Gynaecological Tumours

Question 1

What is the transformation zone?

Answer 1

Transformation zone – glandular epithelium to squamous epithelium – metaplasia in the middle of these. In the young this point is more caudal whilst as we age this moves more cranial.

Question 2

Describe the pathogenesis of CIN and Cervical carcinoma

Answer 2

Pathogenesis: Almost all cases related to high risk HPVs – Most important in pathogenesis of cervical carcinoma: HPV 16 – 60% of cases, HPV 18 – 10% of cases. They infect immature metaplastic squamous cells in transformation zone and produce viral proteins E6 & E7 which interfere with activity of tumour suppressor proteins to cause inability to repair damaged DNA and increased proliferation of cells but most genital HPV infections are transient and eliminated by immune response in months.

Question 3

What are the risk factors for CIN and Cervical carcinomas?

Answer 3

Risk Factors: sexual intercourse, early first marriage, early first pregnancy, multiple births, many partners, promiscuous partner, long term use of OCP, partner with carcinoma of the penis, low socio-economic class, smoking and immunosuppression.

Question 4

How do we screen for CIN and Cervical carcinomas?

Answer 4

Papanicolaou (Pap) test detects precursor lesions and low stage cancers. This allows early diagnosis and curative therapy. Cells from the transformation zone are scraped off, stained with Papanicolaou stain and examined microscopically. Starts age 25 every 3 years then ever 5 years 50-65. Can also test for HPV DNA in cervical cells which is used when the pap test is ambiguous.

Question 5

How do we protect young girls from HPV?

Answer 5

Vaccine against high risk HPVs given to girls which protects for up to 10 years (the most dangerous 10 years). Doesn’t protect against all high-risk types therefore screening is being continued.

Question 6

Describe CIN and its 3 stages, how does the treatment differ between stages?

Answer 6

Dysplasia of squamous cells within the cervical epithelium, induced by infection with high risk HPVs. CIN I – most regresses spontaneously, only a small percentage progresses to CIN II, CIN III (carcinoma in situ). From CIN I to CIN III takes approximately 7 years. Mostly looking for dyskaryosis – abnormal nuclei.

CIN I – follow up or cryotherapy
CIN II and III – superficial excision

Question 7

Describe invasive cervical carcinomas, what it can look like, how and where it spreads and how it presents?

Answer 7

Average age = 45 years, 80% are squamous cell carcinomas, 15% - adenocarcinomas (also caused by high risk HPVs). May be exophytic (stick out) or infiltrative (not easily seen). Spreads: Locally to para-cervical soft tissues, bladder, ureters, rectum, vagina. Lymph nodes – para-cervical, pelvic, para-aortic. Usually presents in a screening abnormality or postcoital, intermenstrual or postmenopausal vaginal bleeding.

Question 8

What are the treatment options for invasive cervical carcinomas?

Answer 8

Micro invasive carcinomas – Treated with cervical cone excision – 5 year survival = 100%
Invasive carcinomas – Treated with hysterectomy, lymph node dissection and, if advanced, radiation and chemotherapy – Overall, 62% 10 year survival

Question 9

What is endometrial hyperplasia and what is it associated with?

Answer 9

Endometrial Hyperplasia – Frequent precursor to endometrial carcinoma. Increased gland to stroma ratio. Associated with prolonged oestrogenic stimulation such as due to: Annovulation (no progesterone production associated with menopause), Increased oestrogen from endogenous sources (e.g. adipose tissue), exogenous oestrogen. If complex and atypical is treated by hysterectomy.

Question 10

What are the clinical features of endometrial adenocarcinoma and how does it present?

Answer 10

Clinical Features – Usual age 55-75 years, unusual before 40 years. Presents with irregular or postmenopausal vaginal bleeding. Early detection and cure often possible – Overall, 75% 10 year survival.

Question 11

What are the two types of endometrial adeocarcinomas?

Answer 11

Endometrioid – More common, mimics proliferative glands i.e. looks like endometrium, typically arises associated with endometrial hyperplasia. Associated with unopposed oestrogen and obesity, spreads by myometrial invasion and direct extension to adjacent structures, to local lymph nodes and distant sites.

Serous carcinoma – Poorly differentiated, aggressive, worse prognosis. Exfoliates – travels through Fallopian tubes, implants on peritoneal surfaces.

Question 12

What benign tumours of the myometrium can occur - describe their appearance?

Answer 12

Leiomyoma = fibroids. Benign tumour of myometrium (uterine smooth muscle). Often multiple ranging from tiny to massive, filling the pelvis. May be asymptomatic or can cause heavy/painful periods, urinary frequency (bladder compression), infertility. Malignant transformation probably doesn’t occur.

Uterine Leiomyomas are well circumscribed, round, firm and whitish in colour. Bundles of smooth muscle – resembles normal myometrium.

Question 13

What is the malignant neoplasia of the myometrium

Answer 13

Uterine Leiomyosarcoma – Uncommon, peak incidence 40-60 years. Highly malignant, doesn’t arise from leiomyomas, metastasises to lungs.

Question 14

When do ovarian tumours generally arise and what is their prognosis?

Answer 14

Approximately 80% are benign and generally occur at 20-45 years. Malignant tumours generally occur at 45-65 years. Ovarian cancers have often spread beyond the ovary by the time of presentation and therefore the prognosis is often poor, commonly bilateral.

Question 15

How do ovarian tumours present?

Answer 15

Presentation – Most non-functional i.e. no hormones, produce symptoms when they become large, invade adjacent structures or metastasize – Mass affects: abdominal pain, abdominal distension, urinary and gastrointestinal symptoms and ascites. Hormonal problems when they are functional – menstrual disturbances and inappropriate sex hormones.

Question 16

How commonly is the other ovary involved with a malignant ovarian tumour?

Answer 16

Approximately 50% spread to other ovary.

Question 17

What is the main biomarker for ovarian cancers and what genetic marker is there?

Answer 17

Serum CA-125 used in diagnosis and to monitor disease recurrence and progression. Known BRCA mutation carriers can be treated with prophylactic salpingooophrectomy.

Question 18

What are the 4 classifications for ovarian tumours?

Answer 18

1. Müllerian epithelium (including endometriosis)
2. Germ cells (pluripotent)
3. Sex cord-stromal cells (form endocrine apparatus of the ovary so can be functional)
4. Metastases

Question 19

What are the risk factors for ovarian epithelial tumours?

Answer 19

Nulliparity or low parity (due to decreased release of ovum when pregnant so less hyperplasia), OCP protective, heritable mutations, e.g., BRCA1 and BRCA2, smoking and Endometriosis within the ovary giving endometrioid ovarian cancers.

Question 20

What are the three types of ovarian epithelial tumours, describe their appearance and pathogenesis? Bonus - what is Pseudomyxoma peritonei

Answer 20

Serous Ovarian Tumours – often spread to peritoneal surfaces and omentum, therefore commonly associated with ascites. Very friable so parts will break off when you touch it.

Mucinous Ovarian Tumours – often very large, cystic masses – can be >25kg, filled with sticky, thick fluid usually benign or borderline.

Endometrioid Ovarian Tumours
Contain tubular glands resembling endometrial glands. Can arise in endometriosis (15-20% of cases). 15-30% have associated endometrial endometrioid adenocarcinoma, probably arising separately.

Pseudomyxoma peritonei – Extensive mucinous ascites, epithelial implants on peritoneal surfaces, frequent involvement of ovaries. Can cause intestinal obstruction. Most likely primary is extra-ovarian, usually appendix.

Question 21

Describe the examples of malignant germ cell ovarian tumours

Answer 21

Non-gestational choriocarcinoma (produces human chorionic gonadotropin, unlike gestational type they are aggressive and often fatal) and Yolk sac tumour (produces α-fetoprotein).

Question 22

What are the three types of ovarian teratomas?

Answer 22

1. Mature (benign) – most common
2. Immature (malignant) – rare, composed of tissues that resemble immature foetal tissue
3. Monodermal (highly specialised)

Question 23

Describe ovarian mature teratomas

Answer 23

Most are cystic also called dermoid cysts as they almost always contain skin-like structures. Usually occur in young women, bilateral in 10-15% of cases. Usually contain hair and sebaceous material, can contain tooth structures. Often tissue from other germ layers also present, e.g., cartilage, bone, thyroid, neural tissue.

Question 24

Describe the two types of monodermal ovarian teratomas

Answer 24

• Struma ovarii, benign, composed entirely of mature thyroid tissue. May be functional and cause hyperthyroidism
• Carcinoid, malignant, may be functional producing 5HT and can cause carcinoid syndrome (even without hepatic metastases!)

Question 25

What are ovarian sex cord stromal tumours?

Answer 25

Derived from ovarian stroma (which is derived from sex cords of the embryonic gonad). Sex cord produces Sertoli and Leydig cells in testes and granulosa and theca cells in ovaries. Tumours resembling all of these four cell types can be found in the ovary. These tumours can be feminising (granulosa/theca cell tumours) or masculinising (Leydig cell tumours).

Question 26

Describe granuloma cell tumours and the affects they have depending on age

Answer 26

Granulosa Cell Tumours – most occur in post-menopausal women. May produce large amounts of oestrogen – If in pre-pubertal girls this may produce precocious puberty. In adult women may be associated with endometrial hyperplasia, endometrial carcinoma and breast disease.

Question 27

Describe ovarian sertoli-leydig cell tumours and the affect they have on women and children

Answer 27

Ovarian Sertoli-Leydig Cell Tumours – often functional. In children may block normal female sexual development, in women can cause defeminisation and masculinisation: breast atrophy, amenorrhoea, sterility, hair loss, hirsuitism with male hair distribution, clitoral hypertrophy and voice changes. Peak incidence in teens or twenties.

Question 28

What are the common metastases to the ovaries?

Answer 28

Most commonly Mϋllerian tumours – Uterus, Fallopian tubes, Contralateral ovary or pelvic peritoneum. Also gastrointestinal tumours (colon, stomach, biliary tract, pancreas, appendix) and breast. Krukenberg tumour = metastatic gastrointestinal tumour within the ovaries – Often bilateral and usually from stomach.

Question 29

How common are vulva tumours, who do they occur in and what types are there?

Answer 29

Uncommon (approximately 3% of female genital cancers). Approximately 2/3rds occur in women over 60 years of age. Types: squamous cell carcinoma – most common type, extramammary Paget’s disease, basal cell carcinoma and malignant melanoma.

Question 30

Describe squamous neoplastic lesions of the vulva including their cause pathogenesis, how it spreads and the age that most commonly affects women.

Answer 30

Approximately 30% are related to HPV infection, usually HPV 16. Peak age: 6th decade. Risk factors the same as for cervical carcinoma. Approximately 70% are unrelated to HPV infection – Peak age: 8th decade. Often occur in longstanding inflammatory and hyperplastic conditions of the vulva, e.g lichen sclerosis.

Arise from vulvar intraepithelial neoplasia (VIN) – In situ precursor, atypical squamous cells within the epidermis (no invasion through basement membrane). Spreads initially to inguinal, pelvic, iliac and para-aortic lymph nodes. Also to lungs and liver. Lesions less than 2cm - 90% five year survival following vulvectomy and lymphadenectomy.

Question 31

What is extramammary Paget’s disease?

Answer 31

Pruritic, red, crusted area usually on labia majora. Malignant cells, singly or in small clusters, along basal layer of epithelium. Probably arises from glandular ducts of vulval skin. Usually no underlying cancer (unlike mammary Paget’s disease). This requires wide local excision.

Question 32

What is gestational trophoblastic disease and what are the main types?

Answer 32

Gestational Trophoblastic Disease. Tumours and tumour-like conditions which show proliferation of placental tissue – villous and/or trophoblastic. Major types: – Hydatidiform mole (complete and partial). Invasive mole – Choriocarcinoma.

Question 33

Describe hydatidiform moles, when they occur, what they look like and how they’re treated.

Answer 33

Non-malignant but associated with invasive mole and choriocarcinoma. Cystic swelling of chorionic villi and trophoblastic proliferation. Occurs due to abnormal fertilisation of an ovum and is usually diagnosed in early pregnancy by USS. Friable mass of thin-walled, translucent, grape-like structures = swollen oedematous villi. Treated with curettage followed by HCG monitoring. If HCG levels don’t fall may indicate invasive mole.

Question 34

What are the two types of hydatidiform moles

Answer 34

Complete Mole – Fertilisation of an egg that has lost it’s female chromosomal material – all genetic material is paternal. Embryos die early and are not seen. HCG levels very high. 15% risk of invasive mole. 2-5% risk of subsequent choriocarcinoma.

Partial Mole – Fertilisation of an ovum by two sperm, foetus usually present. 0.5% increased risk of invasive mole (less common than with complete mole), not associated with choriocarcinoma.

Question 35

What is an invasive hydatidiform mole?

Answer 35

Invasive Mole – Mole that penetrates or perforates uterine wall. Locally destructive – can cause uterine rupture requiring hysterectomy. Produces vaginal bleeding and uterine enlargement. Persistently elevated HCG. Treated with chemotherapy.

Question 36

What is gestational chriocarcinoma, what does it look like, what are its characteristics and how is it treated?

Answer 36

Gestational Choriocarcinoma – Malignant neoplasm of trophoblastic cells derived from previously normal or abnormal pregnancy, no villi present just trophoblast. Rapidly invasive, metastasises widely but responds well to chemotherapy.

Question 37

What is commonly associated with the cause of gestational choriocarciomas?

Answer 37

Incidence: – 50% occur in association with complete moles – 25% following abortion – 22% following a normal pregnancy – 3% in ectopic pregnancies. NB. Non-gestational choriocarcinomas arise from germ cells in the ovary or in the mediastinum.

Question 38

How does gestational choriocarcinoma present and how is it treated?

Answer 38

Gestational Choriocarcinoma – usually presents with vaginal spotting. HCG levels are high. Treated with uterine evacuation and chemotherapy – very high cure rate (cf. non-gestational choriocarcinomas).