Session 11: Tumours of the Reproductive Tracts NOT FINISHED Flashcards
Where might you find tumours in the female reproductive tracts?
Vulva
Cervix
Endometrium
Myometrium
Ovaries
What is a tumour?
Any clinically detectable lump or swelling. A neoplasm is just one type of tumour.
What is a neoplasm?
An abnormal growth of cells that persists after the initial stimulus is removed.
What is a malignant neoplasm?
An abnormal gorwth of cells that persists after the initial stimulus is removed and invades surrounding tissue with potential to spread to distant sites.
Most common vulval cancers.
Squamous cell carcinoma (90%)
Basal cell carcinoma
Melanoma
Soft tissue tumours
Clinical features of vulval cancers.
Lumps
Ulceration
Skin changes
What might you find upon histological investigation of squamous cell carcinoma of vulva?
Atypical squamous cells and keratin formation
What is vulval intraepithelial neoplasia a potential precursor of?
Squamous cell carcinoma
What is the main causative factor of squamous cell carcinoma of the vulva in pre-menopausal women?
HPV
Where does the SCC spread?
Direct to anus, vagina and bladder
Lymph nodes such as inguinal, iliac and para-aortic
Distant metastases to lung and liver
What is the causative agent of vulval squamous cell carcinoma in older women?
Not known but probably related to chronic irritation and long standing dermatoses such as lichen sclerosus.
What is dysplasia?
A pre-neoplastic alteration in which cells show disordered tissue organisation.
It is not neoplastic because the change is reversible.
What type of cancer is most common of the cervix?
Squamous cell carcinomas (80%)
15% are adenocarcinomas
Most common causative agent of cervical cancer.
Almost exclusively HPV (99.5%)
What does squamous cell carcinoma develop from?
Cervical intraepithelial neoplasia (CIN)
Explain how HPV causes cancer of the cervix.
Infect the transformation zone
Produce viral proteins E6 and E7 that inactivate TSGs p53 and Rb.
This leads to uncontrolled cellular proliferation.
Risk factors for CIN and cervical carcinoma
Increased risk of exposure to HPV such as sexual partner with HPV, multiple partners or early age of first intercourse.
Early first pregnancy
Multiple births
Smoking
Low socio-economic status
Immunosuppression
Treatment for CIN
Depends on which stage of CIN.
Treatment of CIN1.
Most commonly regress spontaneously but is followed up by a cervical smear in 1 year time.
Treatment of CIN 2&3.
Needs treatment and is done by large loop excision of transformation zone.
What is the cervical screening programme?
Brush is used to scrape cells from the transformation zone to detect abnormally enlarged nuclei possessing abnormal chromatin. If this is positive there is referral to colposcopy.
You also test for HPV.
Aged 25-49 = every 3 years
Aged 50-64 = every 5 years
Over 65 = only if recent abnormality
What is vaccination against HPV?
Given in girls aged 12-13 and becomes more common in boys as well.
Protects from cervical, vulval, oral and anal cancers.
How do carcinomas of cervix spread?
Spreads initially to iliac and aortic lymph nodes before wider systemic dissemination.
Spread locally to ureters, bladder, and rectum.
Can be extremely distressing with pain and fistula formation
Clinical presentation of invasive cervical cancer.
Bleeding post coital, intermenstrual and post menopausal.
Mass felt
Treatment of invasive cervical cancer.
Hysterectomy
Lymph node dissection
+/- chemoradiation
What types of endometrial cancers are there?
Endometrioid adenocarcinoma
Serous adenocarcinoma
What does endometrioid adenocarcinoma commonly arise from?
Endometrial hyperplasia
Which age group is generally affected by endometrioid adenocarcinoma?
Perimenopausal and older women.
Aetiology of endometrial adenocarcinoma in perimenopausal women.
Unopposed oestrogen from obesity, exogenous oestrogen administration like HRT.
Tamoxifen
Hormone-secreting tumour
Polycystic ovarian syndrome
Early menarche/late menopause (longer exposure to oestrogen)
How can obesity cause a higher risk of endometrial hyperplasia and endometrial adenocarcinoma?
Peripheral adipocytes cause conversion of androgen to oestrogen leading to higher oestrogen levels.
Clinical presentation of endometrial cancer.
Bleeding that is post menopausal.
Intermenstrual bleeding
Mass
How do serous adenocarcinomas differ to endometrioid carcinoma?
Serous are less common and more aggressive.
What is the spread of endometrioid adenocarcinoma?
Cervix, bladder and rectum.
Through the peritoneal cavity and to the regional lymph nodes.
Spread of serous adenocarcinoma.
Travels through fallopian tubes.
Deposits on peritoneal surface via transcoelomic spread.
Associated with collections of calcium called psammoma bodies.
Management of endometrial cancer.
Hysterectomy
Bilateral salpingo-oophorectomy
+/- lymph node dissection
+/- chemoradiotherapy
What are fibroids?
Leiomyoma which are the most common of the myometrium and benign.
Symptoms of fibroids
Heavy menstrual loss, menorrhagia and infertility
Appearance of fibroids.
Pale, homogenous, well circumscribed mass
What can fibroids cause?
Massive uterine enlargement and this results in pressure symptoms in the pelvis.
The growth is oestrogen dependent and they usually regress after the menopause.
What is a malignant tumour of the myometrium?
Leiomyosarcoma
Do leiomyosarcomas arise from leiomyomas?
No
Metastases of leiomyosarcoma.
Spread via blood stream to the lungs
Presentation of ovarian cancer.
Vague and non-specific.
Later symptoms like abdo pain, abdo distension, urinary symptoms and GI symptoms due to mass effect.
Hormonal disturbances
Give types of ovarian tumours.
Surface epithelium (epithelial tumours)
Germ cell tumours
Sex-cord stromal tumours
What are the majority of ovarian tumours?
Epithelial tumours
Serum marker of ovarian cancer.
Ca-125
Cause of ovarian epithelial carcinoma.
BRCA1/2 which are TSGs associated with high grade serous cancers.
What are the histological subtypes of ovarian epithelial tumours.
Serous
Mucinous
Endometroid
All adenocarcinomas
All can be benign, borderline or malignant
Ovarian serous adenocarcinoma with highly atypical cells often show psammoma bodies.
Often spreads to the peritoneal cavity
Ovarian mucous adenocarcinoma showing atypical cells secreting mucin.
Ovarian endometrioid adenocarcinoma
Glands resembling endometrium and may arise in endometriosis.
Most common female germ cell tumour.
Teratoma
Three subtypes of teratoma
Mature
Immature
Monodermal
What do mature teratomas (dermoid cyst) look like on histology?
Contain fully mature differentiated tissue from all germ cells layers.
Often contains skin + hair
What does the presence of immature tissue such as primitve neuroepithelium indicate?
Malignancy and a risk for intra-abdominal spread.
Give other malignant germ cell tumours.
Dysgerminomas which are the equivalent of seminoma in testis.
Choriocarcinoma
Embryonal carcinoma
Yolk sac tumour
Useful tumour markes in malignant germ cell tumours.
Alpha-fetoprotein (AFP)
beta-human chorionic gonatrophin (hCG)
Sex cord stromal tumours in testes
Sertoli cell tumour
Leydig cell tumour
Sex cord stromal tumours in ovaries.
Granulosa cells
Theca cells
What do granulosa cell tumours produce?
Oestrogens that may be responsible for endometrial hyperplasia and adenocarcinoma as it can lead to endometroid adenocarcinoma.
What do sertoli-leydig cell tumours produce?
Androgens that can cause defeminisation, masculinisation, amenorrhoea and infertility.
What might theca and granulosa cell tumours cause in a patient pre-puberty?
Precocious puberty
What might theca and granulosa cell tumours cause in a patient post-puberty?
Breast cancer
Endometrial hyperplasia
Endometrial carcinoma
What might Sertoli-Leydig cell tumours cause in a patient pre-puberty?
Prevents normal female pubertal changes
What might Sertoli-Leydig cell tumours cause in a patient post-puberty?
Sterility
Amenorrhoea
Hirsuitism
Male pattern baldness
Breast atrophy
Common cancers metastasising to ovaries.
Breast cancer
Gastrointestinal cancers
Krukenberg tumour (metastatic GI tumour)
Other gynae tumours endometrial, other ovary, fallopian tube
When in men are tumours of the testis most common?
Aged 15-34
What can testicular tumours be classified as?
Germ cell tumours
Sex-cord stromal tumours
What are the most common sex cord stromal tumours in men?
Sertoli or Leydig cell tumours
Are sex cord-stromal tumours malignant or benign?
Benign and also very uncommon
What are the most common testicular tumours?
Germ cell tumours (they are also all malignant)
Risk factors of testicular cancer.
Cryptorchidism which is an undescended testicle.
That’s why it is important to ask for medical history
Presentation of testicular cancer.
Mass
Usually painless testicular mass but might be painful.
What is the pre-invasive precursor of germ cells tumours?
Intratubular germ cell neoplasia
What can germ cell tumours be divided into?
Seminomas
Non-seminomatous germ cells tumours (NSGCTs)
What percentage of germ cell tumours are seminomas?
50%
Peak age of seminomas
40-50 yrs of age
What can pure NGSCTs be classified as?
Yolk sac tumours
Embryonal carcinomas
Choriocarcinomas
Teratomas
However most NSGCTs are mixed
Yolk sac tumours
Occur in young children and have very good prognosis
Investigations of testicular cancers
Scans and tumour markers
What do yolk sac tumours produce?
AFP
Embryonal carcinomas, choriocarcinomas, and mixed NGSCTs
Occur in young adults
What do choriocarcinomas produce?
beta-human chorionic gonadotropin (hCG)
What do mixed NSGCTs produce?
AFP and hCG
Teratomas in men
Occur in all ages. Arise in prepubertal then usually benign, if in postpubertal always malignant.
Seminomas
10% are also associated with raised serum hCG.
Spread of seminomas
Remain confined to the testis for long periods of time. However when they do metastasise it is by the lymphatics and most commonly to the iliac and paraortic lymph nodes.
Further spread is rare.
Spread of NSGCTs.
Tend to metastasise early and do so via both lympathics and blood. The primary tumour might even be non-palpable.
Treatment of testicular tumours.
Radical orchiectomy
Further treatment of testicular tumours
Depends on whether the tumour is seminoma or NSGCT.
Further treatment of a seminoma.
Radiosensitive and treated therfore with radiotherapy.
Further treatment of NSGCTs.
Aggressive chemotherapy
