11.1: Gynaecological Tumours

Question 1

Where does neoplasm of the cervix tend to begin?

Answer 1

The squamo-columnar junction

Question 2

When does cervical screening start and how frequently is it done? What happens if there are abnormal findings?

Answer 2

Starts at age 25, and every 3 years until 50 and every 5 years from 50-65. Cells are examined and sent for HPV testing:
A) if no HPV found return to screening programme
B) if HPV positive cytology they are retested in 12 months
C) if there are abnormal cells they are referred for a colposcopy (visualize the cervix and try to find abnormal area)

Question 3

What are the potential precursor lesions for cervical cancer histology

Answer 3

Normal -> CIN 1 abnormal nuclei to lower third-> CIN2 occupies 2/3 of lower epithelia -> CIN3 full thickness

CIN: cervical intraepithelial neoplasm

Question 4

What are some of the causes for cervical cancer?

Answer 4

1. HPV - can be predisposed when immunosuppresed
2. E6, E7 genes (FH)
3. Smoking

Question 5

What are some risk factors for cervical cancer?

Answer 5

1. Sex, multiple partners
2. Early first pregnancy increases the risk with each subsequent pregnancy (represents early exposure to STDs at an early age rather than influence of hormone)

Question 6

Describe the clinical presentation of cervical carcinoma and the complications of advanced disease

Answer 6

Early stages are asymptomatic, but as it progresses may have abnormal vaginal bleeding, post coital bleeding, blood stained discharge and pain radiating to the sacral region.

In an advanced disease the local tumour may cause death without every metastasizing as a consequence of the tumour causing urethral obstruction, uraemia and pyelonephritis

Question 7

What are the two most common primary malignancies of the cervix, which is the most common?

Name four other less common malignancies that can occur in the cervix and two common sources of secondary tumours

Answer 7

1. Squamous cell carcinoma**
2. Adenocarcinoma

Other rare variants (still primary): adenosquamous, neuroendocrine, lymphoma, sarcoma

4. Secondary tumours (metastasis from ovary or GIT)

Question 8

What is CGIN and what can it progress to?

Answer 8

Cervical glandular intraepithelial neoplasia that can progress to an adenocarcinoma

Question 9

Name four local complications that can occur due to direct invasion of a cervical carcinoma

Answer 9

Obstruction of ureters, uterus and fistulas of the rectum and bladder

Question 10

Name the vaccine that targets HPV, how effective is it? Who is the vaccine offered to and how will the vaccine regime be changing in the upcoming years?

Answer 10

Gardasil targets all four types of HPV (6,11,16,18) and is 100% effective if the individual is not already exposed.

Vaccination was offered to all girls 12-13 (there was also a catchup for those who weren’t vaccinated <18) but even then they need to continue screening. This year boys aged 12-13 will also be eligible

Question 11

What HPV-linked tumours can the HPV vaccine protect against?

Answer 11

Vulval, penile and head and neck tumours

Question 12

Which hormone stimulates cervical epithelia to undergo hyperplasia? What two kinds of hyperplasia can it become and what does it depend on?

What can be given if atypical cells are found?

Answer 12

Estrogen

Simple and complex depending on how much stroma is between the glands. If atypical cells are found estrogen can be suppressed by administering progesterone.

Question 13

What is the most common tumour of the endometrium?

Answer 13

Endometrial adenocarcinoma

Question 14

What is the most common tumour of the endometrium and what is its 10-year survival rate?

Answer 14

Endometrial adenocarcinoma, 75% 10-year survival

Question 15

Name the two types of endometrial adenocarcinomas and describe their individual precursors and the age groups commonly affected by each. Which is more common?

Answer 15

1. Endometrial carcinoma: 80%: hyperplasia is a precursor, thus the cancer is associated with unopposed estrogen which can occur in women who are nulliparous, have early menarche and late menopause. It is most common in those in the younger bracket of those affected by endometrial cancers (50).
2. Clear cell and uterine serous papillary: usually seen in elderly and there is no background hyperplasia

Question 16

Other than unopposed estrogen, what else are endometrial carcinomas linked with?

Answer 16

Obesity, diabetes, hypertension and HRT (hormone replacement therapy)

Question 17

How do endometrial adenocarcinomas tend to present? (Hint: Link this to the age group affected by peak incidence). What is a rare presentation?

Answer 17

Peak incidence occurs in 55-65 year old and thus tends to present with post-menopausal bleeding and excessive leukorrhea

Uterine enlargement is rare to present with as its only seen in advanced stages

Question 18

What determines the prognosis of endometrial carcinoma?

Answer 18

Type, staging and grading

Question 19

Describe the potential direct spread of endometrial adenocarcinomas

Answer 19

Can spread to myometrium, cervix, ovary or extend to adjacent organs (i.e rectum, bladder)

Question 20

What are the lymphatic drainage sites involved in the spreading of endometrial adenocarcinomas?

Answer 20

Common iliac, external iliac, obturator and periaortic

Question 21

What is the most common tumour of the female repro tract? Describe the tumour and list another name for it

Answer 21

Myometrial tumours or fibroids: smooth muscle leiomyoma which are benign and can be single or multiple

Question 22

What hormone are leiomyomas dependent on and how do fibroids/myometrial tumours often present? (including in pregnant women)

Answer 22

Estrogen dependent,

It can be asymptomatic, heavy/painful periods.
Since they can become very large they may present with uterine enlargement, this can compress the bladder and present with urinary frequency, abdominal distension, ascites, perforation and death :(

Pregnant women may present with sudden pain due to the fibroids becoming infarct (which can also lead to infertility). As well as fetal malpresentation and postpartum hemorrhage if the uterus doesn’t contract following the pregnancy

Question 23

What can a myometrial tumours/ smooth muscle leiomyomas progress to once malignant?

Answer 23

1. Leiomyosarcomas; come from the smooth muscle myometrial layer
2. Endometrial stromal sarcomas (which arise from the endometrial stroma)

Question 24

Which age group is most affected by ovarian neoplasms, are they more commonly benign or malignant?

Answer 24

Younger women: 20-45, 80% are benign

Question 25

Which age groups are more affected by borderline and malignant tumours of the ovary? What hormones can these tumours produce

Answer 25

Borderline: slightly older
Malignant: older women: 45-65
Can produce estrogen/androgens

Question 26

Why is ovarian cancer a the major cause of cancer death over any other gynecological malignancy?

Answer 26

They’re usually asymptomatic and have no precursor, thus they often only present when the disease is advanced. Symptoms can also be confused with IBS

Question 27

How can ovarian tumours be classified in origin? Which ones produce hormones, which is most common and which age groups tend to be affected by each?

Answer 27

1. Surface epithelial cells: Most common, these produce hormones: 20+
2. Germ cells: 25+
3. Sex cord - stroma: All ages
4. Metastasis to ovaries: Variable

Question 28

What can happen as a consequence of the hormones produced by ovarian tumours?

Answer 28

Menstrual disturbances, inappropriate sex hormones

Question 29

Name eight major etiology/associations and some protective factors for ovarian cancer

Answer 29

Protective: OCP and pregnancy prevents the repeated rupture of the epithelium (which happens during normal ovulation) preventing epithelial tumours

RFs:

1. Genetic susceptibility: linked to BRCA1 and 2
2. HRT
3. Smoking
4. Obesity
5. Endometriosis; endometrial tissue arises in another site, benign but over time become epithelial or endometrial tumours
6. Risk of super-ovulation (if the patient is on IVF)
7. Talcum powder
8. Prior cyst

Question 30

What screening and monitoring is offered for ovarian cancer?

Answer 30

No screening in the UK since there’s no reliable test that picks up ovarian cancer at an early stage BUT the disease can be monitored with Ca-125

Question 31

All five types of epithelial ovarian tumours can be benign, malignant or borderline (low malignant potential), name each type. What disease are they associated with?

Answer 31

1. Serous: surface papillary projections
2. Mucinous: can be large, multi local cysts with mucous material inside
3. Endometriosis
4. Clear cell
5. Bremner (transitional/bladder epithelia)

Associated with peritoneal disease or implants

Question 32

What defines a malignant epithelial tumour?

Answer 32

Has stromal invasion and anaplastic cells

Question 33

Why might ovarian cysts present with an acute abdomen (sudden severe abdominal pain)?

Answer 33

The cysts can undergo torsion and cause infarction

Question 34

Which type of tumour frequently produces steroid hormones?

Answer 34

Sex cord-stromal tumours (a type of ovarian tumour)

Question 35

Name the three types of sex cord-stromal tumours and a brief description of each

Answer 35

1. Granulosa cell tumour; any age but has a propensity for late recurrence, can be malignant and is associated with estrogen stimulation (may have hyperplasia in endometrial lining)
2. Thecoma: commonest sex cord tumour, happens in reproductive years and is benign. Also associated with estrogen is stimulation
3. Leydig cell tumour: very rare, usually androgenic stimulation and causes virilisation (male physical characteristics)

Question 36

What is Meig’s syndrome and how can it be resolved?

Answer 36

Syndrome where woman has a thecoma, an ascites and plural effusion - if the thecoma is removed the ascites and plural effusion disappears!

Question 37

Which tumour marker do germ cell tumours produce and what can they be used for?

Answer 37

Hcg and afp, can be used to detect and monitor disease

Question 38

What is the most important germ cell tumour to be aware of? How does it change in its benign vs malignant form?

Answer 38

Mature cystic teratoma/Desmond cyst:
Benign: composed of mature elements of different tissues; skin, hair, teeth, bone, thyroid, etc

Malignant: are immature teratomas composed of fetal type tissue rather than mature tissue

Question 39

Other than normal and immature teratomas, name two other types of teratomas. Briefly describe each and any associated enzymes if necessary.

Answer 39

1. Dysgerminomas: Cancer that begins in germ cells of the females, associated with high levels of serum LDH (lactic dehydrogenase)
2. Monodermal: when there is one particular epithelium

Question 40

Name two types of monodermal teratomas and state whether they are benign or malignant

Answer 40

1. Struma ovarii - thyroid tissue, benign

2. Carcinoid - type of neuroendocrine tumour, malignant

Question 41

Which embryonic tissues do ovarian germ cell extra-embryonic neoplasms tend to arise from and which tumour markers are they associated with?

Answer 41

Yolk sac - afp

Choriocarcinoma- hcg

Question 42

Where are secondary tumours that have metastasized to the ovary likely to originate from?

Answer 42

Genital: endometrial
Extragenital: colonic, gastric (krukenberg tumour), breast

Question 43

What is the pre-invasive indication for vulval tumours?

Answer 43

Vulval intraepithelial neoplasia VIN 1,2,3

*same principle as CIN

Question 44

What is the most common type of vulval tumour? Name three other types that can occur as well

Answer 44

Most common: squamous carcinoma

Others include: adenocarcinoma, basal cell carcinoma and malignant melanoma

Question 45

How is a large vulval carcinoma treated?

Answer 45

Vulvectomy; removal of the vulva

Question 46

Name two aetiologies of vulval tumours and their associations?

Answer 46

1. HIV infection: associated with those who are immunosuppressed and younger
2. Older women: with preexisting skin disorders that cause differentiated VIN, chronic irritation, vulvar dystrophies (such as lichen sclerosis), squamous hyperplasia

Question 47

How are vulva basal cell carcinomas different from squamous call carcinomas?

Answer 47

Squamous can undergo metastasis, but basal cell carcinomas are a locally invasive tumour

Question 48

How can vulva (or other) basal cell carcinomas present? What anatomical aspect of the vulva is most affected by this cancer and what can happen if it goes untreated?

Answer 48

Pearly white or pigmented nodule, ulcerated and mainly affects the labia majora. If neglected it can deeply infiltrate but NOT metastasize

Question 49

What is extra-mammary Paget’s disease? How does it present?

Answer 49

Paget’s disease NOT in the breast but in the vulva: commonly presents with a pruritic (unpleasant itchy) red area on labia majora.

Question 50

Describe extra-mammary Paget’s disease histologically, how does it differ from mammary Paget’s disease?

Answer 50

Adenocarcinoma mucin containing tumour cells infiltrate the epidermis. Unlike breast Paget’s disease only 25% of cases have an underlying adenocarcinoma that arise from the adnexa (parts adjoining an organ)

Question 51

What are the tumours that can arise from placental tissue (gestational trophoblastic disease) and identify the one most common

Answer 51

1. Hydatidiform mole (partial or complete) - most common

2. Invasive mole: partial mole that invades the myometrium, once malignant it becomes choriocarcinoma (primary)

Question 52

Who is at risk of hydatidiform mole tumours? How does the patient present and what would appear on a scan?

Answer 52

Occurs in 1/100 pregnancies, <16 and >50 women

Patient presents with a larger (than normal) uterus and bleeding early in the pregnancy.

On a scan, the placental tissue/chorionic villi appears edematous and cystic (like grapes) and the cells around the villi show abnormal trophoblastic proliferation

Question 53

What is the difference between a complete and partial hydatidiform mole?

Answer 53

Complete: when the patient miscarries there’s usually no fetus as the ovum does not have any female chromosomes, so sperm may duplicate and invade the empty mole to cause 46 XX or XY

Partial mole: fetal tissue is present during the miscarriage and there is dispermy and consequentially a triploid mole (69 XXX/XXY/XYY)

Question 54

What’s the protocol for a patient once they’ve been diagnosed with a hydatidiform mole and which type of mole has more neoplastic potential?

Why would patients that formerly had a hydatidiform mole be advised to not get pregnant?

Answer 54

Monitored by hCG levels (serum and urine), if the levels rise the patient will receive chemotherapy. The complete mole has more neoplastic potential than partial

They will be advised to not get pregnant as this would cause a rise in hcg and may mask the tumour if it were to return

Question 55

When do choriocarcinoma tend to occur? How does it differ from a hydatidiform mole?

Answer 55

*Reminder: they are the malignant version of the mole, and thus usually follows a hydatidiform mole and a miscarriage (rarely a normal pregnancy will occur)

Unlike hydatidiform moles, they have no villi but are malignant tumours of the trophoblast layers (syncytio and cytotrophoblast)

Question 56

Name three sites that choriocarcinomas may spread to hematogenously? How might a patient present as a consequence of this?

Answer 56

High tendency to hematogenous spread to

1. lungs - patient will present with hemoptysis
2. Genital tract
3. Brain

Question 57

Why is the prognosis better if a choriocarcinoma develops in a molar pregnancy?

Answer 57

You’re continuously monitoring the patient, and the patient can be treated earlier