Week 4 - Female Breast/GU Flashcards
(467 cards)
1
Q
When does the reproductive development diverge (differentiate between male & female)?
A
~7 weeks
2
Q
What is the endocervix lined by prior to puberty?
A
Columnar (glandular) epithelium
3
Q
Describe what happens to the cervix during its growth after puberty?
A
Squamo-columnar junction is everted into the vagina & the squamous epithelium adapts to the vaginal environment by squamous metaplasia in the ‘transformation zone’
4
Q
What are the post pubertal cervical changes reversed by?
A
Menopause
5
Q
Describe the clinical significance of the cervical ‘transformation zone’?
A
Unstable differentiation is where most cervical neoplasia develop
6
Q
What is thought to be a necessary cause of cervical cancer & precancer?
A
Persisting infection with an oncogenic strain of Human Papilloma Virus (HPV)
7
Q
What are the 2 prevalent strains of HPV in glasgow?
A
HPV 16 & 18
8
Q
Where are the cervical cells taken from for cytological screening?
A
Cervical transformation zone
9
Q
What is a cervical cytological screening designed to detect?
A
Changes associated with HPV infection & Cervical Intraepithelial Neoplasia
10
Q
What are dyskaryosis?
A
Nuclear abnormalties
11
Q
What does the presence of dyskaryosis suggest?
A
CIN
12
Q
What does the presence of dyskaryosis prompt?
A
Referral to colposcopy clinic for biopsy to detect CIN
13
Q
Does CIN have symptoms?
A
NO
14
Q
Who should undergo cervical cytology screening?
A
Current policy in Scotland is that women aged 25 -65 are invited. That is inclusive of those that have been vaccinated
15
Q
How often should women be screened cervically when 25-50 years old?
A
3 yearly
16
Q
How often should women be screened cervically when 50-65 years old?
A
5 yearly
17
Q
What colour are the cervical superficial squamous cells stained?
A
Pink
18
Q
What colour are the cervical intermediate cells stained?
A
Blue
19
Q
When would you repeat smear screening if it came back negative?
A
Routinely in 3 years
20
Q
When would you repeat smear screening if it came back with a borderline nuclear abnormality?
A
6 months later (X3 Borderline nuclear abnormality refer colposcopy)
21
Q
What would you do if a smear screening test came back with a low/high grade dyskaryosis?
A
Refer to colposcopy
22
Q
What would you do if a smear screening test came back with a glandular abnormality?
A
Refer to colposcopy
23
Q
What would you do if a smear screening test came back with features suggestive of invasion?
A
Urgent referral to colposcopy
24
Q
What type of HPV vaccination (aimed at 12/13year old girls) is Scotland now using?
A
Quadrivalent vaccine to cover against HPV 6, 11, 16 & 18
25
What is HPV testing easier with?
Liquid based cytology
26
What is HPV testing more sensitive than?
Cytology
27
What can HPV testing be used effectively in?
Primary screening in women aged over 30 years
28
HPV tests are very ______, which at present reduced ______?
- Sensitive
| - Specificity
29
What does high risk HPV in the cervix increase the risk of?
CIN
30
What is Gardasil?
HPV vaccination that targets high risk HPV 6,11,16,18
31
What is the downfall of HPV vaccination?
Likely to be important in the long run but
| cannot be assumed that it will prevent all cervical cancer
32
Does most HPV infection progress to CIN or cancer?
NO
33
Describe the colposcopy procedure?
- Cervix visualised
- Washed with acetic acid
- Application of Iodine
- Green light filter
- Abnormal area can be biopsied or treatment performed at the time or at a further appointment
34
What are more than 99% of cervical carcinomas associated with?
HPV infection
35
Describe what the early genes (E1 --> E7) in HPV infection do?
Interact with intracellular molecules to interfere with cell proliferation machinery to replicate the virus
36
Describe what the late genes (L1 & L2) in HPV infection do?
- Encode capsid proteins
| - Disruption of cell cycle checkpoints may contribute to accumulation of oncogenic mutations & carcinogenesis
37
What does BNA stand for in HPV infection?
Borderline nuclear abnormality
38
What types of cells are commonly found on histology of HPV?
Koilocytes
39
Describe the histology of low grade squamous dyskaryosis?
- Normal
- Nuclear:cytoplasmic upto 1/2
- CIN1
40
Describe the histology of high grade (moderate) squamous dyskaryosis?
- Nuclear:cytoplasmic from 1/2 to 2/3
| - CIN2
41
Describe the histology of high grade (severe) dyskaryosis?
- Nuclear enlargement with dense hyperchromasia & course chromatin clumping
- CIN3
42
What are the 2 means of treatment for cervical abnormalities?
1. Bipolar tubal coagulation
| 2. Post cold coagulation
43
What are the 2 immediate complications of cervical treatments (bipolar coagulation & post cold coagulation)?
1. Pain
| 2. Haemorrhage
44
What are the 4 delayed complications of cervical treatments (bipolar coagulation & post cold coagulation)?
1. Secondary haemorrhage (1-2%)
2. Infection
3. Cervical stenosis (~1%)
4. No good evidence of impact on fertility
45
What is the cervical screening programmed designed to pick up specifically?
Squamous lesions
46
What is the name given for endocervical glandular epithelium that undergoes premalignant change?
Cervical Glandular Intraepithelial Neoplasia (cGIN )
47
What is the name given for malignant change in glandular epithelium?
Adenocarcinoma
48
What is a histological feature of an endocervical abnormality?
Pseudostratification
49
What else can a smear test pick up?
Endometrial abnormalities
50
What should always happen when a patient presents with post menopausal bleeding?
Referred to gynaecology for endometrial biopsy
51
What are the 5 possible symptoms of cervical cancer?
1. NONE
2. Pain
3. Post coital bleeding
4. Intermenstrual bleeding
5. Irregular vaginal bleeding
52
Describe how invasive squamous carcinoma of the cervix develops?
Almost always develops from pre-existing CIN, but not all CIN will become squamous cancer
53
What type of CIN are more likely to progress to cancer?
CIN2 & CIN3
54
What is another term for CIN?
Squamous intraepithelial lesion (SIL)
55
Describe the histology of invasive squamous cell carcinoma?
- Blood & polymorphs
- Squamous cells take on bizarre shapes
- Late stage
- Basement membrane has been breached and malignant cells penetrate the stroma
56
What can lead to atopic vaginitis?
Low oestrogen after menopause
57
List the 5 signs & symptoms of atopic vaginitis?
1. Discomfort
2. Dyspareunia (painful sex)
3. Bleeding
4. Polyps
5. Cysts
58
What does VAIN stand for?
Vaginal intra-epithelial neoplasia
59
What are 2 uncommon vaginal cancers?
1. Vaginal intra-epithelial neoplasia (VAIN)
| 2. Squamous carcinoma
60
What can primary cancers of the cervix/ vulva also involve?
The vagina
61
What 5 infections can cervical smear tests also identify?
1. Bacterial vaginosis
2. Thrush (candida albicans)
3. Trichomonas vaginalis
4. Actinomyces
5. Herpes Simplex
62
How is Trichomonas vaginalis usually transmitted?
Sexually transmitted
63
What is a common bacteria associated with the IUD contraceptive coil?
Actinomyces
64
List 8 possible pathologies associated with the female vulva?
1. Inflammatory dermatoses
2. Skin tumours
3. Skin tags
4. Melanocytic nevi
5. Benign cysts
6. Candidiasis (thrush)
7. Lichen planus
8. Lichen sclerosus et atrophicus
65
Describe Vulva Candidiasis (thrush)?
- Common
- May be associated with pregnancy or diabetes
- Bartholin's vestibular gland cysts may become infected with abscess formation
66
What are Lichen planus
| & Lichen sclerosus et atrophicus?
Non-infective inflammations of the vulva
67
What region is Lichen Sclerosus especially associated with?
Anogenital region
68
What 2 things are Vulval Squamous Cell Carcinoma's associated with?
1. Vulvar intraepithelial neoplasia (VIN)
| 2. Dermatoses
69
What age group is more prevalent for Vulval Squamous Cell Carcinoma's associated with VIN?
Exclusively in females less than 60 years old
70
What are Vulval Squamous Cell Carcinoma's associated with VIN usually related to?
High risk type HPV 16/18
71
What is the appearance of Vulval Squamous Cell Carcinoma's associated with VIN?
Warty or Basaloid
72
What age group is more prevalent for Vulval Squamous Cell Carcinoma's associated with dermatoses?
Older age group- most over 60, many over 70
73
Describe Vulval Squamous Cell Carcinoma's associated with dermatoses?
- Well differentiated & keratinising
- Not associated with HPV infection or VIN
- Adjacent squamous hyperplasia &/or lichen sclerosus common
74
Describe the risk of malignancy in Vulval Lichen Sclerosus?
- Generally low
| - But subtle non-HPV related entity called 'differentiated VIN' may have a much greater risk of progression
75
What % of vulval cancers are thought to be HPV dependent?
20%
76
What amount of cervical squamous cancer is HPV dependent?
Almost all
77
What may vulval HPV- associated intraepithelial neoplasia (VIN) develop into?
Invasive squamous carcinoma
78
What may the squamous epithelium of the vagina & perianal skin be affected by?
Pre-neoplastic field change
79
What 2 places could you find ectopic breast tissue?
1. Axilla
| 2. Vulva
80
How is the nipple formed?
Evagination of the mammary pit
81
What is premature thelarche?
- Girls who develop small breasts typically before the age of 3 years
- They do not have other signs of puberty
82
Describe how breasts are developed?
- During puberty
- Cyclical oestrogen & progesterone
- Duct elongation & stromal development
- Lobuloalveolar differentiation
- Continues for a decade, enhanced by pregnancy
83
What 3 things does Duct elongation & stromal development dependant on?
1. Oestrogen
2. Glucocorticoids
3. Growth hormone
84
What 3 things is Lobuloalveolar differentiation dependant on?
1. Progesterone
2. Insulin
3. Growth Hormone
85
Describe the hormonal variation of breast development during the 4 phases of the menstrual cycle?
1. Proliferation in Proliferative phase (3-7)
2. Decreases in Follicular phase (8-14)
3. Myoepithelial changes & proliferation in Luteal phase (15-20)
4. Secretory changes in Secretory phase
86
Describe breast development during pregnancy?
- Early pregnancy lobular enlargement & stromal depletion
- Continued lobular enlargement & secretory change
- Post lactational involution (3 months)
87
What are the 3 breast developmental abnormalities?
1. Hypoplasia/Amastia
2. Macromastia
3. Polymastia/Polythelia
88
Describe Breast Amastia?
Condition where breast tissue, nipple, & areola is absent, either congenitally or iatrogenically
89
Describe Breast Macromastia?
Condition of abnormal enlargement of the breast tissue in excess of the normal proportion
90
Describe Breast Polymastia?
Condition of having an additional breast, may appear with or without nipples or areolae
91
Describe Breast Polythelia?
Presence of an additional nipple alone
92
Describe the population breast screening programme?
- All women 50-70years
- 2 view mammography
- Recalled every 3 years
93
Describe 6 ways to perform breast screening?
1. Xray
2. Recall
3. Examination
4. Lump, asymmetry, distortion, calcification
5. Needle biopsy
6. Open biopsy
94
List the 4 symptomatic reasons why someone would get breast screening?
1. Breast lump
2. Treat pain
3. Nipple discharge
4. Skin changes
95
What is the breast triple assessment?
1. Clinical history
2. Examination
3. Imaging (MMG, US, MRI)
4. Needle biopsy
96
What are the 3 PROS of breast fine needle aspirate?
1. Relatively easy
2. Only mild trauma
3. Immediate report at clinic
97
What are the 3 CONS of breast fine needle aspirate?
1. No architecture, insitu or invasive
2. Requires trained cytologist
3. False positives/negatives
98
What are the 2 PROS of breast core biopsy?
1. Differentiates between insitu & invasive
| 2. Fewer false positives/negatives
99
What are the 2 CONS of breast core biopsy?
1. Takes 24hrs to process & no immediate report
| 2. More local trauma
100
What are the 5 reasons for doing a breast core biopsy?
1. Gives tissue diagnosis with architecture
2. Allows correlation with Mammogram
3. Visualises calcification
4. Allows diagnosis of borderline lesions
5. Enables accurate planning of definitive surgery
101
What are the 5 classifications for breast fine needle aspiration (FNA)?
1. C1- insufficient
2. C2- Benign
3. C3- Atypia Probably Benign
4. C4- Atypia probably malignant
5. C5- Malignant
102
What are the 5 classifications for breast core biopsy?
1. B1- Normal tissue/ insufficient for diagnosis
2. B2- Benign
3. B3- Atypia probably benign
4. B4- Atypia probably malignant
5. B5a/b- Malignant
103
Give 2 examples of benign breast lesion?
1. Fibroadenoma
| 2. Fibrocystic
104
Describe a Fibroadenoma benign breast lesion?
- Young women 20-30
- Discrete mobile lump
- Lesion of stroma & epithelium
105
Describe fibroadenomatoid lesions?
- Well defined rounded opacity
- C2 FNA classification
- B2/B3 core biopsy classificaiton
106
Give 3 examples of fibroadenomatoid lesions?
1. Fibrodenoma
2. Fibroadenomatoid lesion
3. Phyllodes tumour
107
Describe a Phyllodes breast tumour?
- Typically large
- Fast-growing masses
- Form from the periductal stromal cells of the breast
- Pleomorphisim
- Stromal Overgrowth
- Necrosis
108
What are the 3 types of Phllodes breast tumour?
1. Benign
2. Borderline
3. Malignant (treat as sarcoma)
109
What should you always remember when treating Phyllodes breast tumour?
Never shell out
110
Describe a fibrocystic benign breast lesion?
- 30-40years
- Cyclical Variation
- May be painful
- Fibrosis, cysts, apocrine change, epithelial hyperplasia & columnar cell change
111
What is a Radial scar?
Form of sclerosing duct hyperplasia/ parenchymal distortion
112
What 2 ways would you diagnose a radial scar?
1. Core biopsy to exclude carcinoma
| 2. Excision biopsy
113
List 5 ways to differentiate between a radial scar and tubular carcinoma?
1. Pattern
2. Shape of tubules
3. Myoepithelial cells
4. CK5, SMA, P63
5. Calponin, SMM, CD10
114
What is duct ectasia?
Condition in which the lactiferous duct becomes blocked or clogged & can mimic breast cancer
115
List the 5 signs & symptoms of duct ectasia?
1. Nipple discharge/inversion
2. Pain
3. Squamous metaplasia of lactiferous duct
4. Mammary duct fistula
5. Micro dilated ducts & inflammation changes
116
What is duct ectasia linked to?
Smoking
117
Describe the presentation of a breast papillary lesion?
Nipple discharge, blood stained +/- epithelial cells
118
Describe breast papillary lesion?
- Mass often central
- Microcalcification
- Cytology C1, 2, 3, 4, 5
119
What are 2 ways to diagnose a papillary lesion?
1. Core biopsy
| 2. Papillary lesion excise
120
Describe a papilloma?
- Small wart-like growth
- Fibrovascular cores
- Epithelial & myoepithelial cells
- Hyperplasia
- Single/Multiple
121
Describe Pseudo angiomatous stromal hyperplasia (PASH)?
- Hard palpable lump
- Usually premenopausal
- Well defined mass on imaging
- Gross well circumscribed pseudo encapsulated mass
- Dense stroma with anatomizing channels lined by myofibroblasts
122
What is the differential diagnosis of Pseudo angiomatous stromal hyperplasia (PASH)?
Angiosarcoma
123
Describe Granulomatous mastitis?
- Mean age 33 years
- Distinct hard mass
- Usually parous
- Contraceptive pill effect?
124
What is granulomatous mastitis?
Confluent inflammation with abscess formation centred on lobules
125
List 6 potential causes for granulomatous mastitis?
1. TB
2. Sarcoid
3. Fungal/atypical mycobacterial
4. Cat scratch disease
5. Vasculitis
6. Carcinoma associated granulomas
126
What fine needle aspirate classification is granulomatous mastitis?
C5 or false positive
127
What is the management of Granulomatous mastitis?
- Spontaneous resolution
- NSAID's
- Steroids
128
What should you avoid in Granulomatous mastitis?
Open biopsy
129
Describe Diabetic mastopathy?
- Ill defined hard mass.
- Usually < 30yrs
- Dense keloid like stroma
- Perilobular & vascular lymphocytes
130
Give 2 examples of atypical breast proliferations?
1. Atypical ductal hyperplasia
| 2. Atypical lobular hyperplasia
131
How many women does breast carcinoma approximately affect?
1:10
132
What are the 3 risk factors for breast carcinoma?
1. Age- 40-70years
2. Family history- accounts for <5%
3. Hormone environment- menstruation, pregnancy, breast feeding, hormone replacement
133
Describe an insitu breast carcinoma?
- Malignant proliferation of epithelial cells contained within the basement membrane
- NO extension into breast stroma
- No communication with blood vessels or lymphatics
- No possibility of metastases
134
Describe a breast ductal carcinoma in situ?
- Most are mammographically detected
| - May present with lump, nipple discharge or Pagets Disease
135
What happens if breast ductal carcinoma in situ is left untreated?
30% will develop invasive carcinoma in 15 years
136
Describe the prognosis of breast ductal carcinoma in situ?
With adequate surgical treatment prognosis is excellent
137
What is the 3 part treatment for breast ductal carcinoma in situ (DCIS)?
1. Complete Excision
2. Mastectomy +/- Reconstruction
3. Local Excision & Radiotherapy
138
Describe how breast Lobular Carcinomas in situ are detected?
Chance finding in breast biopsies no clinical or mammographic features
139
Describe the presentation of breast Lobular Carcinomas in situ?
Usually multifocal & bilateral
140
What is the risk factor of breast Lobular Carcinomas insitu?
- Developing invasive cancer in either breast
| - 10x greater risk than general population
141
Describe the management of breast Lobular Carcinomas insitu?
Regular follow up via Bilateral mastectomy
142
What is the most common type of breast cancer (>70%)?
Invasive ductal carcinoma
143
Describe the appearance of Invasive ductal carcinoma?
- Variable histology
| - Infiltrating cells in sheets cord & tubules
144
What Invasive ductal carcinoma grading system gives an indication of survival?
Bloom & Richardson Grading
145
What are the 3 morphological features for all types of breast cancers?
1. Tubules
2. Pleomorphism
3. Mitoses
146
What makes up 10% of all invasive breast carcinomas?
Lobular carcinoma
147
Describe the appearance of Lobular carcinoma?
- Signet ring cells & diffusely infiltrative
| - Often multicentric & bilateral
148
Describe the prognosis of Lobular carcinoma?
Usually grade 2 & ER positive (85% 5yr survival)
149
What makes up 3% of all breast carcinomas?
Tubular carcinoma
150
Describe the appearance of Tubular carcinoma?
- Well differentiated
| - Grade 1
151
What % of Tubular carcinoma have a 5 year survival?
95%
152
What is the most common breast cancer in over 75 year olds?
Mucinous/Mucoid carcinoma
153
Describe the appearance of Mucinous/Mucoid carcinoma?
- Well circumscribed tumour with lakes of mucin
| - Well differentiated cells
154
What % of Mucinous/Mucoid carcinoma have a 5 year survival?
90%
155
List the 2 types of routes for breast metastases?
1. Lymphatics- axillary & internal mammary nodes
| 2. Blood spread- lungs, bone, liver, brain etc
156
What should you do in all invasive cancers?
Ultrasound axilla
157
What should you do when the ultrasound shows abnormal axillary nodes?
Core biopsy
158
What should you do if the axillary node core biopsy comes back positive?
Axillary clearance
159
What should you do if the axillary node core biopsy comes back negative?
Sentinel Node biopsy with isotope & blue dye
160
What are the 5 pathological prognostic features of breast cancer?
1. Size of tumour
2. Type of tumour
3. Grade of tumour
4. Node status
5. Hormone receptor status
161
What are the 2 hormone receptors affected in breast cancer?
1. ER (oestrogen receptor)
| 2. PR (progesterone receptor)
162
What scoring system detects which hormone receptors are affected in breast cancer?
Allred score
- Intensity 1-3
- Proportion 1-5
163
What is the Nottingham Prognostic index & what does it do?
- Provides an estimate of prognosis in an individual
- Determines treatment & follow up
- Application of indices based on significant factors
- Allows stratification of treatment in controlled trials & evaluation of therapies
164
Describe the 3 factors involved in the Nottingham Prognostic index?
1. Grade 1-3: grade 1= 1 point, grade 3= 3 points
2. Nodal status: 0 nodes= 1 point, 1-3 nodes= 2 points, 4+ nodes= 3 points
3. Size: cm x 0.2
165
What is the NPI for a good prognostic breast carcinoma group?
NPI <3.4
166
What is the NPI for an intermediate prognostic breast carcinoma group?
NPI 3.41 - 5.4
167
What is the NPI for a poor prognostic breast carcinoma group?
NPI >5.4
168
What are the 6 means of treatment for Invasive breast carcinomas?
1. Mastectomy
2. Lumpectomy + radiotherapy
3. Axillary Surgery
4. Hormone Therapy
5. Chemotherapy
6. Targeted Therapy
169
What does HER2 stand for?
Human epidermal growth factor receptor 2
170
What do 15-20% of breast cancers over-express?
HER2 gene
171
List 3 things that a HER2 over expression is associated with in breast cancer?
1. Poor outcome
2. May be related with response to chemo
3. May be associated with poor response to hormone therapy
172
What treatment is available for HER2 positive breast cancer?
Trastuzumab (Herceptin)
173
What are 4 indicators of increased HER2 production?
1. Increased gene copy number
2. Increased mRNA transcription
3. Increased cell surface receptor protein expression
4. Increased release of receptor extracellular domain
174
List 4 other breast related malignancies?
1. Metastatic disease
2. Lymphoma
3. Sarcoma
4. Angiosarcoma
175
What are array studies?
Signature a collection of genes taken together to classify a distinct group of tumours
176
What are the 4 molecular subtypes for breast cancer?
1. Luminal
2. Her2
3. Basal
4. Normal
177
What are the 5 different oncotype differential diagnoses of breast cancer?
1. ER
2. HER2
3. Proliferation
4. Invasion
5. House keeping
178
What is Oncotype Dx?
Tumor profiling test that helps determine the benefit of using chemotherapy in addition to hormone therapy to treat some estrogen receptor-positive (ER-positive) breast cancers
179
What makes the foetus develop reproductively into a male?
Sex determining region Y (SRY) on the Y chromosome
180
Where do the gonads arise from?
Embryonic urogenital ridges
181
Where do the genital ducts arise from?
Paired mesonephric & paramesonephric ducts
182
What do the mesonephric (Wolffian) ducts develop into?
Male structures
183
What do the paramesonephric (Müllerian) ducts develop into?
Female structures
184
What does SRY direct in the male foetus?
Gonad to become a testis, with spermatogonia, Leydig & Sertoli cells
185
What does testosterone from the Leydig cells stimulate in the male foetus?
Development of mesonephric duct structures
186
What happens if the foetus does not have testosterone from the Leydig cells?
Mesonephric ducts atrophy
187
What does Dihydrotestosterone promote in the male foetus?
Development of prostate, penis & scrotum
188
What causes the regression of paramesonephric ducts in the male foetus?
Anti-Müllerian Hormone / Müllerian Inhibiting Substance from Sertoli cells
189
What 6 structures does the Mesonephric ducts in the male foetus produce?
1. Rete testis
2. Efferent ducts
3. Epididymis
4. Vas deferens
5. Seminal vesicle
6. Trigone of bladder
190
What 4 structures does the Urogenital sinus in the male foetus produce?
1. Bladder (except trigone)
2. Prostate gland
3. Bulbourethral gland
4. Urethra
191
What happens without the SRY gene in the female foetus?
- Gonad develops into an ovary with oogonia & stromal cells
- Without testosterone, mesonephric ducts regress
192
What 4 structures does the paramesonephric ducts in the female foetus produce?
1. Oviducts
2. Uterus
3. Cervix
4. Upper 1/3 of the vagina
193
What 5 structures does the urogenital sinus in the female foetus produce?
1. Bulbourethral glands
2. Lower 2/3 of vagina
3. Vestibule
4. Bladder (except trigone)
5. Urethra
194
What structure does the Mesonephric ducts in the female foetus produce?
Trigone of bladder
195
What do the Primordia of the external genitalia in males develop into?
- Body & glans penis
| - Corpora cavernosum
196
What do the Primordia of the external genitalia in females develop into?
- Body & glans of clitoris
| - Labia
197
What are the 3 foetal Primordia of the external genitalia?
1. Genital tubercle
2. Genital folds
3. Genital swellings
198
Describe the appearance of the fallopian tubes?
- Lined by ciliated columnar epithelium
- Complex plicae
- Layers of smooth muscle
- Peritoneum external surface
199
Give an example of fallopian (ovarian) tube pathology?
Salpingitis
200
What spectrum of diseases does Salpingitis come under?
Pelvic inflammatory disease
201
List the potential infective causes of Salpingitis?
1. Chlamydia trachomatis
2. Mycoplasma
3. Coliforms
4. Streptococci
5. Staphylococci
6. Neisseria gonorrhoeae
202
Describe Tuberculous salpingitis?
- Uncommon
| - Usually associated with tuberculosis of the endometrium
203
Describe the signs & symptoms of Salpingitis?
- Fever
- Lower abdominal or pelvic pain
- Pelvic masses if tubes distended with exudate
or secretions
204
List the 3 possible complications of Salpingitis?
1. Adherence of tube to ovary: tubo-ovarian abscess
2. Adhesions involving tubal plicae increase risk of tubal ectopic pregnancy (rupture of ectopic is life-threatening)
3. Damage or obstruction of tube lumen may produce infertility which may not be easy to treat
205
What can occur when endometriosis is also present in salpingitis?
Compromise ovarian tube function
206
List 3 tubal malignancies?
1. Primary adenocarcinomas (Papillary serous carcinoma)
2. Endometrioid carcinoma
3. Fallopian tube carcinoma
207
When can Fallopian tube carcinomas occur?
BRCA1 mutations
208
Where is about 10% of occult tubal malignancy present?
Fimbria of prophylactic salpingo-oophorectomies
209
What do fallopian tube carcinomas often involve at the time of presentation?
Omentum & peritoneal cavity
210
Where may the origin of some ovarian carcinomas be?
Fallopian tube
211
What does STIC stand for?
Serous Tubal Intraepithelial Carcinoma
212
Describe (STIC) Serous Tubal Intraepithelial Carcinoma?
- Abnormal epithelium distal Fallopian tube
- Limited by basement membrane (B) so in situ
- Nuclear atypia (N) clearly seen
- Likely precursor for high grade serous carcinoma
213
What is mutation in (STIC) Serous Tubal Intraepithelial Carcinoma similar to?
Invasive tumour, including p53
214
Describe the normal structure of an ovary?
- Flat surface epithelium
- Cortex: compact ovarian stroma, small functional cysts, germ cells
- Medulla: hilus cells, vessels, nerves
215
List 2 pathologies of ovaries?
1. Non-neoplastic cysts
| 2. Polycystic ovaries (stein-leventhal syndrome)
216
What are the 3 types of ovarian Non-neoplastic cysts?
1. Inclusion
2. Follicular
3. Luteal
217
List the 7 signs & symptoms of polycystic ovary disease (stein-leventhal syndrome)?
1. Oligomenorrhea
2. Hirsutism
3. Infertility
4. Obesity
5. Over-production of androgens
6. LH high
7. FSH low
218
Describe the appearance of polycystic ovaries (stein-leventhal syndrome)?
- Enlarged
- Multiple subcortical cysts 5-15mm in diameter
- Thickened, fibrotic outer surface
- Lined by granulosa cells with hypertrophic & hyperplastic luteinised theca interna
- Absence of corpora lutea
- Corpora albicantes (ovulation not occurring)
219
What may polycystic ovaries (stein-leventhal syndrome) result in & why?
Type 2 diabetes due to insulin resistance
220
What are the 3 cell types that make up the normal ovary?
1. Surface (coelomic) epithelium
2. Germ cells
3. Sex cord/stromal cells
221
What are the 2 risk factors for epithelial ovarian cancers?
1. Nulliparity
| 2. Family history
222
What may reduce the risk of epithelial ovarian cancers?
Prolonged oral contraceptive use
223
What % of ovarian cancers are familial?
5-10%
224
What are ovarian cancers mostly related to?
BRCA1 & BRCA2 gene mutations
225
What is the % lifetime risk of ovarian cancer in BRCA1 carriers?
~30%
226
Is the risk of ovarian cancer higher in BRCA1 or BRCA2 carriers?
BRCA1 carrier
227
What % of sporadic ovarian cancers have a BRCA mutation?
~9%
228
What % of ovarian cancers have HER2 over expression?
35% (poor prognosis)
229
What % of ovarian tumours have a KRAS mutation & what specific type of tumour is most prevalent for this?
- ~30%
| - Mucinous cystadenocarcinomas
230
What % of ovarian cancers have a p53 mutation & what type of tumour is most prevalent for this?
- ~50%
| - High grade serous cancer
231
What are the 4 genetic alterations associated with sporadic ovarian cancer?
1. BRCA mutation
2. HER2 over-expression
3. KRAS mutation
4. p53 mutation
232
What are surface epithelial ovarian tumours classically thought to arise from?
Coelomic mesothelium on the surface of the ovary
233
What are benign surface epithelial ovarian lesions usually?
Cystic (cystadenoma) with or without a solid stromal component (cystadenofibroma)
234
What do surface ovarian epithelial tumours also have?
Intermediate, borderline category currently referred to as tumours of low malignant potential
235
Describe a factor of ovarian tumours of low malignant potential?
Limited invasive potential & a much beter prognosis than overtly malignant ovarian carcinomas
236
What are the 2 types of malignant epithelial ovarian tumours?
1. Cystic (cystadenocarcinoma)
| 2. Solid (adenocarcinoma)
237
What are the 5 types of ovarian carcinomas?
1. High grade serous (HGSC, 70%)
2. Endometrioid (10%)
3. Clear-cell (10%)
4. Low grade serous (LGSC, 5%)
5. Mucinous (3%)
238
Where are High grade serous carcinomas (HGSC) of the ovary though to often arise from?
Epithelial precursor lesions in the ovarian end of the Fallopian tubes
239
Where are Endometrioid and clear cell carcinomas of the ovary probably from?
Ovarian endometriosis
240
What is an Ovarian endometrioma also known as?
Chocolate cysts
241
Describe the genetics of High grade serous carcinomas (HGSC)?
- p53 & BRCA1 are typically abnormal
| - Inability to repair double stranded DNA breaks leads to chromosomal instability & genomic chaos
242
What are ovarian carcinomas in patients with BRCA1 almost always?
High grade serous carcinomas (HGSC)
243
What are Low grade serous (LGSC) often associated with?
Borderline serous component
244
What % of serous ovarian tumours are benign, borderline or malignant?
- 60% benign
- 15% borderline
- 25% malignant
245
What age group are benign serous ovarian tumours most prevalent?
30-40 years
246
What age group are malignant serous ovarian tumours most prevalent?
45-65 years
247
What % of ovarian cancers does HGSC account for?
~70%
248
What 2 types of tumours are BRAF & K-RAS mutations common in?
1. Borderline tumours
| 2. Low grade serous carcinomas (LGSC)
249
Describe the morphology of benign serous tumours?
- Large
- Cystic (up to 30 - 40 cm) & filled with clear serous fluid
- May be bilateral
- Smooth shiny serosal covering
- Lined by a single layer of tall columnar epithelium
- Some cells ciliated
250
Describe the morphology of borderline serous tumours?
- Complex architecture
- Mild cytologic atypia but no stromal invasion
- Peritoneal implants may be present
251
Describe the morphology of Serous carcinomas?
- Anaplasia of cells
| - Obvious stromal invasion
252
What are Psammoma bodies?
Concentrically laminated calcified concretions
253
Where are Psammoma bodies common?
Papillae of serous tumours in general
254
What is the prognosis of benign & borderline serous tumours?
Excellent outcome (borderline tumours almost 100% survival, & even with peritoneal involvement nearly 75%)
255
What is the prognosis for invasive serous carcinomas?
Poor & depends on stage at diagnosis
256
What are the 3 types of mucinous ovarian tumours & how common are they?
1. 10% Malignant (cystadenocarcinoma)
2. 10% of Low malignant potential (borderline)
3. 80% Benign
257
What 2 factors is the diagnosis of mucinous ovarian tumours dependant on?
1. Architectural complexity
| 2. Cytological atypia
258
What can mimic primary ovarian mucinous carcinomas?
Metastases to the ovary from GI tract ('Krukenberg tumours')
259
What type of tumours are more likely to be primary ovarian mucinous carcinomas?
Large unilateral tumours
260
Describe the morphology of mucinous ovarian tumours?
- Large
- Multilocular
- No psammoma bodies
- Cysts lined by cells with abundant mucinous cytoplasm
261
What is the prognosis of mucinous cystadenocarcinoma compared to serous?
Slightly beter than serous, but stage is more important than histologic type
262
What are ovarian endometrioid carcinomas microscopically characterised by?
Neoplastic tubular glands, similar to those of the endometrium
263
What is the most common type of ovarian endometrioid carcinoma?
Malignant
264
What % of ovarian endometrioid carcinomas are bilateral?
30%
265
~15-20% of women with ovarian endometrioid carcinomas also have what?
Endometrial carcinoma (most are low grade & many arise from endometriosis)
266
How are endometrioid carcinomas like endometrial cancer?
Often lost the PTEN ('phosphatase and tensin homolog') tumour suppressor gene
267
What is ovarian clear cell carcinoma also associated with?
Endometriosis
268
95% of ovarian germ cell tumours are what?
Mature cystic teratomas ('dermoid cysts')
269
What do totipotent germ cells differentiate into?
Mature cells of all 3 germ cell layers:
1. Ectoderm
2. Endoderm
3. Mesoderm
270
What is the most common presentation of germ cell tumours?
- Young women as ovarian masses or are found incidentally on abdominal scans
- May contain foci of calcification associated with bone or teeth
- ~10% bilateral
271
Describe the gross appearance of germ cell tumours?
- Smooth capsule
- Often filled with sebaceous secretion & matted hair
- Sometimes, foci of bone & cartilage, nests of bronchial or GI epithelium, teeth & other recognisable lines of development also present
272
What are 5% of ovarian teratomas in adults?
Immature cystic teratomas with immature neuroectodermal elements, associated with more aggressive behaviour
273
What are teratomas in children?
Rare but much more often immature than in adults
274
What occurs in 1% of ovarian teratomas?
Malignant transformation of one of the tissue elements (squamous carcinoma, adenocarcinoma, sarcomas etc)
275
What are cystic ovarian teratomas prone to?
Torsion (presentation of 10% - 15% of cases), producing an acute surgical emergency
276
What are 4 rare ovarian tumours?
1. Dysgerminoma
2. Embryonal carcinoma
3. Yolk-sac tumour
4. Choriocarcinoma
277
What 3 things do ovarian sex cord-stomal tumours include?
1. Granulosa cell tumours
2. Theca cell tumours
3. Sertoli-Leydig cell tumours
278
When do granulosa cell tumours usually occur?
Postmenopausal women & are not rare
279
What may granulosa cell tumours lead to & why?
Oestrogen over-production may lead to endometrial hyperplasia or endometrial carcinoma
280
Describe Ovarian fibromas & thecomas?
- Benign
- Rare
- Can over-produce oestrogens, esp thecomas
281
What is Meig's syndrome?
Combination of an ovarian fibroma with ascites & pleural effusion
282
What cures Meig's syndrome?
Removal of the tumour
283
What is an ovarian tumour with ascites likely to be?
Carcinoma
284
Describe Brenner tumours?
- Uncommon mixed surface epithelial-stromal tumours
- Usually benign, unilateral, size variable, solid, circumscribed, yellowish
- Often found incidentally
285
Describe Brenner tumours histologically?
Nests of transitional epithelial cells with longitudinal nuclear grooves & abundant fibrous stroma
286
What are the 5 clinical challenges for all ovarian tumours?
1. Often asymptomatic until well advanced
2. Clinical presentations often similar despite biological diversity
3. Torsion common, producing severe abdominal pain
4. Functioning ovarian tumours often come to attention because of the hormones they produce
5. Abdominal swelling due to ascites is common of ovarian malignancy but is also seen in benign tumours
287
List 5 common endometrial pathologies?
1. Adenomyosis
2. Endometriosis
3. Endometrial polyps
4. Endometrial hyperplasia
5. Endometrioid adenocarcinoma
288
List 3 other uterine pathologies?
1. Leiomyoma
2. Leiomyosarcoma
3. Endometrial stomal sarcoma
289
What happens to the foetal coelomic lining epithelium at around 6 weeks?
Forms the lateral müllerian ducts, which grow downwards into the pelvis & fuse with the urogenital sinus
290
What does the fused portion of the müllerian ducts become?
Uterus
291
What does the remaining unfused portion of the müllerian ducts become?
Fallopian tubes
292
What 3 gynaecological organs are derived from the coelomic lining?
1. Endometrial cavity
2. Linings of fallopian tubes
3. Peritoneal covering
293
What are abnormalities of the uterus related to?
Foetal abnormalities in the fusion of the müllerian ducts
294
List the 5 classes of uterine developmental abnormalities?
1. Class U1- dysmorphic uterus
2. Class U2- septet uterus
3. Class U3- bicorporeal uterus
4. Class U4- hemi uterus
5. Class U5- aplastic uterus
295
Describe the basic histology of the uterine endometrium?
Consists of glands & stroma & has a variety of normal appearances depending on the phase of the menstrual cycle, menopausal status etc
296
Describe the basic histology of the uterine myometrium?
Smooth muscle comprising much of the uterus
297
Describe the 3 stages of the normal menstrual cycle?
1. Proliferative phase: stratification in basal area, mitotic activity in dividing area
2. Secretory phase: ovum released from ovary & corpus luteum formed in ovary at day 14, glands are enlarged. Secretion during the progesterone development of vacuoles
3. Menstrual phase: occurs when we don't have implantation of a fertilised egg, the cells in stroma are close together, there is apoptosis
298
Describe the histological appearance of endometrium in a post-menopausal woman?
- Endometrium becomes very thin
- Less glands
- Nucleus takes over the small cells
299
What is endometriosis?
The presence of endometrial tissue outside of the uterus
300
What is adenomyosis?
The presence of endometrial tissue within the myometrium
301
List 8 sites of endometriosis?
1. Ovaries
2. Peritoneal surfaces (including uterine ligaments & rectovaginal septum)
3. Large & small bowel
4. Appendix
5. Mucosa of cervix,
6. Vagina
7. Fallopian tubes
8. Laparotomy scars
302
What are the 3 clinical symptoms of Endometriosis and adenomyosis?
1. Dysmenorrhoea
2. Pelvic pain
3. Infertility
303
What are the 2 pathogenesis theories regarding Endometriosis & adenomyosis?
1. Metastatic theory
| 2. Metaplastic theory
304
Describe the Metastatic theory for Endometriosis & adenomyosis?
Retrograde menstruation or surgical procedures introduce endometrium to sites outwith the uterine cavity
305
Describe the Metaplastic theory for Endometriosis & adenomyosis?
Endometrium arises directly from the coelomic epithelium (i.e. peritoneum) of the pelvis, as this is where endometrium originates from during embryological development
306
Describe the histological appearance of Endometriosis & adenomyosis?
- Endometrial gland & stroma tissue embedded into the omentum
- Scarring
- Blood irritates the perineum --> scarring --> strictures --> pain
307
What are endometrial polyps?
Exophytic masses of variable size which project into the endometrial cavity
308
What drug is endometrial polyps associated with?
Tamoxifen
309
How can endometrial polyps present?
Abnormal bleeding
310
How can endometrial polyps be treated?
Hysteroscope in outpatient clinic
311
Describe the histology of endometrial polyps?
- Haphazardly arranged glands with preservation of a low gland to stroma ratio
- Often thick walled blood vessels & fibrous stroma
- The glands are usually inactive, but can also show
proliferation, secretory changes or metaplasias
312
What 2 things can be occasionally found in endometrial polyps?
1. Cytological atypia
| 2. Frank adenocarcinoma
313
What is Endometrial hyperplasia & adenocarcinoma associated with?
Prolonged oestrogenic stimulation of the endometrium
314
List 3 possible underlying causes for Endometrial hyperplasia & adenocarcinoma?
1. Anovulatory cycles
2. Endogenous sources of oestrogen: obesity, PCOS,
oestrogen secreting ovarian tumours
3. Exogenous sources of oestrogen such as oestrogen only HRT
315
What is the usual symptom for Endometrial hyperplasia & adenocarcinoma?
Postmenopausal bleeding
316
Describe the histological appearance of endometrial hyperplasia?
- Increased gland to stroma ratio
| - Can be seen with or without cytological atypia
317
What is atypical endometrial hyperplasia a known precursor of?
Endometrioid adenocarcinoma
318
How would you manage endometrial hyperplasia?
Progesterone therapy such as Mirena IUS, or hysterectomy
319
How would you manage endometrial adenocarcinoma?
Hysterectomy, with subsequent management depending on tumour grade & stage
320
What is a Leiomyoma?
Benign smooth muscle tumour of the myometrium (maybe single or multiple)
321
Describe the prevalence of Leiomyoma?
- Very common
- Atleast 25% of women, mostly of reproductive age
- Incidence is over 70% by age 50
322
List the 4 symptoms associated with Leiomyomas?
1. Asymptomatic
2. Abnormal bleeding
3. Urinary frequency if large
4. Impaired fertility
323
Describe the histology of Leiomyomas?
- Variable size
- Sharply demarcated round grey-white tumours with a whorled cut surface
- Well circumscribed
- Don't have areas of haemorrhage or necrosis
- Don't invade into myometrial surface
324
How would you manage Leiomyomas?
- Varies depending on number, size & symptoms
- Medical: progesterone secreting IUS, hormonal
therapies, tranexamic acid, GnRH agonists
- Surgical: uterine artery embolisation, myomectomy,
hysterectomy
325
What is a Leiomyosarcoma?
Uncommon malignant smooth muscle tumour of the myometrium (1-2% of uterine malignancies, commonest uterine sarcoma)
326
Describe the prevalence of Leiomyosarcoma?
Peak incidence age 40-60 years, can be pre- or post- menopausal
327
Describe the symptoms of Leiomyosarcoma?
Initially none, then bleeding or pain
328
Describe the macro-pathology of Leiomyosarcoma?
Bulky invasive masses or polypoid, necrosis, haemorrhage & variable cut surface
329
Describe the micro-pathology of Leiomyosarcoma?
Overt cytological atypia, necrosis, mitotic
| activity, infiltrative margin
330
Describe the prognosis for Leiomyosarcoma?
- Spread to lungs, liver & brain
| - 40% 5 year survival
331
What are Endometrial stromal sarcomas (ESS)?
A group of rare tumours of the endometrial stroma (can be low or high grade)
332
Describe the growth pattern of Endometrial stromal sarcomas (ESS)?
Diffusely infiltrative “worm like” growth pattern macroscopically & microscopically
333
Describe the microscopic appearance of Endometrial stromal sarcomas (ESS)?
Low grade tumour cells resemble cells of proliferating endometrial stroma, with mitoses
334
Why are products of conception sent to a pathology lab in some situations?
- Usually to confirm intrauterine pregnancy & look for placentally derived chorionic villi/implantation site
- Identify gestational trophoblastic disease: partial & complete hydatidiform moles & choriocarcinoma
335
What is gestational trophoblastic disease?
Umbrella term for several conditions including hydatidiform moles (partial & complete) & malignant tumours including choriocarcinoma
336
How to hydatidiform moles present?
Either spontaneous miscarriage or abnormalities detected on ultrasound
337
Describe how a partial mole is formed?
Fertilisation of 1 egg by 2 sperm, resulting in a triploid karyotype
338
Describe the microscopic appearance of a partial mole?
Oedematous villi & subtle trophoblast proliferation
339
What is the risk of a partial mole?
Invasive mole, which invades & destroys the uterus
340
How is a complete mole formed?
- Fertilisation of an egg with no genetic material, usually by 1 sperm which duplicates its chromosomal material
- 10% occur when an egg with no genetic material is fertilised by 2 sperm
- Diploid karyotype, usually 46 XX
341
What is the microscopic appearance of a complete mole?
Markedly enlarged oedematous villi with central cisterns & circumferential trophoblast proliferation
342
Describe the 2 risks of a complete mole?
- 10% risk of invasive mole
| - 2.5% risk of choriocarcinoma
343
Describe choriocarcinoma & how its treated?
- Frankly malignant, rapidly invasive & metastastises widely
- Treatable with chemotherapy
344
What are the 4 special characteristics of cancer cells?
1. Uncontrolled proliferation
2. Loss of original function (anaplasia)
3. Invasiveness
4. Metastasis (malignant cells)
345
What are the 3 treatments available for cancer therapy?
1. Surgical removal- only for solid tumours & non-metastasised
2. Irradiation- only if localised
3. Chemotherapy with anticancer drugs- selective toxicity required
346
Describe how normal cells become cancer cells?
- DNA change
- Multi-stage process
- Usually regulatory genes become mutated
347
What are the 2 main categories of genetic change in cancer cells?
1. Inactivation of tumour suppressor genes
| 2. Activation of proto-oncogenes to oncogenes
348
What do cancer chemotherapy drugs mainly effect?
Cell division (affect all rapidly dividing normal tissue)
349
What 3 things do anticancer drugs not reverse?
1. De-differentiation
2. Invasiveness
3. Metastasis
350
List 7 general toxic effects of anticancer drugs?
1. Bone marrow suppression
2. Loss of hair
3. Damage to GI epithelium
4. Liver, heart, kidney
5. In children, depression of growth
6. Sterility
7. Teratogenicity (damage to embryo)
351
What are 4 effects of anticancer's bone marrow suppression?
1. Anaemia
2. Immune depression
3. Prone to infection
4. Impaired wound healing
352
What are the 4 phases in the normal cell division cycle?
1. G1 phase
2. S-phase
3. G2 phase
4. Mitosis
353
What happens in the mitosis phase of the normal cell division cycle?
- Nuclear division
- Cytokinesis
- Can lead to G0 phase which is irreversible differentiation
354
What are the anticancer drugs called that are active only on dividing cells?
Cell-cycle specific drugs
355
What are the anticancer drugs called that are active on diving and resting cells?
Cell cycle-non specific
356
What cells are less sensitive to anticancer drugs?
Resting (G) phase cells
357
What 3 things does a solid tumour consist of?
1. Dividing cells: progressing through cell cycle
2. Resting cells: not dividing but could do so
3. Cells which can no longer divide but contribute to tumour size (not a problem)
358
What cells cause many relapses of cancer?
Resting cells (insensitive to many drugs)
359
What can lead to severe cumulative toxicity?
Prolonged treatment required to reduce chance of relapse from resting cells
360
List the 5 main classes of cancer chemotherapy drugs?
1. Alkylating agents
2. Antimetabolites
3. Cytotoxic antibiotics
4. Microtubule inhibitors
5. Steroid hormones & antagonists
361
Describe how Alkylating agents work (chemotherapy)?
- Form covalent bonds with DNA
- Interfere with both transcription & replication
- Most have 2 reactive groups
- Allow the drug to cross-link
362
Give 5 examples of Alkylating agents (chemotherapy)?
1. Nitrogen mustards
2. Cysplatin
3. Temozolomide
4. Lomustine
5. Busulphan
363
Give 4 examples of Nitrogen mustards (alkylating chemotherapy agents)?
1. Melphalan
2. Chlorambucil
3. Cyclophosphamide
4. Ifosfamide
364
What should you remember about Lomustine (alkylating chemotherapy agents)?
Can penetrate brain
365
What should you remember about Busulphan (alkylating chemotherapy agents)?
"Selective" effect on bone marrow
366
Describe the anticancer drug Mechlorethamine (Nitrogen mustards)?
- First anticancer chemotherapy drug
- Blister agent
- Used to treat Hodgkin’s lymphoma, non-Hodgkins lymphoma
- Highly reactive: must be given IV
367
What is phenylalanine a precursor for?
Melanin
368
Describe Melphalan (Nitrogen mustards)?
- Much more stable, less agressive
- Absorption & distribution possible without extensive alkylation
- Oral drug
369
What 3 things is Melphalan (Nitrogen mustards) used to treat?
1. Myeloma
2. Ovarian cancer
3. Breast cancer
370
Describe Cyclophosphamide (Nitrogen mustards)?
- Prodrug, with activation in the liver by phosphoramidase
| - Much less toxic
371
What protects against Cyclophosphamide (Nitrogen mustards) toxicity?
Aldehyde dehydrogenase (ALDH)
372
Where is Aldehyde dehydrogenase (ALDH) present?
- Bone marrow cells
- Hepatocytes
- Intestinal epithelium
373
What does Cisplatin (other DNA cross-linker) target?
N7 of purine nucleotides
374
What 2 things are Cisplatin (other DNA cross-linker) resistant from?
1. Nucleotide excision repair mechanisms
| 2. Efflux transporters for Copper
375
How to antimetabolites (anticancer drugs) work?
Interfere with nucleotide synthesis or DNA synthesis
376
Give 3 examples of nucleotide synthesis: antifolates (antimetabolites)?
1. Methotrexate
2. Ralitrexed
3. Pemetrexed
377
Give 5 examples of Nucleotide analogues (antimetabolites)?
1. 5-fluorouracil
2. Cytarabine (Ara-C)
3. Gemcitabine
4. Fludarabine
5. Capecitabine
378
Describe Folate antagonists: Methotrexate?
- Higher affinity for Dihydrofolate reductase than folic acid
- Inhibition of dihydrofolate formation
- Inhibition of purine/pyrimidine nucleotide synthesis
- Ultimately, halt to DNA & RNA synthesis
379
Describe Pyrimidine analogues: Fluoro-uracil?
- Prevents thymidine formation
| - Stops DNA synthesis
380
Describe Purine analogues: Mercaptopurines?
- Converted into false nucleotides
- Disrupts purine nucleotide synthesis
- Maybe incorporated into DNA, disrupting helix
381
What does the incorporation of Cytarabine (nucleotide analogue) into DNA cause?
Inhibits DNA polymerases & causes chain termination
382
What do cytotoxic antibiotics (anticancer) mainly act by?
Direct action on DNA as intercalators
383
What is Dactinomycin (cytotoxic Antibiotics) isolated from?
Streptomyces
384
Describe how Dactinomycin (cytotoxic Antibiotics) works?
- Inserts itself into the minor groove in the DNA helix
| - RNA polymerase function is disrupted
385
What is Doxorubicin (cytotoxic antibiotic) from?
Streptomyces
386
Describe how Doxorubicin (cytotoxic antibiotic) works?
- Inserts itself between base pairs
- Binds to the sugar-phosphate DNA backbone
- Local uncoiling
- Impaired DNA & RNA synthesis
387
Give an example of a microtubule inhibitor anticancer drug?
Vinca alkaloids (Vincristine)
388
Describe how Vinca alkaloids (Vincristine) works?
- Bind to microtubular protein
- Block tubulin polymerisation
- Block normal spindle formation
- Disrupt cell division
389
Give 2 examples of steroid hormones that you can use in cancer?
1. Prednisone
| 2. Prednisolone
390
Describe Prednisone?
- Synthetic adrenocortical steroid hormone
| - Converted in the body to active form
391
Describe how Prednisolone works?
Suppresses lymphocyte growth
392
Give an example of hormone antagonists that you can use in breast cancer?
Tamoxifen
393
How does Tamoxifen work?
Antagonist of oestrogen receptor
394
What else can Tamoxifen treat, other than breast cancer?
Ovulatory infertility
395
What are 2 ways of treating prostate cancer?
1. Testosterone receptor antagonist
| 2. Pituitary downregulators
396
Give 2 examples of Testosterone receptor antagonist used to treat prostate cancer?
1. Flutamide (Drogenil)
| 2. Now replaced by Bicalutamide (Casodex)
397
Give an example of Pituitary downregulators used to treat prostate cancer?
Luteinising hormone releasing hormone (LHRH) agonist (Prostap)
398
Describe how Prostap drug works for treating prostate cancer?
- Inhibit release of Luteinising Hormone (LH) which normally stimulates testes to produce testosterone
- Most prostate cancers are dependent on testosterone
399
What are the 4 common conditions of the ovaries?
1. Cysts
2. Polycystic ovaries syndrome
3. Tumors- benign & malignant
4. Torsion
400
What are the 5 common symptoms of ovarian pathology?
1. Menstrual irregularities
2. Pain
3. Hirsuitism/Metabolic syndrome (PCOS)
4. Asymptomatic
5. Bloated abdomen (ascites)
401
What are 3 ways to investigate ovarian pathology?
1. Physical examination- normal (ascites)
2. Serology- CA 125
3. Ultrasound
402
What is a Krukenberg tumour?
Malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract
403
Describe a Dermoid cyst?
Abnormal growth (teratoma) containing epidermis, hair follicles, & sebaceous glands, derived from residual embryonic cells
404
What would a ultrasound colour doppler image appear like for ovarian torsion?
- Absence of blood flow
| - Whirlpool sign
405
What are 2 common fallopian tube conditions?
1. Tubo-ovarian abscess
| 2. Ectopic pregnancy
406
List the signs & symptoms of Tubo-ovarian abscess?
- Pelvic pain
- WCC/CRP increased
- Temperature
- Discharge
407
List the signs & symptoms of ectopic pregnancy?
- Pain
- Missed period
- bHCG increased
- Circulatory collapse
408
Describe the appearance of a Tubo-ovarian abscess on transabdominal ultrasound scan?
- Bilateral complex cystic adnexal masses
- No ovary can be identified that is separate from this collection
- Air in the endometrium & endometritis
409
What are 3 common condtions of the uterus?
1. Uterine fibroids
2. Endometriosis
3. Uterine cancer
410
What are the 4 signs & symptoms of uterine fibroids?
1. Heavy periods
2. Pain
3. Pressure
4. Anaemia in woman of child bearing age
411
What are the 4 signs & symptoms of uterine endometriosis?
1. Progressively painful periods
2. Dyspareunia (pain during sex)
3. Pain with bowel movements
4. Abdominal pain
412
What are the 2 means of treatment for uterine endometriosis?
1. Hormonal therapy
| 2. Analgesia
413
How do you diagnose uterine endometriosis?
Laparoscopy (imaging not helpful in early disease)
414
What are the 2 signs & symptoms of uterine (endometrial) cancer?
1. Post menopausal bleeding/Abnormal bleeding
| 2. Pain
415
How would you diagnose cervical cancer?
Smear test (also can do ultrasound & MRI)
416
What are the 3 signs & symptoms for cervical cancer?
1. Abnormal bleeding
2. Discharge
3. Pain
417
What are the 2 common vaginal pathologies?
1. Bartholin cysts
| 2. Vaginal cancer
418
Describe an Bartholin cyst?
- Small fluid-filled sac just inside the opening of a vagina
- Soft, painless lump that doesn't usually cause problems
- Caused by a blocked secretory duct
419
What does dyskaryosis imply?
Definitely abnormal nuclei & the most likely reason for their presence is significant cervical intraepithelial neoplasia or CIN
420
What is the reason for cervical screening?
Detecting CIN (cervical intraepithelial neoplasia)
421
What is CIN?
Pre-malignant lesion which can be treated before it becomes a cancer
422
What is the cervix external os?
Opening into endocervical canal
423
What is Koilocytes in the cervix a sign of?
Viral infection (human papilloma virus) in the epithelial cells of the squamous cervical mucosa
424
Describe Herpes Simplex Virus II (HSV II) and cervical cancer?
Common genital infection but there is no definite evidence it has a significant role in cervical cancer
425
Describe Cytomegalovirus (CMV) & Human Herpes virus 8 (HHV-8) and cervical cancer?
Other members of the herpes virus family but they are not involved in cervical cancer
426
What does Human Herpes virus 8 (HHV-8) have a role in?
Kaposi’s sarcoma, usually in immunocompromised individuals
427
What is the most appropriate treatment for a cervical HPV infection & why?
- Loop excision of the transformation zone (LETZ) treats abnormal epithelium & assesses lesion by histopathology, confirms CIN & makes sure there is no invasive cancer
- Cone biopsy with scalpel is also effective & appropriate when LETZ is not available
428
What has replaced the a "Pap" smear?
Liquid based cytology (LBC)
429
Describe the appearance of normal cervical squamous cells in cervical cytology?
Abundant cytoplasm & small regular nuclei
430
What does the different cell cytoplasm colours in a cervical cytology reflect?
Differences in keratinisation & are not especially significant, the nuclear changes are more important
431
Describe the appearance of Koilocyte cells in cervical cytology?
‘Clearing’ of the cytoplasm around the nucleus of the cell & is a reliable sign of HPV infection
432
Describe the appearance of moderate dyskaryosis cells (likely CIN 2) in cervical cytology?
As well as some normal looking nuclei there are also enlarged nuclei with abnormally coarse looking chromatin
433
Describe the appearance of severe dyskaryosis cells (likely CIN 3) in cervical cytology?
- Some normal squamous cells & also scattered cells with similar dyskaryotic nuclei & much less cytoplasm (ie the nucleus-to-cytoplasm ratio is abnormally high) - Also a scattering of inflammatory cells
434
Describe the appearance of invasive squamous carcinoma in cervical cytology?
'Dirty looking’ smear reflects necrosis & inflammation
435
What is the ectocervix (up to the transformation zone) lined by?
Non-keratinising stratified squamous
436
Where would simple squamous epithelium be found?
Alveoli of lungs
437
Where would simple columnar epithelium be found?
Digestive tract
438
Where would pseudostratified columnar epithelium be found?
Bronchi
439
Where would transitional epithelium be found?
Urinary tract
440
Describe the shedding process in cervix non-keratinising stratified epithelium?
Stem cells in the basal layer divide asymmetrically to yield a cell which remains as a stem cell & a cell which will proliferate to supply the new cells which will mature as they migrate from the bottom of the epithelium to the top where the differentiated cells are finally shed
441
Where are mitoses most likely to be seen in normal cervical stratified squamous epithelium?
Proliferative zona just above the basal layer of cells
442
What is the cervical epithelium "transit amplifying" population of cells?
A population of cells which is proliferating to make enough new cells to supply the need for renewal of a tissue
443
The cervical epithelial cells _______ towards the surface?
Flatten out
444
What is the endocervix lined by?
Glandular, columnar mucosa
445
What is cervical glandular intraepithelial neoplasia like?
Squamous cervical intraepithelial neoplasia & is also a cancer precursor
446
What cervical neoplasms can both be present in the one patient simultaneously?
CIN & CGIN
447
What is the most striking abnormality in a histology of cervical intraepithelial neoplasia (CIN)?
Imbalance between the zone of proliferation, which is greatly increased, & the zone of differentiation, which is reduced
448
What are 3 histological signs of HPV infection?
1. Koilocytes
2. Dyskeratosis
3. Binucleate or multinucleate cells
449
More than ___ of the epithelium is not differentiating in CIN3?
2/3
450
What histological feature has to be apparent for a squamous carcinoma?
Invasion through the basement membrane
451
What are 3 treatment options for an established invasive squamous carcinoma?
1. Radical surgery
2. Lymph node dissection
3. Radiotherapy may have a role in some cases
452
Describe the histological appearance of a moderately differentiated invasive squamous carcinoma?
- Irregular cords & islands of abnormal squamous cells infiltrate deeply into the subjacent connective tissue of the cervix
- Associated inflammation
453
What do almost all cervical cancers have?
HPV infection (HPV 16, 18)
454
What are genital warts associated with?
HPV 6, 11
455
What are common warts associated with?
HPV 2, 7
456
Describe the histological appearance of a polypoid lesion on the cervix external os?
Normal-looking endocervical glandular epithelium covering, fibromuscular & vascular connective tissue core
457
Describe the prognosis of a polypoid lesion?
Cause is not understood but is not neoplastic & it has no malignant potential
458
Describe the appearance of uterine fibroids (leiomyomas)?
- Several firm, well-defined masses
| - Cut section of these was paler than the surrounding myometrium & had a whorled, 'watered silk' appearance
459
Uterine fibroids (leiomyomas) are usually ____?
Benign
460
What abnormality is present in 40% of leiomyomas?
Clonal cytogenetic abnormalities (ie. Trisomy 12)
461
What are the 3 uses of an MDT?
1. Discuss the diagnosis in all patients who have had a biopsy
2. Make a treatment plan
3. To dicuss scan & possible metastatic cases
462
List the 6 people who are at the MDT?
1. Surgeons
2. Pathologist
3. Medical Oncologist
4. Clinical Oncologist
5. Breast care nurses
6. Audit facilitator
463
What are the 2 first treatments for breast cancer?
1. Surgery (85%): Breast & Axilla
| 2. Neo-adjuvant treatment (15%)
464
List 4 examples of Neo-adjuvant treatment?
1. Radiotherapy
2. Chemotherapy
3. Endocrine
4. HER2 target (Herceptin)
465
What are the 3 local surgical treatments for breast cancer?
1. Breast conserving surgery (75%)
2. Mastectomy (25%)- standard or skin sparing with reconstruction
3. Axillary surgery
466
What are the 6 indications for mastectomy?
1. 1+ tumour in breast
2. Diffuse DCIS
3. Large tumour & small breast
4. Failed breast conserving surgery
5. Recurrent breast cancer after previous surgery & radiotherapy
6. Radiotherapy contraindicated e.g. pregnancy
467
What are the 5 breast cancer post op things we should consider?
1. Is Surgery Complete?
2. Is Radiotherapy Needed?
3. Which Adjuvant therapy?
4. Prognostic Predictor Indices? (Nottingham prognostic index)
5. Clinical Trials?
