19. Malignancy and the reproductive organs Flashcards
define tumour
Any clinically detectable lump or swelling
define neoplasm
abnormal growth of cells that persists after initial stimulus is removed
define malignant neoplasm
same as neoplasm, but it invades surrounding tissues
define metastasis
Malignant neoplasm that has spread to a distant site
define dysplasia
A potentially pre-neoplastic alteration where cells show disordered organization and abnormal appearances
May be reversible
define cancer?
any type of malignant neoplasm -> Ductal carcinoma in situ (DCIS)—or stage 0 breast cancer—is considered a non-invasive or pre-invasive cancer diagnosis.
What are the histological characteristics of cancer cells?
- hyperchromasia (dark staining neuclei)
- pleomorphism - multiple shapes and sizes
- more mitotic figures
- irregular membrane borders?
What 5 regions of the female reproductive tract can be affected by cancer?
Vulva, cervix, endometrium, myometrium and ovaries
What is the the epithelial lining of the vulva?
Keratinised stratified squamous epithelium (labia majora, mons pubis and perineal region)
Non-keratinised for vestibule, hymen and inner surfaces of the labia minora
What type of cancers can affect the vulva, which is most common?
- squamous cell carcinoma (90%)
- basal cell carcinoma
- melanoma
- soft tissue tumours
clinical features of vulval cancers?
Lumps
Ulceration
Skin changes - pigmentation, sensation, pain
What likely to be seen in histology of squamous cell carcinoma?
- Keratin production (e.g. keratin pearls)
- abundant eosinophilic cytoplasm
- atypical squamous cells
- loss of architecture and distingiushment of layers
What is vulval intraepithelial neoplasia (VIN)?
IN SITU Precursor of vulval squamous cell carcinoma
- no invasion through basement membrane
- may or may not develop into SCC
What likely to be seen in histology of VIN?
atypical cells
no invasion of basement membrane
pleomorphic
large nuclei at top - normally nuclei get smaller towards the top
What pathogen is associated with vulval SCC and VIN?
HPV 16
What percent of cases of vulvcal SCC and VIN are associated with HPV, what is the peak age?
30%
- typically earlier if caused by HPV
- peak age is 60
What are vulval SCC and VIN most commonly caused by, what is the peak age?
70% caused associated with longstanding inflammatory conditions (e.g. lichen sclerosus)
- peak age later, around 80
what is the main cause of vulval cancer in pre menopausal women?
HPV
What is lichen sclerosis?
Characterized by thinning of the epidermis and fibrosis (sclerosis) of the dermis
Presents as white patch (leukoplakia) with parchment like vulvar skin
Most commonly seen in postmenopausal women; possible autoimmune etiology
Benign, but associated with slightly increased risk for squamous cell carcinoma
Where do vulval cancer spread to?
Direct extension - Anus, Vagina, Bladder Lymph Nodes - Inguinal, Iliac, Para-aortic Distant Metastases - Lungs, Liver
What epithelial type is found on the endocervix and ectocervix pre menarche?
Columnar epithelia in endocervix and stratified squamos in ectocervix
describe the change in position of squamocolumnar junction after menarche
SCJ changes from being in endocervix to ectocervix - due to effect of oestrogen causing anatomical change so columnar epithelia get pushed outwards.
What is the presence of simple columnar epithelium on the ectocervix called and what happens to it?
Ectropian
- is not equipped to deal with low vaginal pH
- inflammation
- undergoes metaplasia to turn into squamous cell epithelium
What is the transformation zone?
Area between the original squamocolumnar junction (SCJ) and the active SCJ after puberty through reproductive years
- where columnar cells are undergoing metaplasia into squamous cells
What is the risk in the transformation zone?
- Area of squamous metaplasia, increased risk of dysplasia
- dynamic TZ is susceptible to HPV infection
What are the main subtypes of HPV?
6, 11, 16,18
What are the low risk HPV sub types and what do they cause?
6 and 11
- anogenital warts (occur around genitals, anus, mouth etc)
Where do high risk HPV infect and what do they cause?
HPV 16 & 18
Infect the transformation zone
- lead to uncontrolled cellular proliferation
ow do the high risk HPV produce their effects?
Produce proteins: E6 and E7 which inactivate tumour suppressor genes
- E6 inactivates P53
- E7 inactivates Retinoblastoma
how does cervical ectropian appear, what causes it and how is it treated?
It appears as a large reddish area on the ectocervix surrounding the external os. Cervical ectropion can be caused by hormonal changes, pregnancy and being on the pill. It is not linked to the development of cervical cancer or any other condition that causes cancer. Treatment is cauterisation via colposcopy.
What does infection of the transformation zone by HPV lead to?
Dysplasia which leads to Cervical intraepithelial neoplasia (CIN)
what is Cervical intraepithelial neoplasia (CIN) confined to?
Confined to Cervical epithelium (in situ)
What are the categories of CIN?
CIN1: mild dysplasia (1/3 cervical thickness)
CIN2: moderate dysplasia (2/3 thickness)
CIN3: severe (full thickness)
SCC: invasive (through basement membrane)
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
What is the treatment for CIN?
CIN1
• Often regresses spontaneously
• Follow up cervical smear in 1 year
CIN 2 & 3
• Needs treatment - increased risk of development into SCC
• Large Loop Excision of Transformation zone (LLETZ)
How does cervical cancer screening work?
Brush used to scrape cells from
ransformation zone:
- Tested for HPV
- If positive - cells looked at under microscope - for enlarged nuclei possessing abnormal chromatin
How often are women invited for cervical cancer screening?
- Aged 25 - 49 = every 3 years
- Aged 50 - 64 = every 5 years
- Over 65 - only if recent abnormality
What is a prevention measure against cervical cancer?
HPV vaccine
What is the HPV vaccine, what age is it given and what does it protect from?
Gardasil • Recombinant vaccination • Against HPV (subtypes 6/11/16/18) • Given aged 12-13 • Protects from cervical, vulval, oral, anal cancers (males also benefit)
What are 2 types of invasive cervical cancers, which is most common?
- squamous cell carcinoma (most common, consequence of CIN)
- adenocarcinoma (from endocervical glandular cells)
both have aetiology of HPV infection infecting metaplastic squamous cells in TZ
How does an invasice cervical cancer present?
- Bleeding (Post coital, Inter menstrual, Post menopausal)
- Mass
- Screening
What are the stages of cervical cancer and what staging system is used?
FIGO:
1 - confined to cervix
2 - beyond cervix, nut not pelvic wall or lower 1/3 vagina
3 - disease to pelvic wall or lower 1/3 vagina
4 - invades bladder, rectum or metastasis
What is the treatment for invasive cervical cancer?
If advanced:
- Hysterectomy
- Lymph Node Dissection
- +/- Chemoradiotherapy
what is the endometrium composed of ?
glands and stroma
What is endometrial hyperplasia, what is it a pre-cursor to?
Thickening of the endometrium, > 11 cm
- Increased gland:stroma ratio
- can lead to endometrial cancer
How does endometrial hyperplasia present?
Inter-menstrual/postmenopausal bleeding
What causes endometrial hyperplasia?
Excessive oestrogen
What are the causes of excess oestrogen?
Endogenous - Obesity (androgens -> oestrogens) - Early menarche/late menopause - Oestrogen secreting tumours Exogenous - Unopposed oestrogen hormone replacement therapy - Tamoxifen Irregular Cycle - Polycystic Ovary Syndrome
action of tamoxifen?
- treat oestrogen receptor positive breast cancer - block oestrogen receptor in breast but stimulates oestrogen receptors in endometrium
What is the most common cause of endogenous excessive oestrogen?
Obesity
How does obesity cause excess oestrogen?
Peripheral adipocytes convert androgens into oestrogen
- aromatisation
How can early menarche/late menopause predispose to endometrial hyperplasia?
Long life time exposure to oestrogen
How does endometrial cancer present?
- Bleeding (post menopause/ inter mestrual)
- Palpable mass (if large enough)
What are the 2 types of endometrial cancer and which is most common?
- endometrioid adenocarcinoma (most common, arises from hyperplasia)
- Serous adenocarcinoma (more serious)
What are the features of endometrioid adenocarcinoma?
- most common endometrial cancer
- commonly arises from hyperplasia
- resembles normal endometrial glands
Describe the appearance of endometriod adenocarcinoma on histology?
- Looks similar to normal tissue
- increased number of cells
- lots of glands
- reduced stroma
What are the features of serous adenocarcinoma?
- type of endometrial cancer
- less common
- more aggressive
- poorly differentiated cells
Describe the appearance of endometriod adenocarcinoma on histology?
- atypical features
- bug nuclei
- hyperchromatic
- large nuclear to cytoplasm ratio a
- pleomorphism
How does endometrioid adenocarcinoma spread?
Typical spread: invades surrounding tissues (myometrium, vagina, bladder etc)
- lymphatic vessels and blood vessels
How does serous adenocarcinoma spread?
Transcoelomic spread:
Exfoliates: cells break off
- travels through fallopian tubes and deposits on peritoneal surface
What is serous adenocarcinoma associated with?
Psommoma bodies (collections of calcium) - appear dense and dark on histology
peak age of endometrial cancer?
late 60s
What is the management of endometrial cancer?
- Hysterectomy
- Bilateral salpingo-oophorectomy
- +/- lymph node dissection
- +/- chemo radiotherapy
What are 2 types of cancers affecting the myometrium?
- Leiomyoma (fibroid)
- Leiomyosarcoma
What are the features of leiomyoma?
- most common tumour of myometrium
- benign
- pale, homogenous, well circumscribed mass
How does leiomyoma present?
- Can be asymptomatic
- Pelvic pain
- Heavy periods
- Urinary frequency (bladder compression)
Describe the appearance of leiomyoma on histology?
Whorled, intersecting fascicles of benign smooth muscle cells
What are the features of leiomyosarcoma?
- Malignant tumour of smooth muscle
- atypical cells
- doesn’t arise from leiomyoma
Where does leiomyosarcoma metastasise to?
Lungs
How does leiomyosarcoma present?
Vague abdominal pain, abdominal mass, weight loss
origin of Carcinoma?
Epithelial origin. Either adenocarcinoma or squamous cell carcinoma.
origin of sarcoma?
Supportive and connective tissue origin i.e. bones, tissues, cartilage, muscle and fat
origin of myeloma?
Plasma cells of bone marrow
origin of leukaemia
Bone marrow generally (normally overproduction of immature white blood cells)
What are the early symptoms of ovarian cancer and what does this lead to?
- Vague and non-specific
- Delayed diagnosis therefore more developed when diagnosed
What are the later symptoms of ovarian cancer and what are they due to?
Due to the mass effect of the cancer:
- Abdominal pain
- Abdominal distension
- Urinary symptoms
- Gastrointestinal symptoms
- Hormonal disturbances
What serum marker can be tested for in ovarian cancer?
Ca-125
What can serum markers be used for?
- diagnosis
- response to treatment
- monitoring recurrence
What mutation is associated with ovarian cancer, what type more commonly?
BRCA1/2
- Tumour suppressor genes
- Associated with high grade serous cancers
What preventative measurement can be taken in BRCA1/2 mutation?
Associated with breast and ovarian cancer
- prophylactic mastectomy
- prophylactic salpingo-oophrectomy
What 3 parts of the ovaries can be affected by cancer?
- Epithelium
- Germ cells
- Stromal cells (sex cord stromal tumours)
How do ovarian epithelial cancers typically present?
Present as cystic masses
What are the sub types of ovarian epithelial tumours?
Adenocarcinomas
- Serous
- Mucinous
- Endometrioid
What are the features of serous ovarian adenocarcinoma?
- highly atypical cells
- psommoma bodies - stain dark purple
- transcoelomic spread (spread to peritoneal surfaced)
What are the features of mucinous ovarian adenocarcinoma?
- Atypical epithelial cells
- secreting mucin
- big white empty space on histology
what is the growth of leiomyoma dependent on/?
oestrogen dependent and usually regress after menopause
What is the appearance of mucinous ovarian adenocarcinoma on histology?
Large white empty spaces in cells, with nucleus pushed to one side of the cell
- mucin produced washed out in preparation of tissue
What are the features of Ovarian Endometrioid Adenocarcinoma?
- Glands resembling endometrium
- May arise in endometriosis
- May have synchronous endometrial endometrioid adenocarcinoma
how are epithelial ovarian cancers further classified?
benign
borderline
malignant
are germ cell tumours in women usually benign or malignant?
benign
What are the different germ cell tumours that can occur in the ovaries?
- Teratoma
- Dysgerminoma (equivalent of seminoma in testis)
- Choriocarcinoma
- Embryonal Carcinoma
- Yolk Sac Tumour
All malignant (except some teratomas)
What is the most common type of germ cell ovarian tumour and what are its subtypes?
Teratoma:
• Mature cystic teratoma (benign) (dermoid cyst) (most common)
• Immature (malignant)
• Monodermal (highly specialised, one cell type)
What are the features of mature teratoma?
- Contain fully mature- differentiated tissue from all germ cell layers - so an example would be skin epidermis
from the ectoderm, smooth muscle from the endoderm and GI epithelium from the endoderm - Can be bilateral
- Often contains skin + hair structures
What tissues do immature teratomas contain?
Contains immature, embryonal tissue
- malignant
What tissue commonly occurs in monodermal teratomas?
Typically thyroid tissue
What are sex cords?
Responsible for formation of sertoli/leydig cells in males and granulosa/theca cells in females
Which cells do ovarian sex cord tumours resemble?
Can resemble granulosa, theca, sertoli or leydig cells.
How does theca and granulosa sex cord tumours present?
Produce oestrogen:
- in prepubescent patient can cause precocious puberty
- in post-puberty can cause breast cancer, endometial hyperplasia/cancer
How does sertoli/leydig sex cord tumours present in prepubescent female patients?
Produce testosterone
- in prepubescent patient prevents normal female pubertal changes
How does sertoli/leydig sex cord tumours present in post-pubescent female patients?
Produce testosterone
- Sterility
- Amenorrhoea
- Hirsuitism
- Male pattern baldness
- Breast atrophy
What cancers metastasise to the ovaries?
- breast cancer
- GI tumours
- other gynae tumours
- Krukenberg tumour
What are Krukenberg tumors?
- Metastatic GI tumour
- Often gastric
- Signet cells (big foamy cytoplasm, pushes nucleus to periphery of cell)
WHat is a risk factor for testicular cancer?
Cryptorchidism - undescended testes
- 3 to 5 times increased risk of germ cell tumours
- decreases if orchipexy performed before puberty
How do testicular tumors present?
- mass
- +/- pain
- cannot be trans-illuminated
(painless mass for exams)
What investigations are done for testicular cancer?
- scans
- tumour markers
What serum markers are associated with which testicular germ cell cancers?
Alpha fetoprotein (AFP): yolk sac tumours
β hCG: Choriocarcinoma
- both in mixed NSGCT
What are the 2 categories of testicular cancer?
Germ cell and non-germ cell tumours
What is a type of non-germ cell tumour?
Sex cord-stromal tumours
WHat are the most common types of sex cord-stromal tumours seen in the testes?
Sertoli or Leydig cell tumours
- are rare and benign
What is the most common type of testicular cancer pos-puberty?
Germ cell tumours (95%) and all are malignant
What are the 2 categories of germ cell tumours?
Seminomatous and nonseminomatous germ cell tumours (NSGCTs)
What percent of germ cell tumours are seminomas, what is the peak age?
50%, 40-50
What are the features of seminomas in relation to spread?
- confined to testes for long time
- metastasise by lymphatics to iliac and paraortic lymph nodes, further spread is rare
What are the different types of NSGCTs?
- yolk sac
- choriocarcinoma
- teratoma
- embryonal carcinoma
However, many NSGCT are mixed, contain at least 2 types
What ages do NSGCT affect?
- Yolk sac: young childrem
- embryonal carcinomas, choriocarcinomas and mixed: yound adults
- Teratomas: all ages
When are teratomas usually benign or malignant?
Usually benign is prepubertal, and malignant in postpubertal men
How do NSGCT spread?
Tend to metastasise early and do so both via lymphatics and blood vessels
- may present with metastases with the primary testicular tumour being non-palpable
How are testicular cancers managed?
Radical orchiectomy, further treatment depends on type:
- seminomas radiosensitive
- NSGCT aggressive chemotherapy
