(47) Diseases of the reproductive system 2 Flashcards
What is endometriosis?
A condition where endometrial tissue is found outside of the uterus (ectopic endometrium)
What are the different theories as to why endometriosis occurs?
- regurgitation theory
- metaplasia theory
- stem cell theory (stem cells themselves turn into endometrium)
- metastasis theory (spread through lymphatics or vasculature)
In general, what does ectopic endometrium lead to?
Bleeding into tissues and fibrosis
Who does endometriosis occur in?
6-10% of women, 30-40 years old
What are the signs/symptoms of endometriosis?
- 25% asymptomatic
- dysmenorrhoea
- dyspareunia
- pelvic pain
- subfertility
- pain on passing stool
- dysuria
What is dyspareunia?
Pain on sexual intercourse
What is the investigation technique into endometriosis?
Laparoscopy
What does treatment choice for endometriosis (and many other conditions) depend upon?
The patient’s age and whether or not they want to maintain fertility
What are the medical treatments for endometriosis?
- COCP
- GnRH agonists/antagonists
- progesterone antagonists
What are the surgical treatments for endometriosis?
- ablation
- TAH-BSO
What is ablation?
The surgical removal of body tissue
What is a TAH-BSO?
Total Abdominal Hysterectomy Bilateral Salpingo Oophorectomy
- removes the uterus including the cervix and the ovaries including the fallopian tubes
What other conditions is endometriosis also linked to?
- ectopic pregnancy
- ovarian cancer
- IBD
What does COCP stand for?
Combined oral contraceptive pill
What is endometritis?
Inflammation of the endometrium
What may acute endometritis be due to?
- retained product of conception (POC)/placenta
- prolonged ROM
- complicated labour
What do you see on histology in acute endometritis?
Lots of neutrophils (manifestation of acute inflammatory response)
What may chronic endometritis be due to?
- pelvic inflammatory disease (PID)
- retained gestational tissue
- endometrial TB
- IUCD infection
What do you see on histology in chronic endometritis?
Lymphocytes and plasma cells
What are the signs/symptoms of endometritis?
- abdominal/pelvic pain
- pyrexia
- vaginal discharge
- dysuria
- abnormal vaginal bleeding
What investigations are done into endometritis?
- biochemistry/microbiology
- ultrasound scan (USS)
What is the treatment for endometritis?
- analgesia
- antibiotics
- remove cause (eg. remove infected uterine device/retained POC etc)
What are endometrial polyps?
Sessile/polypoid E2-dependent uterine overgrowths (growths from endometrium)
Who do endometrial polyps occur in?
Less than 10% of women (40-50s)
How big are endometrial polyps?
Normally 0.5-3cm in size
What are the signs/symptoms of endometrial polyps?
- often asymptomatic
- intermenstrual bleeding
- post-menopausal bleeding
- menorrhagia
- dysmenorrhoea
Very common cause of abnormal bleeding!
What are the investigations into endometrial polyps?
- USS
- hysteroscopy (camera up into uterus)
There is a link between endometrial polyps and which drug?
Tamoxifen
What are medial treatments for endometrial polyps?
- P4 (progesterone)
- GnRH agonists
What are the surgical treatments for endometrial polyps?
Curettage
What is curettage?
The use of a curette to remove tissue by scraping or scooping - used in the treatment of endometrial polyps
What is the prognosis for endometrial polyps?
Less than 1% turn malignant
What is leiomyomata?
Uterine fibroids
Benign myometrial tumours with E2/P4-depedent growth
A benign smooth muscle neoplasm
Who does leimyomata/uterine fibroids occur in?
20% of women, 30-50s
Why do uterine fibroids tend to regress after menopause?
As they are very responsive/dependent on oestrogen and progesterone
What are the risk factors for leiomyomata/uterine fibroids?
- genetics
- nullparity
- obesity
- PCOS
- HTN
What is nullparity?
Not having any children
What are the signs/symptoms of leiomyomata?
- often asymptomatic
- menometrorrhagia
- symptoms of Fe def. anaemia eg. tiredness, SOB
- subfertility/pregnancy problems
- pressure symptoms eg. constipation, pain on defeacation
What is menometrorhagia? (symptom of leiomyomata)
A condition in which prolonged or excessive uterine bleeding occurs irregularly and more frequently than normal - leads to iron deficient anaemia
What are the investigations into leiomyomata?
- bimanual examination
- USS
What are the medical treatments for leiomyomata/uterine fibroids?
- IUS
- NSAIDs
- OCP
- P4
- Fe2+
What are the non-medical treatments for leimyomata/uterine fibroids?
- artery embolisation (using an embolus to block the artery that provides the fibroid with blood)
- ablation
- TAH
What is the prognosis for leiomyomata/uterine fibroids?
- menopausal regression
- malignancy risk 0.01%
What does the treatment choice for uterine fibroids depend on?
How problematic the condition is, how close to menopause the woman is, whether she wants fertility to be maintained
What is endometrial hyperplasia?
Excessive endometrial proliferation (increased oestrogen and decreased progesterone)
What are the risk factors for endometrial hyperplasia?
- obesity
- exogenous E2
- PCOS
- E2-producing tumours
- tamoxifen
- HNPCC (PTEN mutations)
Why is obesity a risk factor for endometrial hyperplasia?
As there is an increase in circulating oestrogens in obesity
What are the different types of endometrial hyperplasia?
WHO classification
- non-atypical hyperplasia
- atypical hyperplasia
How many endometrial hyperplasia cases progress to carcinoma?
non-atypical hyperplasia = 1-3% progress
atypical hyperplasia = 23-48% are carcinoma on hysterectomy
What are the symptoms of endometrial hyperplasia?
Abnormal bleeding - IMB/PCB/PMB
What are the investigations into endometrial hyperplasia?
- USS
- hysteroscopy +/- biopsy
What are the medical treatments for endometrial hyperplasia?
- IUS
- P4 (progesterone)
What are the surgical treatments for endometrial hyperplasia?
- TAH
What is the prognosis in endometrial hyperplasia?
- endometrial adenocarcinoma
- regression
Describe the stages in the malignant progression of hyperplasia
- normal
- non-atypical hyperplasia
- typical hyperplasia
- endometroid carcinoma
Describe non-atypical hyperplasia
Overgrowth of whole endometrium with simple tubular glands. Varied size and shape, may be dilated. Increased gland to stroma ratio
Describe atypical hyperplasia
Complex patterns of proliferating glands with nuclear atypia. Increased number of mitoses
What is the most common cancer of the female gentile tract?
Endometrial carcinoma
How often does endometrial carcinoma occur?
8500 new cases/2000 deaths per year in the UK
What are the signs/symptoms of endometrial carcinoma?
- PMB/IMB
- pain if late
What are the investigations into endometrial carcinoma?
- USS
- biopsy
- hysteroscopy
What staging system is used in endometrial carcinoma?
FIGO (1-4)
What are the medical treatments for endometrial carcinoma?
- P4 (progesterone)
What are the surgical treatments for endometrial carcinoma?
- TAH-BSO
- adjuvant therapy (chemotherapy, radiotherapy)
What is the prognosis for endometrial carcinoma?
stage 1 = 90% 5 year survival
stage 2-3 =
What is type 1 endometrial carcinoma also called/described as?
Endometroid (75% of cases)
What is type 2 endometrial carcinoma also called/described as?
Serous (25% of cases)
At what age do types 1 and 2 endometrial carcinoma occur?
type 1 = pre-/perimenopausal
type 2 = postmenopausal
What is the pre-existing stage in types 1 and 2 endometrial carcinoma?
type 1 = endometrial hyperplasia
type 2 = endometrial atrophy
What are the mutations in type 1 and type 2 endometrial carcinoma?
type 1 = PTEN, Kras
type 2 = P53
What is the E2 status in types 1 and 2 endometrial cancer?
type 1 = E2 +ve
type 2 = E2 -ve (unresponsive to oestrogen)
What are different grades of type 1 and 2 endometrial carcinoma?
type 1 = can be grade 1, 2 or 3
type 2 = only grade 3
What does PCOS stand for?
Polycystic ovary syndrome
What is polycystic ovary syndrome?
A complex endocrine disorder, with 3 main features…
What are the 3 main features of polycystic ovary syndrome?
- hyperandrogenism
- menstrual abnormalities
- polycystic ovaries
Who does PCOS affect?
6-10% of women (20-30% have polycystic ovaries)
What are the investigations into PCOS?
- USS
- fasting biochemical screen (decreased FSH, increased LH, testosterone and DHEAS)
- oral glucose tolerance test (OGTT)
OGTT is a test for diabetes. Why is it done in suspected PCOS?
PCOS is associated with diabetes
What is the diagnostic criteria for PCOS?
Rotterdam criteria
2/3 of - polycystic ovaries, hyperandrogenism (hirsuitism/biochemical), irregular periods (>35 days)
What is a lifestyle change than can treat PCOS?
Weight loss - since polycystic ovary syndrome occurs in patients who are overweight
What are the medical treatments for polycystic ovary syndrome?
- metformin
- OCP
- clomiphene
Why is clomiphene used in the treatment of PCOS?
Clomiphene stimulates ovulation
What is a surgical treatment for polycystic ovary syndrome?
Ovarian drilling (stimulates ovaries)
Polycystic ovary syndrome has links to which other conditions?
- infertility (as not ovulating regularly, and having irregular periods)
- endometrial hyperplasia/adenocarcinoma
What is primary failure of the gonads called?
Hypergonadotrophic hypogonadism
What hormone changes are there in hypergonadotrophic hypogonadism?
Raised FSH and LH (trying to compensate, but it is the gonads themselves that have failed and are unresponsive)
What are the congenital causes of hypergonadotrophic hypogonadism?
- Turner syndrome (XO)
- Klinefelter’s syndrome (XXY)
What are the acquired causes of hypergonadotrophic hypogonadism?
- infection
- surgery
- chemo-radiotherapy
- toxins/drugs
What is hypogonadotrophic hypogonadism?
Hypothalamic or pituitary failure causing low FSH and LH - secondary failure of the gonads
What are the potential causes of hypogonadotrophic hypogonadism?
- Sheehan’s syndrome
- pituitary tumours
- brain injury
- empty sella syndrome
- PCOS
What is empty sella syndrome?
Where the pituitary gland shrinks or becomes flattened, filling the sella turcica with cerebrospinal fluid on imaging instead of the normal pituitary
What is Sheehan’s syndrome?
Hypopituitarism caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth
How does gonadal failure present?
- amenorrhoea/absent menarche
- delayed puberty
- decreased sex hormone levels
- +/- increased LH and FSH levels
What investigations are done into gonadal failure?
- hormonal profiling
- karyotyping (to rule out congenital causes)
What are the 3 main general types of ovarian neoplasms?
- surface epithelial stromal tumours
- germ cell tumours
- sex-cord stromal tumours
What is the most common type of ovarian neoplasm? (90%)
Epithelial tumours
What are the 3 major histological types of epithelial tumours?
- serous (tubal)
- mucinous (endocervical)
- endometroid (endometrium)
(also transitional cell and clear cell)
Each type of epithelial tumours has what variants?
Benign, borderline and malignant variants
Describe how benign epithelial tumours are further subclassified
Subclassified based on components
- cystic = cytadenomas
- fibrous = adenofibromas
- cystic and fibrous = cystadenofibromas
What are malignant epithelial tumours called?
Cystadenocarcinomas, eg. serous cystadenocarcinoma
What makes up around 15-20% of all ovarian tumours?
Germ cell tumours
Germ cell tumours are classified into which 2 types?
- germinomatous
- non-germinomatous
What is a germinomatous germ cell tumour called?
Dysgerminoma
What are the features of dysgerminoma?
- differentiation towards oogonia
- malignant
- responsive to chemo
Name 3 non-germinomatous germ cell tumours
- teratomas
- yolk sac tumours
- choriocarcinomas
What are the features of teratomas?
- differentiation towards multiple germ layers
- mature = benign, dermoid cysts, 1% malignant transformation
- immature = malignant, often contain embryonal/immature foetal tissue
What are the features of yolk sac tumours?
- differentiation towards extraembryonic yolk sac
- malignant
- responsive to chemo
What are the features of choriocarcinomas?
- differentiation towards placenta
- malignant
- often unresponsive to chemo
What are the treatments for germ cell tumours?
- surgery
- chemotherapy
- radiotherapy
Where do sex cord stromal tumours arise from?
Arise from the ovarian stroma, which was derived from the sex cord of the embryonic gonad (rare)
In general, what can sex cord stromal tumours generate?
Cells from the opposite sex
Name 3 types of sex cord stromal tumours
- thecoma/fibrothecoma/fibroma
- granulosa cell tumours
- sertoli-leydig cell tumours
What do themocas produce?
Benign, thecomas and fibrothecomas produce E2 (also rarely androgens)
Fibromas are hormonally inactive
What are thecomas comprised of?
Spindle cells (plump spindle cells with lipid droplets = thecoma appearance)
What is Meig’s syndrome?
A triad of ascites, pleural effusion/right sided hydrothorax and benign ovarian tumour
What do granulosa cell tumours produce?
E2
Are granulosa cell tumours benign or malignant?
Low grade malignant
What do Sertoli-Leydig cell tumours produce?
Androgens
Are Sertoli-Leydig cell tumours benign or malignant?
10-25% malignant
Thecoma, fibrothecoma, fibroma and granulosa cells are all what?
Cells found in the normal ovary - therefore produce oestrogen
What are sertoli cells and leydig cells?
Sertoli cells = produce sperm, responsive to FSH
Leydig cells = produce testosterone, responsive to LH
Normally male-derived
How common is ovarian cancer in general?
2nd commonest gynae cancer
7,100 women, 4,300 deaths per year in UK
80% = >50 80-90% = epithelial
What are the risk factors for ovarian cancer?
- FH
- increasing age
- PMH breast cancer
- smoking
- E2-only HRT
- Lynch II syndrome
- obesity (weak)
- nulliparity (weak)
What are the protective factors against ovarian cancer?
- OCP
- breastfeeding
- hysterectomy
What are the signs/symptoms of ovarian cancer?
- pain
- bloating
- weight loss
- PV bleeding
- urinary frequency
- anorexia
How is ovarian cancer staged?
FIGO staging 1-4
What are the treatments for ovarian cancer?
- TAH/BSO
- omentectomy
- appendectomy
- lymphadenectomy
- adjuvant chemotherapy
- chemo only in sensitive germ cell tumours
What is the prognosis in ovarian cancer?
Overall 5 years 43% survival
What are the 2 categories of ovarian metastatic tumours?
- Mullerian tumours (most common)
- extra-Mullerian tumours
What are the types of Mullerian ovarian metastatic tumours?
- uterus
- fallopian tube
- pelvic peritoneum
- contralateral ovary
What are the types of extra-Mullerian ovarian metastatic tumours?
- GI tract (large bowel, stomach = Krukenberg tumour, pancreatobiliary
- breast
- melanoma
- kidney and lung (less common)
What are the pathways of metastasis from other sites to the ovary?
- lymphatic or haematogenous spread
- direct extension from the bladder or rectum
What is the prognosis for ovarian metastatic tumours?
- tumours are confirmed histologically
- the prognosis is typically poor
