Gynaecological Tumours Flashcards
Where can gynaecological tumours arise?
Vulva Cervix Endometrium Myometrium Ovary
What is the transformation zone?
Where the endothelium of the cervix undergoes metaplasia from glandular to squamous epithelium
How does the transformation zone differ between older and younger women?
In younger women, the transformation zone is further out into the ectocervix
What are almost all cases of CIN and cervical carcinoma related to?
High risk HPVs
What are HPVs?
DNA viruses
How many types of high risk HPVs are known?
15
What are the most important HPVs in the pathogenesis of cervical carcinoma?
16 and 18
What % of cases of HPV are related to HPV 16?
60%
What % of cases of cervical carcinoma are related to HPV 18?
10%
How does HPV lead to the development of CIN or cervical carcinoma?
Infect immature metaplastic squamous cells in the transformation zone
What is the result of HPV infecting the immature metaplastic squamous cells in the transformation zone?
More common in younger women, as they have more transformation zone available to infect, therefore easier to catch
How does infection with HPV cause CIN?
They produce viral proteins E6 and E7
What do viral proteins E6 and E7 do?
Interfere with the activity of tumour suppressor proteins (p53 and RB) to cause inability to repair damaged DNA and increased proliferation of cells
Activate telomerase to cause cell immortality
What is true of most genital HPV infections?
They are transient and eliminated by the immune response in months
What do the risk factors for CIN and cervical carcinoma relate to?
Mostly related to HPV infection
What are the risk factors for CIN and cervical carcinoma?
Sexual intercourse Early first marriage Early first pregnancy Multiple births Many partners Promiscuous partner Long term use of OCP Partner with carcinoma of the penis Low socio-economic class Smoking Immunosuppression
Describe the prevalence of cervical cancer worldwide?
It is the third most common cancer in women
What has caused the rate of cervical cancer to decrease significantly?
Introduction of screening
What makes cervical cancer a good condition for screening?
Cervix accessible to visual examination
Slow progression from precursor lesions to invasive cancers
Pap test detects precursor lesions and low stage cancers
Allows early diagnosis and curative therapy
How can the cervix be accessed for visual examination?
Colposcopy
How long does the progression from precursor lesions to invasive cancers take?
Years
What does cervical screening involve?
Cells from the transformation zone are scraped off, stained with Pap stain, and examined microscopically
Other than Pap staining, how can cervical screens be interpreted?
Test for HPV DNA in cervical cells - molecular method of screening
How is testing for HPV DNA in cervical cells often used?
To make a judgement when cells are mildly atypical
When do people undergo cervical screening?
Starts at age 25
Every 3 years until age 50
Every 5 years 50-65
What happens if abnormalities are found on cervical screening?
Sent for colposcopy and biopsy
What HPV vaccine is used in the UK?
Gardasil
Who is vaccinated against HPV in the UK?
Girls aged 12-13 years
When was the HPV vaccination programme introduced?
2008
How long does the HPV vaccination protect for?
Up to 10 years
What cancers does the HPV vaccination protect against?
Cervical Vulval and vaginal Genital warts Oral cancers Anal cancers
Is screening still required following the HPV vaccine?
Yes, because it doesn’t protect against all high risk types
What is the controversy surrounding HPV vaccination?
Boys arent vaccinated
Why is it controversial that boys arent vaccinated against HPV?
Could protect against penile cancer
Can be paid for privately
What is cervical intraepithelial neoplasia?
Dysplasia of squamous cells within the cervical epithelium
What is cervical intraepithelial neoplasia induced by?
Infection with high risk HPVs
What are the types of cervical intraepithelial neoplasia?
CIN I
CIN II
CIN III
What is the prognosis of CIN?
Most regress spontaneously, only a small percentage progresses to CIN II
What is the prognosis of CIN II?
A proportion of cases progress to CIN III
What is the prognosis of CIN III?
10% progress to invasive carcinoma in 2-10 years
30% regresses
How long does the transition from CIN I to CIN III take?
Approx 7 years
What is the treatment for CIN I?
Follow up, often biopsy
Cryotherapy
What is the treatment for CIN II and III?
Superficial excision (cone, large loop excision of transformation zone)
What does superficial excision in CIN II and III usually include?
External os, transformation zone, some ectoderm
What is the average age of onset of invasive cervical carcinoma?
45 years
Why does invasive cervical carcinoma have a later age of onset?
Takes longer to develop
What % of invasive cervical carcinomas are squamous cell carcinomas?
80%
What % of invasive cervical carcinomas are adenocarcinomas?
15%
Where are adenocarcinomas of the cervix found?
Higher in the transformation zone or endocervical canal
What are the types of invasive cervical carcinoma?
Exophytic or infiltrative
How does invasive cervical carcinoma spread?
Locally
Lymph nodes
Distally
How does invasive cervical carcinoma spread locally?
Para-cervical soft tissues Bladder Ureters Rectum Vagina
What lymph nodes does invasive cervical carcinoma spread to?
Para-cervical
Pelvic
Para-aortic
How does cervical carcinoma present?
Screening abnormality
Postcoital, intermenstural, or postmenopausal vaginal bleeding
How are microinvasive cervical carcinomas treated?
Cervical cone excision
What is the 5 year survival of microinvasive cervical carcinomas?
100%
How are invasive cervical carcinomas treated?
Hysterectomy
Lymph node dissection
If advanced, radiation and chemotherapy
What is the 10 year survival of invasive cervical carcinomas?
62%
What is the endometrium?
The lining of the cavity of the uterus
How does endometrium appear histologically?
Glands with cellular stroma
What is endometrial hyperplasia a frequent precursor to?
Endometrial carcinoma
What are the histological features of endometrial hyperplasia?
Increased gland to stroma ratio
What is endometrial hyperplasia associated with?
Prolonged oestrogenic stimulation
What can cause prolonged oestrogenic stimulation?
Anovulation
Increased oestrogen from endogenous sources
Exogenous sources
When is anovulation common?
Around the time of the menopause
Where may oestrogen come from endogenously?
Adipose tissue
What is the result of oestrogen coming from adipose tissue?
Endometrial hyperplasia is more common in obese women
Why does endometrial hyperplasia cause endometrial carcinoma?
Because increased cell turnover, so damage to DNA, so increased risk of cancer
How is endometrial hyperplasia treated?
Hysterectomy, if complex and atypical
What is the most common invasive cancer of the female genital tract?
Endometrial adenocarcinoma
What is the usual age of endometrial adenocarcinoma?
55-75 years
Unusual before 40
What is the usual presentation of endometrial adenocarcinoma?
Irregular or postmenopausal vaginal bleeding
What is the prognosis of endometrial adenocarcinoma?
Early detection and cure possible, so overall 75% 10 year survival
What are the potential appearances of endometrial adenocarcinoma?
Polypoid
Infiltrative
What is the most common type of endometrial adenocarcinoma?
More common
What is the less common type of endometrial adenocarcinoma?
Serous carcinoma
How does endometrioid endometrial adenocarcinoma appear histologically
Mimics proliferative glands
In what setting does endometrioid endometrial adenocancer typically arise?
In the setting of endometrial hyperplasia
What is endometrioid endometrial adenocarcinoma associated with?
Unopposed oestrogen
Obesity
Where does endometrioid endometrial adenocarcinoma spread?
Adjacent structures
To local lymph nodes
To distant sites
How does endometrioid endometrial adenocarcinoma spread to adjacent structures?
Myometrial invasion
Direct extension
How does serous endometrial adenocarcinoma differ from endometrioid?
Poorly differentiated
Aggressive
Worse prognosis
How does serous endometrial adenocarcinoma spread?
Exfoliates, travels through Fallopian tubes, implants on peritoneal surfaces
What is the most common tumour of the myometrium?
Leiomyoma (fibroid)
What is a fibroid?
A benign tumour of the myometrium
How many fibroids does a woman typically have?
Often multiple
What size are fibroids?
Range from tiny to massive, filling the pelvis
What are the symptoms of fibroids?
May be asymptomatic, or can cause heavy/painful periods, urinary frequency (bladder compression), infertility
Does malignant transformation occur with fibroids?
No
What does a uterine fibroid look like?
Well circumscribed, round, firm, and whitish in colour
What do fibroids look like histologically?
Bundles of smooth muscle that resembles normal myometrium
What is a uterine leiomyosarcoma?
An uncommon malignant tumour of the myometrium
What is the peak incidence of uterine leiomyosarcoma?
40-60 years
What is the prognosis of uterine leiomyosarcoma?
Highly malignant, and metastasises to lungs
What % of ovarian tumours are benign?
Approx 80%
When do benign ovarian tumours generally occur?
20-45 years (child bearing age)
When do malignant ovarian tumours generally occur?
45-65 years
What % of cancers in women are ovarian cancers?
3%
What is the prognosis for malignant ovarian cancers?
Poor, because many have often spread beyond the ovary by the time of presentation
Are ovarian tumours unilateral or bilateral?
Many are bilateral (benign and malignant)
What is the 1 year survival from ovarian cancer?
70%
What is the 5 year survival from ovarian cancer?
41%
What is the 10 year survival from ovarian cancer?
38%
How do ovarian tumours present?
Mass effects
Hormonal problems
What is the result of most ovarian tumours being non functional, on the presentation?
They only produce symptoms when they become large, invade adjacent structures, or metastasise
What are the mass effects of ovarian tumours?
Abdominal pain
Abdominal distention
Urinary gastrointestinal symptoms
Ascites
What hormonal problems can ovarian tumours present with?
Menstrual disturbances
Inappropriate sex hormones
What % of malignant ovarian tumorus spread to the other ovary?
50%
Where do ovarian tumours spread to?
Regional nodes and elsewhere, e.g. Liver and lungs
What is the cancer marker for ovarian tumours?
CA-125
How is CA-125 used in ovarian cancer?
In diagnosis
Monitor disease recurrence and progression
What mutation are some ovarian cancers associated with?
BRCA
How can carriers of the BRCA mutation be treated?
Prophylactic salpinog-oophrectomy
What are ovarian tumours classified on the basis of?
The tissue from which they have arisen
What are the potential classifications of ovarian tumours?
Mullieran epithelium (including endometriosis)
Germ cells
Sex cord-stromal cells (from endocrine apparatus of the ovary)
Metatases
What are the three main histological types of ovarian Mullerian epithelial tumours?
Serous
Mucinous
Endometrioid
How can all the histological types of ovarian epithelial tumours be classified?
Benign
Borderline
Malignant
What is true of many ovarian epithelial tumours?
Many are cystic
What are the risk factors for ovarian epithelial tumours?
Nulliparity or low parity
Heritable mutations, e.g. BRCA1 and BRCA2
Smoking
Endometriosis within the ovary
Why does nulliparity or low parity increase the risk of ovarian epithelial tumours?
With every ovulation, there is a break in the ovary and healing, which predisposes the cell to cancer due to division and repair of cells
What is protective against ovarian epithelial tumours?
OCP
What are serous ovarian tumours commonly associated with?
Ascites
Why are serous ovarian tumours often associated with ascites?
Because they often spread to peritoneal surfaces and omentum
What are mucinous ovarian tumours?
Often large, cystic masses filled with sticky, thick fluid
Are mucinous ovarian tumours benign or malignant?
Usually benign or borderline
What happens in pseudomyxoma peritonei?
Extensive mucinous ascites, with epithelial implants on peritoneal surfaces, and frequent involvement of the ovarise
What can pseudomyxoma peritonei cause?
Intestinal obstruction
What is the most likely primary in pseudomyxoma peritonei?
Extra-ovarian, usually appendix
How do endometrioid ovarian tumours appear histologically?
Tubular glands resembling endometrial glands
What % of endometrioid ovarian tumours arise in endometriosis?
15-20%
What % of endometrioid ovarian tumours have associated endometrial endometrioid adenocarcinoma?
15-30%
What % of ovarian neoplasms are germ cell ovarian tumours?
15-20%
Give two types of germ cell ovarian tumours?
Teratomas
Non-gestational choriocarcinoma
What does a non-gestational choriocarcinoma do?
Produces human chorionic gonadotrophin
How is non-gestational choriocarcinoma unlike the gestational type?
They are aggressive and often fatal
What are the groups of ovarian teratomas?
Mature (benign)
Immature (malignant)
Monodermal
What is the most common type of ovarian teratoma?
Mature
What are immature ovarian teratomas composed of?
Tissues that resemble immature foetal tissue
What does a monodermal ovarian carcinoma produce?
One kind of highly specialised tissue
What are mature ovarian teratomas also known as?
Dermoid cysts
Why are mature ovarian teratomas also known as dermoid cysts?
As they almost always contain skin-like structures
Who do ovarian mature teratomas usually occur in?
Young women - in their 20s
What % of ovarian mature teratomas are bilateral?
10-15%
What do ovarian mature teratomas usually contain?
Hair and sebaceous material, can contain tooth structures
Often tissues from other germ layers - cartilage, bone, thyroid, neural tissue
What is the most common type of monodermal ovarian teratomas?
Struma ovarii
Are struma ovarii benign or malignant?
Benign
What are struma ovarii composed of?
Entirely of mature thyroid tissue
How do struma ovarii present?
May be functional and cause hyperthyroidism
What are ovarian sex cord stromal tumorus derived from?
Ovarian stroma, which is derived from sex cords of embryonic gonad
What does the sex cord produce?
Sertoli and Leydig cells in testes
Granulosa and theca cells in ovaries
What kind of cells can be present in ovarian sex cord-stromal tumours?
Any of those produced by sex cord
What effect can ovarian sex cord stromal tumours have?
They can be feminising (granulosa/theca cell tumours) or masculinising (Leydig cell tumours)
Who do many granulosa cell tumours occur in?
Post-menopausal women
What may granulosa cells tumours produce?
Large amounts of oestrogen
What is the result of the granulosa cell tumours producing a large amount of oestrogen?
In pre-pubertal girls, may produce precocious puberty
In adult women, may be associated with endometrial hyperplasia, endometrial carcinoma, and breast disease
When is the peak incidence of ovarian sertoli-leydig cell tumours?
Teens/twenties
What do ovarian Sertoli-Leydig cell tumours cause in children?
May block normal female sexual development
What do ovarian Sertoli-Leydig cell tumours cause in women?
Can cause defeminisation and masculinisation;
- Breast atrophy
- Amennorrhea
- Sterility
- Hair loss
- Hisuitism with male hair distribution
- Clitoral hypertrophy
- Voice changes
What is the most common type of tumour that metastasises to the ovaries?
Mullerian tumours
Where do Mullerian metastases to the ovaries come from?
Uterus
Fallopian tubes
Contralateral ovary
Pelvic peritoneum
Other than Mullerian tumours, what other primary sites may metastasise to ovaries?
Gastrointestinal tumours - colon, stomach, biliary tract, pancreas, appendix
Breast
What is a Krukenberg tumour?
A metastatic gastrointestinal tumour within the ovaries
Where is the primary of a Krukenberg tumour?
Usually from stomach
How common are vulval tumours?
Uncommon
What proportion of vulval tumours occur in women over 60 years of age?
Approx 2/3
What kind of cancers are vulval tumours?
Usually squamous cell carcinoma
What % of vulval squamous neoplastic lesions are related to HPV infection?
Approx 30%
What is the peak age for vulval squamous carcinomas related to HPV infections?
6th decade
What are the risk factors for vulval squamous cell carcinomas related to HPV infections?
Same as for cervical carcinoma
What is the peak age for vulval squamous ell carcinomas unrelated to HPV infection?
8th decade
When do vulval squamous cell carcinomas unrelated to HPV often occur?
In longstanding inflammatory and hyperplastic conditions of the vulva, e.g. lichen sclerosis
What is VIN (vulvar intraepithelial neoplasia)?
Atypical squamous cells within the epidermis (no invasion)
What is VIN a precursor to?
Vulval squamous cell carcinoma
Where does vulval squamous cell carcinoma spread to?
Initially to nodes
Lungs
Liver
What nodes does vulval squamous cell carcinoma spread to?
Inguinal
Pelvic
Iliac
Para-aortic
What is the 5 year survival for vulval squamous cell carcinoma lesions less than 2cm?
90%, following vulvectomy and lymphadenectomy
What is gestational trophoblastic disease?
Tumours and tumour like conditions which show proliferation of placental tissue - villous and/or trophoblastic
What are the major trophoblastic diseases?
Hydatidiform mole (complete and partial)
Invasive mole
Choriocarcinoma
What is a hydatidiform mole associated with?
Choriocarcinoma
What is a hydatidiform mole?
Cystic swelling of chorionic villi and trophoblastic proliferation
When does a hydatidiform mole occur?
When there is an abnormally fertilised ovum - ovum that has lost maternal DNA, or 2 sperm fertilise ovum
How is a hydatidiform mole usually diagnosed?
In early pregnancy, with USS
Can present with miscarriage
What groups are at highest risk of hydatidiform mole?
Teenagers, and 40-50 years
What are the types of hydatidiform mole?
Complete
Partial
What does a hydatidiform mole look like histologically?
Friable mass of thin-walled, translucent, grape-like structures - swollen oedematous villi
How is a hydatidiform mole treated?
Curettage, followed by hCG monitoring
What may be indicated if hCG levels don’t fall following treatment for hydatidiform moles?
Invasive mole
What is a gestational choriocarcinoma?
Malignant neoplasm of trophoblastic cells derived from previous normal or abnormla pregnancy
Are villi present with gestational choriocarcinoma?
No
