 1

What types of epithelium are the ectocervix and endocervix?

Answer 1

Ectocervix - non-keratinising, stratified squamous epithelium

Endocervix - columnar epithelium

Question 2

Label the layers of the normal ectocervix?

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Answer 2

The following are from superficial to deep

Exfoliating cells - sampled and tested during a cervical smear

Superficial cells

Intermediate cells

Parabasal cells

Basal cells

Basement membrane

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Question 3

Label the star on this image of normal endocervix?

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Answer 3

Cilia

Question 4

What is the transformation zone (TZ)?

Answer 4

Squamo-columnar junction between ectovervical (squamous) and endovervical (columnar) epithelia

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Question 5

Location of the TZ?

Answer 5

Changes during as life, as a physiological response to menarche, pregnancy and menopause

Pre-menarche - TZ at external cervical os

Menarche - TZ at ectocervix

Menopause - TZ at endovervical canal

Question 6

What is cervical erosion?

Answer 6

Exposure of the delicate endocervical epithelium to the acid environment of the vagina leads to physiological squamous metaplasia

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Question 7

What are Nabothian follicles?

Answer 7

Benign cystic swellings of the endocervical glands

Question 8

What is cervicitis?

Answer 8

Non-specific acute/chronic inflammation

A specific type is follicular cervitis, where there are sub-epithelial reaction lymphoid follicles in the cervix

Question 9

Presentation of cervicitis?

Answer 9

Often asymptomatic

Can lead to infertility, due to simultaneous, silent fallopian tube damage

Question 10

Potential causes of cervicitis?

Answer 10

Many causes but could be infectious, e.g:
• Chlamydia trachomatis (STI)
• HSV infection

Question 11

What are cervical polyps?

Answer 11

Localised inflammatory outgrowths

They are not pre-malignant

Question 12

Presentation of cervical polyps?

Answer 12

Significant cause of vaginal bleeding (if ulcerated)

Question 13

Major neoplastic issues at the cervix?

Answer 13

Cervical Intraepithelial Neoplasia (CIN)

Cervical cancer:
• Squamous carcinoma (most common)
• Adenocarcinoma

Question 14

Explain the method by which HPV infection occurs and how it can lead to cervical cancer

Answer 14

Infect epithelial cells in the cervical mucosa

Most people clear this within 2 years; a small proportion go on to develop cancer

Question 15

Risk factors for CIN or cervical cancer?

Answer 15

Persistence of high risk HPV types (mainly types 16 & 18); a history of many sexual partners increases risk

Vulnerability of SC junction in early reproductive years:
• Earlier age of 1st intercourse
• Long-term use of oral contraceptives
• Non-use of barrier contraception

Smoking

Immunosuppression, e.g: HIV, transplant patients

Question 16

What are the low risk HPV types and what do they do?

Answer 16

HPV types 6 & 11 caused genital warts (AKA condyloma acuminatum); these are thickened, papillomatous squamous epithelium, with cytoplasmic vacuolation (AKA koilocytosis)

Question 17

What are the HPV types and what do they do?

Answer 17

HPV types 16 & 18 cause Cervical Intraepithelial Neoplasia (CIN) and cervical cancer

CIN - infected epithelium remains flat but may show koilocytosis, which can be detected in cervical smears

Cervical cancer (mainly invasive squamous carcinoma) - virus becomes integrated into the host DNA

Question 18

Time period over which HPV infection causes high-grade CIN?

Answer 18

6 months to 3 years

Question 19

Time period over which HPV infection causes invasive cancer?

Answer 19

5-20 years

Question 20

Occurrence of HPV infection?

Answer 20

Lifetime risk is 80%

Most of these patients develop immunity but persistence of the HPV infection increases the risk of disease

Question 21

What is CIN?

Answer 21

Pre-invasive stage of cervical squamous cancer, i.e: it is pre-invasive and non-malignant

It occurs at the TZ and involves dysplasia of squamous cells

Question 22

Presentation of CIN?

Answer 22

Asymptomatic; it is detectable by cervical screening

Question 23

Progressive degrees of dysplasia and neoplasia that lead to CIN?

Answer 23

Normal squamous epitheium

Koilocytosis

CIN I (low grade)

CIN II (high grade)

CIN III (high grade)

Question 24

Histological appearance of CIN?

Answer 24

Delay in maturation / differentiation - immature basal cells occupy more of the epithelium

Nuclear abnormalities:
• Hyperchromasia (black nuclei)
• Increased nucleocytoplasmic ratio
• Pleomorphism

Excessive mitotic activity situated above the basal layers:
• Abnormal mitotic forms

NOTE - CIN is grade I-III based on the severity of the above 3 factors

Koilocytosis is also often present (indicating HPV infection)

Question 25

What is koilocytosis a sign of?

Answer 25

Indicates HPV infection

Question 26

What is CIN I?

Answer 26

Basal 1/3rd of the epithelium is occupied by abnormal cells In this lower 1/3rd, there are a raised number of mitotic figures The surface cells are quite mature but their nuclei are slightly abnormal ADD IMAGE

Question 27

What is CIN II?

Answer 27

Abnormal cells extend to the middle 1/3rd In this middle 1/3rd, there is mitoses and also abnormal mitotic figures ADD IMAGE

Question 28

What is CIN III?

Answer 28

Abnormal cells occupy the full thickness of the epithelium There is the presence of mitoses, often abnormal, in the upper 1/3rd ADD IMAGE

Question 29

Natural history of CIN?

Answer 29

Generally, the higher the grade of CIN, the more likely it is to progress to CIN III or to invasions Whilst many persist, some do regress

Question 30

Occurrence of invasive squamous carcinomas?

Answer 30

Comprise the majority of malignant cervical tumours 2nd most common female cancer Increasingly detected in younger women

Question 31

Prevention of invasive squamous carcinoma?

Answer 31

All develop from pre-existing CIN, so most cases should be preventable with cervical screening

Question 32

Staging of invasive squamous carcinoma?

Answer 32

Stage 1A1: • Depth up to 3mm • Width up to 7mm Requires removal of CIN Stage 1A2: • Depth up to 5mm • Width up to 7mm NOTE - with the above, there is a low risk of lymph node metastases Stage 1B - confined to the cervix Requires radical hysterectomy; big difference between treatment of 1A and 1B Stage 2 - spread to adjacent organs (vagina, uterus, etc) Stage 3 - inv. of pelvic wall Stage 4 - distant metastases OR inv. of rectum or bladder NOTE - if a patient has hydronephrosis as well, this automatically makes them stage 4

Question 33

Symptoms of invasive cervical carcinoma?

Answer 33

At the micro-invasive and early invasive stages, usually asymptomatic and detected at screening Abnormal bleeding: • Post-coital • Post-menopausal • Brownish / blood-stained vaginal discharge • Contact bleeding (i.e: friable epithelium) Pelvic pain Haematuria / urinary infections Ureteric obstruction - leads to hydronephrosis and renal failure; this was a common cause of death from cervical cancer

Question 34

Methods by which squamous carcinoma spreads?

Answer 34

Local - uterine body, vagina, bladder, ureters, rectum Lymphatics (early) - spread to pelvic and para-aortic nodes Haematogenous (late) - spread to liver, lungs, bone

Question 35

Grading of squamous carcinomas?

Answer 35

Well-differentiated Moderately differentiated Poorly differentiated Undifferentiated / anaplastic

Question 36

What is Cervical Glandular Intraepithelial Neoplasia (CGIN)?

Answer 36

Pre-invasive phase of endocervical adenocarcinoma; it originates from endocervical epithelium It is sometimes assoc. with CIN

Question 37

Differences between CIN and CGIN?

Answer 37

More difficult to diagnose on cervical smear than squamous is, so screening is less effective There are no grades, i.e: no low or high grades

Question 38

Occurrence of endocervical adenocarcinoma?

Answer 38

5-25% of cervical cancer; less common than squamous carcinoma ``` Assoc. with: • Higher SE class • Later onset of sexual activity • Smoking • HPV is incriminated (part. type 18) ```

Question 39

Prognosis of endocervical adenocarcinoma?

Answer 39

Poorer prognosis than squamous carcinoma

Question 40

Other HPV-driven disease in gynaecology?

Answer 40

Vulvar Intraepithelial Neoplasia (VIN) Vaginal Intraepithelial Neoplasia (VaIN) Anal Intraepithelial Neoplasia (AIN)

Question 41

What is Vulvar Intraepithelial Neoplasia (VIN)?

Answer 41

Pre-invasive stage of vulvar squamous carcinoma; it is less predictable than CIN but, like CIN, it has 3 grades It is often, but not always, HPV related and often there is concurrent cervical and vaginal neoplasia (CIN and VaIN)

Question 42

Occurrence of VIN?

Answer 42

It is bimodal: • Young women - often multifocal, recurrent or persistent, causing treatment problems • Older women - greater risk of progression to invasive squamous carcinoma

Question 43

Occurrence of vulvar invasive squamous carcinoma?

Answer 43

Usually occurs in elderly women (as an ulcer or exophytic mass)

Question 44

Origin of vulvar invasive squamous carcinoma?

Answer 44

Can arise from normal epithelium or from VIN NOTE - they are usually well-differentiated; the verrucous type are extremely well-differentiated

Question 45

Spread of vulvar invasive squamous carcinoma?

Answer 45

Inguinal lymph nodes (MOST IMPORTANT PROGNOSTIC FACTOR)

Question 46

Treatment of vulvar invasive squamous carcinoma?

Answer 46

Surgical treatment - radical vulvectomy and inguinal lymphadenectomy NOTE - if nodes are +ve for invasion, the survival is worse

Question 47

What is vulvar Paget's disease?

Answer 47

Non-invasive, intraepithelial adenocarcinoma; the tumour cells are in the epidermis and contain mucin It is assoc. with underlying cancers, e.g: sweat gland carcinoma, however this is usually not the case NOTE - it is different from Paget's disease of bone but is similar to Paget's disease of breast

Question 48

Other vulvar diseases?

Answer 48

Infections: • Candida (part. diabetics) • Vulvar warts (HPV types 6 & 11) • Bartholin's gland abscess (blockage of gland duct) Non-neoplastic epithelial disorders: • Lichen sclerosis • Other dermatoses (lichen planus, psoriasis) Atrophy: • Post-menopausal

Question 49

Types of vaginal pathology?

Answer 49

Vaginal Intraepithelial Neoplasia (VaIN) - may also have cervical and vulval lesions Squamous carcinoma - less common than cervical and vulval counterparts; it is a disease of the elderly Melanoma - rare; it may appear as a polyp