Histo: Gynaecological pathology Flashcards
List some gynaecological infections that cause discomofrt but no serious complications.
- Candida
- Trichomonas vaginalis
- Gardnerella
List some gynaecological infections that cause serous complications.
- Chlamydia (infertility)
- Gonorrhoea (infertility)
- Mycoplasma (spontaneous abortion and chorioamnionitis)
- HPV (cancer)
What is the term used to describe infection of the entire female genital tract?
Pelvic inflammatory disease
What are the usual causes of pelvic inflammatory disease?
- Gonococci
- Chlamydia
- Enterococci
List some complications of pelvic inflammatory disease.
- Peritonitis
- Intestinal obstruction due to adhesions
- Bacteraemia
- Infertility
List some complications of salpingitis.
- Plical fusion
- Adhesions to the ovary
- Tubo-ovarian abscess
- Peritonitis
- Hydrosalpinx
- Infertility
- Ectopic pregnancy
What is an ectopic pregnancy?
When the fertilised ovum implants outside the uterus (e.g. in the Fallopian tube)
List some risk factors for cervical cancer.
- HPV
- Many sexual partners (as increased HPV risk)
- Sexually active early (increased HPV risk)
- Smoking
- Immunosuppression
- COCP
What strains of HPV are considered:
- High risk
- Low risk
- High risk = 16, 18
- Low risk = 6, 11
NOTE: these can cause genital and oral warts and low-grade cervical abnormalities
What is the outcome of HPV infection in most people?
- Undetectable within 2 years in 90% of people
- Persistent infection is associated with high-risk HPV types
What feature of high-risk HPV viruses are responsible for the carcinogenic effects of HPV?
- E6 protein - inactivates p53
- E7 protein - inactivates retinoblastoma
What are the two types of HPV infection? Describe them.
-
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)
What is the cervical transformation zone?
This is the point at which the stratified squamous epithelium becomes columnar epithelium.
Describe the classification of cervical intraepithelial neoplasia.
- CIN1 = lower 1/3 of the epithelium
- CIN2 = lower 2/3 of the epithelium
- CIN3 = entire epithelium
In which type of epithelium does CIN occur?
Usually squamous
What is the term used to describe CIN occurring in columnar epithelium?
Cervical glandular intraepithelial neoplasia (CGIN)
What are the two types of cervical cancer?
- Squamous cell carcinoma
- Adenocarcinoma (20%)
Which staging system is used for cervical cancer?
FIGO staging
Outline the screening intervals for cervical cancer screening.
And what does cytology vs histology look for
- 25-49 = every 3 years
- 49-64 = every 5 years
- 65+ = if no screening since 50 or if abnormal test results
Cytology looks for mild moderate or severe dyskaryosis
histology from biopsy (after referral) looks at CIN 1-3 grade
Other than CIN, what else is screened for in some centres?
- 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
What are the two HPV vaccines that are currently available?
- Bivalent = 16 + 18
- Quadrivalent = 6 + 11 + 16 + 18
NOTE: vaccination is done in girls aged 12 years
List some diseases of the uterine body.
- Congenital anomalies
- Inflammation
- Adenomyosis
- Dysfunctional uterine bleeding
- Enodetrial atrophy/hyperplasia
- Leiomyoma
- Endometrial polyp
- Tumours
What is a leiomyoma? Outline its key features.
- A benign smooth muscle cell tumour in the uterus (MOST COMMON uterine tumour) Fibroid!
- Present in > 20% of women > 35 years
- Often multiple
- Usually asymptomatic
What are the three types of leiomyoma?
- Intramural
- Submucosal
- Subserosal
What is endometrial hyperplasia?
- Increase in stromal and glandular tissue of the endometrium
- Usually driven by oestrogen
- Usually occurs in the perimenopausal period
List some causes of endometrial hyperplasia.
- Persistant anovulation (due to persistently raised oestrogen)
- PCOS
- Granuloma cell tumour of the ovary
- Oestrogen therapy
List some risk factors for endometrial carcinoma.
- Nulliparity
- Obesity
- Diabetes mellitus
- Excessive oestrogen stimulation
What are the subtypes of type I endometrial carcinoma?
- Endometrioid adenocarcinoma
- Mucinous adenocarcinoma
- Secretory adenocarcinoma
Secretory NOT serous
Sarah eats meat
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 - a tumour suppressor gene, P13KCA, K-Ras, CTNNB1, FGFR2, p53
What are the subtypes of type II endometrial carcinoma? And what genetic mutations are associated with 2 of them?
papillary, clear cell, serous tumours
(Paul Can’t Stand (it))
Serous - p53 mutation
Clear cell - HER2
What are the key features of type II endometrial carcinoma?
- Older women with endometrial atrophy
- Less oestrogen-dependent
- Arise in atrophic endometrium
- High grade, deeper invasion and higher stage
Which genetic mutations are associated with clear cell and serous cell carcinoma of the endometrium?
Endometrial Serous Carcinoma
- P53 (90%)
- P13KCA (15%) Her2 amplification
Clear Cell Carcinoma
- PTEN
- CTNNB1
- Her2 amplification
List some prognostic factors in endometrial carcinoma.
- Type
- Grade
- Stage
- Tumour ploidy (diploid has a better prognosis)
- Hormone receptor expression
What is:
- FIGO Stage I
- FIGO Stage II
- FIGO Stage III
- FIGO Stage 4
for endometrial cancer
- FIGO Stage I = confined to the uterus
FIGO stage II = spread to cervix
FIGO stage III = spread to pelvic area & upper 2/3 of vagina
- FIGO Stage 4 = Other pelvic organs outside uterus (e.g. bladder, rectum, adnexae and lower 1/3 vagina and other distant spread (e.g. distant lymph nodes)
What is gestational trophoblastic disease?
A spectrum of tumours characterised by proliferation of pregnancy-associated trophoblastic tissue
List three types of gestational trophoblastic disease.
- Complete and partial mole
- Invasive mole
- Choriocarcinoma
What is the prevalence of complete and partial moles?
1 in 1000 pregnancies
How do complete and partial moles present?
Spontaneous abortion
Sometimes detected as abnormal ultrasound
What is a characteristic investigation finding in complete and partial moles?
Very very high hCG
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
Describe how complete and partial moles form.
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
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)
What is choriocarcinoma?
- Rare (1 in 20,000) rapidly invasive and widely metastasising tumour
- tissue that would normally make the placenta
- Responds well to chemotherapy
- 50% arise in moles
- 25% arise in patients with previous abortion
- 22% arise in normal pregnancy
What is endometriosis?
Presence of endometrial tissue outside the uterus
Outline the possible pathogenesis of endometriosis.
- Metaplasia of pelvic peritoneum
- Retrograde menstruation - endometrial lining travels up the fallopian tubes, into the peritoneal cavity and implants outside the uterus
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
What is adenomyosis?
- Ectopic endometrial tissue deep within the myometrium
- Causes dysmenorrhoea (because it bleeds into the muscle layer and causes pain)
Most common functional ovarian cyst overall? Most common ovarian cyst in pregnancy?
- Follicular (most common)
- luteal cysts (common in early pregnancy. May present with intraperitoneal bleeds)
What are some manifestations of polycystic ovarian syndrome?
- Persistant anovulation
- Obesity
- Hirsutism
What three types of tissue do ovaries consist of?
- Surface epithelium
- Ovarian stroma/sex cord (binds all of ovary together)
- Germ cells
List three types of primary specific ovarian tumour and how common they are
Just think about quantity of the cells! More epithelial cells
- Surface epithelial tumours (70%)
- Germ cell tumours (20%)
- Sex cord/stromal tumours (10%)
List some risk factors for ovarian cancer.
Genetic (BRCA1/2) + basically anything that means you ovulate more as ovulation/rupturing of the follicle is damaging to the ovary
- Nulliparity
- Early menarche
- Late menopause
- Genetic predisposition (MOST SIGNIFICANT - BRCA1/2)
- Infertility
- Endometriosis
- HRT
- Inflammation (PID)
List some protective factors for ovarian cancer.
- After pregnancy
- COCP
Outline the classification of epithelial ovarian tumours.
Benign:
- Serous cystadenoma (most common benign epithelial, buzzword: Psammoma bodies)
- Mucinous cystadenoma (buzzword: mucin secreting cells, K-ras 75%)
Malignant
- Endometrioid (buzzword: tubular glands)
- Clear cell (buzzword: clear cells, hobnail appearance)
Give examples of Type 1 and Type 2 ovarian tumours.
- Type 1 = low grade serous, endometrioid, mucinous and clear cell
- Type 2 = mostly serous
List some benign ovarian tumours.
- Serous cystadenoma
- Cystadenofibroma
- Mucinous cystadenoma
- Brenner tumour
What are borderline tumours?
- Tumours where their biological behaviour cannot be predicted based on histology
- Low but definite malignant potential
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
What are the key features of mucinous tumours?
- 10-20% of ovarian tumours
- Composed of mucin-secreting epithelium (may resemble endocervical or GI epithelium)
What are the key features of endometrioid tumours?
- 10-24% of ovarian tumours
- 10-20% associated with endometrisis
- Better prognosis than mucinous and serous
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
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)
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
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
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
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
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)
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
What proportion of ovarian tumours are familial?
Up to 10%
List three familial syndromes associated with ovarian cancer.
- Familial breast-ovarian cancer syndrome
- Site-specific ovarian cancer
- Cancer family syndrome (Lynch type II)
List some specific genetic associations for serous, mucinous and endometrioid carcinoma.
- Serous - BRCA
- Mucinous and endometrioid - HNPCC
What is lichen sclerosus?
Thinning of the vulval epithelium with a layer of hyalinisation underneath
Name a benign tumour of the vulva.
Papillary hidradenoma
List some other types of malignant tumour of the vulva.
- Squamous cell carcinoma (85%)
- Paget’s diase (adenocarcinoma in situ)
- Adenocarcinoma
- Malignant melanoma
- BCC
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
Buzzword for fitz hugh curtis syndrome?
Violin string peri hepatic adhesions
Commonest organisms for PID in the UK vs rest of the world
Chlamydia and gonorrhoea
TB and schistosomiasis
Bulky uterus + dysmenorrhoea?
Adenomyosis
Chocolate cysts on ovaries and powder burns on macroscopy?
Endometriosis
Most common tumour of the female genital tract?
Leiomyoma
Microscopically - bundles of smooth muscle cells?
Fibroid / leiomyoma
Fibroids + severe abdo pain in pregnancy?
Red degeneration of fibroids
Is VIN and CIN metaplasia, dysplasia or hypertrophy?
Dysplasia
Most common benign ovarian tumour in women under 30?
dermoid cyst
FIGO staging for ovarian cancer?
I - only in ovaries
II - spread to pelvis (uterus, fallopian tubes, bladder)
III - spread to peritoneal cavity
IV - spread to abdominal organs e.g. liver
What is the RMI? What is the formula? What is the cut off score?
How do you calculate it?
RMI = U x M x Ca-125
risk of malignancy - Scoring system to estimate the likelihood of malignant cyst
Cut off score 200
U - ultrasound (1 point for each below. Score /3, where 1=1, 3=2-5 ultrasound features)
- multilocular
- evidence of solid areas
- metastases
- ascites
- bilateral lesions
M - menopause
1 point for premenopausal
3 points for post-menopausal
Ca125
- measured in iu/ml
Leading cause of death from gynaecological malignancy in the UK?
Ovarian carcinoma
Most common ovarian cancer?
Epithelial
2nd most common cancer in women woldwide?
Cervical
FIGO staging for cervical cancer?
Stage 0 = CIN
Stage I = cervix only
Stage II = upper 1/3 vagina
Stage III = pelvic side wall and/or lower 1/3 vagina
Stage IV = mets to bladder/bowel
