Cancers Flashcards
(56 cards)
1
Q
What are the types of Cervical Cancer?
A
- Squamous cell cancer (80%)
- Adenocarcinoma (20%)
2
Q
What is the natural history of HPV mediated Cervical Cancer?
A
- HPV: asymptomatic and can be cleared or persist or cause CIN
- CIN is an asymptomatic premalignant condition which can regress, persist or progress to cancer.
- 60% CIN1 regress spontaneously and 30% of CIN3 progress to invasion over 5-10 years.
- It occurs in the transformation zone.
3
Q
What are clinical signs and symptoms of Cervical Cancer?
A
- Abnormal vaginal bleeding: post coital, intermenstrual or postmenopausal bleeding
- Vaginal discharge
4
Q
What are the significant risk factors in the pathogenesis of Cervical Cancer?
A
- Human Papillomavirus (HPV) is the most important factor particularly the serotypes 16,18 & 33.
- Smoking
- Human immunodeficiency virus
- Early first intercourse, many sexual partners
- High parity
- Lower socioeconomic status
- Combined oral contraceptive pill
5
Q
How does HPV causes Cervical Cancer?
A
- HPV 16 and 18 produces oncogenes E6 and E7 respectively.
- E6 inhibits p53 tumour suppressor gene and E7 inhibits the RB suppressor gene
6
Q
What are the qualification criteria for Cervical Screening?
A
- Smear test offer to all women aged between 25 and 64 years
- 25-49 years: 3-yearly screening
- 50-64 years: 5 yearly screening
- Past 64, it cannot be offered
7
Q
What are the aims of cervical cancer screening?
A
- Preventative for 1000-4000 deaths per year.
- Main aim is to detect pre-malignant changes rather than cancer.
- Cervical adenocarcinomas are frequently undetected by screening
8
Q
What are special circumstances encountered in cervical cancer screening?
A
- In pregnancy cervical screening is delayed until 3 months post-partum unless missed screening or previous abnormal smears
- Women who have never been sexually active have very low risk of developing cervical cancer so may wish to opt out of screening
9
Q
What are the methods of Cervical Cancer Screening?
A
- Papanicolaou (Pap) smears – smearing sample unto slide
- Liquid-based cytology – sample is either rinsed into preservative fluid or the brush head is simply removed into the sample bottle containing preservative fluid
10
Q
What are advantages of Liquid-Based cytology?
A
- Reduced rate of inadequate smears
- Increased sensitivity and specificity
11
Q
How is Testing conducted in the NHS?
A
- The NHS has now moved to an HPV first system, i.e. a sample is tested for high-risk strains of human papillomavirus (hrHPV) first and cytological examination is only performed if this is positive.
12
Q
What is done in the presence of a negative Negative hrHPV?
A
Return to normal recall
- 25-49 years: 3-yearly screening
-
50-64 years: 5 yearly screening
- Past 64, it cannot be offered
13
Q
What are the exceptions to returning to normal recall following a normal hrHPV?
A
- Test of cure pathway: Individuals who have been treated for CIN1, CIN2, or CIN3 should be invited 6 months after treatment for a test of cure repeat cervical sample in the community
- Untreated CIN1 pathway
- Follow-up for incompletely excised cervicial glandular intraepithelial neoplasia (CGIN)/stratified mucin producing intraepithelial lesion (SMILE) or cervical cancer
- Follow-up for borderline changes in endocervical cells
14
Q
What occurs if there is a postive hrHPV and the cytology is abnormal?
A
Refer for Colposcopy to determine if there is:
- Borderline changes in squamous or endocervical cells.
- Low-grade dyskaryosis.
- High-grade dyskaryosis (moderate).
- High-grade dyskaryosis (severe).
- Invasive squamous cell carcinoma.
- Glandular neoplasia
15
Q
What occurs if there is a postive hrHPV and the cytology is normal?
A
The test is repeated after 12 months
- If the repeat test is now hrHPV -ve → return to normal recall
- If the repeat test is still hrHPV +ve and cytology still normal → further repeat test 12 months later
- If hrHPV -ve at 24 months → return to normal recall
- If hrHPV +ve at 24 months → colposcopy
16
Q
What happens with an inadequate sample?
A
- Repeat the sample within 3 months
- If two consecutive inadequate samples then → colposcopy
17
Q
How are patients with previous CIN followed up?
A
- The follow-up of patients who’ve previously had CIN is complicated but as a first step, individuals who’ve been treated for CIN1, CIN2, or CIN3 should be invited 6 months after treatment for a test of cure repeat cervical sample in the community.
18
Q
How is Cervical cancer staged?
A
Figo Staging
- Stage 1A: Confined to cervix, only visible by microscopy and less than 7 mm wide (A1 is <3mm deep and A2 is 3-5mm deep)
- Stage 1B: Confined to cervix, clinically visible or larger than 7 mm wide. (B1 = < 4 cm diameter, B2 = > 4 cm diameter)
- Stage 2: Extension of tumour beyond cervix but not to the pelvic wall (A = upper two thirds of vagina, B = parametrial involvement)
- Stage 3: Extension of tumour beyond the cervix and to the pelvic wall (A = lower third of vagina, B = pelvic side wall). IT is stage if it causes hydronephrosis or non-functioning kidney
- Stage 4: Extension of tumour beyond the pelvis or involvement of bladder or rectum (A = involvement of bladder or rectum, B = involvement of distant sites outside the pelvis)
19
Q
How are cancer stage 1B and above treated?
A
Radiotherapy and concurrent chemotherapy
- Radiotherapy may either be bachytherapy or external beam radiotherapy
- Cisplatin is the commonly used chemotherapeutic agent
20
Q
How are cancers at CIN1 treated?
A
- Gold standard of treatment is hysterectomy +/- lymph node clearance. Nodal evaluation and clearance for A2 tumours
- For patients wanting to maintain fertility, a cone biopsy with negative margins can be performed.
- Excisional options are LLETZ and Cold Knife Cone
- Destructive options are Cryocautery, Diathermy, Laser Vaporisation
- Close follow-up of these patients is advised
- Radical trachelectomy is also an option for A2
21
Q
What is a Cervical Ectropion?
A
- On the ectocervix there is a transformation zone where the stratified squamous epithelium meets the columnar epithelium of the cervical canal.
- Elevated oestrogen levels (ovulatory phase, pregnancy, combined oral contraceptive pill use) result in larger area of columnar epithelium being present on the ectocervix
22
Q
What are clinical signs of Cervical Ectropion?
A
- Vaginal discharge
- Post-coital bleeding
23
Q
What is the management for Cervical Ectropion?
A
- Ablative treatment (for example ‘cold coagulation’) is only used for troublesome symptoms
24
Q
What are the 4 main types of ovarian tumours?
A
- Surface derived tumours
- Germ cell tumours
- Sex cord-stromal tumours
- Metastasis
25
What are some malignant ovarian tumours?
* **Serous Cystadenocarcinoma:** Often bilateral. Psammoma bodies seen (collection of calcium)
* **Mucinous Cystadenocarcinoma:** May be associated with pseudomyxoma peritonei (although mucinous tumour of appendix is more common causes)
* **Immature teratoma**
* **Dysgerminoma:** Most common malignant germ cell tumour. Histological appearance similar to testicular seminoma. It is associated with Turner’s syndrome and typically secrete hCG and LDH
* **Yolk Sac Tumour:** Typically, secretes AFP. Schiller-Duval bodies on histology are pathognomonic
* **Choriocarcinoma**: Rare tumour that is part of spectrum gestational trophoblastic disease. Early haematogenous spread to the lung. There are typically, have increase hCG levels
* **Granulosa Cell Tumour:** Produces oestrogen leading to precocious puberty if in children or endometrial hyperplasia in adults. Contain Call-Exner bodies (small eosinophilic fluid-filled spaces between granulosa cells)
* **Krukenberg Tumour:** Metastases from gastrointestinal tumour resulting in mucin-secreting signet-ring cell adenocarcinoma
26
What are features of benign ovarian tumours?
* Divided into:
* Physiological cysts
* Benign germ cell tumours
* Benign epithelial tumours
* Benign sex cord stromal tumours.
* Complex (i.e. multi-loculated) ovarian cysts should be biopsied to exclude malignancy.
27
What are some physiological (functional) cysts?
1. **Follicular cysts** (commonest type)
* Due to rupture of dominant follicle or failure of atresia in non-dominant follicle. Commonly regress after several menstrual cycles
1. **Corpus Luteum Cysts**
* If the corpus luteum doesn’t break down and disappear during the menstrual cycle, the corpus luteum may fill with blood or fluid forming a corpus luteal cyst
* More likely to present with intraperitoneal bleeding
28
What are some bening germ cell tumours?
**Dermoid Cyst (mature cystic teratomas)**
* Linked with epithelial tissue and may contain skin appendages, hair and teeth. Usually asymptomatic but torsion is more likely than with other ovarian tumours
* Most common benign ovarian tumour in women under 30 years of age, median age is 30y and bilateral in 10-20%
* Histopathological analysis reveals **Rokitansky's protuberance**
29
What are some benign epithelial tumours?
1. **Serous Cystadenoma**
* Most common type bearing resemblance to serous carcinoma
* Bilateral in around 20%. Cysts line by ciliated cells
2. **Mucinous Cystadenoma**
* 2nd most common benign epithelial tumour.
* Typically, large and if it ruptures, it may cause pseudomyxoma peritonei. Cysts lined by mucous-secreting epithelium
3. **Brenner Tumour**
* Contain Walthard cell rests (benign cluster of epithelial cells), similar to transitional cell epithelium. Typically have 'coffee bean' nuclei.
30
What are some benign sex cord stromal tumours?
1. **Sertoli-Leydig cell tumour**
* Produces androgens which leads to masculinizing effects
* Associated with Peutz-Jegher syndrome
2. **Fibroma**
* Associated with Meigs’ Syndrome
* Ascites, Pleural Effusion
* Solid tumour consisting of bundles of spindle-shaped fibroblasts
* Typically occur around the menopause classically causing pulling sensation in the pelvis
31
What are some characteristics of ovarian tumours?
* 90% are epithelial with 70-80% of cases being due to serous carcinomas
* Distal end of fallopian tube is often site of origin of many ovarian cancers
32
What are risk factors for Ovarian Tumours?
* **Family history:** mutations of BRCA1 (50%) or BRCA2 gene. HNPCC
* **Many ovulations:** early menarche, late menopause, nulliparity
* **Endometriosis**
33
What are some factors that reduce risk of ovarian tumours?
* COCP
* Breastfeeding
* Multiparity reduces risk
34
What are some signs and symptoms of Ovarian Tumours?
* **Abdominal distension and bloating** (may lead to pressure effects on bladder)
* **Abdominal and pelvic pain**
* Torsion or rupture of cysts lead to severe abdominal pain
* **Urinary symptoms** e.g. Urgency
* **Early satiety**
* **Diarrhoea**
* **Anorexia**
* **Nausea and vomiting**
35
How are Ovarian Tumours investigated?
* Pelvis examination
* FBC, U&E, LFT
* CA125
* Ultrasound is Initial imaging. Report will show:
* Simple: unilocular, more likely to be physiological or benign
* Complex: multilocular, more likely to be malignant
* Laparotomy: may be involved diagnostically as diagnosis is difficult
* Histopathology
* CT to assess peritoneal, omental and retroperitoneal disease
* Cytology of ascitic tap
36
How is CA125 beneficial in the investigation of Ovarian Tumours?
* Testing done initially but endometriosis, menstruation, benign ovarian cysts and other conditions may also raise CA125 level
* If CA125 is raised then an urgent ultrasound scan of abdomen and pelvis should be ordered
* CA125 should not be used for screening for ovarian cancer in asymptomatic woman
37
How is Ovarian cancer staged?
* **Stage 1:** Limited to ovary/ovaries (90%)
* **Stage 2:** Spread to pelvic organs (60%)
* **Stage 3:** Spread to rest of peritoneal cavity, omentum and/or positive lymph nodes (30%)
* **Stage 4:** distant metastases, liver parenchymal or lung involvement (5%)
(survivial rate)\*
38
How are Ovarian tumours referred for investigation?
* **Premenopausal women**: Conservative approach may be taken for younger women (especially if \< 35 years) as malignancy is less common. If the cyst is small (e.g. \< 5 cm) and reported as 'simple' then it is highly likely to be benign. A repeat ultrasound should be arranged for 8-12 weeks and referral considered if it persists.
* **Postmenopausal women**: Physiological cysts are unlikely. Any postmenopausal woman with an ovarian cyst regardless of nature or size should be referred to gynaecology for assessment
39
How is Epithelial Ovarian cancer managed?
* Surgery and chemotherapy (platinum based). Staging laparotomy with total abdominal hysterectomy plus bilateral salpingoophrectomy and debulking.
* In women of reproductive age where the tumour is confined to one ovary, oophorectomy only may be considered
40
What is endometrial hyperplasia?
* Endometrial hyperplasia may be defined as an abnormal proliferation of the endometrium in excess of the normal proliferation that occurs during the menstrual cycle.
* A minority of patients with endometrial hyperplasia may develop endometrial cancer (pre-malignant)
41
What are risk factors for Endometrial Hyperplasia?
* Obesity
* Unopposed oestrogen use
* Tamoxifen use
* Polycystic ovary syndrome
* Diabetes
42
What are types of endometrial hyperplasia?
* Simple
* Complex
* Simple atypical
* Complex atypical
43
What are clinical features of endometrial hyplerplasia?
* Abnormal vaginal bleeding e.g. intermenstrual, postmenopausal
44
How is endometrial hyperplasia managed?
* **Simple endometrial hyperplasia without atypia:** high dose progestogens with repeat sampling in 3-4 months. The Levonorgestrel IUS may be used
* Dilatation and curettage are performed to remove the excess endometrial tissue
* **Atypia:** hysterectomy is usually advised.
45
Which patient group does endometrial cancer often occur in?
* Classically seen in post-menopausal women but around 25% occur before menopause. Usually carries good prognosis due to early detection
* Makes up 2% of uterine cancer and the peak age is 64-74 and rare before 35. Declines in risk after 80yrs
* COCP and smoking are protective
46
What are the types of Endometrial Cancer?
**TYPE 1:** endometrial adenocarcinoma
**TYPE 2:** papillary serous, clear cell, carcinosarcoma
**Sarcoma:** extremely rare
47
How is Endometrial cancer staged?
_Figo Staging_
* **Stage 1:** limited to myometrium
* **Stage 2:** cervical spread
* **Stage 3:** uterine serosa, ovaries/tubes, vagina, pelvic/para-aortic lymph nodes
* **Stage 4:** Bladder/Bowel involvement or Distant metastases
48
What are risk factors for Endometrial cancer?
* Obesity
* Nulliparity
* Early menarche
* Late menopause
* Unopposed oestrogen. The addition of a progestogen to oestrogen reduces this risk (e.g. In HRT). The BNF states that the additional risk is eliminated if a progestogen is given continuously
* Diabetes mellitus
* Tamoxifen
* Polycystic ovarian syndrome (PCOS)
* Hereditary non-polyposis colorectal carcinoma
* Parkinsons
* Previous breast cancer
49
What leads to reduction in risk of Endometrial Cancer?
* Continuous combined HRT
* Combined oral contraceptive pill
* Smoking
* Physical activity
50
What are signs and symptoms of Endometrial Cancer?
* **Postmenopausal bleeding** is the classic symptom
* Premenopausal women may have a change intermenstrual bleeding
* Blood stained watery or purulent vaginal discharge (Less common)
* Pain (less common)
51
What are investigations for Endometrial Cancer?
Women ≥ 55 years with post-menopausal bleeding referred using suspected cancer pathway:
* **1st line investigation** is Trans-vaginal ultrasound – normal endometrial thickness (\<4mm) has high negative predictive value.
* **Hysteroscopy with endometrial biopsy sampling** by Pipelle or dilation and curettage (less commonly)
* Pipelle is where a thin flexible tube is inserted into the uterus via a speculum to remove cells for testing
**If metastases at presentation:** intraperitoneal, lung, bone, brain
* FBC, U&Es, LFTs
* CT chest/abdo/pelvis
* MRI pelvis
52
What is the management of Endometrial Cancer?
* **Localised disease**
* Abdominal hysterectomy with bilateral salpingo-oophrectomy.
* High risk patients have post-operative radiotherapy
* Progestogen therapy sometimes used in frail elderly women not suitable for surgery
* **Advanced disease, inoperable disease or unfit for surgery**
* Chemotherapy
* Radiotherapy
* Hormone and palliative care
53
What are the typical features of those presenting with Vulval Carcinoma?
* Around 80% of vulval cancers are squamous cell carcinomas.
* Most cases occur in women over the age of 65 years.
* Vulval cancer is relatively rare with only around 1,200 cases diagnosed in the UK each year.
54
What are risk factors of Vulval Carcinoma?
* Age
* Human papilloma virus (HPV) infection
* Vulval intraepithelial neoplasia (VIN)
* Immunosuppression
* Lichen sclerosis
55
What are signs/symptoms of Vulval Carcinoma?
* Lump or ulcer on the labia majora
* Associated with itching, irritation
56
How is Vulval Carcinoma managed?
* Surgery
* Radiotherapy
