4 Female GU/ Breast Flashcards
Normal epithelium of: Fallopian tube Ovary Prepubertal ectocervix Prepubertal endocervix
Fallopian tube - ciliated columnar
Ovary - flat/ cuboidal
Prepubertal ectocervix - non-keratinised stratified squamous
Prepubertal endocervix - columnar glandular
Bacterial causes of salpingitis (6)
Chalmydia trachoma's Strep Staph N. gonorrhoea Mycoplasma Coliforms
Complications of salpingitis
Tubo-ovarian abscess/ adherence Ectopic pregnancy (involving plicae) Infertility (damage/obstruction of lumen) Compromised tube function (endometriosis present)
Most common tubal malignancies (3) and precursor
Precursor = STIC serous tubal intraepithelial carcinoma - abnormal epithelium (distal tube), nuclear atypia, contained by BM
- p53 mutation
Papillary serous carcinoma
Endometriod carcinoma
1y BRCA mutations
What is in the ovarian:
Cortex
Medulla?
Cortex - Outer surface, contains germ cells/ cysts and stroma
Medulla - vessels/nerves, hills cells
Symptoms of PCOS (5)
Obesity Oligomenorrhea Hirsuitism T2 diabetes/ insulin resistance Infertility
Mechanism of PCOS and appearance of ovary (4)
Cystic follicles (5-15mm) secrete androgens in presence of high LH, low FSH (normally converts androgens to oestrogen)
Appearance:
Subcortical cysts lines by granulose cells
Then by fibrous, thickened cortex outer later
Absence of corpus lute/albicans as no ovulation
Main genes responsible for sporadic ovarian cancer (4)
BRCA 1 (and 2)
KRAS
BRAF
P53
Types of ovarian tumour (and likely precursors ± mutations)
Epithelial: HG serous - BRCA1 + p53, STIC LG serous - KRAS + BRAF Mucinous - KRAS Clear cell - endometriosis Endometriod - endometriosis, loss of PTEN TSG
Germ cell - teratomas
Sex cord stromal tumours
Names of ovarian tumours:
Benign, intermediate and malignant
Benign:
solid = adenoma
liquid = cystadenoma
Intermediate/ borderline: tumour with low malignant potential
Malignant:
solid = adenocarcinoma
liquid = cystadenocarcinoma
What is also known as a “chocolate cyst”?
Endometriod benign cyst
What 2 ovarian tumour types are associated with endometriosis?
Clear cell carcinoma and endometriosis carcinoma
Main characteristics of:
Serous tumours
Mucosal
Endometrioid
Serous (25% malignant)- serial involvement, filled with clear fluid, psammoma bodies
Mucosal (10% malignant)- blobs of mucous, multilocular
Endometriod (most malignant) - also habe endometrial carcinoma/ endometriosis
Define Krukenberg tumour
Mucinous ovarian tumour which is actually metastases from a tumour of the GIT (typically stomach, appendix, colon) with can mimic 1y ovarian tumour
Genetic factor associated with poor prognosis in ovarian cancer
Her2 gene over expression - in 35%
Risk factors/ reducers in ovarian cancer
Risk: nulliparity and family hx
Reduce: prolonged use OCP - less ovulation cycles so less change
Sex cord stromal ovarian tumour cell types and hormone produced
Leydig and sertoli - androgen
Granulosa/ thecal - oestrogen
Define Meig’s syndrome
Benign ovarian fibroma with pleural effusion and ascites
Define Brenner tumour
Benign ovarian tumour
Combined surface epithelial and stroll components
Well circumscribed, yellow, solid, unilateral
Transitional epithelium, nuclear grooves, fibrous stroma
Presentation of ovarian tumours (5)
Asymptomatic until advanced
SOL: urinary frequency, bowel problems, pain
Torsion: medical emergency, severe abdominal pain
Hormonal effects (if functional tumour)
Ascites (Meig’s/ malignant mets)
Purpose of cervical screening cytology
To detect changes in transitional zone (dyskaryosis) due to HPV or CIN
Appearance of normal cervical cells on smear (superficial, intermediate and endocervical)
> superficial squamous cells - pink, small central nuclei
intermediate squamous cells - blue, slightly larger central nucleus
endocervical - clumps of columnar cells with basal nuclei
What strains of HPV are most likely to cause cancer in scotland and which are vaccinated against
16 and 18
Vaccine = 6, 11, 16, 18
Method of colposcopy
1) Visualise cervix with specula and microscope
2) Wash with acetic acid - removes mucus and may stain abnormality white
3) Add iodine - will stain normal different to abnormal
4) Green light filter - view blood vessels
5) Biopsy/ treat if required
How do certain genes in the HPV contribute to cancer?
Early genes (E1-7) - take over cell proliferative machinery to replicate virus
Late genes (L1-2) encode proteins for viral capsid
Describe koilocytes
Characteristic of HPV, low grade dyskaryosis at minimum
Perinuclear clearing, with dense cytoplasmic condensation around periphery
Epithelium thickness, and nuclear:cytoplasmic ratio in CIN1/2/3
Epithelium:
CIN 1 - 1/3
CIN 2 - 2/3
CIN 3 - full thickness
Ratio:
CIN 1 - up to 1/2
CIN 2 - 1/2 to 2/3
CIN 3 - over 2/3
Malignant/ premalignant forms of endocervical glandular columnar epithelium
premalignant = cGIN (cervical glandular intraepithelial neoplasia) malignant = adenocarcinoma
Treatment options of CIN2/3 and complications
> Large loop excision/ bipolar coagulation - scoop out tissue
> Thermoablation/ cold coagulation - burn away affected tissue
Complications:
>Immediate: haemorrhage, pain
>Delayed: 2y haemorrhage, infection, stenosis
cervical cancer symptoms
Pain Post coital bleeding Irregular bleeding Intermenstrual bleeding None
Infections of the vagina and their characteristic features on histology (5)
> Thrush/ yeast - strands (pseudomicelia) and buds
Bacterial vaginosis - coccobaccili on top of squamous cell, looks granular
Trichomonas vaginalis - stuck onto squamous cells and may see flagellae
Actinomyses - looks like a spider, assoc with IUD
Herpes SV - big blue clumps, intranuclear inclusions
Describe atrophic vaginitis
Post menopausal vaginal inflammation, due to thinning of vagina due to lack of oestrogen
Discomfort, painful intercourse and bleeding
Endometriosis theories (2)
Metastatic - surgery or retrograde menstruation introduces endometrial tissue elsewhere and it attaches and grows as normal
Metaplastic - endometrial tissue arises from polemic epithelium as it does in embryological development
Endometriosis histology:
Normal gland:stoma ratio
Cause of bleeding/ fibrosis etc.
GS ratio is still low
Bleeding from endometriosis, causes fibrosis/structures, which causes pain
Histological appearance of an endometrial polyp
Looks like post-menopausal stroma - no activity
Has thick walled blood vessels
Little cytoplasm
Stroma pink (fibrotic) due to bleeding
Occasionally see cytological atypic/ adenocarcinoma
Endometrial hyperplasia/ adenocarcinoma:
Symptoms (1)
Causes (3)
Histology (2)
Symptoms: post menopausal bleeding
Causes: increased exposure to oestrogen (anovulatory cycles, obesity, PCOS, oestrogen secreting ovarian tumour, HRT)
Histology: Hyperplasia, increase G:S ratio (less space between glands), ± cytological atypia (bigger rounder nuclei)
Endometrial hyperplasia/ adenocarcinoma management
Hyperplasia: progesterone therapy (mirena IUD), hysterectomy
Adenocarcinoma: hysterectomy, then treatment based on grade/stage
Leiomyoma:
Symptoms
Appearance
Management
Symptoms: SOL (urinary infrequency), abnormal bleeding, impaired fertility
Appearance: big round, white/grey, clear edges, whorled out surface, variable size, microscopically identical to normal smooth muscle
Management:
>hormone manipulation (progesterone IUD, GnRH agonist, hormonal therapy),
>stop bleeding (transexamic acid),
>surgery (hysterectomy, myomectomy, uterine artery embolisation)
Characteristic appearance of endometrial stroma sarcoma (ESS)
“worm like” invasion
Low grade: looks like normal proliferating endometrial stroma with mitosis
Describe appearance of normal placental tissue histologically
Chorionic villi:
>Odematous stroma
>2 layers of trophoblast (cytoplasms, syncytio)
>Few small blood vessels with metal RBC nuclei in them
Describe the components of gestational trophoblastic disease (3)
Partial hydatidiform mole: one egg, 2 sperm (triploid)
Complete hydatidiform mole: 0 egg DNA, 2 lots of sperm DNA (either 2 sperm or 1 sperm duplicating DNA)
Choriocarcinoma: rapidly invasive and widely metastasising malignant tumour, but very treatable with chemo
Describe appearance of complete and partial mole on histology
Partial:
>oedematous villi
>slight trophoblastic proliferation
Complete:
> very oedematous massive villi with central cisterns
> lots of circumferential trophoblastic proliferation
> cells huge and pleomorphic (irregular)
FNA and Core biopsy tumour classification
FNA = C
Core biopsy = B
1 - normal/ insufficient 2 - benign 3 - probably benign 4 - probably malignant 5 - malignant (b = invasive)
Describe phyllodes tumour
Fibroadenomatoid lesion - like fibroma has stomal and epithelial parts >stromal overgrowth and necrosis >high cellularity and pleomorphism >irregular margin >mitotic activity
Features of fibrocystic change
And increased risk of carcinoma with hyperplasia
Lumps - bigger and more tender in 2nd half cycle
Fibrosis, cysts, apocrine change, epithelial hyperplasia, columnar cell change, calcification
Florid hyperplasia = 1.5x
Atypical hyperplasia = 4x
Insitu carcinoma = 10x
Describe appearance of radial scar on mammogram
and what would be done to check for malignancy
Stellate appearance
Check presence of myoepithelial tissue
Presentation of duct ectasia vs papillary lesion
DE:
Nipple discharge (brown/ green)
New nipple inversion
Pain
May have SMOLD
Smokers
PL:
Nipple discharge (bloodied epithelial cells)
Central mass below nipple (not always)
Microcalcification
Describe PASH
Pseudo Angiomatous Stomal Hyperplasia (benign)
Rapidly growing hard palpable lump
With lots of small vessels and myofibroblasts
Inflammatory skin changes
Age of onset of: PASH Granulomatous mastitis Fibrocytsic change Fibroadenoma Diabetic mastopathy Breast carcinoma
Fibroadenoma - 20-30 Fibrocytsic change - 30-40 Diabetic mastopathy - <30 Granulomatous mastitis - mid 30s (33) PASH - premenopausal Breast carcinoma - 40-70
Difference between DCIS and LCIS
DCIS - can be removed and cured
>Abnormal cell proliferation
>Enlarged glands
>Necrosis/ calcification
LCIS can occur anywhere in either breast, need regular monitoring
>No calcification/ lump
>Lobules and ducts expanded - abnormal proliferation
3 factors considered when grading breast carcinoma
Grading system used for invasive ductal carcinoma
Tubules
Mitotic activity
Pleomorphism
Characteristic feature of lobular carcinoma on histology
Signet ring cells
Aligned one behind the other
Scoring system for hormone receptor in breast cancer and treatment outcome
Allred scoring system:
0-2 receptors - negative, no treatment
3-5 - positive, poor treatment response
5-8 - positive, good treatment response
Treatment options for breast cancer (hormone receptor +ve) (2)
Tamoxifen - ER antagonist
Aromatase inhibitors
Describe nottingham prognostic index and purpose
Grade: 1 point per grade (1-3)
Size: point = size in cm x0.2
Nodal status: 0=1, 1-3=2, 4+=3
Treatment, followup and prognosis
Treatment for HER2 positive cancers, and testing method for HER2
Herceptin/ transtuzumab
Other sources breast cancers other than carcinoma
Mets
Lymphoma
Sarcoma (Phyllodes or denovo)
Angiosarcoma - previous radiotherapy
Describe the terms used in cancer subtypes: Luminal Basal HER2 Normal
Luminal - ER/PR + (a/b = low/high proliferative)
Basal - ER/PR/HER2 -
HER2 - HER2 +, ER/PR -
Normal - benign
Toxic side effects of cancer chemotherapy general (7)
> Hair loss
Damage GI epithelium - X solids > weaker
Bone marrow suppression - anaemia, bleeding, infection
Liver, heart, kidney
Growth depression children
Infertility/ sterility
Teratogenicity
Alkylating agents cancer chemo:
MOA and main names (3)
MOA: cross link DNA strands to prevent separation for replication, and also inhibit transcription (by-product)
Melphalan
Cyclophosphamide
Cisplatin
Antimetabolites cancer chemo:
MOA and main names (4)
Methotrexate: folate antagonist (prevents dihydrofolate) > X nucleotide synthesis> X DNA/RNA
5-hydro uracil: pyramidine analogue (thymine) > X thymidine > X DNA
Mercaptopurine: purine analogue > flash nucleotides made> into DNA> helix disrupted
Cytarabine: inserts into DNA > inhibits DNApol > chain termination
Cytotoxic antibiotics cancer chemo:
MOA and main names (2)
Dactomycin: binds at minor groove (cis molecules) > inhibits RNA pol
Doxorubicin: binds DNA backbone between strands > local uncoiling> X transcription
Microtubule inhibitor cancer chemo:
MOA and main names (1)
Vincristine (vinka alkyloid)
Blocks cell division at anaphase/metaphase
>Binds microtubule protein > blocks tubular polymerisation & spindle formation
Steroid hormones/antagonists cancer chemo:
MOA and main names (4)
Prednisone: > prednisolone - suppress lymphocyte growth
Tamoxifen: ER receptor blocker (ER+ BrCa)
Bicalutamide: testosterone receptor antagonist (Test dept PrCa)
Prostap: LHRH agonist > dec LH secretion> dec testosterone (Test dept PrCa)
Premalignant variants of skin cancer:
Squamous cell carcinoma
Melanoma
SCC - Bowen’s disease/ actinic keratosis
Melanoma - melanomi in-situ/ lentigo maligna
