Pathology of the Vulva,Cervix and Endometrium

Question 1

Vulva Tumours

Answer 1

A vulva tumour can either be classified as benign and Malignant.

Benign: Condyloma Acuminatum

Premalignant lesions:

• Low grade CIN lesions
• High grade CIN lesions, including carcinoma in situ – HPV induced lesions

Malignant: Squamous Carcinoma

Question 2

Benign: Condyloma Acuminatum

Answer 2

Young sexually active women, especially those with multiple partners, caused by HPV types 6 and 11.

The virus is sexually transmitted sexually

Macroscopic: Warty lesion, up to 5cm in diameter and are ususally multiple

Micro:scopic: Papillomatosis, acanthosis, hyperkeratosis and parakeratosis.

Koilocytes: Epithelial cells with an enlarged irregular nuclei cells and clear cytoplasm in the superficial epithelial layers – indication of HPV infection

Identical lesions may be found on penis

Question 3

Malignant: Squamous Carcinoma

Answer 3

Previously rare and seen mainly elderly women(Cause is not clear)

Has become more common and is being seen in younger women,These tumours are caused by HPV (16&19) and are ass. with cervical carcinoma.

They start as small white areas of epithelial thickening but as they enlarge they ulcerate.

Spreads is mainly lymphatic to the inguinal nodes

Prognosis depends on the stage of the disease

Question 4

Types of Infections

Answer 4

Herpes virus infection - STD, painful ulcer, intra-epidermal vesicle with virus inclusions
Syphilis – primary and secondary forms can affect the genitourinary tract
Granuloma inguinale – donovanosis, STD, chronic ulceration
Lymphogranuloma venereum – Chlamydia trachomatis, ulcer, granulation tissue, fibrosis, fistula, lymphadenopahty
Candida – common, chronic irritation and inflamation

Question 5

Cervical Tumours: Carcinoma of the cervix

Answer 5

1. Squamous carcinoma_ 90%
2. Adenocarcinoma_ 5%\
3. Adenosqaumous Carcinoma_ 3%
4. Undifferentiated Carcinoma_ 2%

Question 6

Classification of HPV-associated intraepithelial lesions of the cervix-Flat condyloma

Answer 6

CIN I-Mild dysplasia/Low Grade CIN

CIN II-Moderate dysplasia/High grade dysplasia

CIN III-Severe dysplasia or carcinoma in situ

Question 7

Cytology Screening Programmes

Answer 7

Erroneously referred to as cervical cancer screening

Aim is to detect atypical cells in pre-invasive stage

Local measures as treatment – diathermy large loop excision of the transformation zone (LLETZ)

Cytology:
Simple, safe, non-invasive
Detect pre-cancerous changes in cervix
Majority from asymptomatic women

National screening program – lower mortality

Cytology detect abnormal (dyskaryotic) nuclei

Degree of abnormality may not always correlate with subsequent histological findings in a biopsy

Not reliable to detect invasion

Liquid-based cytology:

• Cells received suspended in fluid and prepared as a near monolayer on a slide and stained
• Replaced smearing of cells onto glass slide from a spatula

Question 8

Clinical consequence of cervical cytology

Answer 8

The consequences of cervical cytology can be divided into Cytology finding and clinical conseqeuence

Question 9

Cytology Finding

Answer 9

Unsatisfactory

Normal

‘Borderline’ changes or mild dyskaryosis

Persistent ‘borderline’ changes or mild dyskaryosis

Moderate / severe dyskaryosis

Question 10

Clinical Consequence

Answer 10

Repeat immediately

3 or 5 yearly recall

Repeat in 6 months

Refer for colposcopy and biopsy

Refer for colposcopy and biopsy

Question 11

Squamous Carcinoma

Description

Answer 11

Most common malignant tumour in black females in

South Africa, relatively common in white females.

Common throughout Africa, India and parts of South America. The incidence has fallen in most Western countries.

Age: 30 – 70 years.

Incidence is highest in communities with poor socio-economic conditions and where cytology screening is not done.

Question 12

The risk factors and aetiology of Sqaumous Carcinoma

Answer 12

Sexual activity at an early age (16 or younger)
Variety of sex partners
Multiple pregnancies
Numerous marriages
Prostitution
History of venereal disease
Smoking

The risk facors indicate that the casusative agent is probably transmitted during sexual intercourse. The agent incriminated at present is HPV, ESP 16 AND 18, but it is possible that other agents may play a role.

Question 13

The development of the carcinoma

Answer 13

The development of the carcinoma develops after a sequence of CIN I to II to III.

This usually takes place 10-20 yeras,but recently an alarming number of cases have been described where a CIN I lesion progresses to a carcinoma in 2 to 3 years.

Question 14

The pathology of the Squamous Carcinoma

Answer 14

Macro: Initially a white or red area of thickening. Eventually an ulcer or exophytic lesion is formed. The lesion is friable and bleeds easily on contact. Common symptoms of carcinoma are intermenstrual bleeding and contact bleeding.

Micro: The usual features of the sqaumous carcinoma:

• Nests of pleomorphic squamous cells
• Keratinizing or non-keratinizing
• Infiltrate surrounding stroma

Question 15

How does the spread of a squamous carcinoma occur:

Resasons death occurs:

Answer 15

Direct: Uterine corpus, vagina, parametrium, pelvic wall, bladder and rectum.

Lymphatic: iliac and para-aortic nodes

Haematogenous: rare

Death usually due to local disease:

• massive haemorrhage
• Bladder infiltration with urinary tract infections or
• Obstruction and renal failure

Question 16

The prognosis of a squamous Carcinoma

Answer 16

Determined by the clinical stage of the disease at the time of diagnosis and the stage is related to a 5 year survival.

Stage 0: Carcinoma in situ 100%
Stage 1: Limited to cervix 90%
Stage 2: Spread to parametrium or upper vagina 60 %
Stage 3: Spread to pelvic wall or lower vagina 20
Stage 4: Metastases or bladder/rectum involvement5%

Question 17

Adenocarcinoma

Answer 17

Less common than squamous carcinoma but more aggressive.

Increase in the incidence.

Aetiology uncertain, but HPV plays a role.
Smoking is a risk factor.

Precursor lesion: CGIN = cervical glandular intra-epithelial neoplasia, can also be picked up with routine Pap smear.

Question 18

Endometritis

Answer 18

Most often seen after an intra-uterine pregnancy – especially with instrumentation or retained products.

Can be a complication of an IUD

Chlamydia: acute or chronic with lymphocyte infiltration and lymphoid follicles

Tuberculosis: secondary TB, granulomas are seen in the secretory phase of the menstrual cycle

Both conditions can be associated with infertility

Question 19

Endometrial Polyps

Answer 19

Common perimenopausal and post menopausal

Presents with AUB – consists of dilated glands with prominent blood vessels in a fibrotic stroma

Tamoxifen – anti estrogen agent used in breast cancer. Paradoxically cause estrogen effects in the endometrium – can lead to hyperplasia or polyps

Question 20

Endometrial Hyperplasia

Answer 20

Develops as a result of unopposed oestrogen stimulation and leads to thickening of the endometrium.

Some types of hyperplasia develop into endometrial carcinoma.

Symptoms of menorrhagia, post menopausal bleeding.

Sonar shows thickened endometrium. At D&C a larger volume of endometrium than normal is removed.

The source of oestrogen may be:

• Exogenous: oestrogen therapy
• Endogenous: produced by a granulosa cell tumour of the ovary, or the result of obesity( Fat cells convert androstenedione to estrogen)

Question 21

The classification of Endometrial Hyperplasia

Answer 21

Simple hyperplasia: Increase in stroma and glands. Many glands are cystically dilated. No atypia. Little or no chance of malignant change.

Complex hyperplasia: Increase in glands which are branched and crowded. No cellular atypia. Small chance of malignant change.

Complex atypical hyperplasia: As above but with cellular atypia. Significant chance of malignant change.

Question 22

Endometrial Tumours

Answer 22

Benign: Endometrial polyp

Malignant: Endometrial adenocarcinoma
Malignant mixed tumour ( MMMT)

Question 23

Endometrial Carcinoma

Answer 23

Peak incidence 50 to 70 years, common in white patients(Rarely premenopausal)

Often associated with high oestrogen levels and often follows on hyperplasia – endometroid adenocarcinoma.

Sometimes no obvious underlying cause.

Question 24

Risk factors ass. with Endometrial Carcinoma

Answer 24

• Anything that results in unopposed oestrogen stimulation.
• Obesity, especially in combination with diabetes and hypertension.
• Nulliparous women-Usually present with post menopausal bleeding.

Question 25

Pathology of an Endometrial Carcinoma

Answer 25

Some tumors are not associated with raised oestrogen and develop in a background of atrophy.

They are often more aggressive types.

Macro: Starts as irregular area of thickening in fundus. Later forms a diffusely infiltrative tumour or an exophytic lesion filling the uterine cavity.

Micro: Adenocarcinoma – endometroid, clear cell or papillary serous carcinoma

Question 26

Spread of an Endometrial Carcinoma

Answer 26

Direct – myometrium and parametrium

Lymphatic – iliac and para-aortic

Haematogenous – seldom - lung/liver

Question 27

Prognosis of an Endometrial Carcinoma

Answer 27

Dependent on the stage:

Stage I: only myometrial invasion, 90% 5 year survival

Stage II and III: advanced disease, 10% 5 year survival

Question 28

Malignant mixed tumour / MMMT

Answer 28

Malignant mixed mullerian tumour.

Carcinosarcoma.

Mainly elderly black women.

Consists of a mixture of malignant epithelium and stroma ( often cartilage, bone and striped muscle).

Highly malignant with an extremely poor prognosis