Pathology Flashcards
List some causes of abnormal uterine bleeding in adolescence/ early reproductive life?
DUB usually due to anovulatory cycles
Pregnancy/miscarriage
Endometritis
Bleeding disorders
List some causes of abnormal uterine bleeding in reproductive life/ peri menopause?
Pregnancy/miscarriage DUB: anovulatory cycles, luteal phase defects, Endometritis Endometrial/endocervical polyp Leiomyoma Adenomyosis (endometrial tissue in the myometrium) Exogenous hormone effects e.g. HRT Bleeding disorders Hyperplasia Neoplasia: cervical, endometrial
List some causes of abnormal uterine bleeding in post menopause?
Atrophy Endometrial polyp Exogenous hormones: HRT, tamoxifen (for breast cancer) Endometritis Bleeding disorders
Hyperplasia
Endometrial carcinoma
Sarcoma
Endometrial thickness of ___1____ in postmenopausal women or ___2___ in premenopausal women is generally taken as an indication for biopsy
1) >4mm
2) > 16mm
2 methods of sampling the endometrium?
endometrial pipelle- this is an outpatient procedure not requiring anaesthesia but only provides a limited sample
dilatation and curettage- cervix is dilated so that part of the endometrium can be scraped off, more invasive but gives a better sample
Required history when you send an endometrial biopsy?
Age Date of LMP (last menstrual period) and length of cycle Pattern of bleeding Hormones (is she on any hormones?) Recent pregnancy
Do not need to know number of pregnancies, drugs without hormonal influences etc.
A sample of the endometrium from what phase of the cycle is least informative?
menstrual phase
What is abnormal uterine bleeding vs dysfunctional uterine bleeding?
AUB encompasses all causes
DUB is AUB with no organic cause
DUB is irregular uterine bleeding that reflects a disruption in the normal cyclic pattern of ovulatory hormonal stimulation to the endometrial lining (no organic cause)
What is the most common indication for endometrial sampling?
abnormal uterine bleeding
Most cases of DUB are due to what?
anovulatory cycles which are commonest at either end of reproductive life
Explain why anovulatory cycles cause DUB?
If you don’t ovulate there is no corpus luteum so there is no progesterone boost which causes the proliferative endometrium to develop into the secretory endometrium so then there is just continued growth of the endometrium without going into secretory phase so this continued growing endometrium breaks down irregularly
If the women then has an ovulatory cycle then it varies the pattern of bleeding even more
What can cause anovulation?
most common at either end of reproductive life but other causes include PCOS, hypothalamic dysfunction, thyroid disorders, hyperprolactinaemia
Organic causes of AUB can be split into?
causes in the endometrium or causes in the myometrium
List some endometrial causes that can cause AUB?
Endometritis
Polyp
Miscarriage
List some myometrium causes that can cause AUB?
Adenomyosis
Leiomyoma
Endometritis can be acute or chronic
if its acute form there is an infiltrate of ___1_____ and in chronic form there is _____2_______ causes include ________3__________
1) neutrophils
2) lymphoplasmacytic
3) pelvic inflammatory disease, retained products of conception, intrauterine device related
Describe tuberculous endometritis?
now uncommon in UK, histlogically there are epitheliod granulomas within the endometrium
Endometrial polyps are ___1___ they are usually ___2___ but may present with ____3_____ they are almost always benign but ___4_____
1) common
2) asymptomatic
3) bleeding or discharge
4) endometrial carcinoma can present as a polyp
With miscarriage as a cause of AUB what is it important to rule out
molar pregnancy
What is adenomyosis?
this is when there are endometrial glands and storma within the myometrium which causes menorrhagia and dysmenorrhoea
What is a leiomyoma?
aka fibroids
tumours of the smooth muscle of the uterus
The cervix has two parts, describe the histology of each?
the endocervix: tall mucus secreting epithelium
the ectocervix: non-keratinised squamous epitheliumm
From puberty onwards the squamo columnar junction of the cervix presents on _________
the vaginal surface of the external os
Why is the squamo columnar junction of the cervix important?
this is an area where physiological squamous metaplasia occurs which means sometimes dysplasia can develop, so it is where cervical squamous carcinoma and its precursor CIN begin
What is CIN?
cervical intraepithelial neoplasia is teh pre invasive stage of cervical cancer where there is dysplasia, it is asymptomatic and detectable by cervical screening
Describe genital warts?
these are caused by low risk HPV strains 6 and 11
the warts have an exophytic growth pattern and papillomatous squamous epithelium are present
koilocytes will also be present indicating HPV infection
What are koilocytes?
cells with wrinkled pyknotic (condensation of chromatin) nucleus and perinuclear cytoplasmic clearing (lighter area around the nucleus)
due to infection with HPV
Koilocytes indicate infection with ____
HPV
Describe CIN 1?
Basal 1/3 of epithelium is occupied by abnormal cells
raised numbers of mitotic figures in lower 1/3
surface cells are quite mature but nuclei slightly abnormal
Describe CIN 2?
Abnormal cells extend to middle 1/3
mitoses in middle 1/3
abnormal mitotic figures
Describe CIN 3?
means cervical carcinoma in situ
abnormal cells occupy the full thickness of the epithelium
mitoses are often abnormal in the upper 1/3
90% of cervical cancers are _____
squamous carcinoma
Where do most squamous cell carcinomas of the cervix arise?
Most arise at the squamo columnar junction
Cervical SCC arises from _____
pre-existing CIN (therefore most cases prevented by screening)
Describe local, lymphatic and haematogenous spread of cervical carcinoma?
until very late stage disease stays in pelvis spreads locally to uterine body, vagina, bladder, ureters and rectum
lymphatic spred can occur early via iliac nodes then to aortic nodes and up
haematogenous spread occurs late to the liver, lungs and bone
(most people are dead before it has time to metastasise)
What is CGIN?
This is preinvasive adenocarcinoma and is more difficult to diagnose on a smear
What percentage of cervical cancer is adenocarcinoma?
10%
Is adenocarcinoma of the cervix related to HPV?
yes
Where does most adenocarcinoma of the cervix arise?
endocervical canal
Apart from cervical cancer list some other HPV driven diseases?
vulvar intraepithelial neoplasia, VIN
Vaginal intraepithelial neoplasia, VaIN
Anal intraepithelial neoplasia, AIN
List some conditions of the vulva that can present as leukoplakia?
VIN
Candida
Lichen Sclerosus
Describe the two types of VIN?
VIN of usual type = precursor of hpv driven SCC
Differentiated VIN (dVIN) is not related to hpv but still a precursor of SCC. The SCC tends to be more invasive. There is often a background of inflammatory dermatoses such as lichen sclerosus.
Describe vulvar invasive SCC?
rare
usually elderly women, ulcer of exophytic mass
can arise from normal epithelium or VIN
mostly well differentiated
spread to inguinal nodes or not is the biggest prognostic factor
Describe primary tumours of the vagina?
these are rare and a disease of the elderly, more often a spread from cervix of vulva
What 3 forms does endometrial hyperplasia occur in?
simple, complex and atypical
Describe simple endometrial hyperplasia?
tends to occur in the peri-menopausal period, it is due to excess oestrogen stimulation, particularly associated with anovulatory cycles but rarely with oestrogen therapy or oestrogen secreting tumours. There is general distribution of glands and storm, glands are dilated but not crowded, cytology is normal. Clinically there is irregular, frequent and heavy bleeding.
Describe complex endometrial hyperplasia?
hyperplasia is focal and glands but not stroma are affected. Thus the glands appear crowded but show no atypic so no increase in malignancy.
Describe atypical endometrial hyperplasia?
hyperplasia is focal and cytological atypic with mitotic figures is common. This is considered pre-cancerous and there is a risk of adenocarcinoma developing.
What type of cancer is endometroid carcinoma?
adenocarcinoma - because it’s glandular epithelium
How do endometrial cancers commonly present?
bleeding in post-menopausal patients
Most endometrial carcinomas are _____
type 1 - endometrioid tumours
What are endometroid carcinomas related to?
unopposed oestrogen (ie oestrogen without progesterone to stop the endometrium growing) and with atypical hyperplasia
List 2 risk factors for endometrial carcinomas? What type are they the biggest risk factor for?
obesity
lynch syndrome/ HNPCC
biggest risk factor is for endometroid but they have been shown to be related to the other types
Explain why obesity is a risk factor for endometrial cancer?
adipocytes express aromatase that converts ovarian androgens into oestrogen which induces endometrial proliferation
SHBG levels are also lower in obese women so more active hormone, insulin is also elevated and ILGF exerts a proliferative effect of the endometrium
Explain why lynch syndrome/ HNPCC is a risk factor for endometrial cancer?
lynch syndrome causes micro satellite instability due to a defect in mismatch repair genes, it increases the risk of colorectal and endometrial cancers (all cancers but endometroid is the most common)
Describe type 2 endometrial carcinomas?
type 2 tumours include serous and clear cell types, precursor lesions are termed serous endometrial intraepithelial carcinoma, these are more aggressive than endometroid/ type 1, clear cell is less common than serous and may be hard to differentiate from clear cell spread from other sites
Describe tumours other than carcinomas of the endometrium?
other tumours include stromal tumours and carcinosarcomas which have features of both endometrial carcinoma and sarcoma
Are leiomyoma common?
yes- very common
Clinical features of leiomyoma?
menorrhagia and infertility
Describe macroscopic appearance of leiomyoma?
benign, circumscribed growths derived from uterine smooth muscle (myometrium)
the tumour is firm, round, white with a whorled (spiral) structure
white on background of yellowish myometrium
they vary in size from mm to cm, frequently multiple and can be found in any part of the uterus
Describe microscopic appearance of leiomyoma?
the cells are typical long spindle muscle cells arranged in interlacing bundles
Are leiomyomas linked to obesity?
probably, they are more common with increasing BMI
Describe leiomyosarcoma?
rare tumour of smooth muscle of uterus, it can arise from existing leiomyoma but usually does not
they have a poor prognosis
List five categories of ovarian cysts?
follicular, luteal, endometriotic, epithelial, mesothelial
What are the two types of functional cyst?
follicular and luteal
Describe follicular cysts?
the follicle has failed to rupture and is filled with more fluid instead, these can be several cm in diameter
When do lots of follicular cysts occur?
in PCOS
get bilateral, multiple follicular cysts
Describe luteal cysts?
these occur when the follicle ruptures to release the egg but then seals up and swells with fluid
Prognosis of functional cysts?
most functional cysts resolve on their own and may be completely asymptomatic
What is endometriosis?
this consists of deposits of endometrium outside the uterine cavity
these endometrial glands and storm are still under the influence of hormones and will break down at bleed at the time of menstruation
they cause pelvic inflammation, infertility and pain
In endometriosis what type of cyst can develop in the ovary?
chocolate cyst
Macroscopically what is seen with endometriosis?
peritoneal spots or nodules, fibrous adhesions (because the lesions cause inflammation) and chocolate cysts
Microscopically what is seen with endometriosis?
endometrial glands and stroma with haemorrhage, inflammation and fibrosis
3 proposed pathogenesis of endometriosis?
retrograde spill of menstrual debris
metaplasia of tissues in mullein/ paramesonephric duct elements
lymphatic and blood borne emboli of endometrial tissue
Complications of endometriosis?
pain, cyst formation (in ovaries can destroy surrounding tissue), adhesions, infertility, ectopic pregnancy, increased risk of malignancy due to cyst undergoing malignant change to endometriod adenocarcinoma
Describe the theories for cells of origin for epithelial ovarian tumours?
in all epithelial tumours the cell of origin is not entirely clear, the current hypothesis is that the tumours arise from the mesothelial cell layer that lines the ovarian cell surface which undergoes a metaplastic change to become any cell that arises from embryonal coelomic epithelium
List some epithelial ovarian tumours? Which are more common
Serous and Mucinous- more common
endometroid carcinoma
clear cell carcinoma
brenners tumour
Describe serous ovarian tumours?
the epithelium resembles that of fallopian tubes, can be benign, borderline or malignant
malignant serous cystuadenocarcinoma is commonest malignant tumour of ovary, classified as low grade or high grade, can arise from serous tubal intraepithelial carcinoma (STIC)
Describe mucinous ovarian tumours?
resembles epithelium from the endocervix
secretes mucin
Describe endometroid and clear cell carcinoma of the ovaries?
both have strong associations with endometriosis of the ovary
arising directly from the endometriosis or with a focus of endometriosis in the background
they are histologically similar to those of the endometrium
Describe brenners tumours of the ovary?
these are essentially benign and show islands of transitional epithelium in a fibrous stroma
Describe progression in ovarian cancer?
spread in early stages is by direct extension to the pelvic peritoneum
the serous carcinoma seeds widely in the peritoneal cavity and only later are lymphatics invaded and metastases appear
the mucinous variety rarely spreads by lymphatics
overall 5 year survival is only 30%, death often in 2-3 years due to cachexia and renal and intestinal dysfunction
Where do sex cord/ stromal tumours of the ovary arise?
from the stroma of the ovary (supporting connective tissue)
List some sex cord/ stromal tumours of the ovary?
fibroma
thecoma
granulosa cell tumour
sertoli- leydig cell tumour
Describe thecomas and fibromas of the ovary?
thecoma and fibroma are a spindle cell tumour
fibroma is a benign collagenous tumour similar to a thecoma but does not produce oestrogen
Describe granulosa cell tumours?
these are composed of cells resembling the granulosa cells lining graafian follicles, all are potentially malignant and they secrete oestrogen
Describe sertoli leydig cell tumours in the ovaries?
these are very rare but may produce androgens causing virilisation, usually a small yellow tumour within the ovary
What percentage of all ovarian tumours do germ cell tumours make up?
15-20%
2 main types of germ cell tumour? other types?
immature teratoma and mature teratoma
yolk sac tumour and choriocarcinoma which are both extra embryonic
also a mixed germ cell tumour and dysgerminoma (same as seminoma in testes)
Describe mature cystic teratomas?
AKA “dermoid cyst”
this is what 95% of germ cell tumours are, they are benign, because they have pluripotent potential can see sebum, hair, teeth, nervous tissue, respiratory, intestinal epithelium and thyroid
very occasionally the squamous epithelium can undergo malignant change
Describe immature teratomas?
these are predominantly solid and are malignant
they contain embryonic tissues typically of primitive nerve tissue and mesenchymal tissue
Describe metastatic tumours of the ovary?
they can come from anywhere
the commonest is stomach, colon, breast and pancreas
must be considered in all cases, particularly when tumours are bilateral and small
