Flashcards in Repro Session 12 Deck (121):
What are almost all cases of cervical cancer related to?
High risk HPV strains 16 and 18
Describe the pathogenesis of CIN and cervical carcinoma from HPV infection.
Infection of immature metaplastic squamous cells in transformational zone --> production of viral proteins in E6&7 --> inability to repair damaged DNA and inhibited apoptosis
What are the risk factors for cervical carcinoma associated with increased risk of HPV infection?
Sexual intercourse, early 1st marriage, early 1st pregnancy, multiple births, multiple partners, promiscuous partner, long-term use of OCP
What are the risk factors for cervical carcinoma associated with the immune response to HPV infection?
Low SES class, smoking, immunosuppression
Why does having a partner with carcinoma of the penis increase the risk of developing cervical carcinoma?
Associated with HPV
What is cervical intraepithelial neoplasia?
Dysplasia of squamous cells within the cervical epithelium
Describe the progression of CIN.
Starts as CINI, most of which spontaneously regress but some develop into CINII and CINIII
What are the treatment options for the 3 stages of CIN?
I: follow-up +/- cryotherapy
II and III: superficial excision
How long does the progression of CIN typically take?
What are the outcomes of CINIII?
30% regress, 10% progress to invasive carcinoma
How does cervical carcinoma present?
~45% as screening abnormality or postcoital/intermenstrual/postmenopausal vaginal bleeding
What is the distribution of types of cervical carcinoma?
80% SCC, 15% adenocarcinomas
How does cervical carcinoma of either type spread?
Locally by invasion to paracervical soft tissues, bladder, ureters, rectum, vagina; via lymph to paracervical, pelvic or para-aortic nodes; distally
What is the treatment for microinvasive cervical carcinoma?
Cervical cone excision
What is the 5-year survival rate for treated microinvasive cervical carcinoma?
What is the treatment for invasive cervical carcinoma?
Hysterectomy +/- lymph node dissection, radiation, chemotherapy
What is the 10-year survival rate for treated invasive cervical carcinoma?
What frequently precedes endometrial adenocarcinoma?
What changes are seen in endometrial hyperplasia?
Increase in gland:stroma ratio +/- abnormal cells
What is endometrial hyperplasia associated with?
Prolonged oestrogen stimulation
What are risk factors for endometrial adenocarcinoma?
Anovulation, excess adipose tissue, OCP use
What are the treatment options for endometrial hyperplasia?
What is the most common invasive cancer of the female genital tract?
When does endometrial adenocarcinoma usually present?
How does endometrial adenocarcinoma typically present?
With irregular or postmenopausal vaginal bleeding
Why does endometrial adenocarcinoma have a high 10-year survival rate?
Early symptoms are alarming so pts present early
What are the two type of endometrial adenocarcinoma?
Endometrioid and serous carcinoma
What are the differences between the two type of endometrial adenocarcinoma?
Endometrioid: more common, mimics proliferative glands
Serous carcinoma: less common, poorly differentiated, aggressive with a worse prognosis
How does endometrioid endometrial adenocarcinoma spread?
Myometrial invasion, direct extension to adjacent structures, local lymph nodes and distant sites
How does serous carcinoma endometrial adenocarcinoma spread?
Tumour cells exfoliate and travel through Fallopian tubes where they can implant on peritoneal surfaces and cause death
Why is cervical carcinoma suitable for screening?
High incidence, simple and easy test, slow progression from identifiable precursor lesion and has a curative treatment
How is cervical carcinoma screening carried out?
Cells from transformational zone are scraped, stained with Papanicalou stain and examined by microscopy to look for dyskaryosis. Followed by colposcopy/biopsy if needed
Why are molecular methods of cervical cancer screening not currently used?
Test for HPV in cervical cells is not available for all high risk types
Why is cervical carcinoma screening required when there is an effective HPV vaccine in routine use?
Vaccine only protects for 10 years and is not effective against all high-risk types
Who is invited for cervical carcinoma screening?
25-50 y.o. Females 3-yearly
50-65 y.o. Females 5-yearly (unless abnormal result)
What is leiomyoma?
Benign tumour of smooth muscle
What are the S/S of leiomyoma of the myometrium?
Asymptomatic or heavy/painful periods, urinary frequency, infertility
Do leiomyomas of the myometrium undergo malignant transformation?
How does leiomyoma of the myometrium appear macroscopically?
Well circumscribed, round, firm and whitish
How does leiomyoma of the myometrium appear microscopically?
Well differentiated, appearing as normal smooth muscle
What is uterine leiomyosarcoma?
Uncommon tumour presenting at 40-60 y.o. and is highly malignant
Where does leiomyosarcoma metastasise to early in its disease process?
Is uterine leiomyosarcoma associated with leiomyoma?
What is the treatment for leiomyosarcoma?
Total abdominal hysterectomy
Are the majority of ovarian tumours benign or malignant?
At what age do benign ovarian tumours tend to present?
At what age do malignant ovarian tumours tend to present?
Why is the prognosis of malignant ovarian tumours poor?
Often spread beyond ovary by the time of presentation
Where do malignant ovarian tumours spread before presentation?
50% to opposite ovary, liver, lungs, regional lymph nodes
What are the S/S of non-functional ovarian tumours?
Abdominal pain, abdominal distension, urinary and GI S/S, ascites
What are the S/S of non-functional ovarian tumours due to?
What are the S/S of functional ovarian tumours?
Mestrual disturbances, inappropriate sex hormones
When is prophylactic salpingoophorectomy indicated in ovarian tumours?
Gene analysis positive for BRCA mutation
What serum marker can be used for ovarian tumours?
What are the four cell origins of ovarian tumours?
Müllerian epithelium, germ cells, sex-cord stromal cells and metastases
What are the 3 main histological types of Müllerian epithelial ovarian tumours?
Serous, mucinous, endometrioid
How can all types of Müllerian epithelium ovarian tumour be classified?
Benign, borderline or malignant
What are the risk factors for Müllerian epithelium ovarian tumours?
Nulliparity, low parity, BRCA1&2, smoking, endometriosis
What is the consequence of serous Müllerian epithelium ovarian tumours being friable and fragile?
Often exfoliate and spread to peritoneal surfaces causing ascites
How do mucinous Müllerian epithelium ovarian tumours appear macroscopically?
Large cystic masses filled with sticky fluid
How are most mucinous Müllerian epithelium ovarian tumours classified?
How can mucinous and endometrioid Müllerian epithelium ovarian tumours be differentiated microscopically?
Mucinous have glands with goblet cells, endometrioid have tubular glands resembling endometrial glands
What is pseudomyxoma peritonei?
Exfoliation and invasion of tumour cells (commonly appendix) with epithelial implantation in the ovaries or peritoneal surfaces --> intestinal obstruction and mucinous ascites
What are endometrioid ovarian tumours seen in 15-20% of cases of?
What associated condition do 15-30% of endometrioid ovarian tumours have simultaneously?
Endometrial endometrioid adenocarcinoma
What are the 3 groups of ovarian germ cell tumours?
Mature (benign), immature (malignant), monodermal (highly specialised)
What are the majority of germ cell ovarian tumours?
Benign cystic teratomas with many tissue types
Who are germ cell ovarian tumours typically seen in?
What is non-gestational choriocarcinoma?
Malignant ovarian germ cell tumour that is aggressive and fatal
What do non-gestational choriocarcinoma secrete?
What do yolk-sac tumours secrete?
What type of tumours are yolk sac tumours?
Malignant ovarian germ cell
What is stroma ovarii?
Monodermal ovarian germ cell tumour of benign functioning thyroid tissue
What is the name of the malignant monodermal ovarian germ cell tumour that secretes 5HT?
How do carcinoid ovarian tumours lead to carcinoid syndrome?
Release 5HT that is not rapidly metabolised by the liver due to the venous drainage of the ovary
Which cells can sex-cord stromal ovarian tumours resemble?
Sertoli, Leydig, granulosa, theca
Who do granulosa cell ovarian tumours present in?
What are the effects of a granulosa cell tumour in a pre-pubertal girl?
What are the effects of a granulosa cell tumour in an adult woman?
Endometrial hyperplasia and carcinoma, breast disease
What is the peak incidence of of Sertoli-Leydig cell tumours?
What are the effects of Sertoli-Leydig cell tumours?
Delayed puberty, defeminisation, masculinisation inc breast atrophy, sterility, hair loss, hisutism, clitoral hypertrophy
What are the most common origins of ovarian metastases?
Müllerian tumours from the uterus, Fallopian tubes, contralateral ovary, pelvis or peritoneum
What non-Müllerian tumour metastases are seen in the ovaries?
GI tumours or lobular breast tumours
What is a Krukenberg tumour?
Often bilateral metastatic GI tumour (usually stomach) within the ovaries
How does a tumour in the stomach become a Krukenberg tumour?
Erodes through stomach wall, cells exfoliate and undergo trasceolomic spread
Describe the epidemiology of vulval tumours.
Uncommon, ~3% of female genital tumours with 2/3 of pts >60 y.o.
What are the types of vulval tumour?
Squamous cells carcinoma, basal cell carcinoma, extra mammary Paget's disease, malignant melanoma
What is the precursor to SCC of the vulva?
Vulvular intraepithelial neoplasia (VIN)
What is VIN?
In situ precursor of SCC of the vulva with atypical squamous cells within the epidermis
How is VIN identified macroscopically?
White patches on non-keratinised skin and brown patches on keratinised skin
If SCC of the vulva presents in the 6th decade what is the likely association?
Are the majority of vulval SCCs related to HPV?
No, ~70% unrelated
Do vulval SSCs not related to HPV tend to present earlier or later than those that are related?
What risk factors are associated with non-HPV related vulval SSC?
Longstanding inflammatory and hyperplastic conditions of the vilva e.g. Lichen sclerosus
What is lichen sclerosus?
Band of chronic inflammation above the BM leaves a sclerotic band of tissue. Autoimmune
How do vulval SSCs spread initially?
Via lymph to inguinal, pelvic, iliac and para-aortic nodes
Where can SCCs of the vulva spread outside of the lymphatic system?
Lungs and liver
What treatment of vulval SCC gives 90% 5-year survival?
Vulvectomy and lymphadenectomy
What is the most common site of extra-mammary Paget's disease?
Describe extra mammary Paget's disease of the vulva.
Itchy, red, scaly plaques in areas rich in apocrine glands
What are tumours of gestation?
Tumours and tumour-like conditions that show proliferation of placental tissue
What types of tissue may proliferate in gestational tumours?
Villous and /or trophoblastic
Describe the pathogenesis of hyaditiform mole.
Cystic swelling of chorionic villi and trophoblastic proliferation creates a friable mass of thin-walled, translucent grape-like structures
Who are the highest risk age groups for hyaditiform mole?
Teenagers and 40-50 y.o.
How are hyaditiform moles usually diagnosed?
In early pregnancy by US or presenting as a miscarriage
What other gestational tumours are hyaditiform moles associated with that are more aggressive and have a poorer prognosis?
Invasive mole and choriocarcinoma
What is a complete hyaditiform mole?
Sperm fertilises an empty ovum that undergoes implantation to form a disorganised mass of trophoblast cells with no foetal tissue
What is a partial hyaditiform mole?
2 spermatid fertilise 1 ovum so there is too much DNA and too much trophoblast resulting in trophoblast growth overtaking foetal tissue development resulting in a lack of foetal development
How are hyaditiform moles managed?
Curettage and hCG monitoring
What is an invasive mole?
Mole that penetrates/peforates the uterine wall
Do invasive moles metastasise?
When is a hysterectomy indicated in an invasive mole?
If local destruction causes uterine rupture
What are the S/S of an invasive mole?
Vaginal bleeding, uterine enlargement, persistently high hCG
What does persistently high hCG following curettage of hyaditiform mole indicate?
What treatment is used for invasive mole if the uterus is not perforated?
How does gestational choriocarcinoma arise?
Normal/abnormal pregnancy with no villi present leads to a malignant neoplasm of trophoblastic cells
How does gestational choriocarcinoma progress?
Rapidly invasive and metastasises widely
What treatment does gestational choriocarcinoma respond well to?
Describe the incidence of gestational choriocarcinoma presentations.
50% associated with complete moles, 25% after abortion, 22% after normal pregnancy, 3% in ectopic pregnancy
What are the S/S of gestational choriocarcinoma?
Vaginal spotting, raised hCG