O&G Pathology Flashcards
What are the three possible types of endometrial hyperplasia?
Simple
Complex
Atypical (precursor of carcinoma)
Describe the difference in appearance between simple, complex and atypical hyperplasia
SIMPLE:
- Glands and stroma
- Dilated not crowded
- Cytology = Normal
COMPLEX:
- glands
- crowded
- Cytology = Normal
ATYPICAL:
- glands
- crowded
- Cytology = Atypical
- high N:C ratio
What are the precursor lesions to the main two types of endometrial carcinoma?
Endometrioid carcinoma = atypical hyperplasia
Serous carcinoma = serous intraepithelial carcinoma
What underlying conditions should you consider when a patient presents with endometrial carcinoma?
- polycystic ovary syndrome
- Lynch syndrome (HNPCC)
What is thought to cause endomeTROID carcinomas?
- unopposed oestrogen
- atypical hyperplasia
What is thought to cause SEROUS/CLEAR CELL endometrial carcinomas?
- Not associated with unopposed oestrogen
- TP53 often mutated
Why does obesity cause an increased endometrial cancer risk?
Adipocytes = express aromatase (converts androgens to oestrogens)
Sex hormone-binding globulin levels = lower
=> level of free active hormone is higher
Level of insulin-binding globulins = reduced
=> free insulin levels = elevated
=> Insulins exert proliferative effect on endometrium like oestrogen
How do SEROUS/CLEAR CELL endometrial carcinomas usually spread?
- along Fallopian tube mucosa and peritoneal surfaces
=> patients may present with extrauterine disease
Which type of endometrial carcinoma is more aggressive?
Serous/Clear cell
What characterises Serous endometrial carcinoma on histology?
complex papillary and/or glandular structure
+ diffuse, marked nuclear pleomorphism
How do clear cell endometrial carcinomas appear on histology?
Lots of “clear” cell spaces in comparison to other forms of cancer
Endometroid/Mucinous cancers are graded but Serous/Clear cell are not. TRUE/FALSE?
TRUE
- serous/ clear cell not formally graded
How are endometrial cancers graded?
Based on amouont of solid growth in tumour
Grade 1 5% or less solid growth
Grade 2 6-50% solid growth
Grade 3 >50% solid growth
How are endometrial cancers staged?
Stage I confined to endometrium
Stage II cervical stroma
Stage III (A = local spread, C = regional lymph nodes)
Stage IV bladder/bowel mucosa or distant mets
Endometrial tumours can also occur in the stroma. What are these called?
Endometrial Sarcomas
- usually high grade
can also get carcinosarcomas which are a mix of both
Give examples of tumours which can arise from the myometrium?
Leiomyomas (benign fibroids)
Leiomyosarcomas (rare, malignant)
How would patients usually present with a leiomyosarcoma?
- age >50
- abnormal vaginal bleeding
- palpable pelvic mass
- pelvic pain
Leiomyosarcomas have a poor prognosis even if confined to uterus at time of presentation. TRUE/FALSE?
TRUE
What phase is the endometrium in during each stage of the ovarian menstrual cycle?
Ovarian Follicular Phase = Endometrial Menstruation
Ovulation = Endometrial Proliferation
Ovarian Luteal Phase = Endometrial Secretory
The endometrial secretory phase ALWAYS lasts how many days?
14
Describe the histological appearance of the endometrium during the secretory phase
- Increasing tortuosity
- Lumenal secretions
What may cause dysfunctional uterine bleeding in adolescence and early reproductive life?
Anovulatory cycles (PCOS)
Pregnancy/miscarriage
Endometritis
Bleeding disorders
What may cause DUB during reproductive age?
Anovulatory cycles Pregnancy/miscarriage Endometritis Bleeding disorders Polyp Fibroid Adenomyosis Hormone effects Hyperplasia/Neoplasia: cervical, endometrial
What may cause Post-Menopausal DUB?
- Atrophy
- Polyp
- Exogenous hormones: HRT, tamoxifen
- Endometritis
- Bleeding disorders
Hyperplasia
Endometrial carcinoma
Sarcoma
TVUS can measure endometrial thickness. What measurements would indicate a need for biopsy?
> 4mm in postmenopausal women
(>16mm in premenopausal)
= generally taken as an indication for biopsy
How can the endometrium be sampled?
Pipelle biopsy
Dilatation and curretage
What are the adv/disadv of Pipelle biopsy vs D+C?
Pipelle
- no dilatation needed
- no anaethesia
- Outpatient procedure
- safe
- May only get a Limited sample
D+C
- more thorough sampling method
- however can miss 5% hyperplasias/cancers
A biopsy during which phase of the endometrial cycle is the least informative?
Menstrual phase
- endometrium is falling away therefore difficult to pick anything up on biopsy
What can be seen histologically if patients have anovulatory cycles?
Proliferation phase never moves into secretory as no ovulation has occurred
=> disordered proliferation begins to take place
What usually protects the endometrium from infection?
- Cervical mucous plug
- Cyclical shedding of endometrium
What organisms can cause endometritis?
Neisseria
Chlamydia
TB
CMV/HSV
What causes of endometritis are non-infective?
IUD
Postpartum/Postabortal/Post curettage
Granulomatous (sarcoid, foreign body post ablation)
Associated with leiomyomata or polyps
How can you tell histologically if a patient has miscarried?
There will be chorionic villi in the sample (retained products of conception)
- Foetal RBCs will be visible on sample
What characterises a molar pregnancy on histology?
Swollen chorionic villi
Which type of mole has a higher risk of progressing to a choriocarcinoma?
Complete Hydatidiform Mole
What is the characteristic feature of adenomyosis on histology?
Endometrial glands and stroma within the myometrium
What are the main types of cysts arising from the ovaries?
Follicular e.g. polycystic ovaries – Luteal – Endometriotic – Epithelial – Mesothelial
What causes the formation of a follicular cyst?
- form when ovulation doesn’t occur
=> Follicle doesn’t rupture but grows into cyst
Follicular cysts usually resolve. TRUE/FALSE?
TRUE - Usually resolve over a few months
What is endometriosis?
- Endometrial glands and stroma outside uterine body
What sites does endometriosis normally present in?
– Ovary (‘chocolate’ cyst) – Pouch of Douglas – Peritoneal surfaces, including uterus – Cervix, vulva, vagina – Bladder, bowel etc
How does endometriosis look MACROscopically?
Peritoneal spots or nodules
Fibrous adhesions
Chocolate cysts
Other than endometrial glands and stroma in the wrong place, how can endometriosis be identified microscopically?
Haemorrhage
inflammation
fibrosis
What are the main complications of endometriosis?
- Pain
- Cysts
- Adhesions
- Infertility
- Ectopic pregnancy
- Malignancy (endometrioid carcinoma)
How are epithelial ovarian tumours classified?
Benign - No cytological abnormalities, Does not invade stroma
Borderline - Cytological Abnormality but no stroma invasion
Malignant - Stromal invasion present
What is the difference between high grade and low grade serous carcinoma?
Different precursor lesions
High grade:
- Serous TUBAL intraepithelial carcinoma
(most tubal in origin)
Low grade:
- Serous borderline tumour
What type of ovarian cancers does endometriosis predispose to?
Endometrioid and Clear Cell carcinoma
How is a primary diagnosis of ovarian cancer often made?
- Ascitic fluid
- patients often present with ascites
What is a Brenner Tumour? Is it normally benign, borderline or malignant?
- tumour of transitional eptihelium
- usually BENIGN
Most germ cell ovarian tumours are known as what?
Mature Teratomas
also called “dermoid cysts”
What can be found in teratomas?
– contain all 3 layers of ectoderm, mesoderm and endoderm
– cystic, containing sebum and hair
– skin, respiratory epithelium, gut, fat common
What other types of germ cell tumour can arise in the ovary?
Immature teratoma Dysgerminoma (young women/children) Yolk sac tumour Choriocarcinoma (due to molar preg.) Mixed germ cell tumour
What types of sex cord/stromal tumour may arise in the ovary?
- Fibroma/Thecoma (Benign)
- Granulosa cell tumour (all potentially malignant)
- Sertoli-Leydig cell tumours (Rare)
Metastases to the ovary most commonly come from where?
Stomach
Colon
Breast
Pancreas
When must you suspect metastases to the ovary?
If bilateral tumour tissue appears
Briefly describe Figo Ovarian Cancer Staging
1A - one ovary
1B - both ovaries
2A - uterus/fallopian tube
2B - intraperitoneal
3A - Retroperitoneal lymph node/microscopic beyond pelvis
3B Macroscopic metastasis beyond pelvis <2cm
3C Macroscopic peritoneal metastasis >2cm
4 Distant metastasis
When should you consider a diagnosis of ectopic pregnancy?
- female of reproductive age
- amenorrhoea
- acute hypotension
- acute abdomen
What is the transformation zone?
- Squamo-columnar junction between ecto and endocervix
What can physiologically change the position of the transformation zone?
- menarche
- pregnancy
- menopause
What can cause cervical erosion?
- Exposure of endocervix to acid environment of vagina
=> physiological squamous metaplasia
What HPV virus strains are most high risk for cervical cancer?
16 and 18
Other than HPV, what makes the Squamocolumnar junction more vulnerable to develop cervical cancer?
- age at first intercourse
- long term use of oral contraceptives
- non-use of barrier contraception
- Smoking: 3 x risk
- Immunosuppression
What strains of HPV are responsible for genital warts?
6 and 11
What is the normal time line between HPV and cancer?
HPV infection - High grade CIN
6 months - 3 years
High Grade CIN - Invasive Cancer
5 -20 years
What is cervical intraepithelial neoplasia?
- Precursor stage of cervical cancer
- transformation zone.
- Dysplasia
- Asymptomatic but detected by cervical screening
Describe the stages between normal squamous epithelium and neoplasia
Koilocytosis
CIN1
CIN2
CIN3
How does CIN appear on histology?
- Nuclear abnormalities
- hyperchromasia
- nucleocytoplasmic ratio
- pleomorphism
- Excess mitotic activity
What is the difference between CIN I, II and III?
CIN I - Basal 1/3 of epithelium = abnormal cells
CIN II - Abnormal cells extend to middle 1/3
CIN III - Abnormal cells occupy full thickness of epithelium
CIN III is the most likely to progress to invasion. TRUE/FALSE?
TRUE
>12%
What are the symptoms of invasive cervical carcinoma?
- Abnormal bleeding
- Brownish or blood stained vaginal discharge
- Contact bleeding – friable epithelium
- Pelvic pain
- Haematuria / urinary infections
- Ureteric obstruction / renal failure
Describe how invasive cervical carcinoma can spread
Local
- uterine body
- vagina
- bladder
- ureters
- rectum
Lymphatic (pelvic and para-aortic nodes)
Haematogenous
- liver
- lungs
- bone
What is CGIN in comparison to CIN?
Cervical Glandular Intraepithelial Neoplasia (CGIN)
- occurs from endocervical epithelium
- harder to recognise than squamous
What can CGIN progress to?
Endocervical Adenocarcinoma (glandular malignancy)
What can predispose to endocervical adenocarcinoma?
Higher S.E. Class
Later onset of sexual activity
Smoking
HPV again (HPV18)
Endocervical adenocarcinoma has a worse prognosis than squamous. TRUE/FALSE?
TRUE
Where else can HPV cause intraepithelial neoplasia to occur?
Vulvar Intraepithelial Neoplasia, VIN
Vaginal Intraepithelial Neoplasia, VaIN
Anal Intraepithelial Neoplasia, AIN
Describe the difference in presentation of vulvar intraepithelial neoplasia in young women vs older women.
Young women
- recurrent
=> causing treatment problems
Older women
- risk of progression to invasive squamous carcinoma.
How is vulvar invasive squamous carcinoma treated?
radical vulvectomy
inguinal lymphadenectomy
Describe the appearance of vulvar pagets disease
Crusting rash
Tumour cells in epidermis (contain mucin)
no underlying cancer
tumour arises from sweat gland in skin
What other non-neoplastic epithelial disorders can occur in the vulva?
Lichen Sclerosis
Lichen planus
Psoriasis
Post-menopausal atrophy
Vaginal melanoma may appear as a polyp. TRUE/FALSE?
TRUE
