Crash Course: gynae and breast Flashcards
Hyperplasia
Increased no. cells
e.g. parathyroid hyperplasia
Hypertrophy
Increased size of cells
e.g. HOCM, LVH
Metaplasia
Reversible change from 1 cell type to another
e.g. Barrett’s oesophagus
Dysplasia
Reduced differentiation of cells
Decreased grading of cells i.e. replacement of norma cells with abnormal cells
Basement membrane intact
e.g. CIN
Neoplasia
Uncontrolled abnormal growth of cells + tissues
Benign or malignant (if invades BM)
What is the vulva composed of?
vaginal opening
labia majora
labia minora
clitoris
What are the 3 grades of VIN?
- Bottom 1/3
- Bottom 2/3
- Full thickness
Through basement membrane = cancer
What are the 2 types of VIN? Which patient group is more commonly affected by each?
Usual: Young
Differentiated: Older
Give 3 risk factors for usual VIN
HPV 16 + 18
Smoking
Immunosuppression
What is a risk factor for differentiated VIN?
Lichen sclerosis
Which type of VIN is more likely to progress to squamous cell carcinoma of the vulva?
Differentiated VIN
What is the predominate type of vulval carcinoma? In which patients is this more common? What risk factor may be in their history?
Primary vulval carcinoma (95%)
(Squamous cell carcinoma)
Older
Lichen sclerosis/ HPV
What is the less common type of vulval carcinoma?
In which patients is this more common?
Clear cell (5%)
(Adenocarcinoma)
Teenagers
Give 5 signs and symptoms of vulval carcinoma
Visible painless lesion
Ulcerated
Difficulty urinating
Itching, irritation
FLAWS
Describe the anatomy/ histology of the cervix
Ectocervix: Squamous
Transition zone- lower part of cervical canal
Endocervix: Columnar
In which part of the cervix is there a high degree of replication and thus increased susceptibility to infection + cancer?
Transformation zone
What are the 3 grades of CIN?
- Bottom 1/3
- Bottom 2/3
- Full thickness
Through basement membrane = cancer
What cellular change characterises both CIN and VIN?
Dysplasia
Proliferation of poorly differentiated cells
Hasn’t invaded BM
Cervical cancer predominantly is which cell type?
SCC: 80%
Adenocarcinoma: 20%
Give 5 risk factors for CIN
HPV
Smoking
Immunosuppression
COCP
High parity
What happens for most people infected with HPV?
Nothing.
Immune system eliminates HPV
HPV undetectable within 2y in 90%
Which proteins encoded by HPV lead to proliferation of epithelium?
E6 + E7 bind to + inactivate 2 tumour suppressor genes:
E6 inactivates P53
E7 inactivates Retinoblastoma gene (Rb)
In those who do not clear HPV infection what occurs?
HPV remains latent within cells
At time of immunosuppression/ stress, can become activated
Viral DNA replication
Resulting in cytological + histological changes of cancer
What are the screening intervals for cervical cancer?
25: 1st invitation
25-49: Every 3y
50-64: Every 5y
65+: Only if 1 of last 3 was abnormal
What are the 2 types of proliferation in the endometrium?
Benign: Leiomyomas (fibroids)
Malignant: Adenocarcinomas 80% (SCC 20%)
What are 2 types of adenocarcinoma in the endometrium?
Endometrioid: 80%
Non-endometrioid: 20%
What are Leiomyomas?
Smooth muscle tumour of myometrium.
Commonest uterine tumour
40% of women >40y
AKA fibroid
Usually multiple
May be intramural, submucosal or subserosal
What is the pathophysiology of leiomyomas?
Oestrogen dependent growth
Enlarge during pregnancy
Regress during menopause
Describe leiomyomas macroscopic appearance
Large white well circumscribed bundles
Describe microscopic appearance of leiomyomas
Purple bundles of smooth muscle cells
What is endometriosis?
Presence of endometrial tissue outside the endometrium
What is endometriosis caused by?
vascular or lymphatic dissemination of endometrial cells
What is the name for endometrial tissue occuring within the myometrium?
Adenomyosis
Give 2 macroscopic features of endometriosis
Powder burns: red-blue/ brown vesicles
Chocolate cysts: endometriomas on ovaries
Describe endometriosis microscopically
Endometrial tissue is darker hence appearance of “powder burns”
In which women is each type of endometrial adenocarcinoma more common?
Endometriod: Peri-menopausal + Increased lifetime oestrogen exposure
Non-endometriod: Post-menopausal
What are the 3 types of endometriod cancer of the endometrium?
Secretory
Endometriod
Mucinous
What are the 3 non-endometroid types of cancer of the endometrium?
Papillary
Clear cell
Serous
What is the pathophysiology of each type of endometrial adenocarcinoma?
E: Related to oestrogen excess
NE: Unrelated to oestrogen excess
Which mutations are related to each type of endometrial adenocarcinoma?
E: PTEN (TSG in >50%)
NE: PTEN, P53, HER-2
Give 3 key features of Pelvic inflammatory disease
- Ascending infection ascending from vagina + cervix to uterus, Fallopian tubes + ovaries
- Inflammation (e.g. endometritis, salpingitis)
- Formation of adhesions
What is Fits-Hugh Curtis syndrome? What buzzwords are associated with this? What symptom?
Complication of PID in which adhesions form around liver
“Violin strings” + “Peri-hepatic lesions”
RUQ pain due to peri-hepatitis
Give 3 classes of causes of PID
Ascending e.g. STI
External contamination e.g. TOP, abortion
Other
Name 2 ascending causes of PID
N. gonorrhoea
C. trachomatis
Name 1 external contamination causes of PID
S. aureus
Give 2 ‘other’ causes of PID
TB
Schistosomiasis
What are the 2 main types of physiological ovarian cyst?
Follicular (most common)
Corpus luteum (in early pregnancy)
Give 2 features of follicular ovarian cysts
Due to non-rupture of dominant follicle or failure of atresia in a non-dominant follicle
Commonly regress after several menstrual cycles
What causes formation of a corpus luteum cyst?
During menstrual cycle if a pregnancy doesn’t occur the corpus luteum breaks down + disappears.
If this doesn’t happen the corpus luteum may become filled with blood or fluid become a corpus luteal cyst
How do corpus luteal cysts most commonly present?
Intraperitoneal bleeds
What is the most common benign ovarian tumour in under 30s?
Dermoid cyst (germ cell)
Give 3 features of dermoid cysts
a.k.a mature cystic teratomas
Usually lined with epithelial tissue: contain skin, hair + teeth
A/w torsion
What densely echogenic nodule arises in mature cystic teratomas?
Rokitansky’s protuberance
Solid protuberance projecting from a dermoid cyst
What is the most common malignant ovarian cancer in younger women? What management is used?
Dysgerminoma (germ cell)
Sensitive to radiotherapy
What is the most common benign ovarian epithelial tumour?
Serous cystadenoma
Give 2 histological features of serous cystadenomas
Columnar epithelium
Psammoma bodies
Give 3 features of ovarian mucinous cystadenomas
2nd most common benign epithelial tumour
Typically very large + become massive
May cause pseudomyxoma peritonei
What is seen on histology in ovarian mutinous cystadenomas?
mucin secreting cells
Name 2 malignant epithelial ovarian tumours
Endometriod carcinoma
Clear cell carcinoma
Give 3 features of endometriod ovarian tumours
Co-exist with endometrial cancer + endometriosis
Histology: tubular glands
Raised CA125
Give 2 features of ovarian clear cell carcinoma
A/w endometrioma
Histology: clear cells, hobnail appearance
What are the sex cord tumours in the ovary?
Granulosa/ theca cell tumours
Sertoli/ Leydig cell tumours
Give 5 manifestations of granulosa/ theca cell tumours in the ovary
Secrete oestrogen:
PMB
IMB
Breast enlargement
Endometrial cancer
Breast cancer
What histological feature are granulosa/ theca cell tumours characterised by?
Call-exner bodies
Give 4 manifestations of sertoli/ leydig cell tumours
Secrete androgens:
Virilisation
Defeminisation
Breast atrophy
Hirsuitism
Enlarged clitoris
Which is the most common ovarian malignancy in the general population?
Serous carcinoma
What occurs in breast lobules?
Milk is produced + stored during pregnancy + breastfeeding
What is the function of breast ducts?
Carry milk from lobules to the nipple where it exits the body
(lymph flows in opposite direction)
What is involved in a triple assessment?
- Clinical: Hx + Examination
- Imaging: USS (<35y) or Mammography (>35y)
- Pathology: FNA or core biopsy
What is the difference between fine needle aspiration cytology and core biopsy?
FNA: Collects sample of cells. Use when suspect content to be liquid e.g. cyst
Core biopsy: Collects core of tissue. Use when contents appears more solid
Both used for grading
What coding is used for FNA cytology?
C1: Inadequate sample
C2: Benign
C3: Atypia
C4: Suspicious of malignancy
C5: Malignant
What coding is used for core biopsy?
B1: Normal
B2: Benign
B3: Uncertain
B4: Suspicious
B5a: DCIS
B5b: Invasive carcinoma
Give 3 signs of mastitis
Erythematous +/- discharge from nipple
Tender breast
Fevers
Name 2 inflammatory causes of breast lump
Mastitis
Fat necrosis
Name 2 types of mastitis
Lactational: within 6w postpartum due to milk stasis, may have CRACKED nipple
Non-lactational: >6w postpartum or not currently breastfeeding
What is seen microscopically in mastitis?
Abundance of neutrophils
What is the management of mastitis?
Conservative:
warm compresses,
analgesia,
elevation,
continue breastfeeding bilaterally
If unresolved after 12-24h
Medical: oral abx (usually Fluclox as S. aureus most common organism)
What indicates breast abscess rather than mastitis? How is this treated?
Fluctuant swelling
Extreme pain
Swinging fevers
Tx: IV Abx + Incision + drainage
What is fat necrosis?
Inflammatory reaction to damaged adipose tissue
Give 3 buzzwords/ phrases associated with fat necrosis
Breast trauma (e.g. RTA)
Previous radiotherapy
Unilateral underlying mass, changing acutely
How does fat necrosis appear microscopically?
Large damaged fat lobules
Irregular in breast tissue
List 3 causes of benign breast lump
Fibroadenoma
Fibrocystic disease
Duct ectasia
What are the 2 types of fibroadenoma?
Fibro– (stomal)
Glandular (epithelial)
What is the most common breast lump in women aged 20-40? What is this caused by?
Fibroadenoma
Oestrogen driven: causes cyclical pain + thus regress during menopause
What 7 buzzwords/ phrases are associated with fibroadenoma?
Single 1-5cm
Unilateral
Spherical
Well demarcated
Firm/ rubbery
Painless
Mobile a.k.a. “breast mouse”
What is the management for fibroadenoma?
< 3 cm → conservative
> 3 cm → surgical excision
What is a phyllodes tumour?
Aggressive malignant fibroepithelial neoplasms arising from breast stroma
i.e. malignant version of fibroadenomas
Give 3 features of phyllodes tumours
EXTREMELY rare
>50s
Structurally similar to fibroadenoma
Give 3 buzzwords associated with phyllodes tumours
Artichoke appearance
Frond-like
Branching
What is fibrocystic disease?
Fluid filled sacs in breast
Common ~7%
Pre/ peri-menopausal women
Give 7 buzzwords associated with fibrocystic disease
Single or multiple “LUMPINESS”
Unilateral or bilateral
Cyclical pain
Well demarcated
Fluctuant
Transilluminable
Clear nipple discharge
Give 2 red flags on biopsy of initially suspected fibrocystic disease
FNA is blood-stained
Core biopsy reveals complex cystic contents
What is duct ectasia?
When mammary duct gets blocked, usually by milk stasis
Leads to dilatation, lump formation + localised infection
How may duct ectasia present on clinical examination?
Sub/ peri-areolar mass
Firm, thick yellow, green, brown discharge
On microscopy what can be seen in duct ectasia?
Proteinaceous material inside duct
Nipple discharge contains macrophages + proteinaceous material
In which patient group is duct ectasia more common?
Smokers
Name 2 proliferative causes of breast lumps
Intraductal papilloma
Radial scar
What is intraductal papilloma?
Benign neoplasms growing within the ducts of breast: “well defined nodule within a duct”
Presents similarly to malignancy but does NOT invade the basement membrane
In which patient groups is intraductal papilloma seen?
Peri and post menopausal women
What are the 2 types of intraductal papilloma? How do they present?
- Peripheral: small ductules affected- clinically silent with subareolar mass
- Central: large ductules affected- blood or clear nipple discharge
Describe the histological appearance of intraductal papilloma
Dilated ductule with papillary mass
(not covering entire duct)
What is a radial scar?
Benign sclerosing lesion caused by impaired healing post-injury e.g. radiotherapy
Can present as a lump
What 3 buzzwords are associated with radial scars?
Central
Fibrous (a/w scar formation)
Stellate area (a/w scar formation)
What are proliferative pre-malignant breast conditions?
Intraductal proliferative lesions a/w increased risk of developing subsequent invasive breast carcinoma
Usually ASYMPTOMATIC
What are the 3 proliferative pre-malignant breast lumps? List in order of increasing risk of cancer
Usual epithelial hyperplasia
Flat epithelial atypia
In situ lobular neoplasia
Give 4 epidemiological facts about breast cancer
Commonest cause of cancer in the UK
1/7 females
Rare in <35s
Increases with age
List 3 genetic risk factors for breast cancer
BRCA 1/2 (autosomal dominant)
FH +ve
Li Fraumeni syndrome
List 5 lifetime oestrogen exposure related risk factors for breast cancer
Early menarche
Late menopause
Nulliparity
Late first child
COCP
List 3 lifestyle risk factors for breast cancer
Alcohol
Smoking
Poor diet
What are the 2 types of non-invasive breast cancer?
Ductal carcinoma in situ (3-5%)
Lobular carcinoma in situ (1%)
Limited to ducts/ lobules by basement membrane
How does non-invasive breast cancer usually present?
DCIS: Microcalcifications in asymptomatic
LCIS: Incidental finding
Describe histology of DCIS
ducts filled with atypical epithelial cells (not invading surrounding tissue)
What are the 3 types of invasive breast cancer?
Invasive ductal carcinoma (85%)
Invasive lobular carcinoma (10%)
Paget’s disease (2%)
What are invasive breast cancers?
Malignant epithelial tumours which infiltrate breast, + have capacity to metastasize
What is the most common breast cancer in women?
Invasive ductal carcinoma
Describe histological features of ductal and invasive lobular carcinoma
Ductal: big, pleomorphic cells
Invasive: cells in chains/ single file
What are the histological features of tubular and mucinous breast cancer?
Tubular: Well-formed tubules
Mucinous: Extracellular mucin
What grading system is used for breast cancer?
Nottingham Grading system
Which 3 features are scored in the Nottingham grading system?
Nuclear pleomorphisms
Tubule formation
Mitotic activity
What are the 3 grades of breast cancer?
Grade 1 = well differentiated (<5)
Grade 2 = moderately differentiated (6-7)
Grade 3 = poorly differentiated (8-9)
What are all breast cancers assessed for?
ER, PR + HER-2 status
Name 2 targeted treatments of breast cancer
Tamoxifen: anti-ER in breast
Herceptin: monoclonal Ab to HER-2
What is the most important prognostic indicator in breast cancer?
Axillary lymph node status
