Lecture 17 - Tumours Of The Reproductive Tract Flashcards
Go to the last slide and label the testes:
1 = vas deferens
2 = epididymis
3 = rete testes
4 = tail of epididymis
5 = Seminferous tubule
6 = tunica vaginalis
7 = tunica albuginea
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 perisist after the initial stimulus is removed and it invades surrounding tissue with potential to spread to distant sites
What is metastasis?
Malignant neoplasm that has spread to a distant site
What is metaplasia?
When 1 cell type differentiates into a another cell type
What is dysplasia?
A potentially pre-neoplastic alteration where cells show disordered organisation and abnormal appearances
May be reversible
How rare are vulval cancers?
Who do they arise most in?
Quite uncommon
Older patients
What is the most common type of vulva cancer and why?
Squamous cell carcinoma
The vulva is essentially just made of skin
What are the most common types of vulval cancers from most common to least common?
SQUAMOUS CELL CARCINOMA
Basal cell carcinoma
Melanoma
Soft tissue tumours
What are some clinical features of vulval cancers?
Lumps or bumps
Ulcerations
Skin changes (pigments, sensation or pain)
What are the 3 main layers to skin?
Superfical to deep?
Epidermis
Dermis
Subcutaneous tissue
What are the normal layers to normal skin/epidermis?
From deep to superficial
Basement membrane
Stratum basale (basal layer)
Stratum spinosum
Stratum granulosum
Stratum Corneum
Go to the last slide and label the layers of the epidermis:
1 = basement membrane
2 = stratum basale (basal layer)
3 = stratum spinosum
4 = stratum granulosum
5 = stratum Corneum (corny layer)
Go to the last slide and look at image 3 of vulval epidermal tissue:
What is being pointed at and what does this indicate?
Keratin formation = swirly appearance
Squamous cell carcinoma of the vulva
Since squamous cell carcinomas produce keratin
What is Vulval Intraepithelial Neoplasia (VIN)
In situ precursor of vulval squamous cell carcinoma
Where there are abnormal atypical cells that do not break through the basement membrane
What is meant by IN SITU?
Cells have not broken through the basement membrane
Is Vulval Intraepithelial neoplasia and vulval squamous cell carcinoma related to HPV?
Most are not (usually due to longstanding inflammation)
Some are (HPV16)
What are the 3 ways that vulval cancer can spread?
Direct extension (anus, vagina, bladder)
Lymph nodes ( Inguinal, iliac, para-aortic)
Distal metastases (lungs and liver)
What are the 2 parts of the cervix?
Endocervix
Ectocervix
What is the difference between the ectocervix and endocervix?
Endocervix not exposed to the acidic environment of the vagina
Ectocervix adapted to be exposed to the acidic environment of the vagina
Both have different cell types
What are the different cell types of the endocervix and ectocervix?
Endocervix = simple columnar epithelium
Ectocervix = stratified squamous epithelium
What can happen if the endocervix comes into contact with the acidic vaginal environment for a long time?
Why may this happen?
Metaplastic change to squamous epithelium
During menstruation n
What is the area called where metaplastic transition can occur at the cervix?
Transformation zone
What is there an increased risk of at the transformation zone where Metaplasia is occurring?
Dysplasia (pre-neoplastic change)
But is reversible
What type of virus is the Human Papilloma Virus (HPV)?
DNA virus
What are the 4 main types of HPV?
Which ones are low risk?
Which ones are high risk??
HPV 6,11,16,18
Low risk (warts) = HPV 6, 11
High risk (cancer) = HPV 16, 18
What part of the cervix does the high risk HPV 16 and 18 infect?
Transformation zone (which is already at an increased risk of Metaplasia then dysplasia)
What harmful proteins does HPV 16 and 18 produce once its infected the cervical transformation zone?
E6
E7
What affect does the production of the E6 and E7 proteins have once the cervical transformation zone has been infected?
E6 inhibits p53
E7 inhibits retinoblastoma gene
These are both TUMOUR SUPPRESSOR GENES
This leads to uncontrolled cellular proliferation
What is CIN (Cervical Intraepithelial Neoplasia)?
Dysplasia that is confined to the cervical epithelium (IN SITU)
What causes CIN (cervical Intraepithelial neoplasia)?
HPV infection
(E6 and E7 inhibiting p53 and Rb gene leading to uncontrolled proliferation)
What are the 3 division of CIN grading?
CIN 1 = mild dysplasia (bottom 1/3)
CIN 2 = moderate dysplasia (bottom 2/3s)
CIN 3 = severe dysplasia (full thickness dysplasia)
Squamous cell carcinoma (cervix) invades the basement membrane
What are the risk factors for CIN and cervical carcinoma?
Inc risk to HPV exposure:
-sex with HPV
-multiple partners
-early first age intercourse
Early first birth
Multiple births
Smoking
Low socioeconomic status
Immunosupression
How is CIN 1 treated?
Often spontaneously reverses
(Dysplasia reversible at this stage)
Follow up cervical smear in a year
How is CIN 2 and 3 treated?
Needs treatment since could go onto to cause squamous cell carcinoma
Large loop excision of transformation zone
May do a colposcopy
What is the age range and frequency of screening for cervical cancer?
25 - 49 = 3years
50 - 64 = 5years
65+ only if there’s a recent abnormality
What type of cells are taken in a cervical screening?
Cells from transformation zone looking for HPV
What is cytology?
Study of individual cells
What changes can be seen in dysplasia/neoplastic cells in cytology?
Large nuclei
Pleomorphism
Irregular nuclear outlines
Hyperchromatic nuclei
What is the name of the HPV vaccine?
Gardasil
What HPV subtypes of vaccinated against by the Gardasil vaccine?
HPV 6,11,16,18
Why may the HPV vaccine be given to boys a well as girls?
It protects from oral and anal cancers as well as cervical and vulval cancers
What is the most common type of invasive cervical cancer?
Squamous cell carcinoma (CIN is the precursor)
What is the less common type of cervical cancer that’s not SQUAMOUS CELL CARCINOMA?
Adenocarcinoma from the endocervical glandular cells
How does invasive cervical cancer present?
Bleeding (post coital, Intermenstrual or post menopausal)
Palpable mass
How is cervical cancer staged?
TNM
Or FIGO system (used for gynae tract cancers)
How is cervical cancer treated?
Hysterectomy
Lymph node dissection
Chemoradiotherapy
Go to the last slide and label image 4:
What type of tissue is this?
1 = glands
2 = stroma
Endometrial tissue
What is endometrial hyperplasia?
When the endometrium is thickened
Increased gland:stroma ratio
What can endometrial hyperplasia be a precursor to?
What can it cause?
Can be precursor to endometrial cancer
Canc cause Intermenstrual / post menstrual bleeding
What generally causes endometrial hyperplasia?
Excess oestrogen
What are the endogenous causes of excessive oestrogen leading to endometrial hyperplasia?
Obesity (more androgens to oestrogens by adipocytes)
Early menarche late menopause (inc lifetime oestrogen exposure)
Oestrogen secreting tumours
What are some exogenous causes of inc oestrogen causing endometrial hyperplasia?
Unopposed oestrogen HRT (no progesterone just oestrogen)
Tamoxifen
What is tamoxifen used to treat?
What is its down side?
Treat oestrogen receptor postive BREAST cancer
Increases risk of endometrial cancer
What condition increases risk of endometrial cancer?
Polycystic ovary syndrome
How does endometrial cancer present?
Bleeding (post + Intermenstrua)
Palpable mass
The most common type of gynae cancer
What are the 2 types of endometrial cancer?
Endometrioid adenocarcinoma
Serous adenocarcinoma
What is the most common type of endometrial cancer?
Endometrioid adenocarcinoma
What usually causes Endometrioid adenocarcinoma?
How does it look on histology?
From endometrial hyperplasia
The tissue resembles normal endometrial glands
How does serous adenocarcinoma differ to Endometrioid adenocarcinoma in histological appearance?
Serous adenocarcinoma is more aggressive and has poorly differentiated cells that dont resemble normal glands (hyper chromatic)
Look at the last slide and identify the 2 different types of endometrial cancer from image 5 and image 6:
Why?
5 = Endometrioid adenocarcinoma
6 = serous adenocarcinoma
5 is much more well differentiated and resembles endometrial glands more
6 is much more poorly differentiated (hyperchromatic, pleomorphic) and doesn’t resemble glandular tissue
How does Endometrioid adenocarcinoma spread?
Direct invasion
Lymph
Blood
How does serous adenocarcinoma spread?
The cells exfoliate (break off from main tumour)
They then pass through the fallopian tubes to the peritoneal space
TRANSCOELOMIC SPREAD
Look at image 6 on last slide:
What is the arrow pointing to which is common in Serous adenocarcinoma of the endometrium?
Psammoma bodies which are deposits of calcium
How is endometrial cancer managed?
Hysterectomy
Bilateral salpingo-oophorectomy
Lymph node dissection
Chemoradiotherapy
What is a hysterectomy?
Removal of cervix and uterus
What is a bilateral salpingo-oophrectomy?
Removing both fallopian tubes and ovaries
What is a benign tumour of the myometrium called?
Leiomyoma (fibroid)
What do leiomyomas look like?
Pale
Homogenous (look same all the way through)
Well circumscribed
How do Leiomyomas present?
Depends on size
Asymptomatic
Pelvic pain
Heavy periods
Urinary frequency
How do leiomyomas appear on histological image?
Look at slide 56
Intersecting fasicles of benign smooth muscle cells
What is a malignant tumour of smooth muscle (myometrium) called?
Leiomyosarcoma
What is the most common metastatic location of a leiomyosarcoma?
Lung
What are some early symptoms of ovarian cancer?
Vague and non specific symptoms
Whic lead to a delayed diagnosis
What are some late symptoms of ovarian cancer which are dependant on location?
Abdominal pain
Abdominal distension/bloating
Urinary symptoms
GI symptoms
HormonaL disturbances
What is the main tumour marker released by ovarian cancers?
Ca-125
Cancer antigen 125
What is the tumour suppressor gene that is mutated indicating high grade serous cancers?
BRCA1/2
If a BRCA1/2 mutation is detected what is a prophylactic measure that is often taken?
Prophylactic salpingo-oophrectomy
What cells make up the ovary and so can become cancerous?
Epithelial lining (epithelial tumours)
Germ cells (germ cell tumours)
Stromal cells (sex cord stromal tumours)
What is a cyst?
Sac lined by epithelium containing a fluid
What are the 3 main ovarian epithelial tumours?
All ADENOCARINOMAS:
Serous
Mucinous
Endometrioid
How can ovarian serous adenocarcinoma constrict the intestines producing GI symtoms?
Cells exfoliate
Enter into peritoneum through Fimbriae spreading to the peritoneal space
Look at the last slide at image 7 and 8:
Which one is ovarian Endometrioid adenocarcinoma and which one is ovarian mucinous adenocarcinoma and why?
7 = ovarian Endometrioid adenocarcinoma
8 = ovarian mucinous adenocarcinoma
7 can see glands resembling endometrium
8 can see goblet cells producing mucin
What is endometriosis?
Where is its most common location?
Endometrioid tissue outside the uterus
Ovaries
What is the most common germ cell tumour?
Teratoma
What are the 3 subtypes of teratoma?
Mature (benign)
Immature (malignant)
Monodermal (highly specialised)
How does a mature teratoma/dermoid cyst appear?
Contains fully mature differentiated tissue from all germ layers
Can have hair, skin, teeth, GI tissues etc
What are some other germ cell tumours?
Dysgerminoma (like seminoma in testis)
Choriocarcinoma
Embryoblast carcinoma
Yolk sac tumour
What are some sex cord stromal tumours from ovarian stroma?
Ovaries:
-granulosa cells (convert androgens to oestrogen)
-theca cells (make androgens)
Testes:
-Sertoli cells (spermatogenesis)
-leydig cells (testosterone production)
What affect do theca and granulosa cell tumours have on someone before they reach puberty and why?
Precocious puberty
Since produce oestrogen
What affect do theca and granulosa cell tumours have on someone after they have reached puberty and why?
Breast cancer
Endometrial hyperplasia
Endometrial carcinoma
Elevated oestrogen
What affect do sertoli and leydig cell tumours have on women before puberty and why?
Prevents normal female pubertal changes since produces testosterone
What affect do sertoli and leydig cell tumours have on women after puberty and why?
Infertility
Amenorrhoea
Hirsuitism
Male pattern baldness
Breast atrophy
Produce testosterone
What structure is a common metastatic location?
Ovary
What is a krukenberg tumour?
Metastatic GI tumour often from the stomach (gastric) that goes to the ovary
What is the main risk factor for testicular cancer?
Cryptorchidism (undescended testicle)
How do testicular cancers present?
What investigations are done?
Palpable mass which may be painful
Scans like ultrasound
Tumour markers
What are some testicular cancer tumour markers?
B-HCG
AFP (Alpha fetoprotein)
What germ cell tumour is B-HCG indicative of?
Choriocarcinoma (can be testicular or ovarian)
What tumour marker is AFP (alpha fetoprotein) elevated in?
Yolk sac germ tumour
Why is AFP not a perfect indication of Yolk sac tumours?
Elevated in liver cancer too
What are the subtypes of testicular cancers?
Germ cell or non germ cell
Germ cell split into seminomatous and non seminomatous
Non germ cell split into sex cord stromal and other
What is the most common type of testicular cancer?
What category is this part of?
Seminoma
Germ cell tumour which is seminomatous
What are some germ cell non-seminomatous testicular cancers?
Teratoma
Yolk sac tumour
Choriocarcinoma
Embryonic carcinoma
What are the 2 non germ cell sex cord stromal testicular cancers?
Leydig cell tumour and sertol cell tumour
