Female GU/breast Flashcards
What is salpingitis and how does it present?
pelvic inflammatory disease affecting fallopian tubes
fever, lower abdominal or pelvic pain, pelvic masses
Name three complications associated with salpingitis.
tubo-ovarian abscess
tubal ectopic pregnancy
infertility
What are the two most common tubal malignancies? What gene mutation is associated with it?
serous tubal carcinoma
endometriod carcinoma
BRCA1
List the four features of polycystic ovaries.
oligomenorrhoea, hirsutism, infertility, obesity
What four sporadic mutations are associated with ovarian neoplasms?
BRCA, HER2 overexpression, KRAS mutation, p53
Which three cell types do ovarian neoplasms arise from?
surface epithelium, germ cells, sex cord/stromal cells
Both benign and malignant ovarian surface epithelial tumours can be cystic and stromal. Describe how their naming is different.
- benign: cystic = cystadenoma. Solid = cystadenofibroma
- malignant: cystic = cystadenocarcinoma. Solid = adenocarcinoma
Carcinomas of the ovaries may be HGSC, LGSC, endometrial, clear cell and mucinous. How do each of these arise?
- HGSC: epitheial precursor lesions in fallopian tubes. Abnormal p53 and BRCA1
- endometrioid and clear cell: ovarian endometriosis
- LSGC: abnormal KRAS and BRAF
Describe the appearance of benign serous ovarian tumours.
large cystic tumours, smooth shiny serosal covering
cysts filled with clear serous fluid, lined by a single layer of tall columnar epithelium
Describe the morphology of serous ovarian carcinoma.
cell anoplasia, obvious stromal invasion Psammona bodies (concentrically laminated calcified concretions) in the papillae
Which type of ovarian tumour appears large, multifocular and without psammona bodies? It also mimics a Krukenburg tumour, one which has metastases from the GI tract.
mucinous
The PTEN tumour suppressor gene is often lost in which type of ovarian cancer and where is said neoplasm though to arise?
endometrial carcinoma
endometriosis
Aside from endometrial carcinoma, which other ovarian cancer is though to arise from the endometrium?
clear cell carcinoma - poor prognosis
Describe the gross appearance of a mature germ cell ovarian tumour.
smooth capsule, often filled with sebaceous fluid and hair, bone, cartilage, teeth, thyroid, GI, resp. tissue
How does an immature cystic teratoma differ from a mature one?
contains immature neuro-ectodermal elements - more aggressive
What is the major complication associated with cystic teratomas?
prone to torsion which is an acute surgical emergency
How can ovarian sex cord tumours develop into endometrial hyperplasia/carcinoma?
granulosa and theca cell tumours produce oestrogen
What is Meig’s syndrome?
ovarian fibroma, ascites, pleural effusion
What are Brenner tumours?
uncommon mixed surface epithelial-stromal ovarian tumours - usually benign, unilateral, variable size, solid, yellow
Describe the histological appearance of Brenner tumours.
nests of transitional epithelial cells with longitudinal nuclear grooves and abundant fibrous stroma
Name four common developmental abnormalities of the breast.
ectopic breast tissue
breast hypoplasia
stromal overgrowth
nipple inversion
List 5 common inflammatory conditions of the breast and their causes.
- acute mastitis: associated with breast feeding
- granulomatous inflammation: sarcoidosis, TB, vasculitis, cat scratch disease
- idiopathic granulomatous mastitis
- foreign body reactions: around implants
- recurrent subareolar abscesses: mamillary fistula, smoking, squamous metaplasia of lacteriferous ducts
- periductal mastitis: often asymptomatic but may have discomfort, a mass, nipple retraction, calcified luminal secretions, middle aged, smoker
- fat necrosis following trauma
List 5 fibrocystic changes which can be seen on biopsy of breast tissue.
adenosis apocrine metaplasia epithelial hyperplasia radial scars intraduct papilloma: benign tumour of epithelium lining of mammary ducts
Describe the two types of stromal proliferations seen in the breast.
- Diabetic fibrous mastopathy
- stromal fibrosis with infiltrating lymphocytes
- type 1 DM, usually in women - Pseudo-angiomatous stromal hyperplasia
- proliferation of myoblasts
- may cause mass and require biopsy to exclude malignancy
What are the three common benign breast neoplasms?
fibroadenoma: overgrowth of epithelium and stroma
Phyllodes tumour
adenoma
Describe the characteristics of breast fibroadenoma.
presents in young women, regresses after menopause, usually firm, non-tender, <25-30mm
Describe the histological appearance of Phyllodes tumour and what this means for its treatment.
combining epithelium and mesenchyme, with increased stromal cellularity, mitotic activity, cytological atypia, infiltrative border
require surgical excision, unlike FA, with a margin of breast tissue
In which benign neoplasm does the nipple’s appearance mimic that Paget’s disease of the nipple?
adenoma
Briefly outline the stages of the menstrual cycle.
- 3-7d: proliferative stage
- 8-14d: decreases in follicular phase
- 15-20d: myoepithelial changes and proliferation in luteal
- secretory changes
List some of the risk factors associated with development of breast malignancy.
early menarche, late menopause, corticosteroid use, HRT, obesity, alcohol, family history
What are the symptoms of breast malignancy?
- new lump or thickening of breast or axilla
- altered size, shape or feel of breast
- skin changes: puckering, dimpling, oedema, rash, redness
- nipple changes: tethering/inversion, discharge, eczema like changes
How would you investigate a suspected breast malignancy?
- clinical exam
- imaging: US, mammography, MRI
- fine needle aspirate
- core biopsy
- excisional biopsy
Breast cancers are excised with a margin and followed by radiotherapy. What drugs are also available? (3)
steroid hormone receptor antagonists e.g. tamoxifen
aromatase inhibitors e.g. Letrazole
herceptin - for cancers which overexpress Her2
What index is used to determine prognosis following surgery in breast cancer?
Nottingham Prognosis Index
NPI = [0.2 x S] + N + G
S: size of the index lesion (cm)
N: 0 nodes = 1, 1-3 nodes = 2, >3 nodes = 3
G: Grade I = 1, Grade II = 2, Grade III = 3
<2.4 = excellent prognosis, > 5.4 = poor prognosis
Define an in situ carcinoma.
malignant proliferation of epithelial cells contained within the basement membrane - no extension to breast stroma, no communication with blood vessels or lymphatics nor possibility of metastases
How are ER+ breast cancers classified?
Luminal A: low grade, less proliferation, better prognosis
Luminal B: high grade, more proliferation, do less well
How are ER- breast cancers classified?
- normal breast-like
- HER2 molecular expression
- basal-like - overlap with cancers which occur in BRCA1 carriers
What are the indicators of HER2 gene amplification?
- increased gene copy number
- increased mRNA transcription
- increased cell surface receptor protein expression
- increased release of receptor extracellular domain
Discuss how FNA and core biopsy are classified.
1 normal or insufficient 2 benign 3 atypia, probably benign 4 atypia, probably malignant 5 malignant
What are the benefits of using core biopsy over FNA?
differences in situ vs invasive fewer false positives and negatives correlation with mammogram visualises calcification diagnosis of borderline lesions
Describe the changes in the cervical epithelium that occur during puberty and menopause.
- prior to puberty: ectocervix = non-keratinising stratified squamous, endocervix = columnar
- with growth of cervix after puberty, the squamocolumnar junction is everted into the vagina and the squamous epithelium adapts to the vaginal environment by metaplasia in the ‘transitional zone’
- these changes are reversed during menopause - it is in this region that most cervical cancers arise
Which two strains of the human papilloma virus are most common in Glasgow?
16 and 18
Discuss the purposes of cervical screening, including who is offered the test.
women aged 25-50: 3 yearly. 50-65: 5 yearly
- samples cells from the transitional zone to detect changes ass. w/ HPV and cervical intraepithelial neoplasia
- dyskaryosis (nuclear abnormalities) suggestive of CIN - referral to colposcopy
To what ages of girls is the HPV vaccine offered and which strains does it cover?
12/13
6, 11, 16, 18
Describe the progression of cervical intraepithelial neoplasia.
CIN 1: low grade dyskaryosis with koilocytosis - confined to basal 1/3 epithelium
CIN 2: high grade squamous dyskaryosis - confined to basal 2/3 epithelium
CIN 3: severe dysplasia with neoplastic cells (cervical carcinoma in situ) - may involve full thickness
CIN 2 and CIN 3 are more likely to progress to invasive squamous cervical carcinoma
What is the commonest treatment available for cervical carcinoma in situ? What are the complications associated with this treatment?
LETZ : loop excison of transitional zone
pain, haemorrhage, infection, cervical stenosis, infertility
What are the symptoms of cervical cancer?
- often asymptomatic
- postcoital bleeding, intermenstrual bleeding, irregular vaginal bleeding, pain
What impact does low oestrogen have on the vagina after menopause?
atrophic vaginitis with discomfort, dysparenuia and bleeding
List some infections common to the vagina.
bacterial vaginosis, thrush, trichomonas, vaginalis, actinomyces (IUCD), herpes simplex
Name some non-cancerous pathologies of the vulva.
skin tags
melanocytic nevi
benign cysts
What are two non-infective inflammations of the vulva?
- lichen planus
- lichen sclerosus: ass. w/ anogenital skin in females and vulval squamous carcinoma
Differentiate between vulval squamous cell carcinoma association with VIN and dermatoses.
- VIN: females < 60, associated with CIN and invasive cervical cancer, HPV 16 and 18, warty or basaloid cancer
- dermatoses: older age group, well differentiated and keratinising, no associated with HPV, adjacent squamous hyperplasia and/or lichen sclerosus
Describe when developmental abnormalities of the uterus occur.
at 6 weeks, coelomic lining epithelium forms the lateral mullerian ducts, which grow downwards into the pelvis and fuse with the urogenital sinus
fused = uterus, unfused = fallopian tubes
What abnormalities can occur in the development of the uterus?
dysmorphic uterus, septate uterus, bicorporeal uterus, hemi uterus, aplastic uterus
What is the difference between endometriosis and adenomyosis?
endometriosis: presence of endometrial tissure outside of the uterus
adenomyosis: endometrial tissue within myometrium
Where might endometriosis spread and what symptoms is it associated with?
ovaries, peritoneal surfaces, bowels, appendix, cervix mucosa, vagina, fallopian tubes
dysmenorrhoea, pelvic pain, infertility
Briefly describe the two mechanisms by which it is thought that endometriosis develops.
- Metastatic theory: retrograde menstruation
2. Metaplastic theory: endometrium arises directly from coelomic epithelium as this is where the endometrium develops
What are endometrial polyps?
exophytic masses of variable size which project into the endometrial cavity
Which drug are endometrial polyps associated with?
tamoxifen
How do endometrial polyps present and how can they treated?
present with abnormal bleeding
treated via hysteroscope in outpatient clinic
Describe the microscopic appearance of endometrial polyps.
haphazardly arranged glands with preservation of a low gland to stroma ratio
thick walled blood vessels and fibrous stroma
glands are usually inactive but can show proliferation, secretory changes or metaplasia
Discuss the possible causes of endometrial hyperplasia and adenocarcinoma.
anovulatory cycles
endogenous: obesity, PCOS, oestrogen secreting ovarian tumours
exogenous: oestrogen only HRT
What is the main symptom of endometrial hyperplasia?
post menopausal bleeding
What does an increased gland:stroma ratio in the endometrium indicate?
endometrial hyperplasia
Atypical EH is a precursor to which condition?
endometriod adenocarcinoma
Discuss the different management plans for endometrial hyperplasia and adenocarcinoma.
- hyperplasia: progesterone therapy e.g. Mirena IUS, hysterectomy
- adenocarcinoma: hysterectomy
What name is given to a benign muscle tumour of the myometrium that is often asymptomatic but may present with abnormal bleeding, urinary frequency and impaired fertility?
leiomyoma/fibroids
Describe the pathology of leiomyomas.
sharply demarcated round grey-white tumours with a whorled cut surface
microscopically, resemble normal smooth muscle
What are the management options available for leiomyoma?
- varies depending on number, size and symptoms
- medical: progesterone secreting IUS, hormonal therapies, tranexamic acid, GnRH agonists
- surgery: uterine artery embolisation, myomectomy, hysterectomy
Define leiomyosarcoma.
uncommon malignant smooth muscle tumour of the myometrium
peak incidence 40-60 years
Give three areas where a leiomyosarcoma may spread and what impact does this have on 5 year survival rate?
lungs, liver, brain
40%
Which type of endometrial cancer has a diffusely infiltrative ‘worm-like’ growth pattern?
endometrial stromal sarcoma
What is gestational trophoblastic disease?
a group of pregnancy-relater disorders including hydatidiform moles and choriocarcinoma
How do hydatidiform moles present?
spontaneous miscarriage, abnormalities detected on US
How does a partial mole develop and what risk does this pose to the uterus?
fertilisation of one egg by two sperm
microscopy shows oedematous villi and subtle trophoblast proliferation
risk of invasive mole which destroys uterus
How does a complete mole develop and what risk does this pose to the uterus?
fertilisation of an egg with no genetic material usually by one sperm which duplicates its chromosomal material
microscopy shows enlarged oedematous villi with central cisterns and circumferential trophoblast proliferation
risk of invasive role and choriocarcinoma (malignant, invasive, metastases widelty, treated with chemo)
What are the four special characteristics of cancer cells?
uncontrolled proliferation, loss of original function, invasiveness, metastasis
List some of the toxic effects associated with cancer chemotherapy.
bone marrow suppression - anaemia, immune suppression, infections, impaired wound healing loss of hair damage to GI epithelium liver, heart, kidney in children, depression of growth sterility teratogenicity (damage to embryo)
What kinds of drugs are used as chemotherapy?
alkylating agents antimetabolites cytotoxic antibiotics microtubule inhibitors steroid hormones and antagonists
Describe the mechanism of action of alkylating agents.
form covalent bonds with DNA, interfere with both transcription and replication
Nitrogen mustards are a type of alkylating agent. Can you name three and what their indications are?
1 mechlorethamine: Hodgkins and NHL
2 melphalan: multiple myeloma, ovarian and breast cancer
3 cyclophosphamide: many cancers
Each of the antimetabolites disrupts DNA synthesis. Can you list all 4 and give an example of each?
1 folate antagonists e.g. methotrexate
2 pyrimidine analogues e.g. fluoro-uracil
3 purine analogues e.g. mercaptopurines
4 nucleotide analogues e.g. cytarabine
Dactinomycin and doxorubicin are examples of which type of chemotherapy drugs that has a direct action on DNA as intercalators?
cytotoxic antibiotics
Name one microtubule inhibitor and describe its mechanism of action.
vincristine
bind to microtubular protein and blocks spindle production and so disrupts cell division
In which type of breast cancers is tamoxifen used as a treatment?
those which are oestrogen dependent to stimulate their growth
as tamoxifen is an oestrogen receptor antagonist
How would you treat prostate cancer?
most as dependent on testosterone
therefore, testosterone receptor antagonists e.g. flutamide, bicalutamide
What causes a so-called ‘chocolate cyst’ on the ovaries on US?
endometriosis
