Female GU and Breast Flashcards
Describe developmental abnormalities involving the breast
- Ectopic (Heterotopic) Breast Tissue
- Commonest congenital abnormality
- Most often on ‘milk line’ between axilla and groin
- Absent Nipple
- Nipple with Little Glandular Development
- Breast Hypoplasia
- Macromastia
- Stromal overgrowth leading to excessive breast size, occasionally begins at puberty (juvenile hypertrophy) or during pregnancy (gestational hypertrophy)
- Nipple Inversion
- Asymmetry
Describe periductal mastitis
Periductal Mastitis/Plasma Cell Mastitis/Duct Ectasia
A dilation of central lactiferous ducts, periductal chronic inflammation and scarring
Often asymptomatic but there may be discomfort, a mass, nipple retraction or inversion
Calcified luminal secretions may be seen on mammogram
It is commonest in middle age and is associated with smoking
Describe fat necrosis of the breast
The initial change is disruption of fat cells where vacuoles with the remnants of necrotic fat cells are formed
They then become surrounded by lipid-laden macrophages, multinucleated giant cells, and acute inflammatory cells
Fibrosis develops during the reparative phase peripherally enclosing an area of necrotic fat and cellular debris
Eventually, fibrosis may replace the area of degenerated fat with a scar, or loculated and degenerated fat may persist for years within a fibrotic scar
May follow trauma
Benign, but biopsy may be required to exclude cancer
Describe intraduct papilloma of the breast
A benign tumour of the epithelium lining of the mammary ducts
Solitary central papillomas are thought to be innocuous if there is no epithelial atypia
Multiple papillomas (papillomatosis) are thought to be slightly more likely to be associated with malignancy elsewhere in the same or the contralateral breast
Describe fibroadenoma of the breast
About 25% of asymptomatic women have at least one fibroadenoma in which there is characteristic overgrowth of epithelium and stroma
Symptomatic fibroadenomas are commonest in young women
Usually regarded as a benign neoplasm, hormone-sensitive and regress after the menopause
Usually firm, non-tender, mobile, usually <25-30mm
Rare fibroadenomas in adolescent girls may become very large
Describe the ranges of fibrocystic change in the breast
Very common and frequent benign breast condition
Tends to be multifocal and bilateral and may cause breast tenderness and nodularity
Ranges from small/large cysts, increased amounts of glandular tissue (adenosis), increased fibrous stroma, epithelial hyperplasia (of usual or occasionally atypical type)
State factors modifying breast cancer risk
Early Menarche
Late Menopause
Being Older at First Pregnancy
Oral Contraceptive Use
HRT
Obesity
Alcohol
Family History (BRCA1/BRCA2)
Protective factors include Exercise and Breast Feeding
Describe signs and symptoms of breast cancer
- New lump or thickening in breast or axilla
- Altered shape, size or feel of the breast
- Pain
- Skin changes:
- Puckering
- Dimpling
- Skin oedema (orange peel)
- Rash
- Redness
- Nipple changes:
- Tethering/inversion
- Discharge
- Eczema-like change
- Widespread inflammation
- Redness
Describe the diagnosis of breast cancer
- Clinical Examination
- Imagine
- USS
- X-Ray Mammography
- MRI
- Fine Needle Aspiration Cytology
- Core Biopsy
- Excisional Biopsy
- May be diagnostic, therapeutic or both
- Women between 47 and 73 are invited for triennial 2-view mammography breast screening and may self-refer after 73
Describe the importance of steroid hormone receptors in breast cancer
About 80% of breast cancers overexpress oestrogen receptors (ER) and progesterone receptor (PR)
ER/PR positive carcinomas are likely to respond to endocrine treatment (e.g. with Tamoxifen which in breast is predominantly an ER antagonist)
In endometrium and bone, Tamoxifen has a significant agonistic effect and there is elevation of endometrial cancer risk in women treated with Tamoxifen
Describe the importance of Her2 status in breast cancer
As a group, cancers which overexpress Her2 have a worse prognosis than other breast cancers
But treatment with the monoclonal antibody Trastuzumab (Herceptin) and other Her2 targeted therapies has improved outcomes
Adjuvant Herceptin reduces the risk of relapse in women with Her2 +ve breast cancer and prolongs survival in women with metastatic breast cancer
Describe the grading of breast cancers
Based on Nuclear Pleomorphism, Number of Mitoses per mm2 and Degree of Gland Formation by the Cancer Cells
Grade 1 - Well-Differentiated and Slow Growing
Grade 2 - In Between
Grade 3 - Poorly Differentiated and Fast Growing
Describe the Nottingham Prognostic Index
Prognostic index for breast cancer, following surgery
(Tumour Size x 0.2) + Grade + LN Involvement
0 Nodes = 1
1-3 Nodes = 2
4+ Nodes = 3
Higher the NPI, the lower the 5 Yr SR
Describe the molecular classification of breast cancer
The main distinction is still between ER -ve and ER +ve cancers
Luminal A ER+ cancers tend to be low grade, less proliferative and have a better prognosis
Luminal B ER+ cancers tend to be high grade, more proliferative and potentially do less well
In the ER- cancer group, there are three subtypes; normal breast-like, Her2 or basal-like
Describe the management options for breast cancer
Surgery (wide local excision plus radiotherapy or mastectomy for larger cancers)
Endocrine targeted treatment can help prevent relapse at distant sites
in triple negative cancers especially, adjuvant chemotherapy is important
1 in 3 potential episodes of metastatic relapse can be prevented by adjuvant chemotherapy
Describe cervical intraepithelial neoplasia (CIN)
Replacement of normal squamous epithelium by neoplastic squamous cells
Basement membrane remains intact
The neoplastic cells have the usual morphological features, abnormally intense staining (hyperchromasia), greater variability (pleomorphism) and fail to mature properly (and go on proliferating with mitotic cells visible) as they migrate from the base of the epithelium to its surface
Immature and dividing cells are confined to the basal 1/3 of the epithelium in CIN 1, the basal 2/3 in CIN 2 and persist into the surface 1/3 in CIN 3
Invasive squamous carcinoma of the cervix almost always develops from pre-existing CIN, but not all CIN will become squamous cancer
CIN 2 and CIN 3 are more likely to progress than CIN 1
Describe squamous metaplasia of the cervical transformation zone
Prior to puberty, the ectocervix is covered by non-keratinising stratified squamous epithelium and the endocervix is lined by columnar (glandular) epithelium
With growth of the cervix after puberty, the squamo-columnar junction is everted into the vagina and the squamous epithelium adapts to the vaginal environment by squamous metaplasia in the ‘transformation zone’
These changes are reversed at the menopause
This zone of unstable differentiation is where most cervical neoplasia develop
Describe the effect of HPV on the cervix
More than 99% of cervical carcinomas are associated with HPV infection
Even in the absence of CIN, HPV infection does visibly affect the cells of the cervical squamous epithelium
Even in the absence of productive infection, viral DNA can persist extra-chromosomally or integrated into the host’s cells
High risk HPV types 16 and 18 are strongly associated with CIN 2, CIN 3 and cervical cancer
State the outcomes of cervical smear reporting
- Negative
- Repeat Routinely in 3 Years
- Borderline Nuclear Abnormality
- Repeat 6 Months
- (If 3 x BNAs - Refer to Colposcopy)
- Mild, Moderate or Severe Dyskaryosis
- Refer to Colposcopy
- Features SUggestive of Invasion
- Urgent Referral to Colposcopy
Describe the features and effects of Salpingitis
Part of the spectrum of pelvic inflammatory disease
Most commonly infective (mainly bacterial - chlamydia trachomatis, mycoplasma, coliforms, streptococci, staphylococci, Neisseria gonorrhoea)
Usually considered to be an ascending infection
Symptoms include fever, lower abdominal/pelvic pain and pelvic mass (if tubes distended with exudate or secretions)
Complications: Adherence of tube to ovary (tubo-ovarian abscess); Adhesions involving tubal plicae increase risk of ectopic pregnancy; Damage or obstruction of tube lumen may produce infertility which may be difficult to treat
Describe the features and effects of non-neoplastic cysts of the ovaries
Non-neoplastic cysts include inclusion, follicular and luteal cysts
Symptoms include oligomenorrhoea, hirsutism, infertility, over-production of androgens by cystic follicles, high LH and low FSH
Effects include enlarged ovaries, multiple subcortical cysts (5-15mm), thickened and fibrotic outer surface, absence of corpus lutea and corpus albicans (as ovulation is not occurring) and insulin resistance (which may lead to T2DM)
Describe the processes, features and effects of ovarian surface epithelial tumours
Thought to arise from coelomic mesothelium on the surface of the ovary
Benign lesions usually cystic (cystadenoma) with or without a solid stromal component (cystadenofibroma)
Malignant epithelial tumours (carcinomas) may be cystic (cystadenocarcinoma) or solid (adenocarcinoma)
Carcinomas may be high grade serous (HGSC), endometroid, clear-cell, low grade serous (LGSC) or mucinous
HGSC is closely associated with p53 and BRCA1 mutations
Most women with ovarian cancer present late and in many the prognosis is poor
(Surface epithelial tumours also have an intermediate, borderline category called tumours of low malignant potential which have limited invasive potential and a much better prognosis)
Describe ovarian sex cord/stromal tumours
These include granulosa and theca cell tumours which often secrete oestrogen and (uncommonly) Sertoli-Leydig cell tumours which may secrete androgens
Granulosa cell tumours usually occur in post-menopausal women and are not rare (oestrogen overproduction may lead to endometrial hyperplasia or endometrial carcinoma)
Ovarian fibromas and thecomas are usually benign and not rare
Describe the features of ovarian germ cell tumours
95% of ovarian germ cell tumours are mature cystic teratomas (dermoid cysts)
Totipotent germ cells differentiate into mature tissues of all 3 germ cell layers
Mostly found in young women as ovarian masses or found incidentally on abdominal scans
May contain foci of calcification associated with bone or teeth
Approx. 10% are bilateral
Grossly they appear smooth, filled with sebaceous secretions and matted hair
Sometimes foci of bone and cartilage, nests of bronchial or GI epithelium, teeth and other recognisable lines of development may be present
About 5% of ovarian teratomas in adult are immature cystic teratomas, associated with more aggressive behaviour
Describe endometrial carcinoma
Usually in older women, over 50 years of age
May be accompanied by background endometrial hyperplasia and oestrogen excess
Lynch syndrome is also a risk factor
Must be excluded in cases of post-menopausal bleeding
Investigations include endometrial biopsy, transvaginal ultrasound or hysteroscopy
Bilateral salpingo-oophorectomy is usually appropriate as well as hysterectomy
Prognosis is stage dependent, but other factors include grade, lymphovascular space invasion and tumour cells in peritoneal washings
Carcinosarcoma (Malignant Mixed Mullerian Tumour) are high grade serous carcinomas of the endometrium with a worse prognosis
Describe leiomyomas (fibroids) of the uterine smooth muscle
Extremely common, often multiple, almost always benign smooth muscle tumours of the uterine body
Symptoms include dysmenorrhoea, menorrhagia and discomfort
Most active during the reproductive years and involute following the menopause
Hormonal treatments may relieve symptoms but occasionally surgery is appropriate
Uterine artery embolisation by interventional radiology is an alternative option
Describe leiomyosarcomas of the uterus
Rare, but the most common non-epithelial malignancy
Soft mass, poorly circumscribed outline
May cause haemorrhage and necrosis
Much more abnormal histology
Vascular invasion may spread via the bloodstream to the lungs
Poor long-term prognosis
Describe adenomyosis
Basal endometrium extends abnormally into hyperplastic myometrium
May co-occur with endometriosis
Peaks between 35 and 50
Pts often present with dysmenorrhoea and menorrhagia
May be focal or diffuse
In diffuse involvement, the uterus becomes bulky and heavier
Describe endometriosis
Presence of endometrial glands and stroma outside the body of the uterus
Mechanisms are not fully understood but include retrograde menstruation, local metaplasia of surface epithelium and dissemination via the bloodstream
Inflammation, cysts and scarring associated with endometriosis can cause significant symptoms and compromise fertility
Describe Gestational Trophoblastic Disease
A group of conditions characterised by excessive proliferation of trophoblasts
The classical hydatidiform mole is a mass of large oedematous chorionic villi
Complete Mole - No Foetus - Unispermis or dispermic fertilisation of an ‘empty’ egg (genotype 46XX or 46XY)
Partial Mole - Foetus Usually Present - Haploid egg fertilised by one sperm which reduplicates, or by 2 sperm (genotype 69XXY or 92XXXY)
Risk of progression to chorioncarcinoma
Requires monitoring of hCG levels
Describe the Alkylating Agent class of chemotherapy drug
e.g. Cyclophosphamide, Cysplatin, Melphalan
Form irreversible covalent bonds with DNA to interfere with transcription and replication
Used in a range of cancers from lymphoma (mechlorethamine), multiple myeloma, ovarian and breast cancer (melphalan)
Describe the Anti-Metabolite class of chemotherapy drug
e.g. Methotrexate, 5-Fluorouracil, Mercaptopurines, Cytarabine
|nterfere with nucleotide or DNA synthesis
Methotrexate - Folate Antagonist
5-Fluoriuracil - Pyrimidine Analogue
Mercaptopurines - Purine Analogues
Describe the Cytotoxic Antibiotic class of chemotherapy drug
e.g. Dactinomycin, Doxorubicin
Act mainly by direct action on DNA as intercalators
Dactinomycin disrupts function of RNA polymerase by inserting itself into the minor groove of the DNA helix
Doxorubicin inserts itself between base pairs to impair DNA and RNA synthesis
Describe the Microtubule Inhibitor class of chemotherapy drug
e.g. Vincristine
Binds to microtubular protein, blocks tubulin polymerisation and normal spindle formation to disrupt cell division
Describe the Steroid Hormone and Antagonist class of chemotherapy drug
Tumours may be responsive to a hormone which make it regress, or it may be relient on a hormone to grow, in which case an antagonist of the hormone will suppress growth
Prednisolone - Suppressed lymphocyte growth
Tamoxifen - Oestrogen receptor antagonist used in ER+ve breast cancers
Casodex (Bicalutamide) - Testosterone receptor antagonist used in prostate cancers which are testosterone dependent
Describe the principles of cancer chemotherapy
Cell cycle drugs are only effective on the subset of the cell population currently undergoing cell division
Resting (G) phase cells are therefore less sensitive to these drugs and care the cause of many relapses
The aim must be for a total kill and prolonged treatment is required to reduce the chance of relapse from resting cells
Chemotherapy drugs do not reverse de-differentiation, invasiveness or metastasis
General side effects include bone marrow suppression, hair loss, damage to GI epithelium, organ damage, sterility, teratogenicity and depression of growth in children
