S11) Cancers of the Reproductive Tracts Flashcards Preview

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Flashcards in S11) Cancers of the Reproductive Tracts Deck (59)
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Where can gynaecological tumours arise?

- Vulva

- Cervix (neck of uterus)

- Endometrium (lining of uterus)

- Myometrium (body of uterus)

- Ovary 


What are the clinical features of vulval tumours?

- Uncommon 

- Approx. 2/3rds occur > 60 years of age

- Usually squamous cell carcinoma 


How many vulval squamous neoplastic lesions are related to HPV infection? 

30% HPV-related (6th decade) – risk factors the same as for cervical carcinoma

- 70% HPV-related (8th decade) – often occur in longstanding inflammatory and hyperplastic conditions of the vulva e.g. lichen sclerosis 


What is vulvar intraepithelial neoplasia?

- Vulvar intraepithelial neoplasia involves atypical squamous cells within the epidermis (no invasion)

- It is an in situ precursor of vulval squamous cell carcinoma 


How does vulval squamous cell carcinoma spread?

- Spreads initially to inguinal, pelvic, iliac and para-aortic lymph nodes

- Thereafter spreads to lungs and liver 


Almost all cases of CIN and cervical carcinoma are related to high risk HPVs.

How does an HPV infection lead to these conditions?

⇒ Infects immature metaplastic squamous cells in transformation zone

⇒ Produces viral proteins E6 & E7 which interfere with activity of TSGs to cause inability to repair damaged DNA and increase cell proliferation


What are the risk factors for CIN and cervical carcinoma?


- Early first sexual intercourse

- Early first marriage/pregnancy

- Multiple births

- Sexual promiscuity

- Immunosuppression (cannot clear HPV infection)


Why is cervical screening successful?

- Cervix accessible to visual examination (colposcopy) and sampling

- Slow progression from precursor lesions → invasive cancers (years)

- Pap test detects precursor lesions and low stage cancers

- Allows early diagnosis and curative therapy 


What does cervical screening involve?

- Cells from the transformation zone are scraped off

- Cells are stained with Pap stain

- Cells are examined microscopically

- Cervical cells can be tested for HPV DNA


In cervical screening, abnormalities are referred for colposcopy and biopsy.

What sort of abnormalities could be seen? 

- Increased nuclear:cytoplasmic

- Irregular nuclear outlines

- Hyperchromatic nuclei


What are the advantages of vaccinating men against HPV too?

- Reduce risk of oral and penile cancer

- Reduce risk of transmission of HPV

- Protect girls who cannot be vaccinated (herd immunity)


What is Cervical Intraepithelial Neoplasia?

- CIN is a dysplasia of squamous cells within the cervical epithelium, induced by infection with high risk HPVs

- Three stages: CN I mostly regresses spontaneously, some progress to CN II (in situ carcinoma) and 10% may progress to an invasive carcinoma (CN III – 2-10 years)


What is the treatment for CIN?

- CIN I – follow-up or cryotherapy

- CIN II & CIN III – superficial excision (LLETZ – large loop excision of transformation zone) 


What are the different types of invasive cervical carcinomas?

- 80% – squamous cell carcinomas

- 15% – adenocarcinomas (also caused by high risk HPVs) 


Which age group is usually affected by invasive cervical carcinoma?

Average age = 45 years 


What do invasive cervical carcinomas look like?

Exophytic (external) or infiltrative (stromal invasion through basement membrane)


Identify the three ways in which invasive cervical carcinomas spread

Locally to para-cervical soft tissues, bladder, ureters, rectum, vagina

- Lymphatic system to para-cervical, pelvic, para-aortic nodes

- Distally 


How does cervical carcinoma present?

- Screening abnormality

- Postcoital, intermenstrual or postmenopausal vaginal bleeding 


How are cervical carcinomas treated?

- Microinvasive carcinomas: cervical cone excision

- Invasive carcinomas: hysterectomy, lymph node dissection and radiation and chemotherapy (if advanced)


Describe the structure and location of the endometrium

Location: lines internal cavity of uterus

- Structure: glands are within a cellular stroma 


Why is endometrial hyperplasia a frequent precursor to endometrial carcinoma? 

- Increased gland:stroma ratio

- Associated with prolonged oestrogenic stimulation:

I. Annovulation

II. Increased oestrogen from endogenous sources (e.g. adipose tissue)

III. Exogenous oestrogen


What are the clinical features of endometrial adenocarcinoma?

Most common invasive cancer of the female genital tract

- Usual age: 55-75 years

- Presents with irregular or postmenopausal vaginal bleeding 


What do endometrial adenocarcinomas look like?

Polypoid or infiltrative 


Identify the two types of endometrial adenocarcinoma

- Endometrioid endometrial adenocarcinoma

- Serous carcinoma


What are the clinical features of endometrioid endometrial adenocarcinoma?

- More common

- Mimics proliferative glands

- Arises due to endometrial hyperplasia

- Spreads by myometrial invasion to local lymph nodes and distant sites

- Associated with unopposed oestrogen and obesity


How do endometrioid endometrial adenocarcinoma look? 


What are the clinical features of serous carcinoma (endometrial adenocarcinoma)?

Poorly differentiated

- Aggressive

- Exfoliates, travels through oviducts and implants on peritoneal surfaces 


What is the commonest tumour of the myometrium?

- Leiomyoma – benign tumour of myometrium (fibroid) 

- Probably most common tumour in women 


What are the clinical features of a leiomyoma?

- Often multiple

- Range from tiny → massive

- Asymptomatic or heavy/painful periods, urinary frequency, infertility 

- Malignant transformation rare


What does a uterine leiomyoma look like?

- Well circumscribed, round, firm and whitish in colour

- Bundles of smooth muscle (resembles normal myometrium)


Describe the clinical features of the malignant tumour of the myometrium

Uterine leiomyosarcoma: 

- Uncommon

- 40-60 years

- Doesn’t arise from leiomyomas

-  Metastasises to lungs 


What are the clinical features of ovarian tumours?

- 80% are benign – 20-45 years

- 20% are malignant  – 45-65 years

- Many are bilateral 


Why do ovarian cancers have such a poor prognosis (70% 1 year survival)?

Ovarian cancers have often spread beyond the ovary by the time of presentation and therefore the prognosis is often poor


How do ovarian tumours present?

- Most non-functional  – produce symptoms when large, invasive or metastasise

- Mass effects – abdominal pain and distension (GI & urinary symptoms)

- Ascites

- Hormonal problems – menstrual disturbances and inappropriate sex hormones 


What are the clinical features of malignant ovarian tumours?

- Approx 50% spread to other ovary

- Metastasise to regional nodes and elsewhere

- Some associated with BRCA mutations


Which tumour marker is used in the diagnosis and monitoring of ovarian carcinoma recurrence and progression?

Serum CA-125


How do we classify ovarian tumours?

Dependent on the tissue from which they have arisen:

- Müllerian epithelium (including endometriosis)

- Germ cells (pluripotent)

- Sex cord-stromal cells (form the endocrine apparatus of the ovary)

- Metastases 


What are the three main histological types of ovarian epithelial tumours?

- Serous

- Mucinous

- Endometrioid 


How can one classify ovarian epithelial tumours?

- Benign

- Borderline

- Malignant 


What are the risk factors for ovarian epithelial tumours?

- Nulliparity / low parity

- Oral contraceptive pill (protective)

- Heritable mutations e.g. BRCA1 and BRCA2

- Smoking

- Endometriosis 


How do serous ovarian tumours present?

Often spread to peritoneal surfaces and omentum, therefore commonly associated with ascites 


How do mucinous ovarian tumours present?

- Large, cystic masses – can be >25kg

- Filled with sticky, thick fluid

- Usually benign/borderline 


What is pseudomyxoma peritonei?

- Pseudomyxoma peritonei is a condition caused by cancer cells (mucinous adenocarcinoma) which produce extensive mucinous ascites due to epithelial implants on peritoneal surfaces

- There's frequent involvement of ovaries which can cause intestinal obstruction


How do endometrioid ovarian tumours present?

- Contain tubular glands resembling endometrial glands

- Can arise in endometriosis (15-20%)

- Associated with endometrial endometrioid adenocarcinoma (15-30%)


What are the clinical features of germ cell ovarian tumours?

- Most are teratomas

- Usually benign 


Identify some malignant germ cell ovarian tumours

- Dysgerminoma (resembles seminoma of testes)

- Yolk sac tumour

- Choriocarcinoma

- Embryonal carcinoma 


Identify and describe the three types of ovarian teratomas

Mature (benign) – most common

- Immature (malignant) – rare, composed of tissues that resemble immature foetal tissue

- Monodermal (highly specialised) 


What are the clinical features of ovarian mature teratomas?

- Most are cystic

- Almost always contain skin-like structures, usually contains hair, sebaceous material and tooth structures

- Usually occur in young women

- 10-15% bilateral


The most common types of monodermal ovarian teratomas is the struma ovarii.

Describe its clinical features


- Composed entirely of mature thyroid tissue

- May be functional and cause hyperthyroidism 


Describe the clinical basis of ovarian sex cord-stromal tumours 

- Derived from ovarian stroma (which is derived from sex cords)

- Sex cord produces Sertoli & Leydig cells (testes) and granulosa and theca cells (ovaries)

- Tumours resembling all of these four cell types can be found in the ovary and can be feminising or masculinising


What are the clinical features of granulosa cell tumours?

- Most occur in post-menopausal women

- May produce large amounts of oestrogen → precocious puberty in pre-pubertal girls

- Associated with endometrial hyperplasia, endometrial carcinoma and breast disease in adults


What are the clinical features of ovarian Sertoli-Leydig cell tumours?

- Blocks normal female sexual development (in children – functional)

- Causes defeminisation and masculinisation (in women – functional): breast atrophy, amenorrhoea, sterility, hair loss

- Peak incidence in teens/ twenties 


Metastases to the ovaries are most commonly due to Mϋllerian tumours. 

Identify the structures involved


- Uterus

- Fallopian tubes

- Contralateral ovary

- Pelvic peritoneum 


Metastases to the ovaries are most commonly due to Mϋllerian tumours. 

Identify some other tumours which metastasise to the ovaries

- GI tumours (colon, stomach, biliary tract, pancreas, appendix)

- Breast tumour

- Krukenberg tumour


What is a Krukenberg tumour?

- A Krukenberg tumour is a metastatic gastrointestinal tumour within the ovaries

- It is often bilateral and usually from stomach 


Identify three tumours which occur in the testes

- Germ cell tumours 

- Sex cord-stromal tumours

- Lymphomas 


What are the two different types of germ cell tumours?

- Seminomas

- Non-seminomatous germ cell tumours (NSGCTs)


What are the two types of sex cord-stromal tumours?

- Sertoli cell tumours

- Leydig cell tumours


Identify four types of non-seminomatous germ cell tumours (NSGCTs) 

- Yolk sac tumours

- Embryonal carcinomas

- Choriocarcinomas

- Teratomas