O&G JC107: Abnormal Vaginal Bleeding: Gynaecological Cancer Flashcards
Common cause of abnormal vaginal bleeding
Benign causes:
Uterine (PALM):
1. Endometrial polyps
2. Adenomyosis
3. Fibroids
4. Endometrial hyperplasia
5. Pregnancy-related
6. Dysfunctional uterine bleeding (i.e. without identifiable cause)
Ovarian:
1. Anovulation
Cervical:
1. Cervical polyps
2. Cervical erosion
Vaginal:
1. Atrophic vaginitis
2. Lacerations
Malignant causes:
- Can occur at any part of genital tract
How to tell source of bleeding: History taking
- Age + ***Stage of reproductive life
- Pre-menarche
- Pregnant
- Peri-menopausal
- Post-menopausal - Bleeding pattern / Menstrual history
- **Amount
- **Regular / Irregular
- **Abnormal bleeding
–> **Intermenstrual bleeding (Endometrial cancer)
–> **Post-menopausal bleeding (Endometrial cancer)
–> **Post-coital bleeding (Cervical cancer)
–> Clots - Provoking factors
- **Coitus
- **Trauma (vaginal lacerations)
- ***Stress (e.g. medical students) –> Hypothalamic amenorrhoea - Associated symptoms
- **Abdominal pain
- **Urinary / Bowel symptoms (e.g. Uterine fibroids may cause pressure symptoms on urinary bladder –> urinary frequency) (also rule out **haematuria / **blood in stools mistaken as vaginal bleeding)
- Anaemic symptoms
***記: COC (Contraceptive, Obstetrics, Cervical smear)
5. Contraceptive history
- possibility of pregnancy?
- on hormones e.g. OC pills?
- Obstetric history
- Cervical smear history
- smear up to date?
- have regular smear?
- smear results - Drug history
- **Anticoagulation (cause menorrhagia)
- **HRT (cause abnormal uterine bleeding)
- **OC pills
- **Herbal medications (may contain estrogen) - Family history
- CA ovary, breast, colon
Physical examination
General examination
1. Pallor
2. Bleeding tendency (e.g. easy bruising)
3. Constitutional symptoms (e.g. cachexia)
Abdominal examination
1. Inspection
- Scars
- **Distension (e.g. ovarian mass, ascites, pregnancy)
- **Signs of pregnancy (e.g. linea nigra, fetal movement in advanced gestation)
- Palpation
- Mass
- Tenderness (e.g. elicit rebound, guarding for peritoneal signs) - Percussion
- Ascites - Auscultation
- Fetal heart
Pelvic examination
1. Inspection
- Vulva
- Vagina / Cervix (by Speculum examination)
—> **Lesions / Bleeding sites
—> **Atrophic changes
—> ***Genital prolapse (cause ulcers)
- Bimanual examination of Uterus
- Position (Anteverted, Retroverted, Axial)
- Size
- Mobility
- ***Adnexal masses (estimate size) - Rectal examination
- Endometriosis (nodularity in PoD)
Investigations
Cervix
1. **Cervical smear
- collect cells from cervix for cytological diagnosis
- for cervical cancer screening, effective in picking up abnormal cells from cervix before obvious lesion / cervical cancer become apparent
- abnormal smear –> proceed to **Colposcopy
- Colposcopy
- examination of cervix with Colposcope
- apply Acetic acid –> Lugol’s iodine to cervix to visualise abnormal lesions
- lesions seen –> proceed to Cervical biopsy for histological diagnosis - ***Cervical biopsy
- punch biopsy
- obvious lesion / mass at cervix
- histological diagnosis
Uterus
1. ***Endometrial aspirate (biopsy)
- Pipelle aspirator (can be performed in clinic)
- ***Hysteroscopy (Diagnostic)
- visualise uterine cavity -
**Hysteroscopy + **Curettage (H+C)
- can be performed during Hysteroscopy to ascertain any endometrial pathology - USG
- Transvaginal / Transabdominal
- readily available
- look at endometrial ***thickness, other pathologies
- sagittal view of uterus: Trilaminar layer of endometrium
–> outer echogenic basal layer
–> middle hypoechoic functional layer
–> inner echogenic stripe at the central interface
Common gynaecological cancers
- Cervical cancer –> cause abnormal vaginal bleeding
- Endometrial cancer –> cause abnormal vaginal bleeding
- Ovarian cancer
Epidemiology of gynaecological cancers
Endometrial cancer (Corpus uteri cancer)
- 4th most common female cancer
- 11th in mortality
- Median age at diagnosis: 55
- ↑ incidence in HK (associated to risk factors e.g. obesity)
- 70% presents at stage 1 (∵ mostly symptomatic)
Ovarian cancer
- 6th
Cervical cancer
- 7th
- 8th in mortality
- Median age at diagnosis: 54
- 25% presents at stage 1, 25% stage 2, 40% stage 3+4 (advanced stage)
***Risk factors for Cervical cancer
- ***HPV
- Early sex
- Multiple sex partners
- STD
- Smoking
- Lower socioeconomic class
- OC pills
- Immunosuppression
***Clinical features of Cervical cancer (SpC OG + Felix Lai)
- Asymptomatic
- Bleeding
- Irregular menstrual bleeding
- Heavy menstrual bleeding
- Intermenstrual bleeding
- ***Post-coital bleeding (most specific presentation of cervical cancer, DDx: cervicitis) - Vaginal discharge
- Blood stained or unpleasant smell - Metastatic symptoms
- Bowel and urinary changes (invasion into bladder / rectum)
—> Haematuria, Haematochezia
- Constitutional symptoms
- Dyspnea
- Jaundice
- Pelvic or low back pain (bone pain)
History taking of Cervical cancer
- Age
- Median 54 - Bleeding pattern
- ***Post-coital bleeding - Associated symptoms
- Early disease: ***not much (usually picked up during cervical screening)
- Late disease: Back pain, Leg edema - Contraceptive / Sexual history
- OC pills
- ***Sexually active? (or Had been?) - Cervical smear history
- Regular screening?
- Last one?
- Results? - Obstetric history
- Parity - Family history
- ***not related
Physical examination of Cervical cancer
General examination
Pelvic examination
1. Normal appearance cervix in early stage + ***Asymptomatic (∴ cervical cancer screening is effective)
- Growth on cervix
- **Exophytic (cauliflower, contact bleeding)
- **Endophytic (infiltrative, barrel shape cervix)
- ***Ulceration
–> must take cervical biopsy to confirm nature of lesion - PV + PR examination (SpC Revision)
- ***Clinical staging: Assess extent of vaginal + parametrial spread
Investigations of Cervical cancer
Diagnosis
1. Punch biopsy
Plan of management
1. Blood test
- CBP
- LRFT
- Tumour markers
- SCC: SCC Ag level
- Adenocarcinoma: CA125 (SpC OG) - Imaging
- CT
- MRI abdomen + pelvis
- PET-CT
- PET-MRI
–> assess renal tract / extent of spread / LN involvement
(SpC OG
4. Cystoscopy / Sigmoidoscopy (for invasion into bladder / rectosigmoid area
- seldom done now)
- Examination under anaesthesia (EUA)
- for difficult P/E / biopsy
- seldom done now)
Spread of Cervical cancer
- Local
- laterally to parametrium
- downward to vagina
- anteriorly to bladder
- posteriorly to rectum, PoD, sacrum - Distal
- via LN chains to Pelvic / Para-aortic LN
***Staging of Cervical cancer
FIGO staging
1. Clinical
2. Pathological (新加)
3. Imaging (新加)
Stage 1: Cervix only (5-year survival 85%)
- 1A: Microscopic
—> 1A1: <3mm deep (SpC Revision)
—> 1A2: >=3 to <5mm
- 1B (1-3): Macroscopic, Confined to cervix (1-3 depend on size of mass)
—> 1B1: <2cm in greatest dimension
—> 1B2: >=2 to <4cm
—> 1B3: >=4cm
Stage 2: Upper vagina / Surrounding structures (e.g. parametrium) (5-year survival 75%)
- 2A: Upper 2/3 vagina
- 2B: Parametrium
Stage 3: Lower vagina / Pelvic wall / Pelvic/Para-aortic LN / Hydronephrosis/Non-functioning kidney (5-year survival 50%)
- 3A: Lower 1/3 vagina
- 3B: Pelvic sidewall / Hydronephrosis
- 3C: Pelvic / Para-aortic LN
Stage 4: Bladder / Rectum / Distant metastasis (5-year survival 25%)
- 4A: Bladder, Rectum
- 4B: Distant metastasis
- Add notation (r: imaging, p: pathology) to indicate findings that are used to allocate case to the stage
Treatment modalities in Cervical cancer
- Surgery
- for early stage (e.g. Stage 1)
- Stage 1A1: Cone biopsy / **Simple hysterectomy: very very early (microscopic **<3mm deep)
- Stage 1A2: **Wertheim’s hysterectomy (Radical hysterectomy + Pelvic lymphadenectomy)
–> remove uterus + upper vagina + parametria + pelvic LN
–> **laparotomy (tend to use) / laparoscopic route (↑ recurrence risk + poorer overall survival?)
- advantages:
–> preserve Ovarian function (less chance of osteoporosis / heart disease associated with early menopause)
–> avoid long-term morbidities of Radiotherapy (e.g. bladder, bowel, vaginal stenosis)
- Stage 1B1, Early 2A: **Radical hysterectomy + Pelvic lymphadenectomy / RT
- Stage 1B2, Late stage 2 / above: **Chemoradiation
(SpC OG
Advantages of Cone vs Hysterectomy:
- preserve fertility
- less invasive / complications
Disadvantages of Cone vs Hysterectomy:
- more difficult to monitor for recurrence after procedure (e.g. in endocervix —> difficult to brush)
- need for re-procedure if margin positive)
- ***Radiotherapy
- for early stage if surgery not suitable / high risk (e.g. elderly with comorbidities)
- for late stage (e.g. >= Stage 2)
- External beam + Brachytherapy - ***Chemotherapy
- in combination with Radiotherapy (Chemoirradiation)
- to ↑ sensitivity of Radiotherapy
- for recurrence
- e.g. Cisplatin - Targeted therapy (Bevacizumab) / Immunotherapy (Pembrolizumab)
- in combination with Chemotherapy
- to prolong progression-free survival + overall survival
Prognostic factors in Cervical cancer
- Stage
- LN metastasis (i.e. Stage 3)
- Histology
- common histology (e.g. SCC, Adenocarcinoma, Adenosquamous carcinoma): better prognosis
- rarer histology (e.g. Neuroendocrine small cell carcinoma): poorer prognosis
SpC Revision:
4. Parametrial involvement
5. Size + Depth of stromal invasion
6. Lymphovascular permeation
7. Age (Controversial)
Endometrial / Corpus cancer (Felix Lai)
Types:
1. Type 1 endometrial carcinoma (80%)
- Endometroid histology Grade 1 / 2 (Low-grade) (Endometroid histology is least aggressive)
- Preceded by intraepithelial neoplasm (***Endometrial hyperplasia)
- Estrogen responsive
- Favourable prognosis
- Type 2 endometrial carcinoma (10-20%)
- Endometroid histology Grade 3 (High-grade) + Non-endometroid histology (Serous, Clear cell, Mucinous, Squamous, Transitional cell, Mesonephric, Undifferentiated)
- NOT clearly associated with estrogen stimulation
- Poor prognosis
Histological grading:
- Good correlation between grade and prognosis
- Grade 1: Well differentiated, gland forms are conspicuous, mitotic figures are moderately numerous
- Grade 2: Patchy differentiation, gland forms much less prominent and many deposits consist of infiltrating single cell columns / solid masses
- Grade 3: Consist of solid masses of malignant cells of varying sizes and shapes with little / no stroma, mitoses are numerous
Mode of spread:
- Local spread: Myometrium / Cervix / Vaginal / Ovary / Fallopian tubes
- Lymphatic spread: Pelvic + Paraaortic LN
- Distant spread: Lungs
Risk factors for Endometrial / Corpus cancer
- Age
- A disease of ***post-menopausal women - Excessive ***endogenous estrogen
- Early menarche
- Late menopause
- Nulliparity
- Obesity
- PCOS
- Estrogen-secreting tumours (e.g. Ovarian granulosa cell tumours)
- Endometrial hyperplasia - ***Exogenous estrogen
- Unopposed estrogen therapy (uncommon now)
- Tamoxifen therapy - Miscellaneous
- Family history of breast, ovarian, CRC cancer
- ***Lynch syndrome (lifetime risk 15-60% depend on type of mutation)
- DM
- HT
***Clinical features of Endometrial cancer
**Abnormal bleeding
1. Change in menstrual pattern (frequency, duration, volume)
2. Prolonged bleeding
3. **Intermenstrual bleeding
4. Irregular bleeding
5. ***Post-menopausal bleeding
SpC Revision:
6. Abnormal vaginal discharge
7. Symptoms of late disease (e.g. SOB, back pain)
Investigations of Endometrial cancer
- > 40 yo (be careful!!!)
- need Endometrial sampling (Endometrial aspirate with Pipelle samplers) - Post-menopausal bleeding
- ***Transvaginal USG (endometrial thickness >=5mm (>4mm (self notes)): ↑ risk of endometrial pathology) (NOT Transabdominal USG (SpC PP)) -
**Hysteroscopy + **Biopsy (gold standard)
- If ***high risk:
—> Taking Tamoxifen
—> Endometrial thickness >4mm
—> Recurrence or refractory symptoms despite treatment for atrophic changes
SpC Revision:
4. Blood test
- CA125 as baseline (for some endometrial cancer)
- MRI abdomen / pelvis
- for depth of myometrial invasion / any distal spread - CXR
Spread of Endometrial cancer
- Locally
- Cervix
- Vagina
- Tubal metastasis
- Ovarian metastasis - LN
- via LN chains to Pelvic / Para-aortic LN
***Staging of Endometrial cancer
FIGO staging: ***Surgically staged!!!
Stage 1: Uterus (5-year survival 85%)
- 1A: No / <50% myometrial invasion
- 1B: >=50% myometrial invasion
Stage 2: Cervix, Cervical stroma but not beyond uterus (5-year survival 75%)
Stage 3: Outside uterus (5-year survival 45%)
- 3A: Serosa of uterus / Adnexa
- 3B: Vaginal / Parametrial
- 3C: Pelvic / Para-aortic LN
Stage 4: Bladder / Rectum / Distant metastasis (5-year survival 25%)
- 4A: Bladder / Rectum
- 4B: Distant (Intraabdominal metastasis / Inguinal LN)
Treatment of Endometrial cancer
Total hysterectomy + **Bilateral salpingo-oophorectomy (THBSO: **Standard) +/- Lymphadenectomy
- Remove uterus + both ovarian tube + ovaries
- Laparotomy: Size of the uterus **>12 weeks size / Anticipated intra-abdominal **adhesions from previous surgeries
- Laparoscopic: ***Early disease (confined to uterus)
Lymphadenectomy:
- in High risk disease
—> High grade endometrioid carcinoma
—> Deep myometrial invasion
—> Large tumour
High risk group (even LN -ve):
- e.g. Serous carcinoma / Clear cell carcinoma
- **Brachytherapy +/- **Chemo (to ↓ recurrence risk)
LN +ve:
- Need post-op **Chemo +/- **RT (to ↓ recurrence risk)
If LN not done:
- ***External RT if high risk of recurrence
Prognosis of Endometrial cancer (SpC Revision)
Prognostic factors:
1. Age
2. Stage
3. Histology
4. Spread outside uterus
5. LN involvement
Prognosis:
5-year survival:
- Stage 1A: nearly 90%
- Stage 2: 70%
- Stage 3: 50%
- Stage 4: 20%
Summary
Cervical cancer:
- Asymptomatic at early stage —> need ***screening
Endometrial cancer:
- Symptomatic at early stage —> presents with ***abnormal bleeding
If treated early, both can have good prognosis
Endometrial hyperplasia (SpC OG)
- Proliferation of endometrial glands or irregular size and shape with an increase in endometrial gland: stromal ratio ***>50% compared with normal proliferative endometrium
- ***Pre-malignant lesion of endometrial adenocarcinoma
- Diagnosed by ***Endometrial biopsy
Risk factors:
1. Female
2. Obesity
3. Nulliparity
4. Exposure to unopposed endogenous estrogen: PCOS, estrogen-secreting tumour (granulosa cell tumour in ovary)
5. Exogenous estrogen: Tamoxifen, HRT
2 types:
1. Endometrial hyperplasia without atypia (EH)
- Risk of progression: <5%
2. Endometrial hyperplasia with atypia (AH)
- Risk of progression: **30%
- Risk of concomitant carcinoma: **40-50%
Endometrial hyperplasia without atypia (EH):
1. Early ***H+C
- r/o CA corpus and other pathology
- Medical
- **Levonorgestrel intrauterine system (Mirena) (1st line) (Effective (>90% regression rates))
- **High dose continuous oral progesterone (e.g. norethisterone, medroxyprogesterone actetate)
(No Depo-provera (self notes)) - Surgical
- ***Hysterectomy (discussed in post-menopausal patients or those on Tamoxifen)
Endometrial hyperplasia with atypia:
1. Surgical
- **Hysterectomy +/- **BSO
