Gynae Pathology

Question 1

Describe the epithelium of the cervix.

Answer 1

Outer part is the ectocervix lined by squamous epithelium.
Inner part is the endocervix lined by glandular epithelium. These cells secrete mucin.
The transformation zone is the junction of the ectocervix and the endocervix.

Question 2

What is the clinical significance of the

transformation zone?

Answer 2

Pre-malignant and malignant lesions tend to arise at this location.

Question 3

Describe the histology of the ectocervix.

Answer 3

Stratified squamous non-keratinising epithelium. Numerous layers of cells piled on top of each other with movement from cuboidal and young to squamous and old. This has a protective function.
At the base the nuclei are close together and as you move towards the surface the nuclei are further apart.
Nuclei small and look the same.

Question 4

Describe the histology of the endocervix.

Answer 4

Single layer of glandular epithelium. The nuclei are at the base of the cell and the cells contain abundant pale staining mucous.

This epithelium lines the surface and dips down into the stroma.

Question 5

What is the aim of cervical screening?

Answer 5

The detection of premalignant conditions which if untreated could go on to develop into invasive cancer.

Question 6

Which pre-malignant changes in the cervix are picked up on cervical screening?

Answer 6

Cervical Intraepithelial Neoplasia (CIN).

(Most pre-invasive abnormalities affect the squamous epithelium. Rarely get pre-invasive lesions involving the endocervical glands).

Question 7

What is the next stage for each of these results from a cervical smear.

• Negative
• Unsuitable
• Borderline nuclear changes
• Mild dyskaryosis
• Moderate dyskaryosis
• Severe dyskaryosis.

Answer 7

-Negative: means normal smear. Continue with routine screening every 3-5 years.
-Unsuitable: e.g. not enough cells on the slide, a lot of blood, a lot of inflammatory cells. Repeat asap in 3 months.
- Borderline nuclear changes: unknown if changes are pre-malignant or reactive. Repeat after 6 months.
-Mild dyskaryosis: repeat after 6 months. If noticed on 2 consecutive smears then refer to gynaecologist. (Often regresses back to normal within 6 months).
-Moderate dyskaryosis &
-Severe dyskaryosis:
Refer to a gynaecologist as a significant lesion may be present.

Question 8

What is dyskaryosis of a cervical smear?

How is it classified?

Answer 8

Dyskaryosis is the presence of abnormal nuclei in a cervical smear.

It is classified as follows:
CIN I is mild dyskaryosis.
CIN II is moderate dyskaryosis.
CIN III is severe dyskaryosis.

Question 9

Describe the histological appearance of koilocytosis?

What does this finding indicate?

Answer 9

Slightly enlarged nuclei.

It is a manifestation of HPV infection within the cervix.

Question 10

Describe the cytological appearance of:

• CIN I
• CIN II
• CIN III

Answer 10

• CIN I: Nuclei are enlarged and nuclear chromatin is abnormal with a speckled appearance.
• CIN II: The nucleus occupies approximately 2/3 of the cell and nuclear chromatin is abnormal with a speckled appearance.
• CIN III: The nucleus is very big compared to the size of the cell. There are alternate dark and light coloured areas within the nucleus indicating abnormal chromatin.

Question 11

Name the pre-malignant conditions of the cervical epithelium.

Answer 11

Squamous epithelium - Cervical Intraepithelial Neoplasia (CIN).

Glandular - Cervical Glandular Intraepithelial Neoplasia (CGIN).

Question 12

How are squamous pre-malignant lesions classified?

Answer 12

Koilocytosis
CIN I
CIN II
CIN III

USA:
Low grade squamous intraepithelial lesion (LSIL) - koilocytosis and CIN I (similar histological appearance and management).
High grade squamous intraepithelial lesion (HSIL) - CIN II and CIN III (similar histological appearance and management).

Question 13

Describe the histological appearance of koilocytosis.

Answer 13

In the basal layers (columnar cells) thee nuclei are slightly enlarged.

The nuclei towards the surface (squamous cells) are much larger and very irregular in shape.

Question 14

Describe the histological appearance of CIN I.

Answer 14

Koilocytes towards the surface with larger nuclei and irregular shape.

The cells in the lower 1/3 epithelium are very enlarged and abnormal. Abnormal cells confined to this lower 1/3.

Question 15

Describe the histological appearance of CIN II.

Answer 15

Enlarged, abnormal cells extend 2/3 way up the squamous epithelium.

Question 16

Describe the histological appearance of CIN III.

Answer 16

Abnormal cells occupy the full epithelial thickness.

There is no maturation - normal stratified squamous epithelium has columnar cells at the base and and squamous cells at the surface.

There are mitotic figures present.

Question 17

How are glandular pre-malignant lesions classified?

Answer 17

Glandular dysplasia/Low grade CGIN.

Adenocarcinoma in situ/ High grade CGIN.

Question 18

Describe the histological appearance of high grade CGIN (adenocarcinoma in situ).

Answer 18

There is loss of the pale staining mucin from normal endocervical glandular epithelium.
Nuclei heap on top of each other.
Apoptotic bodies indicate individual cell death.
Mitotic figures present.

Question 19

What is the significance of a CIN diagnosis?

Answer 19

• Risk of progression to invasive cervical cancer.
  CIN I - risk quite low and many cases will regress if untreated.
  CIN III - risk high
  However risk is variable as some CIN III may even regress to normal.
• Slow progression from low grade lesion to invasion (10-15 years for CIN I to develop into invasive cancer).

However - can’t predict which will regress and which will progress so treat ALL when they are picked up.

Question 20

How are preinvasive lesions managed?

Answer 20

Gynaecologist looks at cervix with colposcope and takes a biopsy of the abnormal areas. Decide on:
- Ablation by freezing or cauterisation for low grade lesions.
- Excision of high grade lesions by cone or loop biopsy.
(Sent for histopathologist who confirms no incase cancer and then follow up smear at 6 months then every year for 10 years)
-Cytoloical +/- colposcopic follow up

Question 21

Describe the aetiology of preinvasive lesions and invasive cervical cancer.

Answer 21

• HPV
  Low risk type (6 and 11 associated with koilocytosis and CN I)
  High risk type (16 and 18 associated with low and high grade lesions with potential to become invasive cancer)
• Early age at first intercourse and multiple partners are risk factors for HPV infection as it is spread by sexual contact
• Smoking - synergistic effect with HPV
• Oral contraceptives ????? (glandular lesions)

Question 22

Name types of invasive cervical cancer.

Answer 22

• Squamous carcinoma (85%)
• Adenocarcinoma (10-15% but incidence increasing)
• Rarer subtypes e.g. small cell carcinoma, adenosquamous carcinoma.

Question 23

Briefly describe the stages of cervical cancer:

• Stage I including Ia
• Stage II
• Stage III
• Stage IV

Answer 23

• Stage I - cancer is confined to the cervix.
  Ia - micro invasive carcinoma. Max depth 5mm and length 7mm.
• Stage II - carcinoma extends beyond the cervix but not to pelvic wall. Involves vagina but not lower 1/3.
• Stage III - carcinoma extends to the pelvic wall and involves the lower 1/3 vagina.
• Stage IV - cancer has spread beyond the pelvis or has clinically involved the mucosa of the bladder or rectum.

Question 24

Describe the histology of a Grade Ia microinvasive squamous carcinoma.

Answer 24

CIN III confined within the basement membrane.

Spot of cells has come of the epithelium involved by CIN III and invaded the underlying tissues. At this stage it is <1mm in size.

Question 25

Describe the histological appearance of squamous carcinoma of the cervix.

Answer 25

Squamous carcinoma invades the cervical stroma.

Question 26

Describe the histological appearance of: - Adenocarcinoma of the cervix - Adenosquamous carcinoma of the cervix. - Small cell carcinoma of the cervix.

Answer 26

Consult textbook.

Question 27

What is the treatment for each of these stages of Cervical Cancer? - Stage 1A1 - Other Stage 1 - > Stage 1

Answer 27

- Stage 1A1: Cone/loop biopsy (histopathologist ensures margins are clear of tumour) or simple hysterectomy (older patient happy to have her uterus removed). - Other Stage 1: Radical hysterectomy (remove ligaments surrounding uterus and upper vagina)and pelvic lymphadenectomy + chemoradiation depending on status of margins. - >Stage 1: Chemoradiation.

Question 28

What is the Prognosis for Stage Ia and Ib cervical cancer?

Answer 28

Stage 1A - excellent prognosis, expect cure. Small % will have lymph node metastases. Stage 1B - guarded. Prognosis generally good but depends on factors such as size, differentiation, surgical margins, lymphovascular permeation, lymph node status)

Question 29

What epithelium lines the vulvula?

Answer 29

Part of the skin - keratinising stratified squamous epithelium with underlying skin appendix structures.

Question 30

Name and describe the two vulval dystrophies.

Answer 30

Lichen sclerosis - sclerosis/fibrosis within the dermis. Surface squamous epithelium also atrophic. Squamous cell hyperplasia.

Question 31

What is the presentation and significance of a vulval dystrophy.

Answer 31

Presentation: - Pruritis - Pain - Leukoplakia. Significance: Small risk of progression to invasive squamous carcinoma.

Question 32

Name the preinvasive lesions of the vulva. How do they present?

Answer 32

``` Vulval Intraepithelial Neoplasia (VIN). Categorised into VIN I VIN II VIN III ``` Present in a similar way to a vulval dystrophy - pain, pruritus and leukoplakia (gross lesion). May be picked up when patient is being followed up for CIN (HPV associated).

Question 33

Name the two types of VIN and describe their differences.

Answer 33

- Bowenoid/undifferentiated: younger, associated with HPV, multifocal, associated withCIN and VAIN, low risk of invasion. - Simplex/differentiated: older, no association with HPV, may be associated with vulval dystrophies, unifocal, no association with CIN, high risk of invasion.

Question 34

Describe the histological appearance of VIN III.

Answer 34

Similar to CIN III. | Atypical nuclei and mitotic figures present throughout the epithelial matrix.

Question 35

Name the different types of Vulval Squamous Carcinoma and their differences.

Answer 35

- Bowenoid/undifferentiated: rarer (this type of VIN has low risk of developing invasive carcinoma). Associated with HPV, younger females. - Simplex/differentiated: more common, not associated with HPV, association with vulval dystrophy, older.

Question 36

Describe the histological appearance of Squamous Carcinoma of the Vulva.

Answer 36

Atypical squamous cells invade the vulval stroma.

Question 37

Describe the stages of vulval carcinoma.

Answer 37

- Stage I: Tumour confined to vulva and/or perineum, <2cm. - Stage II: Tumour confined to vulva and/or perineum >2cm. - Stage III - tumour of any size with spread to lower urethra and/or vagina and/or anus and/or unilateral lymph node metastasis. - Stage IV: Tumour invades upper urethra/bladder mucosa/rectal mucosa/pelvic bone/ bilateral regional lymph nodes.

Question 38

What is the treatment for vulval carcinoma.

Answer 38

- Stage 1A - surgical excision i.e. when <1mm in size there is very little chance of lymph node involvement. (Tumour spreads in a very predictable way to lymph nodes on same side, then to contralateral nodes). - >Stage 1A - surgical excision and groin lymph nodes. - Advanced - chemoradiation.

Question 39

Explain Paget's Disease and its presentation.

Answer 39

Paget's disease is an adenocarcinoma arising in the squamous epithelium of the vulva and is confined to the squamous epithelium of the vulva. It can be primary (arises from stem cell with potential to develop down a squamous or glandular pattern) or secondary from internal organs (colorectum, bladder, cervix). It presents with Pruritis, burning, eczema and ulceration.

Question 40

Describe the histological appearance of Paget's Disease.

Answer 40

The vulval squamous epithelium is replaced by very large adenocarcinoma cells.

Question 41

How is Paget's Disease managed?

Answer 41

Surgical excision with free margins and exclude other internal malignancy.

Question 42

What is the prognosis for Paget's Disease?

Answer 42

Recurrences, which may be multiple, are common, even when excision margins are clear. Dermal invasion associated with poorer prognosis. Sometimes can develop invasive adenocarcinoma.