11.2 Tumours Of The Reproductive Tract Flashcards
Where might HPV cause tumours?
Vulva
Cervix
What precursor conditions of the reproductive tract may develop on to invasive cancers?
Human Papilloma virus
Endometriosis / endometrial hyperplasia
Vulval interepithelial neoplasia (VIN)
Cervical intraepithelial neoplasia (CIN)
What is a tumour?
Any clinically detectable lump or swelling
What is a neoplasm?
An abnormal growth of cells that persists after the initial stimulus is removed
What is a malignant neoplasm?
An abnormal growth of cells that persists after the initial stimulus is removed and invades surrounding tissue with potential to spread to distant sites
What are metastasis?
Malignant neoplasm that has spread to a distant site
What is dysplasia?
A potentially pre-neoplastic alteration where cells show disordered organization and abnormal appearances. May be reversible
How common are vulval cancers?
Uncommon - 3% of all female cancers
What is the most common cancer of the vulva?
Squamous cell carcinoma
What cancers can be found at the vulva?
Squamous Cell Carcinoma
Basal Cell Carcinoma
Melanoma
Soft tissue tumours
How might a vulval ulcer present?
Lumps
Ulceration
Skin changes (pigmentation/sensation/pain)
What are the 2 normal layers of the skin?
Epidermis
Dermis
Subcutis
What are the layers of the epidermis?
Stratum Corneum Stratum granulosum Stratum spinosum Stratum basale Basement membrane
Skin cells are a labile cell population, what does this mean?
Labile cells are cells that multiply constantly throughout life. These cels are only alive for a short period of time
What happens as skin cells mature?
They ascend up the epidermal layers from the stratum basale to the stratum Corneum.
Nuclei get smaller, cytoplasm increases. At top we get variable levels of keratinisation
What happens to the skin in squamous cell carcinoma?
Lose all architecture of the skin. Cant differentiate between dermis and epidermis. Cell look atypical with varying nuclei and lack of maturation.
SCC produces keratin (pink) , seen as whirls/pearls of spherical keratin production
What is VIN?
Vulval intraepithelial neoplasia is an in situ precursor of vulval squamous cell carcinoma.
Atypical cells in situ, no invasion through basement membrane. May or may not develop into squamous cell carcinoma
How do atypical cells look?
Loss of maturation down the epithelial layer.
Nuclei look large, and different from surrounding cells. Larger amount of cytoplasm
Are VIN and vulval SCC related to HPV?
Yes - 30% of cases. Usually HPV 16. In younger patients (60s not 80s). Risk factors are the same as per cervical carcinoma
No -70%. Usually associated with longstanding inflammatory conditions (e.g. lichen sclerosus. Peak age of onset = 80s
What is lichen sclerosis?
A long-term skin condition, usually affecting post-menopausal women. Causes itching and white patches of skin of genitalia
How does vulval cancer spread?
Direct extension
Lymph nodes
Distant metastases.
Where does vulval cancer spread to via direct extension?
Anus
Vagina
Bladder
Where does vulval cancer spread to via lymph nodes?
Inguinal
Iliac
Para-aortic
Where does vulval cancer spread to via distant metastases?
Lungs
Liver
Before mensuration, what are the 2 parts of the cervix?
Ectocervix
Endocervix
What is the ectocervix?
Part communicating with the vagina. Has a low pH. Covered in stratified squamous epithelium
What is the endocervix?
Not in contact with vagina, more distal towards uterus. Has simple columnar epithelium
Why might a cervical ectropion develop during menstration?
During mensuration, oestrogen causes anatomical change to cervix - everts. Simple columnar epithelial now exposed to the low pH of the vagina. Endocervix cannot not cope with this acidic environment and become inflammed. Causes a cervical ectropion.
What is a cervical ectropion?
When cells of the endocervix develop outside their normal region and are exposed to a low pH. Froms a red and inflammed patch of columnar epithelium. Results in metaplasia
What is the transformational zone?
An area of the cervix where stratified squamous epithelium meets columnar epithelium
Why is the transitional zone a common place for cervical cancer?
As after menstruation, the columnar cells descend and can undergo metaplasia to from stratified squamous epithelium. Metaplasia increases risk of dysplasia. Dysplasia can progress to become neoplasia
What is the human papilloma virus?
A DNA virus. Is sexually transmitted. Low risk and high risk subtypes.
What are low risk HPV subtypes and how do they often present?
HPV 6 and HPV 11
Often cause warts on skin, mouth, genitalia
What are high risk HPV subtypes and how do they present?
HPV 16 and HPV 18
Can lead to cancer, especially in cervical transformational zone (preferentially infect here)
Describe how high risk HPV can result in cervical cancer
- preferentially infect the cervical transformational zone
- high risk HPV produce viral proteins (E6 + E7)
- E6 and E7 proteins inactivate tumour suppressor genes (p53 and retinoblastoma gene)
- uncontrolled cellular proliferation due to inactivation of tumour suppression genes
What is cervical intraepithelial neoplasia?
CIN is in situ dysplasia of the cervical epithelium. Does not break through the basement membrane. Caused by HPV infection.
Divided into 3 different types ( CIN 1/2/3)
What determines whether CIN is type 1/2/3?
Thickness of cervical epithelium that is displaying abnormal cellular features
CIN 1 = bottom third only
CIN 2 = bottom 2 thirds
CIN = full thickness
What happens if the abnormal cells from CIN break through basement membrane?
Progressed to invasive squamous cell carcinoma
What is a mitotic figure?
A cell undergoing division on a slide. Too many/abnormal location may indicate pathology
What is the stroma?
Supporting connective tissue under the epithelium that contains glands and blood vessels.
What are the risk factors for CIN and cervical carcinoma?
- Increased risk of exposure to HPV (Sexual partner with HPV / Multiple partners)
- Early age of first intercourse
- Early first pregnancy
- Multiple births
- Smoking
- Low socio-economic status
- Immunosuppression ( not able to fight HPV infection )
What is the treatment of cervical intraepithelial neoplasia?
CIN1 • Often regresses spontaneously • Follow up cervical smear in 1 year CIN 2 & 3 Needs treatment: • Colposcopy +/- Large Loop Excision of Transformation zone (LLETZ)
Describe the cervical cancer screening programme?
Very successful • Aged 25 – 49 = every 3 years • Aged 50 – 64 = every 5 years • Over 65 – only if recent abnormality Brush used to scrape cells from transformation zone: Tested for HPV If positive – cells looked at under microscope
How might a cells from a cervical cancer screening test present if positive?
Large nucleus
Pleomorphism
Irregular nucleur outlines
How do we protect against cervical/vulval/oral and anal cancers?
Vaccination against HPV = Gardasil
• Recombinant vaccination
• Against HPV (subtypes 6/11/16/18)
• Given aged 12-13
What are the different types of invasive cervical cancer?
Squamous cell carcinoma (most common)
Adenocarcinoma
How does invasive cervical cancer present?
Bleeding - Post coital, Inter menstrual, Post menopausal)
Palpable abdominal mass
Picked up on screening occasionally.
How are invasive cervical cancers staged?
TNM
Figo system
How is advanced invasive cervical cancer treated?
Hysterectomy
Lymph Node Dissection
+/- Chemoradiotherapy
Describe the structure of the endometrium
Consists of single layer of columnar epithelium on the stroma. Within the stroma are tubular glands and spiral arteries.
What is endometrial hyperplasia?
An increased number of cells in the endometrium. Increased gland:stroma ratio. Thickened endometrium >7mm. Can be a precursor to endometrial cancer.
How is endometrial hyperplasia investigated?
Ultrasound look at thickness of endometrium. If greater than 7mm then a biopsy taken. Histological diagnosis
How does endometrial hyperplasia present?
Inter-menstrual/post- menopausal bleeding
What causes endometrial hyperplasia?
excessive oestrogen.
Endogenous
- Obesity (adiposcytes convert androgens into oestrogens)
- Early menarche/late menopause ( increased lifetime amount)
- Oestrogen secreting tumours
Exogenous
- Unopposed oestrogen hormone replacement therapy (HRT)
- Tamoxifen ( treatment for breast cancer )
Irregular Cycle
- Polycystic Ovary Syndrome
What risk factors are associated with Tamoxifen?
Drugs used to oestrogen receptor positive breast cancer. Blocks oestrogen receptors in the breast but stimulates oestrogen receptors in the endometrium. Can increase the risk of endometrial cancer
How does endometrial cancer typically present?
Bleeding (Post menopausal/Inter menstrual)
Palpable Mass
What are common cancers of the endometrium?
Endometriosis adenocarcinoma (most common) Serous adenocarcinoma
What is endometriosis adenocarcinoma?
Type of endometrial cancer. Resembles normal endometrial glands but glands are growing into each other. Cells appear atypical. Commonly arises from hyperplasia
What is serous adenocarcinoma?
A type of endometrial cancer. More aggressive, less common. Poorly differentiated cells, dont resemble normal endometrial glands.
Why is it important to differentiate endometrioid adenocarcinoma from serous adenocarcinoma?
As the spread of cancer is very different
How does endometrioid adenocarcinoma spread?
Direct invasion. Into myometrium and then into local regions/surrounding organs
How does serous adenocarcinoma spread?
Exfoliates - cells break off from main tumour.
Travels through Fallopian tubes
Deposits on peritoneal surface (Transcoelomic spread - across serous cavities)
What features are identifiable in serous adenocarcinoma?
Associated with collections of calcium - dark circular bodies (Psammoma bodies)
How is endometrial cancer managed?
Hysterectomy
Bilateral salpingo- oophorectomy
+/- lymph node dissection
+/- chemo radiotherapy
What is a leiomyoma?
Benign tumour of the myometrium
A.k.a fibroid
How does a leiomyoma appear?
Pale, homogenous, well circumscribed mass
How does leiomyoma present?
Depends on size Asymptomatic Pelvic pain Heavy periods Urinary frequency (bladder compression if big)
How do leiomyomas appear microscopically?
Whorled, intersecting fascicles of benign smooth muscle cells
What is a leiomyosarcoma?
Malignant tumour of smoothie muscle in myometrium. Atypical cells. Can metastasis to lung.
How does ovarian cancer present?
Early symptoms -Vague and non-specific -Delayed diagnosis Later symptoms -Abdominal pain -Abdominal distension -Urinary symptoms -Gastrointestinal symptoms -Hormonal disturbances
What can be used to help diagnose ovarian cancer?
Ca -125 - Serum marker (diagnosis/monitoring recurrence)
BRCA1/2 - Tumour suppressor genes. Associated with high grade serous cancers. Prophylactic salpingo-oophrectomy
What type of cancers can occur in the ovary?
Lined by epithelium - Epithelial tumours
Contains germ cells - Germ cell tumours
Contains stromal cells - Sex cord stromal tumours
Is also a site for metastatic spread
How do ovarian cystic tumours present?
Cystic masses containing fluid
What are the cost common subtypes of ovarian epithelial tumours?
Adenocarcinomas (Serous, Mucinous, Endometrioid)
Can all be benign, borderline, malignant
How does an ovarian serous adenoma present on microscopy?
Highly atypical cells
Psammoma bodies (calcium collection)
Tumour deposits in peritoneum
- spread via transcoelomic spread into peritoneum from ovaries
How does ovarian mucinous adenocarcinoma present on microscopy?
Atypical epithelial cells
Cells with big empty open cells, look similar to goblet cells. These cells secrete mucin
How does ovarian endometrioid adenocarcinoma present on microscopy?
Glands resembling endometrium
May arise in endometriosis. May have synchronous endometrial endometrioid adenocarcinoma
What is the most common germ cell tumour?
Teratoma ( mature/immature/monoderm )
What is a mature teratoma?
A dermoid cyst. Benign. Contain fully mature, differentiated tissue from all germ cell layers. Can be bilateral. Often contains skin + hair structures
Where do sex cord stromal tumours occur?
In the ovarian stroma
What are the effects of theca and granulosa cell tumours?
Produce Oestrogen
Patient pre-puberty? - Precocious puberty
Patient post-puberty? - Breast cancer, Endometrial hyperplasia, Endometrial carcinoma
What are the effects of sertoli/leydig cell tumours?
Produce testosterone Patient pre-puberty? Prevents normal female pubertal changes Patient post-puberty? Infertility Amenorrhoea Hirsuitism Male pattern baldness Breast atrophy
Where are common sites of cancers that metastases to the ovary?
Breast cancer
GI cancers
Krukenberg tumour
Other gynae tumours
What is a risk factor of testicular cancer?
Cryptorchidism (undescended testicle)
How does testicular cancer present?
Mass +/- pain
What investigations can be done for testicular cancer?
Scans (USS)
Tumour markers - useful in germ cell testicular tumours
What are tumour markers of testicular cancer?
Beta hCG - produced in a choricarcinoma
Alpha fetoprotein - present in yolk sac tumours but also produced in liver cancer
What are the subtypes of testicular tumours?
- Germ cell
- seminomatous (seminoma/spermatocytic seminoma)
- non-seminomatous - Non-germ cell
- sex cord stromal
- other (lymphoma/metastases - rare)
What is the causative agents of vulval squamous carcinoma?
Pre-menopausal women: HPV (VIN)
Post-menopausal women: long-standing dermatomes , lichen sclerosus, squamous hyperplasia.
