Gynaecological Malignancies

Question 1

What kind of epithelium is found in the cervix?

Answer 1

• Has 2 types:
  
  • Vaginal portion has stratified squamous cells.
  • Supravaginal part contains columnar cells.
  • Where they meet is the squamo-columnar junction.

Question 2

Describe squamous metaplasia in the cervix.

Answer 2

Refers (in the cervix) to the physiological replacement of the everted columnar epithelium on the ectocervix with newly formed squamous epithelium from the columnar reserve cells. Where this occurs is called the transformation zone and this is where most cancers will arise.

Question 3

Which virus is implicated in cervical cancer? Describe.

Answer 3

• Almost all squamous cervical cancers are caused by HPV.
• HPV is a family of viruses with >100 subtypes, ~80 of which are associated with the development of cervical cancer.
• ~80% of adults have ben exposed to HOV during their lifetime, but 90% of people clear the virus within 2 years of exposure.
• ~70% of cervical cancers are caused by HPV 16 & 18.
• Incidence of cervical cancer is falling due to vaccination against HPV.

Question 4

How are abnormal cells classified and graded in the cervix?

Answer 4

• Abnormal cells = CIN (cervical intraepithelial neoplasia) – this is graded 1-3.
• The number shows how deep the cell changes go into the outer surface of the cervix.
• CIN1 – 1/3 of the thickness of outer cervix is affected. Highly unlikely that these cell changes will develop into cervical cancer; they will likely go back to normal by themselves. CIN1 is not treated but patients are invited back for cervical screening after 12 months instead of the usual 5 years.
• CIN2 – 2/3 of thickness of outer surface is affected. Higher chance that these cells will develop into cervical cancer (this risk is ~5%). Dependent on situation whether treatment or just monitoring every 6 months until cell changes have gone.
• CIN3 – highest grade; full thickness of outer surface of the cervix is affected. If not treated, more likely these cell changes will develop into cancer (~12%). Treatment is offered.

Question 5

What are the risk factors for development of cervical cancer?

Answer 5

• Risk factors can be split into 3 groups.

1. Risk factors for those who do not attend screening
   
   • Socioeconomic class
   • Geographical location
2. Risk factors for those who have increased exposure to HPV
   
   • Those with +++ sexual partners
   • Those who are sexually active at a young age
3. Risk factors which affect the immune system
   
   • Smokers
   • Immune deficiencies / diseases

Question 6

What are the symptoms of cervical cancer?

Answer 6

• Intermenstrual bleeding
• Postmenopausal bleeding
• Abnormal discharge
• Dyspareunia

Question 7

How should ?cervical CA be investigated?

And what should you consider if cervical cancer is confirmed?

Answer 7

• EXAMINE THE PATIENT PROPERLY.
• On speculum examination you might see distorted cervix or a growth.
• On bimanual, you may find a pelvic mass.
• If you suspect cervical cancer, refer to colposcopy. They can biopsy.
• If cervical cancer is confirmed, consider CT chest, abdo and pelvis to look for metastatic disease.

Question 8

How is cervical cancer staged?

Answer 8

• 80% of cervical cancers are squamous cell carcinoma.
• 20% are adenocarcinoma.
• Stage 1a – cancer involves the cervix but has not spread to nearby tissue and a very small amount of cancer only visible under a microscope is found deeper in the tissues of cervix.
• Stage 1b – cancer involves the cervix but has not spread nearby.
• Stage 2a – Spread into nearby areas, but still inside the pelvic area. Beyond cervix into upper 2/3 of vagina.
• Stage 2b – cancer has spread to nearby areas – tissue around the cervix.
• Stage 3 – cancer has spread throughout pelvic area. Lower part of vagina or ureters can be involved.
• Stage 4a – cancer has spread to other areas such as bladder or rectum.
• Stage 4b – distant metastasis (lungs etc.).

Question 9

Describe the management of cervical cancer.

Answer 9

• Depends on grade and stage and age of patient. Whether or not you are trying to preserve fertility also has an impact on how you manage.
• Trachelectomy is the removal of the cervix and the upper part of the vagina. This is an option if disease is less widespread and patient wants option of future pregnancy.
• If disease is more widespread hysterectomy is an option. If it is even more widespread, may consider pelvic excenteration.
  
  • Pelvic exenteration (or pelvic evisceration) is a radical surgical treatment that removes all organs from a person’s pelvic cavity. The urinary bladder, urethra, rectum, and anus are removed. The procedure leaves the person with a permanent colostomy and urinary diversion.
• Neoadjuvant chemotherapy or radiotherapy may be offered depending.

Question 10

What is the prognosis for patients with cervical cancer?

Answer 10

• Stage 1a – 5 year survival is 99%.
• Stage 1b – 5 year survival is 90-95%.
• Stage 2a - 5 year survival is 70-90%.
• Stage 2b - 5 year survival is 60-70%.
• Stage 3 - 5 year survival is 30-50%.
• Stage 4 - 5 year survival is 20%.

Question 11

What is the most common gynaecological cancer in the UK?

Answer 11

Endometrial cancer

Question 12

What are the layers of the uterus?

What is the blood supply to the uterus?

Answer 12

• Endometrium (split in 2)
  
  • Functional layer (shed during menstruation)
  • Basal layer
• Myometrium
• Perimetrium
• Blood supply to uterus is from uterine artery which is a branch of internal iliac.

Question 13

Describe the endometrial cycle.

Answer 13

• Proliferative phase is fuelled by oestrogen (which is secreted by the ovary). At the start of proliferative phase there is proliferation of the stroma and the glands. Moving through the proliferative phase, the glands become large and dilated and their vessels become more prominent.
• Secretory phase – driven by progesterone. Progesterone acts to induce secretory changes in the glands and the blood supply increases further. Nearer the end of the cycle the stroma becomes more vascular and oedematous. As the level of progesterone drops near the end of the cycle, the endometrium breaks down and menstruation occurs. This is in response to the drop in progesterone.

Question 14

What are the 2 types of endometrial cancer?

And what are their subtypes?

Answer 14

• 80% of endometrial cancers are adenocarcinomas.
• Within this, there are 2 subdivisions:
  
  • Type 1 - endometroid cancers. These are very much linked to excess oestrogen. They tend to be slow growing and are less likely to spread.
    
    • Grade I
    • Grade II
    • Grade III
  • Type 2 - non-endometroid cancers (~10% of endometrial cancers). These are not linked by the same extent to excess oestrogen. They are faster growing and much more likely to spread.
    
    • Serous
    • Clear cell
    • Carcinosarcoma

Question 15

What are the risk factors for endometrial cancer?

Answer 15

• Most endometrial cancers are linked to excess oestrogen so many risk factors are associated with this.
• Nulliparity - have had more ovulatory cycles, so oestrogen exposure is greater.
• Late menopause for the same reason.
• Obesity - fat produces oestrogen. Endometrial cancer is strongly linked to obesity.
• PCOS
• Use of tamoxifen
• Genetics - Lynch syndrome (autosomal dominant condition associated with bowel, ovarian and endometrial cancer). Lifetime risk in these patients of endometrial CA between 30 and 60%.

Question 16

What are the protective factors for endometrial cancer?

Answer 16

• Tobacco smoking
• COCP - the longer it is taken the greater the benefit. This outlasts when you stop taking the pill.
• Use of progestogens - progesterone-releasing IUS (Mirena).

Question 17

How does endometrial cancer present?

Answer 17

• 90% of patients with endometrial cancer present with post-menopausal bleeding.
  
  • However, only 10% of patients with post-menopausal bleeding actually have endometrial cancer; it is a common presentation.
• In pre-menopausal women - intermenstrual bleeding or heavy menstrual bleeding.
• Often there are no other symptoms unless it has metastasised or is very advanced disease.

Question 18

How should ?endometrial cancer be investigated?

Answer 18

• First step after thorough history and proper examination is TVUSS.
  
  • This examines endometrial thickness. Endometrium should be thin in post-menopausal women.
  • If thickness >5mm, this is concerning - this reflects 10% risk of cancer.
• If endometrium is thickened, need tissue sample. Usually done using Pipelle biopsy. Some cramping but usually well tolerated.
• The other way to get tissue biopsy is through hysteroscopy.
• Other investigations:
  
  • Consider FBC (anaemia - blood loss).
  • LFTs - metastasis.
  • CT / MRI to look at node involvement and consider any spread.

Question 19

Describe the staging of endometrial cancer.

Answer 19

• Stage 1 – carcinoma which is confined to the corpus uteri (body of the uterus).
• 1a – In the endometrium and less than ½ of the myometrium is invaded.
• 1b – the same as 1a only more than ½ of the myometrium is invaded.
• 2 – there is invasion into the cervical stroma.
• 3 – local or regional spread beyond the uterus.
• 4 – involvement of the bladder, bowel mucosa or distant metastases. This is much more serious.

Question 20

Describe how endometrial cancer is managed.

Answer 20

• Surgical management is the mainstay of treatment.
• In stage 1 the management is usually total abdominal hysterectomy and bilateral salpingo-oophorectomy.
• In stage 2 the management is usually exploratory laparotomy and surgical staging. Often it is taken further; radical hysterectomy and often dissect the nodes bilaterally (pelvic nodes) and consider para-aortic lymph node clearance. Also get pelvic and peritoneal washings for cytology. May even take some omentum if concerned about spread to here.
• With increasing frequency, the hysterectomys are being done laparascopically.
• Also medical therapies – radiotherapy is often given post-operatively in later stages of this cancer.
• Radiotherapy also used if there is recurrence.
  
  • May be primary treatment in patients who are too frail and unsuitable for major surgery.
• Chemotherapy is reserved for stage 3 or 4 disease.
  
  • Response rate to chemo in endometrial cancer is relatively poor.
• There are new hormonal therapies starting to be used also.

Question 21

What is the prognosis for patients who have been diagnosed with endometrial cancer?

Answer 21

• Stage 1 – 95% 5 year survival.
• Stage 2 – 70% 5 year survival.
• Stage 3 – 40% 5 year survival.
• Stage 4 - 15% 5 year survival.

Question 22

Which gynae cancer causes the highest death rate in the UK?

Answer 22

Ovarian cancer

Question 23

Where does lymph from the ovaries drain?

Answer 23

Para-aortic nodes

Question 24

Describe the 3 parts of the ovary.

Answer 24

• Ovary has 3 components:
  
  • Surface layer (formed of simple cuboidal epithelium (germinal epithelium).
  • Cortex is outer part, largely comprised of connective tissue stroma and supports thousands of follicles. Each primordial follicle contains an oocyte, which is surrounded by a single layer of follicular cells.
  • Medulla is inner part comprised of supporting stroma which contains rich neurovascular network which enters the hilum of the ovary through the meso-ovarium.

Question 25

Describe the different types of ovarian cancer.

Answer 25

• Epithelial cancer, accounting for 90% of malignant ovarian cancers.
  
  • Serous
  • Mucinous
  • Endometriud
  • Clear cell
  • Brenner
• Germ cell cancer starts from germ cells (cells that are designed to form eggs) within the ovaries.
  
  • Most common in younger women (particularly <35) and have high survival rate. Often curable.
  • Usually present with rapidly-enlarging abdominal mass causing considerable pain or they rupture or undergo torsion (which means they are found at an earlier stage than, say, epithelial tumours).
    
    • Teratoma
    • Dysgerminoma
    • Yolk sac tumour
    • Choriocarcinoma
• Stromal cell cancer begins in the cells that hold the ovaries together and produce female hormones.
• Account for <5% of all ovarian tumours.
  
  • Granulosa / theca cell tumours
  • Fibroma
  • Androblastoma
  • Gonadoblastoma

Question 26

What are the risk factors for the development of ovarian cancer?

Answer 26

• Age is the main risk factor. 1/2 of all women diagnosed with ovarian cancer are >65.
  
  • ALTHOUGH - can also present in the young; each year ~1000 cases of ovarian cancer in women <50.
• FHx is important. Although ~80% of ovarian cancers are sporadic, ~20% are genetic (BRCA gene).
• Obesity
• Smoking
• HRT
• Endometriosis is a risk factor but this link is poorly understood.

Question 27

What are the protective factors for ovarian cancer?

Answer 27

• COCP reduces the chance of ovarian cancer by ~50% if taken for 10 years or more.

Question 28

Describe how ovarian cancer presents.

Answer 28

• Can be insidious. 58% of patients present with advanced disease.
• Can present with:
  
  • Persistent bloating
  • Abdominal pain
  • Increased urinary frequency
  • Fatigue
  • Weight loss
  • Loss of appetite

Question 29

When and how should women who present with ?ovarian CA be investigated?

Answer 29

• If women present in GP with ≥1 symptoms of abdominal distension / bloating, feeling full quickly, difficulty eating or urinary symptoms of <12 months duration but occurring more than 12x/month, diagnosis of ovarian cancer should be considered.
• If considering ovarian cancer as a diagnosis, you should do CA125.
  
  • CA125 is a tumour marker. It can be raised due to many things so is not specific. If CA125 is >35, should arrange pelvic and abdo USS.

Question 30

What is RMI? How is it calculated?

Answer 30

• RMI = risk of malignancy index.
• Ultrasound score x menopause score x CA125.
• Ultrasound score is made up using the findings of the scan.
  • If no abnormalities score = 0.
  • If there is 1 abnormality = 1.
  • If 2 or more score =3.
• Menopause score:
  
  • 1 point if pre-menopausal.
  • 3 points if post-menopausal.
• If RMI>250, urgent referral to gynae oncology for review.
• Also, a woman <40 consider about other tumour markers:
  
  • Alpha fetoprotein
  • Beta HCG
  • These are more likely to be raised in germ cell tumours which younger people are more likely to have.
• Consider CT chest, abdo and pelvis for mets.

Question 31

Describe the staging of ovarian cancer.

Answer 31

Question 32

Describe the management of ovarian cancer.

Answer 32

• If epithelial ovarian cancer is suspected (very much based on clinical suspicion and imaging), it is usual to proceed to surgery straight away. Usually to have total abdominal hysterectomy and BSO. This is in order to obtain histological confirmation to do a proper staging and do tumour debulking.
• Treatment depends on stage and grade of cancer.
• Chemotherapy may be offered; we know this can work well in some ovarian cancers.
• There may be a need for further surgery (removing more pelvic organs).

Question 33

What is the prognosis for patients with ovarian cancer?

Answer 33