Pathology of the Ovary Flashcards
What are paratubal cysts?
They are cysts on ovaries derived from mullarian duct remnants and are very common with no clinical consequence.
What is an adenomatoid tumour?
Benign neoplasm derived from the mesothelium.
What kind of mutation or cancer affects the Fallopian tubes to cause premalignant STIC cancers?
Particularly prevalent in people with BRCA mutations and in women with high grade serous carcinoma of the ovary.
Frequently show p53 mutations
How are premalignant STIC or in situ serous carcinomas treated>
Spread rapidly through the peritoneum so removal of tubes prior to malignant spread is indicated to prevent ovarian cancer
What are BRCA mutations?
Breast cancer associated mutations
What does BRCA do?
Genes that make tumour suppressor proteins.
If there is a BRCA mutation then DNA is not repaired leading to mutations. People with inherited BRCA1 and BRCA2 are at risk of
What mutations result in breast and ovarian cancer?
Breast: Background lifetime risk = BRCA1/2
Ovarian: Background risk is 2% BRCA1 is 45% and BRCA2 is 80%
What kind of tumours are ovarian tumours classified as?
For exam: They are surface epithelial tumours.
However new research is showing that they arise from fimbrial end of fallopian tubes (so not from the ovary itself)
Where do ruptured cystic follicles come from?
They come from unruptured graafian or in follicles that ruptured but then stuck shut.
What is polycystic ovarian syndrome?
Lots of follicles are formed but no ovulation
High androgen production and insulin resistance.
Pathophysiology is poorly understood.
What are the associated disorders with polycystic ovarian syndrome?
Diabetes Mellitus 2
Obesity
Metabolic disorders
What are the macroscopic clinical symptoms of polycystic ovarian syndrome?
Macro: Globoid enlarged ovaries with multiple cysts ‘string of pearls USS’
What are the microscopic clinical symptoms of polycystic ovarian syndrome?
Thick ovarian capsule
Uniform cystic follicles
Partially regressing follicles
No corpus luteum or albicantia due to no cycling.
What percentage of cancers in women are ovarian cancer?
5% of cancers in women
What percentage of ovarian neoplasms are benign?
80%
What age group gets more benign ovarian neoplasms and what age group gets more malignant neoplasms?
Benign: 20 - 40 years
Malignant: 40 - 70 years
Malignant ones tend to present late and are more likely to be bilateral.
What are the following neoplasms called?
Benign and cystic
Benign, cystic and fibrous
Benign and mostly fibrous
Malignant
Cystadenoma
Cystadenofibroma
Adenofibroma
Adenocarcinoma or cystadenocarcinoma (late presenting, malignant and tend to be bilateral)
Why is ovarian cancer so deadly?
It is common (5th most common cancer in women)
Make up quarter of female genital tract cancer but cause half of deaths.
Vague clinical signs (bloating, fatigue, or no signs)
When advanced: Compressive sx ascites, mets.)
HIgh stage at presentation (late)
No screening tests available
What are the types of surface epithelial tumours of the ovary?
Serous: Benign / borderline / malignant forms. Malignant form is split into 2 categories (low and high grade serous carcinomas)
Mucinous: Benign / borderline / malignant forms
Endometrioid: Benign / borderline / malignant forms
Clear cell: Benign / borderline / malignant forms
Brenner: Benign / borderline / malignant forms
What are the types of mixed epithelial/stromal tumours of the ovaries?
Adenosarcomas
MMMT
What tumours can arise from the sex cord/stroma of the ovaries?
Granulosa/thecal tumours
Fibromas
What tumours arise from germ cells?
Teratomas
Dysgerminomas
Yolk sac tumours
Choriocarcinoma
Where do tumours of the ovary metastasize?
Colon
Appendix
Stomach
Breast
Pancreas
What mutation causes type 1 surface epithelial carcinomas?
KRAS/BRAF/ERBB2 mutations
Then loss of tp36 or CDKN2A/B
What are the classifications of surface epithelial tumours of the ovaries?
Type 1 - low grade that arise in setting of borderline tumours and/or endometriosis (eg low grade serous, endometrioid, mucinous)
Type 2 - STIC and high grade serous carcinoma
What mutations cause type 2 surface epithelial carcinomas?
p53 mutations
How are type 1 and type 2 lesions different?
Type 1: low grade with precursor lesion in a stepwise fashion, represented by cystadenomas and borderline tumours, most often presents early (low stage), often remains low grade by can progress to high grade. Mutation = K-ras/BRAF (65%) and TP53 (8%)
Type 2: High grade, arises de novo, and most often presents at high stage, is rapidly growing, aggressive, and caused by p53 mutation (in about 70% of cases), k-ras/BRAF are rare in these cancers.
Which cancers are type 1 and which are type 2?
Type 1 includes: Serous carcinoma, mucinous endometrioid, and clear cell carcinomas as well as transitional cell carcinoma. (Brenner and non-Brenner)
Type 2 includes: Serous carcinoma, and malignant mixed mullerian tumours.
What are the macroscopic and microscopic features of benign, borderline, and malignant tumours? What is the prognosis for these tumours?
Benign: Macroscopically a simple cyst, microscopically simple flat lining. Prognosis is excellent.
Borderline: Macroscopically a complex cyst, microscopically a branching complex architecture. Prognosis: may recur / progress.
Malignant: Macrscopically shows invasion, microscopically shows b/i plus solid and invasive areas. Prognosis is possibly lethal.
What percentage of borderline serous tumours are bilateral?
25%
What microscopic features do borderline serous ovarian lesions have?
They have papillary excrescences, non-invasive but recur, can implant into peritoneum, and have a small risk of malignant transformation.
What microscopic features do benign serous ovarian lesions have?
Serous inclusion cysts / aka cortical inclusion cysts lined by tubal type ciliated cells. Benign serous cystadenoma same but bigger.
What is the 5y survival rate of borderline serous ovarian lesions?
5y survival if confined to the ovary is 100%
If peritoneum is involved 60%
What are the potential complications of low grade serous ovarian carcinomas?
Can widely spread to peritoneal surfaces but progress slowly and cause intestinal obstruction.
What is 5y survival of high grade serous carcinomas?
<25%
What are the important histological features of high grade serous ovarian carcinomas?
Markey nuclear atypia and ‘monster cells’
What mutations are associated with high grade serous ovarian carcinoma?
P53 and BRCA
How is histology different between benign and borderline mucinous ovarian lesions?
Benign: Tend to be multiloculated, huge, and seen in combo with benign teratoma. Have tall columnar cells with apical mucin. Mostly resembles intestinal epithelium, minority resemble endocervix.
Borderline: Older women, rarely bilateral, cystic and solid, more cytological and architectural atypia, non-invasive with intermediate prognosis.
What causes “jelly belly”?
Was previously thought to be mucinous ovarian carcinoma but now is associated with appendix neoplasms.
What mutations are associated with endometrioid ovarian lesions?
Alterations that increase PI3K/AKT pathway signalling (PTEN, PIK3CA, ARID1A and KRAS), MMR, and beta-catenin.
What conditions are associated with endometrioid ovarian lesions?
May be synchronous with endometrial endometrioid adenocarcinoma.
May arise from endometriosis
What is the 5y survival rate of endometrioid ovarian lesions if stage 1?
75%
What percentage of endometrioid ovarian lesions are bilateral?
40%
What ages are endometrioid ovarian lesions most common in?
50 - 60 yos
What rare surface epithelial tumours affect the ovaries?
Brenner (transitional): majority are benign
Clear cell: Majority malignant, associated with endometriosis
MMMT (Malignant Mixed Mullarian Tumour): Always malignant poor prognosis, malignant epithelium + malignant stroma = MMMT. Dismal prognosis.
What are the types of sex cord stromal tumours and what do they produce?
Granulosa and thecal cell -> Produce oestrogens
Sertoli-leydig -> androgens
Hilus (Pure leydig cell neoplasm) -> androgens.
What are the types of sex cord stromal tumours that affect ovaries and what do they do?
Oestrogen producing tumours -> result in endometrial hyperplasia and carcinoma
Androgen producing tumours block puberty or cause amenorrhoea +/- hirsutism and clitoral enlargement.
Who most commonly gets granulosa tumours?
Post menopausal women
What mutations lead to granulosa tumours?
FOXL2 mutations
What is a fibrothecoma? What is their prognosis?
When the thecoma > fibroma -> hormones
With ascites and R hydrothorax
Almost all are benign
What is the prognosis like in granulosa tumours?
They are low grade but often recurs later in life
What are the effects of sertoli-leydig tumours?
Masculinisation, 20 - 30yo, mostly benign
What mutations lead to sertoli-leydig tumours?
DICER1
What is the prognosis like in teratomas?
Most ovarian teratomas are benign. Most testicular teratomas are malignant with exception of those in prepubertal boys.
What kind of tissue do teratomas form?
Can form all kinds of body tissues. (brain matter can be attacked by immune system which goes to brain and causes psychosis)
What kind of tumours are immature teratomas?
Malignant, rare, seen in teens.
Tissue resembling foetal rather than mature tissue.
Usually immature neuroepithelium
Reasonable prognosis.
What kind of tumours are monodermal teratomas?
Struma ovarii composed of ovarian tissue can be functional -> Hyperthyroidism. Rare can get follicular or papillary thyroid carcinoma
What kind of behaviour do yolk sac tumours exhibit?
Differentiate along the extraembryonic yolk sac line and make AFP.
Schiller-Duval body. (looks like a glomerulus)
Rapidly growing mass, responds well to chemo
What kind of behaviour do choriocarcinomas exhibit?
Can be placental or ovarian in origin. If ovarian they are very aggressive, metastasize early, are often fatal and make HCG.
What tumours metastasize to the ovaries often?
Colon, appendix, stomach, breast, pancreas
What is a krukenburg tumour?
Bilateral ovarian metastases - classically mucin producing signet ring gastric carcinoma (commonly from colon, appendix, and stomach.
What is endometriosis?
Ectopic endometrial tissue outside of the uterus.
What are the consequences of endometriosis?
Infertility
Pelvic pain
Dysmenorrhoea
What are the microscopic and macroscopic features of endometriosis?
Macroscopic: Chocolate cyst, powder burns
Microscopic: Endometrial glands and stroma, haemorrhage.
What causes endometriosis?
4 theories:
Regurgitation: retrograde flow through tubes (90% of women have retrograde menstruation but 10% have endometriosis)
Benign metastasis: Spread via blood vessels/lymphatics
Metaplasia: Endometriosis arises from mesonephric remnants or pelvic mesothelium
Extrauterine stem cells: Stem cells from bone marrow differentiate into endometrial tissue
What conditions is endometriosis associated with?
Ovarian clear cell carcinoma
Ovarian endometrioid adenocarcinoma along with shared PTEN and ARID1A
Where are ectopic pregnancies most common?
90% are tubal
What are the chances of an ectopic pregnancy and what increases these chances?
Chances are 1/200 this is increased by:
PID
Adhesion
IUD
Endometriosis
What are the symptoms of an ectopic pregnacny?
Pain
Shock +/- vaginal bleeding
Death
How should women presenting with abdominal pain +/- PV bleeding be treated?
Pregnant until proven otherwise.
investigate with 2x cannula and take blood for group and hold
Pregnancy test
Then medical/surgical management.
