Repro22 - Malignancy of the Reproductive Tract

Question 1

5 features of vulval cancer

Risk Factors x2
Type of Cancer
Clinical Presentation x3
Histological Features x3
Spread (3 types)

Answer 1

1. ) Risk Factors- uncommon (3% of all female cancers),
   - long standing inflammatory conditions (e.g. lichen sclerosus), has peak onset in the 80s (70% of cases)
   - HPV(16) has peak onset in the 60s (30% of cases
2. ) Type of Cancer - squamous cell carcinoma (90%) most common is the vulva is mainly skin
   - vulval intraepithelial neoplasia (VIN) is the in-situ (no invasion) precursor to squamous cell carcinoma
   - others: basal cell carcinoma, melanoma, soft tissue tumour

3.) Presentation - lumps, ulceration, skin changes

4. ) Histological Features - of SCC
   - atypical squamous cells, loss of architecture
   - keratin formation in squamous cell carcinomas
5. ) Spread - distant metastases spread to lungs and liver
   - direct extension: anus, vagina, bladder
   - lymph nodes: inguinal, iliac, para-aortic

Question 2

6 features of cervical cancer

Risk Factors x5
Effect of HPV
Cervical Intraepithelial Neoplasia (CIN)
Treatment
Screening
Vaccination

Answer 2

1. ) Risk Factors - increased risk of exposure to HPV:
   - multiple partners, early age of first intercourse
   - others: early first pregnancy, multiple births, smoking, immunosupression
2. ) Effect of HPV - infects the transformation zone
   - produces viral proteins (E6/E7) which inactivate TSGs (p53 and Rb) –> uncontrolled cellular proliferation
3. ) Cervical Intraepithelial Neoplasia (CIN) - in-situ precursor to invasive SCC caused by HPV infection
   - CIN1 –> CIN2 –> CIN3 –> SCC (invasive)
   - risk of progression increases as you move up stages
4. ) Treatment - depends on stage
   - CIN1: do nothing, often regresses spontaneously
   - CIN2/3: large loop excision of transformation zone
   - cervical cancer uses FIGO staging
5. ) Screening - brush used to scrape cells from transformation zone and are tested for HPV
   - 25-49 every 3 years, 50-64 is 5 years, >65s only if recent abnormality
6. ) Vaccination - HPV vaccine (Gardasil) against 4 main HPV subtypes (6, 11, 16, 18) given aged 12-13
   - protects from cervical, vulval, oral, anal cancers

Question 3

What is the transformation zone and why does it have increased risk of cancer?

What is it?
Pre-Menarche
Early Reproductive Age
Ectropian
Squamous Metaplasia

Answer 3

1. ) What is it? - lining of the ectocervix
2. ) Pre-Menarche - it is squamous epithelium to provide resistance to acidic environment in vagina
3. ) Early Reproductive Age - oestrogen causes simple columnar in endocervix to grow out into ectocervix
4. ) Ectropian - columnar epithelium exposed to acidic environment leads to inflammation
5. ) Squamous Metaplasia - simple columnar –> squamous epithelium for protection against pH
   - metaplasia increases the risk of dysplasia

Question 4

3 features of invasive cervical cancer

Type of Cancer
Clinical Presentation
Treatment

Answer 4

1. ) Type of Cancer - mainly squamous cell carcinoma/CIN
   - less commonly, adenocarcinomas from endocervical glandular cells
2. ) Presentation - bleeding, mass, screening
   - bleeding: post-coital, intermenstrual, post menopausal

3.) Treatment - if advanced: hysterectomy (remove uterus) lymph node dissection +/- chemotherapy

Question 5

4 features of endometrial cancer

Epidemiology/Risk Factors x2
Endometrial Hyperplasia
Clinical Presentation x2
Treatment

Answer 5

1. ) Epidemiology/Risk Factors
   - most common gyanaecological tract cancer
   - peak onset in post-menopausal women (mid 60s)
2. ) Endometrial Hyperplasia - thickened endometrium >11mm, caused by excessive oestrogen
   - can be a precursor to endometrial cancer
3. ) Clinical Presentation - bleeding, mass
   - inter-menstrual or post-menopausal
4. ) Treatment - surgical +/- chemotherapy
   - hysterectomy, lymph node dissection, bilateral salpingo-oophorectomy (fallopian tubes and ovaries)

Question 6

3 groups of causes of endometrial hyperplasia

Endogenous x3
Exogenous x2
Irregular Cycle x1

Answer 6

1. ) Endogenous - oestrogen production within the body
   - obesity: adipocytes convert androgens –> oestrogen
   - long exposure: early menarche/late menopause
   - tumour: e.g. sex cord stromal ovarian cancers
2. ) Exogenous - outside the body
   - unopposed oestrogen hormone replacement therapy
   - tamoxifen (breast cancer medication)

3.) Irregular Cycle - polycystic ovarian syndrome (PCOS)

Question 7

2 types of endometrial cancer

Endometrioid Adenocarcinoma
Serous Adenocarcinoma

Answer 7

1. ) Endometriod Adenocarcinoma - more common
   - well differentiated: resembles endometrial glands
   - commonly arises from endometrial hyperplasia
   - can spread to the bladder, bowel and other organs
2. ) Serous Adenocarcinoma - more aggressive
   - poorly differentiated cells
   - transcoelomic spread: exfoliates and travels through fallopian tubes to deposit on peritoneal surface
   - associated w/ calcium collections (Psammoma bodies)

Question 8

3 features of myometrial cancer

Leiomyoma
Clinical Presentation
Leiomyosarcoma

Answer 8

1. ) Leiomyoma (fibroid) - benign tumour of SM
   - pale, homogenous, well circumscribed mass
   - whorled, intersecting fasicles of benign SMCs
2. ) Clinical Presentation - pelvic pain, heavy periods, polyuria (bladder compression)
   - can be asymptomatic if really small
3. ) Leimyosarcoma - malignant tumour of smooth muscle
   - atypical cells, and can metastasise to the lungs
   - DOES NOT arise from a leiomyoma

Question 9

4 features of ovarian cancer

Types of Ovarian Cancer
Metastases to Ovaries
Clinical Presentation
Treatment/Management

Answer 9

1. ) Types of Ovarian Cancer - depends on the cell type
   - epithelial, germ cell, sex cord stromal
   - also a site for metastatic spread
   - no of ovulations (no pregnancy or pill) is a risk factor for epithelial since there is more epithelial turnover
2. ) Metastases to Ovaries - breast, endometrial, fallopian tube, other ovary
   - GI: krukenberg tumour (often gastric adeno…) with mucin secreting signet cells in the ovaries
3. ) Clinical Presentation - often delayed diagnosis since the early symptoms are vague and non-specific
   - later symptoms arise due to the physical mass:
   - abdominal pain/distension, urinary and GI symptoms, hormonal disturbances
4. ) Managment - tumour marker(Ca-125) and screening
   - screening for BRCA1/2 TSG mutation which are associated w/ high grade serous cancers
   - prophylactic salpingo-oopherectomy can be done

Question 10

3 types of ovarian epithelial tumours

Ovarian Serous Adenocarcinoma
Ovarian Mucinous Adenocarcinoma
Ovarian Endometriod Adenocarcinoma

Answer 10

1. ) Ovarian Serous Adenocarcinoma - very atypical cells
   - associated w/ calcium deposits (Psammoma bodies)
   - often spreads to peritoneal surface
2. ) Ovarian Mucinous Adenocarcinoma - atypical epithelial cells which secrete mucin
   - white, round deposits in glands
3. ) Ovarian Endometriod Adenocarcinoma - glands resembling endometrium in the ovaries
   - may arise in endometriosis
   - can occur w/ endometrial endometrioid adeno…

Question 11

4 features of ovarian germ cell tumours

3 types of teratomas
Other germ cell tumours x4

Answer 11

1. ) Mature (benign) Teratoma - contains fully mature, differentiated tissue from all germ cell layers
   - can contain teeth, skin, hair, cartilage etc.
   - called dermoid cysts due to the skin + hair structures
2. ) Immature (malignant) Teratoma - contains immature, not fully differentiated embryonal tissue
3. ) Monodermal Teratoma - highly specialised, contains only one tissue type, often thyroid
4. ) Other Germ Cell Tumours - all malignant
   - choriocarcinoma, embryonal carcinoma, yolk sac tumour, dysgerminoma (= seminoma in testis)

Question 12

2 forms of ovarian sex cord stromal tumours

Testes
Ovaries

Answer 12

1. ) Ovaries - granulosa cells and theca cells
   - can produce oestrogen –> precocious puberty
   - oestrogen can also cause breast cancer, endometrial hyperplasia/carcinoma
2. ) Testes - sertoli-leydig tumours
   - produce testosterone which can prevent normal female pubertal changes in patients pre-puberty
   - in post-pubertal patients, can cause sterility, hirsutism, amenorrhoea, male pattern baldness, breast atrophy

Question 13

Testicular Cancer

Risk Factors
Clinical Features
Investigations
Management

Answer 13

1. ) Risk Factors
   - cryptorchidism (4-10x), previous malignancy, FH
   - Kleinfelter’s syndrome
   - demographic: 20-40yrs, caucasaian, north european
2. ) Clinical Features
   - unilateral painless testicular lump/mass
   - mass is irregular, firm, fixed, does not transilluminate
   - evidence of mets: weight loss, back pain, SOB
3. ) Investigations
   - tumour markers: PLAP, ß-hCG, AFP, LDH
   - scrotal USS, staging CT w/ contrast
   - biopsy not performed to prevent seeding of cancer
4. ) Management - depends on tumour subtype, disease stage, and risk scoring
   - surgery, radiotherapy, chemotherapy
   - surgery: inguinal radical orchidectomy
   - semen analysis and cryopreservation offered

Question 14

Types of Testicular Tumours

Broad Classsifications
Seminomatous (inc tumour markers)
Non-Seminomatous (inc tumour markers)
Sex-Cord Stromal
Other

Answer 14

Classifications- germ cell (95%) vs non-germ cell

• germ cell: seminomatous or non-seminomatous
• non germ cell: sex cord stromal or other

1. ) Seminomatous (SGCT)
   - good prognosis, remain localised until quite late
   - tumour markers: placental alkaline phosphatase (PLAP), ß-hCG (only 15%), LDH (non-specific)
2. ) Non-Seminomatous (NSGCT)
   - worse prognosis, metastasise early
   - yolk sac tumours + teratomas: AFP
   - choriocarcinoma (ß-hCG), embryonal carcinoma
   - tumour markers: AFP, ß-hCG, LDH (non-specific)
3. ) Sex-Cord Stromal - usually benign
   - leydig cell tumours, sertoli cell tumours
   - secretes androgens and oestrogens respectively

4.) Other - lymphoma (older men), mets (very rare)