Gynaecological Cancer Flashcards
What is the pathogenesis of cervical cancer?
High risk HPVs (sexually transmitted)
- DNA viruses (15 high risk types)
- HPV16 = 60% of cases, HPV18 = 10% of cases
- infect immature metaplastic squamous cells in transformation zone
- provide viral proteins which interfere with activity of tumour suppressor proteins —> inability to repair damaged DNA & increased proliferation of cells
- most genital HPV infections are transient & eliminated by the immune system in months
What are the risk factors for cervical cancer?
- sexual intercourse
- early first marriage/pregnancy
- multiple births
- many partners
- promiscuous partner
- long term use of OCP
- partner with carcinoma of the penis
- low socio-economic status
- smoking
- immunosuppression
Describe the process of cervical screening.
3rd most common cancer in women, but decreasing in rate since introduction of screening
- every 3yrs from age 25yrs-50yrs
- every 5yrs from age 50yrs-65yrs
Cervix accessible to visual examination (colposcopy)
Slow progression from precursor lesions to invasive cancers (years) so screening can detect precursor lesions before progression.
Scrape off cells from transformation zone and stain using Papanicolau (Pap)
Can also test questionable histological samples for HPV DNA
HPV vaccine given to girls, protects for up to 10yrs, but not against all the high risk types
What is cervical intraepithelial neoplasia?
Dysplasia of squamous cells within the cervical epithelium, induced by high risk HPVs
- CIN I = most regress spontaneously —> follow-up or cryotherapy
- CIN II
- CIN III = 10% progress to invasive carcinoma in 2yrs-10yrs, 30% regress
CIN I —> CIN III usually 7yrs
CIN II & III —> superficial excision (cone/large loop excision of transformation zone)
Describe the pathology and treatment of cervical carcinomas.
Average age ~45yrs
- 80% squamous cell carcinomas, 15% adenocarcinomas
- exophytic or infiltrative
- spreads locally to para-cervical soft tissues, bladder, ureters, rectum, vagina
- presents as screening abnormality or postcoital, intermenstrual, or postmenopausal bleeding
Microinvasive carcinoma —> cervical cone excision —> 100% 5yr survival
Invasive carcinoma —> hysterectomy, lymph node dissection, +/- radiation & chemotherapy —> 62% 10yr survival
What is the pathology of endometrial hyperplasia? How is it treated?
Frequent precursor to endometrial carcinoma
Increased gland:stroma
Associated with prolonged oestrogenic stimulation:
- anovulation
- endogenous oestrogen e.g. adipose
- exogenous oestrogen e.g. HRT, tamoxifen (anti-oestrogen in the breast, oestrogen analogue in the endometrium)
If complex or atypical, treated by hysterectomy
What is the pathology of endometrial adenocarcinoma? What are the different subtypes?
Most common invasive cancer of the female genital tract
- usually occurs at 55yrs-75yrs (unusual before 40yrs)
- usually presents with irregular or postmenopausal vaginal bleeding
- overall 10yrs survival = 75%
- polypoid or infiltrative
- endometrioid or serous
What is the pathology of endometrioid endometrial adenocarcinoma?
More common subtype
- mimics proliferative glands
- typically arises in setting of endometrial hyperplasia
- associated with unopposed oestrogen & obesity
- spreads by myometrial invasion & direct extension to adjacent structures
What is the pathology of serous endometrial adenocarcinoma?
Less common than other subtype
- poorly differentiated
- aggressive, worse prognosis
- exfoliates (sheds) —> travels through Fallopian tubes —> implants on peritoneal surfaces
What is the pathology of uterine leiomyoma?
Fibroids - most common tumour in women
- benign tumour of myometrium (malignant transformation probably doesn’t occur)
- resembles normal myometrium
- well circumscribed, round, firm, whitish
- can be tiny or massive
- asymptomatic OR heavy/painful periods, urinary frequency (bladder compression), infertility
What is the pathology of uterine leiomyosarcoma?
Very rare
Peak incidence 40yrs-60yrs
- highly malignant
- does NOT arise from leiomyomas
- metastasises to the lungs
What is the pathology of ovarian tumours? What are the different subtypes?
80% benign - 20yrs-45yrs
Malignant tumours - 45yrs-65yrs (3% of all cancers in women)
Prognosis is often poor:
- 70% 1yr survival
- 41% 5yr survival
- 38% 10yrs survival
Most non-functional (do not produce hormones) —> symptoms caused by mass e.g. abdominal pain, abdominal distension, urinary & GI symptoms, ascites
Hormone-secreting —> menstrual disturbances, inappropriate sex hormones
Serum CA-125 used to diagnose & monitor malignant ovarian tumours
Known BRCA mutation carriers offered prophylactic salpingo-oophrectomy
Types:
- Müllerian epithelium
- Germ cell
- Sex cord stromal
- Secondary tumours
What are the risk factors for ovarian tumours involving the Müllerian epithelium?
- nulliparity or low parity
- OCP protective (prevents ovulation —> epithelium is not required as often)
- BRCA 1/2
- smoking
- endometriosis (increased cell turnover)
What are the different types of Müllerian epithelium ovarian tumours?
SEROUS = often spread to peritoneal surfaces & ovulation —> ascites
MUCINOUS = large, cystic masses filled with sticky, thick fluid (can be 25kg+); benign or borderline
- –> pseudomyxoma peritonei = condition caused by mucinous ascites, epithelial implants on peritoneal surfaces, frequent involvement of the ovaries
- can cause intestinal obstruction
- most likely primary is extra-ovarian, usually appendix
ENDOMETRIOID = tubular glands resembling endometrial glands, can arise in endometriosis (15%-20%), 15%-30% have associated endometrial endometrioid adenocarcinoma
What are the different types of germ cell ovarian tumours?
15%-20% of all ovarian neoplasms
Most are teratomas (usually benign): mature (benign), immature (malignant), monodermal (struma ovarii or carcinoid)
MATURE TERATOMA = most are cystic (dermoid cysts as they contain skin-like structures)
- usually in young women
- bilateral in 10%-15% of cases
- usually contain hair & sebaceous material, can contain teeth
- often tissue from other germ layers present e.g. cartilage, bone, thyroid, neural tissue
MONODERMAL - STRUMA OVARII =
- benign
- mature thyroid tissue
- may be functional —> hyperthyroidism
MONODERMAL - CARCINOID =
- malignant
- may be functional —> 5HT —> carcinoid syndrome
Malignant types include non-gestational choriocarcinoma (produces hCG, aggressive and often fatal), yolk sac tumour (produces alpha-fetoprotein)
What are the different types of sex cord ovarian tumours?
Derived from ovarian stroma (themselves derived from sex cords of embryonic gonad)
Can be feminising (granulosa/thecal cell tumours) or masculinising (Leydig-Sertoli cell tumours)
GRANULOSA CELL TUMOURS =
- usually post-menopausal women
- may produce large amounts of oestrogen —> precocious puberty, endometrial hyperplasia/carcinoma, breast disease
SERTOLI-LEYDIG CELL TUMOURS =
- peak incidence teens-20s
- may block normal female sexual development or cause defeminisation/masculinisation —> breast atrophy, amenorrhoea, sterility, hair loss, hirsutism, clitoral hypertrophy
Give some examples of secondary ovarian tumours.
Müllerian ovarian tumours (uterus, Fallopian tubes, contralateral ovary, pelvic peritoneum)
GI tumours (inc. Krukenberg tumours, usually from stomach)
Breast tumours
What is the pathology of vulval tumours?
Uncommon - 3% of female genital cancers
2/3 in women over 60yrs
Squamous cell carcinomas:
- 30% related to HPV (usually HPV16 - 60yrs)
- 70% unrelated to HPV (usually 80yrs); instead due to longstanding & hyperplastic conditions of the vulva e.g. lichen sclerosus (idiopathic white plaques on the skin around the genitals)
- arise from vulval intraepithelial neoplasia (VIN) = atypical squamous cells within the epidermis (no invasion)
- spreads initially to inguinal, pelvic, iliac, & para-aortic lymph nodes —-> lungs & liver
- lesions
What is gestational trophoblastic disease? What are the different subtypes?
Tumours & tumour-like conditions which show proliferation of placental tissue (villous or trophoblastic)
Hydratidiform mole
Invasive mole
Gestational choriocarcinomas
What is the pathology of hydratidiform moles? How are they treated?
1-3 in 1000 pregnancies
Associated with invasive moles & choriocarcinomas
Complete or partial
- cystic swelling of chorionic villi & trophoblastic proliferation (no foetus or dead foetus - larger proportion of parental chromosomes present)
- usually diagnosed in early pregnancy/presents as miscarriage
- highest risk for teenagers & 40yrs-50yrs
- friable mass of thin-walled, translucent, grape-like structures = swollen oedematous villi
- treated with curettage + hCG monitoring
What is the pathology of invasive moles? How is it treated?
Mole penetrating/perforating the uterine wall
Locally destructive —> uterine rupture (requires hysterectomy)
Causes vaginal bleeding & uterine enlargement
Persistently elevated hCG
Treat with chemotherapy
What is the pathology of gestational choriocarcinomas? How are they treated?
Malignant neoplasm of trophoblastic cells derived from previously normal/abnormal pregnancy (no villi present)
- rapidly invasive, metastasises widely but responds well to chemotherapy
- 50% in association with complete moles, 25% following abortion, 22% following normal pregnancy, 3% in ectopic pregnancy
- usually presents with vaginal spotting
- high hCG levels
Treated with uterine evacuation & chemotherapy (high cure rate)
note: non-gestational choriocarcinomas arise from germ cells in the ovary or in the mediastinum
