week 3 part 1 Flashcards
What are the sub-types of Epithelial cell tumours (ovarian cancer)
Serous tumours (the most common) Endometrioid carcinomas Clear cell tumours Mucinous tumours Undifferentiated tumours
Serous cystadenoma
Most common benign ovarian tumour, often bilateral
Cyst lined by ciliated cells (similar to Fallopian tube)
Serous cystadenocarcinoma
Malignant - Often bilateral
Psammoma bodies seen (collection of calcium)
Mucinous cystadenoma
Benign - Cyst lined by mucous-secreting epithelium (similar to endocervix)
Mucinous cystadenocarcinoma
Malignant - May be associated with pseudomyxoma peritonei (although mucinous tumour of appendix is the more common cause)
Brenner tumour
Benign ovarian growth - Contain Walthard cell rests (benign cluster of epithelial cells), similar to transitional cell epithelium. Typically have ‘coffee bean’ nuclei.
Dermoid Cysts / Germ Cell Tumours
These are benign ovarian tumours. They are teratomas, meaning they come from the germ cells. They may contain various tissue types, such as skin, teeth, hair and bone. They are particularly associated with ovarian torsion. Germ cell tumours may cause raised alpha-fetoprotein (α-FP) and human chorionic gonadotrophin (hCG).
Teratoma
Mature teratoma (dermoid cyst) - most common: benign Immature teratoma: malignant
Dysgerminoma
Most common malignant germ cell tumour
Histological appearance similar to that of testicular seminoma
Associated with Turner’s syndrome
Typically secrete hCG and LDH
Yolk sac tumour
Malignant
Typically secrete AFP
Schiller-Duval bodies on histology are pathognomonic
Granulosa cell tumour
Malignant
Produces oestrogen leading to precocious puberty if in children or endometrial hyperplasia in adults.
Contains Call-Exner bodies (small eosinophilic fluid-filled spaces between granulosa cells)
Sertoli-Leydig cell tumour
Benign
Produces androgens → masculinizing effects
Associated with Peutz-Jegher syndrome
Fibroma
Benign
Associated with Meigs’ syndrome (ascites, pleural effusion)
Solid tumour consisting of bundles of spindle-shaped fibroblasts
Typically occur around the menopause, classically causing a pulling sensation in the pelvis
Kruckenberg tumour
A Kruckenberg tumour refers to a metastasis in the ovary, usually from a gastrointestinal tract cancer, particularly the stomach. Kruckenberg tumours have characteristic “signet-ring” cells on histology, which look like signet rings on under a microscopy.
Risk factors for ovarian cancer
Age (peaks age 60) BRCA1 and BRCA2 genes Increased number of ovulations Obesity Smoking Recurrent use of clomiphene
Protective factors for ovarian cancer
Having a higher number of lifetime ovulations increases the risk of ovarian cancer. Factors that stop ovulation or reduce the number of lifetime ovulations, reduce the risk:
- Combined contraceptive pill
- Breastfeeding
- Pregnancy
Presenting features of ovarian cancer
Abdominal bloating Early satiety (feeling full after eating) Loss of appetite Pelvic pain Urinary symptoms (frequency / urgency) Weight loss Abdominal or pelvic mass Ascites
Why is there hip or groin pain in some ovarian cancers?
An ovarian mass may press on the obturator nerve and cause referred hip or groin pain.
The two-week referral criteria for ovarian cancer
- Ascites
- Pelvic mass (unless clearly due to fibroids)
- Abdominal mass
Investigations for ovarian cancer
- CA125 blood test (>35 IU/mL is significant)
2. Pelvic ultrasound
The risk of malignancy index (RMI)
Estimates the risk of an ovarian mass being malignant, taking account of three things:
- Menopausal status
- Ultrasound findings
- CA125 level
Women under 40 years with a complex ovarian mass require tumour markers for a possible germ cell tumour: what are those markers?
Alpha-fetoprotein (α-FP)
Human chorionic gonadotropin (HCG)
CA125
CA125 is a tumour marker for epithelial cell ovarian cancer. It is not very specific, and there are many non-malignant causes of a raised CA125
Causes of raised CA125 tumour markers
- Endometriosis
- Fibroids
- Adenomyosis
- Pelvic infection
- Liver disease
- Pregnancy
The International Federation of Gynaecology and Obstetrics (FIGO) staging system
Staging system for ovarian cancers
Stage 1: Confined to the ovary
Stage 2: Spread past the ovary but inside the pelvis
Stage 3: Spread past the pelvis but inside the abdomen
Stage 4: Spread outside the abdomen (distant metastasis)
Benign ovarian cysts
Benign ovarian cysts are extremely common. They may be divided into physiological cysts, benign germ cell tumours, benign epithelial tumours and benign sex cord stromal tumours. Complex (i.e. multi-loculated) ovarian cysts should be biopsied to exclude malignancy.
Physiological cysts (functional cysts)
- Follicular cysts
2. Corpus luteum cyst
Follicular cysts
o commonest type of ovarian cyst
o due to non-rupture of the dominant follicle or failure of atresia in a non-dominant follicle
o commonly regress after several menstrual cycles
Corpus luteum cyst
o during the menstrual cycle if pregnancy doesn’t occur the corpus luteum usually breaks down and disappears. If this doesn’t occur the corpus luteum may fill with blood or fluid and form a corpus luteal cyst
o more likely to present with intraperitoneal bleeding than follicular cysts
Dermoid cyst
- also called mature cystic teratomas. Usually lined with epithelial tissue and hence may contain skin appendages, hair and teeth
- most common benign ovarian tumour in woman under the age of 30 years
- median age of diagnosis is 30 years old
- bilateral in 10-20%
- usually asymptomatic. Torsion is more likely than with other ovarian tumours
Serous cystadenoma
i. the most common benign epithelial tumour which bears a resemblance to the most common type of ovarian cancer (serous carcinoma)
ii. bilateral in around 20%
Mucinous cystadenoma
i. second most common benign epithelial tumour
ii. they are typically large and may become massive
iii. if ruptures may cause pseudomyxoma peritonei
Benign epithelial tumours
Arise from the ovarian surface epithelium
- Serous cystadenoma
- Mucinous cystadenoma
Risk of Malignancy Index (RMI)
The RMI I is the most effective for women with suspected ovarian cancer. This is also recommended by the National Institute for Health and Care Excellence (NICE) guideline on ovarian cancer[8]. It should not be used for premenopausal women though.
RMI I combines three pre-surgical features: serum CA 125 (CA 125); menopausal status (M); and ultrasound score (U).
Simple ovarian cysts management
do not require treatment
Women with small (less than 50 mm in diameter) simple ovarian cysts management
No treatment
Women with simple ovarian cysts of 50-70 mm management
should have yearly ultrasound follow-up and those with larger simple cysts should be considered for either further imaging (MRI) or surgical intervention
Complications of ovarian cancer and cysts
- Torsion of an ovarian cyst can occur.
- Haemorrhage is more common for tumours of the right ovary.
- Rupture of an ovarian cyst can occur.
- Infertility can occur as a result of ovarian tumours or their treatment
Uterine fibroid
Fibroids are benign smooth muscle tumours of the uterus. They are thought to occur in around 20% of white and around 50% of black women in the later reproductive years
Uterine fibroid associations
more common in Afro-Caribbean women
rare before puberty, develop in response to oestrogen
Uterine fibroid presentation
> may be asymptomatic > menorrhagia > lower abdominal pain: cramping pains, > bloating > urinary symptoms, e.g. frequency > subfertility
Uterine fibroid diagnosis
Transvaginal ultrasound
Asymptomatic fibroids treatment
No treatment is needed other than periodic review to monitor size and growth
Medical Treatment to shrink/remove fibroids
GnRH agonists may reduce the size of the fibroid but are typically useful for short-term treatment
Surgical treatment to shrink/remove fibroids
- myomectomy
- hysteroscopic endometrial ablation
- hysterectomy
- uterine artery embolization
Endometrial cancer
Endometrial cancer is a common oestrogen-dependent gynaecological cancer which tends to affect older women. Unlike cervical cancer, it is not currently screened for in the UK.
Myometrium
the thick layer of smooth muscle and connective tissue lying beneath the endometrium. It contracts during a period to reduce blood loss (causing cramps) and during labour to expel the foetus. It often gives rise to benign growths called fibroids (leiomyomas) but rarely undergoes malignant change.
Parametrium
the parametrium is a fibrous fascial layer which lines the outer surface of the upper part of the cervix and separates it from the bladder. It contains the uterine artery and the ovarian ligament. The parametrium is important, as cervical cancers often spread out to invade it as they grow.
Perimetrium
The perimetrium is the membranous layer of visceral peritoneum which lines the outer surface of the whole uterus, apart from a small area anteriorly where it deflects forwards to cover the bladder.
Endometrium
The endometrium is the thin inner mucous membrane which lines the cavity of the uterus and is shed during the monthly menstrual period. Its high cell turnover makes it the most common site for cancers of the uterus to develop.
The wall of the uterus has four distinct layers: what are they?
the endometrium, myometrium, parametrium and perimetrium (peritoneum)
Postmenopausal bleeding (PMB)
is vaginal bleeding occurring after 12 months of amenorrhoea in a woman of menopausal age or who has experienced the menopause – this affects 4-11% of postmenopausal women and accounts for 5% of all gynaecology outpatient referrals
Uterine sarcomas
these are tumours arising from the myometrium and connective tissues of the uterus
this is a rare diagnosis with an aggressive clinical course and a poor prognosis
2% leiomyosarcoma
1% carcinosarcoma (aka mixed mesodermal Mullerian tumour)
<1% endometrial stromal carcinoma
Symptoms of endometrial cancer
- postmenopausal bleeding
- in pre- or perimenopausal women (20-25% of cases), symptoms can include intermenstrual bleeding or menorrhagia
- increased vaginal discharge
- pyometra (a collection of pus in the uterine cavity)
- symptoms of advanced disease include pelvic pain, pelvic mass, leg swelling, haematuria, PR bleeding, weight loss and fatigue
- symptoms of metastatic disease
Cervical cancer
Cancer of the cervix tends to affect younger women, peaking in the reproductive years. 80% of cervical cancers are squamous cell carcinoma. Adenocarcinoma is the next most common type. Very rarely there are other types, such as small cell cancer.
Cervical cancer associations
Cervical cancer is strongly associated with human papillomavirus. Children aged 12 – 13 years are vaccinated against certain strains of HPV to reduce the risk of cervical cancer.
What strains of HPV are associated with cervical cancer?
type 16 and 18, as they are responsible for around 70% of cervical cancers and also the strains targeted with the HPV vaccine. There is no treatment for infection with HPV. Most cases resolve spontaneously within two years, while some will persist.
Risk factors for cervical cancer
>
Increased risk of catching HPV Later detection of precancerous and cancerous changes (non-engagement with screening) • Early sexual activity • Increased number of sexual partners • Sexual partners who have had more partners • Not using condoms • Smoking • HIV • Combined contraceptive pill use for more than five years • Family history
Appearances that may suggest cervical cancer need urgent referral; what are they?
Appearances that may suggest cervical cancer are: • Ulceration • Inflammation • Bleeding • Visible tumour
Cervical Intraepithelial Neoplasia
A grading system for the level of dysplasia (premalignant change) in the cells of the cervix. CIN is diagnosed at colposcopy (not with cervical screening)
Cervical Intraepithelial Neoplasia grading criteria
- CIN I: mild dysplasia, affecting 1/3 the thickness of the epithelial layer, likely to return to normal without treatment
- CIN II: moderate dysplasia, affecting 2/3 the thickness of the epithelial layer, likely to progress to cancer if untreated
- CIN III: severe dysplasia, very likely to progress to cancer if untreated CIN III is sometimes called cervical carcinoma in situ.
dyskaryosis
Dyskaryosis refers to the change of appearance in cells that cover the surface of the cervix. A smear test or cervical screening test is used to detect abnormal cells in your cervix (the entrance to your womb). Regular screening monitors changes in the cells.
The cervical screening program involves performing a smear for women (and transgender men that still have a cervix): how often is a smear test carried out?
- Every three years aged 25 – 49
* Every five years aged 50 – 64
Vulval cancer
Vulval cancer is rare compared with other gynaecological cancers. Around 90% are squamous cell carcinomas. Less commonly, they can be malignant melanomas.
Risk factors for vulval cancer
Advanced age (particularly over 75 years)
Immunosuppression
Human papillomavirus (HPV) infection
Lichen sclerosis
Vulval intraepithelial neoplasia (VIN)
Vulval intraepithelial neoplasia (VIN) is a premalignant condition affecting the squamous epithelium of the skin that can precede vulval cancer. VIN is similar to the premalignant condition that comes before cervical cancer (cervical intraepithelial neoplasia).
High grade squamous intraepithelial lesion
High grade squamous intraepithelial lesion is a type of VIN associated with HPV infection that typically occurs in younger women aged 35 – 50 years.
Symptoms of vulval cancer
Vulval lump Ulceration Bleeding Pain Itching Lymphadenopathy in the groin
