Gynae and testes

Question 1

Explain the pathogenesis of cervical carcinoma, in particular highlighting the role of metaplasia in the transformation zone, persistent high risk HPV infection and development of CIN

Answer 1

columnar mucosa–> meytaplastic squamous mucosa due to vaginal acid and metaplasia–> CIN (pre-cancer) often caused by persistant high risk HPC infection–> squamous cell carcinoma

Question 2

What is the term used for dysplasia (premalignancy) in the cervix?

Answer 2

cervical intraepithelial neoplasia (CIN)

Question 3

Define dyskaryosis and understand how the term is used differently from CIN.

Answer 3

Dyskaryosis refers to abnormalities of the cell nucleus eg. an irregular shape, an increased size. It is a term that is only used in cervical smear reports.

Dyskaryosis is a diagnosis rendered on a cervical smear.

CIN is a diagnosis which can only be rendered on a cervical biopsy.

Question 4

Explain how the detection and treatment of CIN forms the basis of cervical screening

Answer 4

The sample is tested for high risk HPV (hrHPV) subtypes using a PCR test.

In the absence of hr-HPV, it is essentially not possible to develop CIN.

Question 5

Give an overview of the management of an abnormal smear.

Answer 5

If the hr-HPV test is negative, the woman is returned to routine recall.

If the hr-HPV test is positive, the same sample is used to prepare a glass slide. A representative thin layer of cells is spread on the slide and stained with the Papanicolaou (‘Pap’) stain. This cytology sample is examined by trained biomedical scientists who look for dyskaryotic cells.

A smear showing dyskaryosis is a good predictor of the presence of CIN in the cervix:
• Low grade (mild) dyskaryosis - predicts the presence of CIN 1 in the cervix
• High grade (moderate) dyskaryosis - predicts the presence of CIN 2 in the cervix
• High grade (severe) dyskaryosis - predicts the presence of CIN 3 in the cervix

If cytology is abnormal–> colposcopy referral

If hrHPV + and cytology - then re-screen in a year

Women are screened every 3 years from 25-49yr and every 5 years from 50-64yr.

Question 6

Describe the clinical presentation of symptomatic cervical cancer

Answer 6

PCB
offensive vaginal discharge
ulcer or mass on cervix

Question 7

most common cervical cancer

Answer 7

squamous cell carcinoma

Question 8

What is used to stage cervical cancer?

Answer 8

FIGO system

Question 9

suitable investigations for a patient with post menopausal bleeding

Answer 9

Speculum examination
Biopsy
Staging- examination under anaesthesia or CT abdo/pelvis

Question 10

Most common type of endometrial cancer

Answer 10

adenocarcinoma

Question 11

what is a premalignant lesion in the endometrium called?

Answer 11

atypical hyperplasia

Question 12

staging of endometrial cancer

Answer 12

FIGO

Question 13

What causes atypical hyperplasia?

Answer 13

by high levels of unopposed oestrogens

Question 14

Describe the pathology of ovarian mature cystic teratomas.

Answer 14

Mature cystic teratomas (‘dermoid cysts’) are common benign tumours, typically occurring in the pre- menopausal age group. They are often asymptomatic, but rupture is painful.
Teratomas are germ cell tumours1 which form normal tissue structures:
• most teratomas contain elements derived from all three embryonic layers (ectoderm, mesoderm and endoderm).
Teratomas arising in the ovary are typically cystic tumours lined by skin with underlying sebaceous glands and hair follicles. The cyst becomes filled with thick greasy sebaceous material and hair.

Question 15

Describe the pathology of ovarian cancer using serous carcinoma as an example

Answer 15

High grade serous carcinoma (HGSC) is the most common malignant ovarian tumour. On naked eye examination, HGSC may be purely solid but more commonly it has solid and cystic components.

Microscopically, HGSC is composed of pleomorphic cells with hyperchromatic nuclei and high nuclear:cytoplasmic ratios, often arranged in a papillary (finger-like) architecture

Question 16

Ovarian cancer staging system

Answer 16

FIGO

Question 17

What is a seminoma

Answer 17

seminoma: a type of germ cell tumour which arises in the seminiferous tubules of the testes. Seminoma usually spreads late via lymphatics to para-aortic retroperitoneal lymph nodes; chemotherapy to treat involved retroperitoneal nodes may be employed (if required).

Question 18

what is the main RF for development of CIN and cervical cancer

Answer 18

persistent high risk HV infection

Question 19

what are the main HPV subtypes that cause cervical cancer?

Answer 19

16 and 18

Question 20

how does HPV cause cancer

Answer 20

HPV viral DNA integrates into host cell DNA in the cervical squamous epithelium. The virus preferentially infects cells in the TZ since these cells are undergoing metaplasia and altered gene expression.
The viral E6 and E7 gene products interact with and inhibit tumour suppressor gene products, P53 and retinoblastoma protein (RB), respectively. These proteins are important for cell cycle control and apoptosis. Inactivation of these genes, which occurs with high risk HPV infection, can induce uncontrolled cell proliferation. High risk HPV infection is a prerequisite for cervical cancer but only a small proportion of HPV infections progress to either high grade CIN or cancer. Progression to malignancy requires one or more cofactors eg. smoking, immunosuppression etc.

Question 21

what happens at colposcopy?

Answer 21

At colposcopy, the cervix is exposed using a speculum. The colposcopist carefully examines the cervix using the colposcope, both before and after the application of acetic acid.
Certain abnormal colposcopic appearances are associated with CIN eg. acetowhite epithelium. However, CIN is a histological diagnosis and so a biopsy is required to confirm the diagnosis.

Question 22

How is CIN managed?

Answer 22

CIN 1 is usually managed by observation and regular follow up smears.

CIN 2 and 3 are usually managed by excision of the transformation zone with cutting diathermy under local anaesthesia – ‘large loop excision of the transformation zone’ (LLETZ). The specimen is sent to the laboratory to be carefully examined histologically by a pathologist.
Patients who have had a LLETZ for CIN are offered a repeat smear and high risk-HPV testing 6 months later.

Question 23

Other cancers caused by HPV

Answer 23

vervix
vaginal
vulval
anal 
penis
anus
oropharyngeal

Question 24

causes of unopposed oestrogen

Answer 24

• polycystic ovaries syndrome (a common cause in young women).
• obesity (peripheral aromatisation of androgens to oestrogens).
• tamoxifen therapy (tamoxifen is a selective oestrogen receptor modulator (SERM) - it is an antagonist in the breast and is used in the treatment of breast carcinoma, it is an agonist in the endometrium).
• anovulatory cycles in the perimenopause (falling numbers of follicles in the ovaries leads to a failure of ovulation. Anovulatory cycles do not produce a corpus luteum and so there is no progesterone to stimulate a switch from proliferative to secretory phase).
• unopposed oestrogen HRT (combined oestrogen-progesterone HRT and OCP are protective).

Question 25

Other cancers caused by HPV

Answer 25

vervix
vaginal
vulval
anal 
penis
anus
oropharyngeal

Question 26

what is endometrial hyperplasia?

Answer 26

an increase in the number of endometrial glands relative to the endometrial stroma ie. the glands become more closely packed. It results in a thickening of the endometrium, which can be seen at hysteroscopy or on imaging

Question 27

presentation of endometrial hyperplasia

Answer 27

Endometrial hyperplasia usually presents clinically as abnormal vaginal bleeding - intermenstrual, polymenorrhoea (unusually frequent periods) or postmenopausal.

Question 28

3 acute presentations of ovarian mass

Answer 28

ovarian torsion
rupture
haemorrhage

Question 29

RFs for developing ovarian carcinomas

Answer 29

number of ovulations

family history

Question 30

Ix for suspected ovarian cancer

Answer 30

CA125

US

Question 31

Compare and contrast ovarian and testicular tumours using teratoma, seminoma and carcinoma as examples

Answer 31

Ovary:

• benign tumours are common
• 5th most common cancer
• carcinoma is the most common type
• cancer has a bad prognosis

Testis

• benign tumours are rare
• testicular cancer is uncommon, but is the most common cancer in 15-49yo
• germ cell tumours are the most common type
• good prognosis

Question 32

2 types of testicular germ cell tumour

Answer 32

seminoma

non-seminomatous