Gynae Flashcards
How is Fallopian tube inflammation called?
salphingitis
What is Ovarian inflammation called?
Oophritis
What is PID
Infection ascending from vagina and cervix up to uterus and Fallopian tubes, leading to inflammation (endometritis, salpingitis) and the formation of adhesions.
What are the most common organisms causing PID?
Chlamydia trachomatis and N. gonorrhoea are most common organisms in UK.
In the world: TB and schistosomiasis
What are the complication of PID?
- 10% have Fitz Hugh Curtis syndrome – RUQ pain from peri-hepatitis + “violin-string” peri- hepatic adhesions
- Infertility
- ↑Risk of ectopic pregnancy
- Bacteraemia → SEPSIS
- Tubo-ovarian abscess
- Chronic PID
- Peritonitis
- Plical fusion – fimbrial ends of fallopian tubes adhere together
What is the aetiology of sealpingitis?
Fallopian tube inflammation
Usually due to direct ascent from vacina (except TB)
What is the epidemiology of cervical cancer?
2nd most common cancer affecting women worldwide
Bipmodal age distribution:
1. 30-39
2. >70
What is the aetiology and risk factors for the development of cervical cancer?
95% are associated with HPV infection (especially type 16 and 18)
Many sexual partners, early sexual activity
smoking
immunosuppression
Which HPV tpyes cause genital warts
6& 11
Which HPV types cause cervical cancer?
16&18
What is prognosis of Cervical Cancer?
Depending on Grade:
5 year survival:
90% Grade 1
10% Garde IV
What tissue can uterine tumours arise from?
All (eptheilal/ stroma and muscular layeR)
What are tisk factors for endometrial epithelial tumours
Any that cause overstimmulation of endometirum (hormonal)
what is the most common Endometiral Cancer?
Endometrioid
How does mismattch reapir mutation lead to Carcinom?
Common mutations found
Essentially mutations and mistakes in genes are not detected and repaied –> mutation accumulate
What are the most common pathogens causing PID secondary to termination of pregancy?
S. aureus
Streptococcus
C. perfringens
Coliforms
What are the clincal symptoms of PID?
bilateral lower abdo pain
deep dyspareunia
vaginal bleeding/discharge
fever
adnexal tenderness
and cervical excitation
Name 3 organisms that have serious complications if infecting the female genital tract
Chlamydia: major cause of infertility
Gonorrhoea: major cause of infertility
Mycoplasma: causes spontaneous abortion and chorioamnionitis
HPV: implicated in cancer
What is Cervical intraepithelial neoplasia?
Dysplasia at the Transitional Zone of the Cervix as a result of infection by HPV 16 & 18
Usually epithelial cells (not glandlar cells) undergo transformation
How is CIN graded on histology?
Devided into Grades 1-3
CIN 1 = dysplasia confined to deepest 1/3 of epithelium
CIN 2 = lower 2/3
CIN 3 = full thickness, but basement membrane intact
What is the prognosis for CIN?
60-90% of CIN 1 reverts to normal over 10-23 months
30% of CIN 3 progress to cervical cancer over 10 years if left untreated
What are the two main tissue types of cervical carcinoma?
How common are they?
Majority (80%): Squamous Cell Carcinoma
20%: Adenocarcinoma
What is the difference between pruductive and non-productive HPV infection?
- Non-productive/latent (infection occured but no cellular changes + infection can only be diagnosed by molecular methods)
- Productive → cytological and histological changes (CIN or cervical carcinoma)
How does HPV infection cause Cervical carcinoma? (Molecular mechanisms)
Cervical proteins inhibit TSG
HPV encodes E6 and E7 proteins which inactivate 2 TSG
(TSGs):
1. E6 inactivatesP53→proliferation
2. E7 inactivates Retinoblastoma (Rb) gene→ proliferation
How many people with cervix infected with HPV will develop cancer?
Usually HPV becomes undetectable in 90% of cases within 2 years
10% of persistent infection are at high risk of developing malignancy
What is the frequency of cervical smears (prevention) for women in the UK?
What parameters are looked at during cervical smear screening in the UK?
How good are they?
- Cytology: 50-95% sensitiviy to detect high-grade CIN and SCC
- HPV-DNA test: RNA probe to detect presence of the most common cancer-associated HPV types
At what age is the HPV vaccine administered?
What strains does it prevent?
Offered to Girls and Boys 12-13 years
In England, they are offered
1st dose in school Year 8
2nd dose offered 6 to 24 months after the 1st dose
Vaccinating against 6,11 (warts), 16+18 (cancer) (for Gardasil9)
How is Cervical Carcinoma Staged?
Usually staged using the FIGO system
Stage 0: CIN
Stage I: ONLY Cervix (47%)
Stage II: spread into UPPER 1/3 VAGINA
Stage III: spread into PELVIC SIDE WALL and/or LOWER 1/3 VAGINA
Stage IV:
METASTASIS beyond pelvis to bladder/bowel
What are risk factors for the development of endometrial carcinoma?
Nulliparity
Obesity
Diabetes mellitus
Excessive oestrogen stimulation
What histological types are most endometrial cancers?
85% are adenocarcinomas (incl. endometrioid, serous and clear cell adenocarcinoma)
15% are Squamous Cell Carcinomas
What are the characteristics of an endometrioid adenocarcinoma?
Oestrogen dependent/independent?
What mutations?
Risk factors?
Stage at presentation?
Most common form (80%, looks simialr to endometrial tissue)
- Are oestrogen dependent
- Risk factors: E2 excess: obesity, anovulatory amenorrhoea (e.g. PCOS), nulliparity, early menarche, late menopause, tamoxifen
- Often associated with atypical endometrial hyperplasia
- Develop through the accumulation of mutations of different genes (PTEN mutation in >50% of genes)
- Can present high and low grade/stage at presentation
What is the epidemiology of endometrial cances?
What is the epidemiology of endometrioid adenocarcinoma vs. clear cell/ seroud?
Most common gynaecological malignancy in developed countries, causing 6% of new cancer cases in women (4th common malingnancy in women)
Endometrioid: perimenopausal most common
Serous/clear cell: post-menopausal most common
What are the characteristics of serous and clear cell adenocarcinoma of the endometrium?
Oestrogen dependent/independent?
What mutations?
Risk factors?
Stage at presentation?
Older, postmenopausal
Less oestrogen dependent
Arise in atrophic endometrium
High grade, deeper invasion, higher stage
Serous cell
- P53 mutations in 90%
- PI3KCA mutations in 15% Her-2 amplification
Clear cell
- PTEN mutation
- CTNNB1 mutation
- Her-2 amplification
How are endometrial carcinomas staged?
FIGO system:
1. Stage 1 – Cancer ONLY in uterus
2. Stage 2 – spread to CERVIX
3. Stage 3 – spread to PELVIC AREA
4. Stage 4 – METASTASIS to rectum/bladder/distal organs
How are serous cells and clear cell endometrial cancers graded?
How are endometrioid adenocarcinoma graded?
- Serous, clear cell, mixed, undifferentiated, dedifferentiated and carcinosarcoma are considered high grade.
Endometrioid in FIGO 3 grade system graded
What is the epidemiology of leiomyomas?
Fibroids
Benign smooth muscle tumour (myometrium)
20% of women >35yrs
(oestrogen dependent- enlarge during prengnacy, shrink post-menopausal)
What is a leiomyosarcoma?
Epidemiology?
Prognosis?
Usual characteristics
Malignant counterpart of a leiomyoma
Usually
- single, solitary lesion with local invasion and blood spread
- Rare, but most common in post-menopausal women
- 5 year survival 20-30%
What is the epidemiology of endometriosis?
Common - 10% of premenopausal women
What are features that make you more suspicious of malignancy in an ovarian cyst?
+ Multi-locular more likely to be malignant
What is a functional ovarian cyst?
Functional = the cysts develop as a result of physiological processes
Result from a disruption in the development of follicles or the corpus luteum and often resolve on their own
What are the 3 different sub-groups of functional ovarian cysts?
- Follicular cysts (most common cyst in young women, when graafian follicle does not rupture and continues to grow)
- Corpus luteum cyst (failed regression of corpus luteum, associated with pregnancy or progesterone only pills)
- Theca lutein cyst - multiple bilateral cysts due to overstimmulation by gonadotrophin (ofen ß-hCg)
What are different non-functional ovarian cysts? What are their characteristics?
- Chocolate cysts - endometriosis: cyst with blood or other fluids
- Dermoid cysts - bening teratoma
- Cystadenoma (serous or mucinous) - bening counterparts of the malignant sub-types
What is the most common type of ovarian tumours?
What is its epidemiology?
Epithelial tumours (95% of malignant tumours)
However:most ovarian tumours are benign
50% found in 45-65 yo, otherwise post-menopausal
What are the 2 most common types of benign ovarian epitheliam tumours?
- Serous Cystadenomas
- Mucinous cystadenomas
What is serous cystadenoma?
What is it’s epidemiology?
Most common benign epithelial ovarian tumours
usually in women aged 30-40
What type of tumour is a mucinous cystadenoma?
What is its epidemiology?
What would be findings on histology?
2nd most common bening epithelial tumour of the ovaries
Affects younger women
usually derived from mucin secreting cells (seen on histology)
What genetic mutation is commonly seen in mucinous cystadenomas?
What hormone does it commonly secrete?
K-ras mutation present in 75% of cases
Most common oestrogen-secreting tumour
mucinous cystadenomas 2nd most common benign epithelial tumours of ovary
What is pseudomyxoma perionei?
What is is associated with?
Peritoneal spread of mucinous tumours
Ovarian epithelial tumours (mucinous cystadencarciomas) might spread to periotoneal cavity and form more mucinous tumours
Most commonly arise from appendix, but can also come from ovaries
What is endometrioid ovarian cancer?
What are common histological findings?
What is the prognosis?
Mimics endometrium – i.e. form tubular glands (therefore endometriosis is a risk factor)
Usually better differentiated and better prognosis than high-grade serous carcinomas
A 60 yo patient presents wih an ovarian cyst. Biopsy of the cyst shows psammoma bodies - whatt is the most likely diagnosis?
High-grade serous carcinoma
Psammoma bodies are calcified, concentric rings
What is the most common type of ovarian cancer?
High-grade serous carcinomas
Serous cystadenocarcinomas (80%)
What tumours is a raise in Ca125 associated with (sub-types)?
What other diesease might lead to a rise in this?
CA-125 is used as a tumor marker for epithelial ovarian cancer
- but can also be elevated in
- endometriosis
- cirrhosis
- and malignancies (e.g., uterine leiomyoma).
What are risk factors for the devlopment of ovarian cancer?
- Nulliparity
- infertility
- early menarche
- late menopause
- +ve Family history of Ovarian/breast cancer
- Endometriosis
- smoking (mucinous tumours only)
- obesity
- IUD
Protective
- COCP
What genetic mutations are associated with familiar ovarian cancer?
What is their inheritence pattern?
Most common: association with mutations in BRCA 1 + BRCA 2 (>90%) (familial breast-ovarian cancer syndrome)
- Cancer family syndrome (Lynch type II)
Usually inherited autosomal dominantly
What gene is mutated in Lynch II syndrome?
What does it increase the risk of?
Inherited Cancer type with mutations in various DNA mismatch repair genes
Hereditary nonpolyposis colorectal cancer - usually presents with Colorectal Carcinoma (CRC) but 40% also associated with ovarian cancer (endometrioid and clear cell types)
What genetic mutations are commonly seen in high-grade ovarian serous carcinoma?
Alteration in P53, in virtually all
BRCA1 or BRCA2 abnormalities (germline and somatic mutations; BRCA1 promoter methylation)
What are common genetic mutations in low grade ovarian serous carcinoma?
Distinct pathogenesis from high grade serous carcinoma.
Low grade, relatively indolent, arise de novo or from borderline ovarian tumours.
Mutations in KRAS, BRAF.
No association with BRCA mutations.
What is the risk factor for development of endometrioid carcinoma?
- Endometriosis
- (Endometrial cancer present in 10-15%)
What is the most importnat risk factor in the developemnt of clear cell ovarian carcinomas?
Strong association with endometriosis
What is a Kurkenberg tumour?
What is a common histological finding?
Ovarian metastases associated with primary cancers of stomach, breat and colon
Buzzword on histology: Mucin producing signet ring cells
What are characteristics of borderline ovarian tumours?
Borderline of malignant and Bening
Bening:
1. well-diferentiated
2. do not invade BM
Malignant
1. nuclear pleomorphism
2. cellular atypia
3. spread to adjacent structures
What ovarian cancer sub-types are associated with endometriosis?
- Endometrious
- Clear cell
What are usual presenting features of ovarian cancer?
- increased abdominal girth/bloating
- persistent pelvic/abdominal pain
- early satiets
And even more unspecific
- fativue, change in bowel habits + urinary frequency
? Adnexal mass
What tumour markers can be used for Preop and follow up planning in epithelial ovarian cancers (mucinous)
For all: Ca125
but also: Ca19-9
What types of ovarian cancers can increased the tumour marker inhibin?
Granulosa cell tumours
(only useful in follow-up)
What types of ovarian cancers can increased the tumour marker hCG
dysgerminoma
Chariococarcinomas
What types of ovarian cancers can increased the tumour marker AFP?
Endodermal yolk sac
Teratomas
What investigations would you do in a women with suspected ovarian cancer?
Calculate risk of a Malignancy index
1. Menopausal state
2. Pelvic ultrasound
3. CA125 levels
If intermediate or High
1. CT Abdo Pelvs / MRI
Usually then straight into surgical removal, biopsy only done if diagnosis uncertain or primary chemotherapy is considered
What staging system is used to stage ovarian cancers?
FIGO saging
What are the characteristics of sex-cord stromal ovarian tumours?
What is the epidemiology?
Account for 10% of ovarian tumours
Similar epidemiology, but some sub-types can present younger
But 90% of all hormone-producing tumours
What is the most common sex-cord ovarain tumour?
What are the others?
Most common: Graunulosa cell ttumours (presents with large pelvic mass or pain due to torsion)
Others
1. Sertoli-Leydic cells (produce androgens, rarely oestrogens)
others
What tumour markers would you order if you suspected a germ-clel tumour?
Depending on sub-type
Collectively can order
- AFP (yolk sac, immature teratoma, embryonal(
- LDH
- ß-hCG (Choriocarcinoma, dysgerminoma)
What is the epidemiology of germ-cell ovarian tumours?
What is the most common sub-type?
Account for 10% of ovarian tumours
Usually present in young women
Most common
1. Dysgerminjoma (50%) - sometimes ß-HCG
2. Yolk-sac tumours (10-15%) - AFP
3. Teratomas (10%)
4. non-gestational choriocarcinomas are very rare
