Histo: Gynaecological pathology Flashcards
1
Q
List some gynaecological infections that cause discomofrt but no serious complications.
A
- Candida
- Trichomonas vaginalis
- Gardnerella
2
Q
List some gynaecological infections that cause serous complications.
A
- Chlamydia (infertility)
- Gonorrhoea (infertility)
- Mycoplasma (spontaneous abortion and chorioamnionitis)
- HPV (cancer)
3
Q
Pelvic inflammatory disease definition
A
Infection of one or more of reproductive organs - uterus, ovaries, fallopian tubes
4
Q
What are the usual causes of pelvic inflammatory disease?
A
- Gonococci
- Chlamydia
- Enterococci
5
Q
List some complications of pelvic inflammatory disease.
A
- Peritonitis
- Intestinal obstruction due to adhesions
- Bacteraemia
- Infertility
- Liver capsule inflammation –> adhesions –> fitz-hugh curtis syndrome
6
Q
List some complications of salpingitis.
A
- Plical fusion
- Adhesions to the ovary
- Tubo-ovarian abscess
- Peritonitis
- Hydrosalpinx
- Infertility
- Ectopic pregnancy
7
Q
What is an ectopic pregnancy?
A
When the fertilised ovum implants outside the uterus (e.g. in the Fallopian tube)
8
Q
List some risk factors for cervical cancer.
A
- HPV
- Many sexual partners
- Sexually active early
- Smoking
- Immunosuppression
9
Q
What strains of HPV are considered:
- High risk
- Low risk
A
- High risk = 16, 18
- Low risk = 6, 11
NOTE: these can cause genital and oral warts and low-grade cervical abnormalities
10
Q
What is the outcome of HPV infection in most people?
A
- Undetectable within 2 years in 90% of people
- Persistent infection is associated with high-risk HPV types
11
Q
What feature of high-risk HPV viruses are responsible for the carcinogenic effects of HPV?
A
- E6 protein - inactivates p53
- E7 protein - inactivates retinoblastoma
12
Q
What are the two types of HPV infection? Describe them.
A
-
Latent (non-productive)
- HPV DNA continues to reside within basal cells
- Infectious virions are not produced
- Replication of viral DNA is coupled to replication of epithelial cells
- This means that complete viral particles are not produced
- Cellular effects of HPV are not seen
-
Productive
- Viral DNA replication occur independently of host chromosomal DNA synthesis
- Large amount of viral DNA and infectious virions are produced
- Characteristic cytological and histological featuers are seen (halo around the nucleus - koilocyte)
13
Q
What is the cervical transformation zone?
A
This is the point at which the stratified squamous epithelium becomes columnar epithelium.
14
Q
Describe the classification of cervical intraepithelial neoplasia.
A
- CIN1 = lower 1/3 of the epithelium
- CIN2 = lower 2/3 of the epithelium
- CIN3 = entire epithelium
basement membrane INTACT - premalignant + pre-invasive
15
Q
In which type of epithelium does CIN occur?
A
Usually squamous
16
Q
What is the term used to describe CIN occurring in columnar epithelium?
A
Cervical glandular intraepithelial neoplasia (CGIN)
17
Q
What are the two types of cervical cancer?
A
- Squamous cell carcinoma
- Adenocarcinoma (20%)
18
Q
hpv vaccine provides protectiona gainst which strains
A
most common low risk and high risk strains:
gardasil - 6,11,16,18
19
Q
Which staging system is used for cervical cancer?
A
FIGO staging
20
Q
Outline the screening intervals for cervical cancer screening.
A
- 25-49 = every 3 years
- 49-64 = every 5 years
- 65+ = if no screening since 50 or if abnormal test results
21
Q
Other than CIN, what else is screened for in some centres?
A
- High risk HPV using molecular genetic analysis
- Hybrid captue II (HC2) HPV DNA test - smear is mixed with fluid containing RNA probes that match 5 low-risk and 13 high-risk types of HPV
22
Q
What are the two HPV vaccines that are currently available?
A
- Bivalent = 16 + 18
- Quadrivalent = 6 + 11 + 16 + 18
NOTE: vaccination is done in girls aged 12 years
23
Q
List some diseases of the uterine body.
A
- Congenital anomalies
- Inflammation
- Adenomyosis
- Dysfunctional uterine bleeding
- Enodetrial atrophy/hyperplasia
- Leiomyoma
- Endometrial polyp
- Tumours
24
Q
What is a leiomyoma? Outline its key features.
A
- A benign smooth muscle cell tumour in the uterus (MOST COMMON uterine tumour)
- Present in > 20% of women > 35 years
- Often multiple
- Usually asymptomatic
25
What are the three types of leiomyoma?
* Intramural - most common
* Submucosal
* Subserosal
26
What is endometrial hyperplasia?
* Increase in stromal and glandular tissue of the endometrium
* Usually driven by oestrogen
* Usually occurs in the perimenopausal period
27
List some causes of endometrial hyperplasia.
* Persistant anovulation (due to persistently raised oestrogen)
* PCOS
* Granulosa cell tumour of the ovary
* Oestrogen therapy
28
List some risk factors for endometrial carcinoma.
* Nulliparity
* Obesity
* Diabetes mellitus
* Excessive oestrogen stimulation
29
What are the subtypes of type I endometrial carcinoma?
* Endometrioid adenocarcinoma
* Mucinous adenocarcinoma
* Secretory adenocarcinoma
| 85% endometrial cancer
30
What are the key features of type I endometrial carcinoma?
* Younger patients
* Oestrogen-dependent
* Often associated with atypical endometrial hyperplasia
* Low-grade tumours that are superficially invasive
* Genetic mutations: PTEN, P13KCA, K-Ras, CTNNB1, FGFR2, p53
31
What are the subtypes of type II endometrial carcinoma?
Serous and clear cell tumours
| 15% of endometrial cancer
32
What are the key features of type II endometrial carcinoma?
* Older patients
* Less oestrogen-dependent
* Arise in atrophic endometrium
* High grade, deeper invasion and higher stage
33
Which genetic mutations are associated with the two types of type II endometrial carcinoma?
**Endometrial Serous Carcinoma**
* P53 (90%)
* P13KCA (15%) Her2 amplification
**Clear Cell Carcinoma**
* PTEN
* CTNNB1
* Her2 amplification
34
List some prognostic factors in endometrial carcinoma.
* Type
* Grade
* Stage
* Tumour ploidy (diploid has a better prognosis)
* Hormone receptor expression
35
What is:
* FIGO Stage I
* FIGO Stage 4
in endometrial cancer
* **FIGO Stage I** = confined to the uterus
* **FIGO Stage 4** = Other pelvic organs outside uterus, adnexae and vagina and other distant spread (e.g. distant lymph nodes)
36
What is gestational trophoblastic disease?
A spectrum of tumours characterised by proliferation of pregnancy-associated trophoblastic tissue
37
List three types of gestational trophoblastic disease.
* Complete and partial mole
* Invasive mole
* Choriocarcinoma
38
What is the prevalence of complete and partial moles?
1 in 1000 pregnancies
39
How do complete and partial moles present?
Spontaneous abortion
Sometimes detected as abnormal ultrasound
| severe vomiting
40
What is a characteristic investigation finding in complete and partial moles?
Very very high hCG --> can cause hyperthyroid symptoms due to similar structure of HCG to TSH
41
What are the chances of moles progressing to malignancy?
* NO partial moles progress to malignancy
* 2.5% of complete moles progress to malignancy
* 10% of complete moles develop into locally destructive invasive moles
42
Describe how partial mole form.
**Partial mole**
* A normal ovum containing 23X gets fertilised by TWO sperm leading to the presence of 3 sets of chromosomes (2 paternal + 1 maternal)
* Dispermia → diandry
* Overdose of male chromosomes driver proliferation
* Can also occur due to fertilisation of a normal egg by a sperm carrying unreduced paternal genome (46XY)
| fetal material present
43
describe how complete hydatitiform mole forms
**Complete mole**
* Occurs when you get fertilisation of an EMPTY egg
* Reduplication of the 23X from sperm results in a homozygous diploid 46XX genome
* Can also occur due to fertilisation of an empty egg by 2 sperms with 2 independent sets of 23X or 23Y
44
Macrosopic and US appearance of complete mole
macrosopic - bunch of grapes
US - snowstorm
45
Prevalence and prognosis of choriocarcinoma?
Who does it occur in?
* Rare (1 in 20,000) rapidly invasive and widely metastasising tumour
* Responds well to chemotherapy
* 50% arise in moles
* 25% arise in patients with previous abortion
* 22% arise in normal pregnancy
| Mets to brain, lung, vagina, kidney, liver
46
What is endometriosis?
Presence of endometrial tissue outside the uterus
| 10% of pre-menopausal women
47
Outline the possible pathogenesis of endometriosis.
* spontaneous metaplasia of pelvic peritoneum
* Retrograde menstruation - endometrial lining travels up back the fallopian tubes, into the peritoneal cavity and implants outside the uterus
48
endometriosis vs adenomyosis
endometriosis - endometrial tissue outside of uterus
adenomyosis - endometrial tissue within the myometrium (still in uterus)
49
Why is endometriosis an issue?
* It is functional and bleeds at the time of menstruation
* Can lead to pain, scarring and infertility
* May develop hyperplasia or malignancy
50
macroscopic endometriosis appearance
power burns and chocolate cysts (endometrioma)
51
What is adenomyosis?
* Ectopic endometrial tissue deep within the myometrium
* Causes dysmenorrhoea (because it bleeds into the muscle layer and causes pain)
52
List two types of non-neoplastic functional ovarian cysts.
* Follicular and luteal cysts
* Endometriotic cyst
53
follicular ovarian cyst pathophysiology
dominant follicule doesn't undergo rupture to release egg during ovulation
or
non dominant follicle doesn't undergo atresia
54
corpus luteal cyst formation
corpus luteum does not degrade following release of egg --> filled with blood or fluid
(once dominant follicle releases egg its remnants form corpus luteum)
often identified in early pregnancy --> should spontaneously regress
55
What are some manifestations of polycystic ovarian syndrome?
* Persistant anovulation
* Obesity
* Hirsutism
56
What three types of tissue do ovaries consist of?
* Surface epithelium
* Ovarian stroma
* Germ cells
57
List three types of primary specific ovarian tumour.
* Surface epithelial tumours
* Sex cord stromal tumours - post menopausal
* Germ cell tumours - 15-21 AND 60-69
58
List some risk factors for ovarian cancer.
increased estrogen exposure
* Nulliparity
* Early menarche
* Late menopause
* HRT
* Genetic predisposition (MOST SIGNIFICANT)
* Infertility
* Endometriosis
* Inflammation (PID)
59
List some protective factors for ovarian cancer.
* After pregnancy
* OCP
60
Outline the classification o epithelial ovarian tumours.
**Type 1**
* Low grade
* Relatively indolent and arise from well characterised precursors (benign tumours) and endometriosis
* Mutations: K-Ras, BRAF, P13KCA, Her2, PTEN, beta-catenin
**Type 2**
* HIGH GRADE
* Aggressive
* P53 mutation in 75% of cases
* NO precursor lesion
61
Give examples of Type 1 and Type 2 ovarian tumours.
* Type 1 = low grade serous, endometrioid, mucinous and clear cell
* Type 2 = mostly serous
62
List some benign ovarian tumours.
* Serous cystadenoma
* Cystadenofibroma
* Mucinous cystadenoma
* Brenner tumour
63
What are borderline tumours?
* Tumours where their biological behaviour cannot be predicted based on histology
* Low but definite malignant potential
64
What are the key features of serous tumours?
* MOST COMMON type of ovarian tumour
* Usually cystic
* 30-50% bilateral
* Benign tumours are lined by bland epithelium
* Borderline tumours have a more complex, atypical epithelial lining with papillae but no invasion through the basement membrane
* Malignant tumours are invasive with a poor prognosis
65
What are the key features of mucinous tumours?
* 10-20% of ovarian tumours
* Composed of mucin-secreting epithelium (may resemble endocervical or GI epithelium)
66
What are the key features of endometrioid tumours?
* 10-24% of ovarian tumours
* 10-20% associated with endometrisis
* Better prognosis than mucinous and serous
67
What are the key features of clear cell tumours?
Strong association with endometriosis
NOTE: called clear cell because the cytoplasm contains a lot of glycogen
68
List four types of sex cord stromal tumours.
* Fibroma
* Granulosa cell tumour (may produce oestrogen)
* Thecoma (may produce oestrogen (rarely androgens))
* Sertoli-Leydig cell tumour (may be androgenic)
69
What are the key features of germ cell tumours?
* 20% of ovarian tumours
* 95% are benign
* Mainly occur in \< 20 years
* Classified based on how they differentiate
70
What are the four main types of germ cell tumour?
* **Dysgerminoma** - no differentiation
* **Teratoma** - from embryonic tissues
* **Endodermal sinus tumour** - from extraembryonic tissue (e.g. yolk sac)
* **Choriocarcinoma** - from trophoblastic cells which would form the placenta
71
What are the key features of a mature teratoma?
* Most common type of germ cell tumour
* Benign
* May show different lines of maturation but all tissues will mature to adult-type tissues
* Teeth and hair are common
72
What are the key features of an immature teratoma?
* Indicates presence of embryonic elements (most commonly neural tissue)
* Malignant tumour that grows rapidly, penetrates the capsule and forms adhesions
* Spreads within peritoneal cavity and metastasis to the lymph nodes, lungs, liver and other organs
73
What is a mature cystic teratoma with malignant transformation?
When any type of mature tissue within a teratoma becomes malignant (most commonly squamous cell carcinoma)
74
Name two secondary ovarian tumours.
* Krukenberg Tumour - bilateral metastases composed of mucin-producing signet ring cells (usually from breast or gastric cancer)
* Metastatic colorectal cancer
75
What proportion of ovarian tumours are familial?
Up to 10%
76
List three familial syndromes associated with ovarian cancer.
* Familial breast-ovarian cancer syndrome
* Site-specific ovarian cancer
* Cancer family syndrome (Lynch type II)
77
List some specific genetic associations for serous, mucinous and endometrioid carcinoma.
* Serous - BRCA
* Mucinous and endometrioid - HNPCC
78
What is lichen sclerosus?
Thinning of the vulval epithelium with a layer of hyalinisation underneath
79
what are the types of VIN
what are they associated with
usual - associated with HPV infection 16,18, warty or basaloid presentation, 95% of VIN
differentiated - associated with lichen sclerosus, older women, keratinised squamous cell, higher risk of malignant progression
80
Name a benign tumour of the vulva.
Papillary hidradenoma
81
List some other types of malignant tumour of the vulva.
* Squamous cell carcinoma (85%)
* Paget's diase (adenocarcinoma *in situ*)
* Adenocarcinoma
* Malignant melanoma
* BCC
82
What are some diseases that can affect the vagina?
* Congenital anomalies (e.g. atresia)
* Tumours (rare)
* Carcinoma (squamous cell carcinoma)
* Adenocarcinoma (increased risk of clear cell carcinoma in women with threatened miscarriage treated with diethyl stillbosterol)
* Rhabdomyosarcoma
