Disease of Reproductive System - Part 1 Flashcards
1
Q
What do the majority of the malignancies in the breast arise from
A
Epithelial cells
Hence they are carcinomas
2
Q
Do malignant tumours from connective tissue in the breast regularly?
A
No relatively rare
They are called sarcomas
3
Q
What is a VIN
A
Vulval intraepithelial neoplasm
4
Q
What is a CIN
A
Cervican intraepithelial neoplasm
5
Q
What is CGIN
A
Cervical glandular intraepithelial neoplasm
6
Q
What is a VaIN
A
Vaginal intraepithelial neoplasm
7
Q
What is a AIN
A
Anal intraepithelial neoplasm
8
Q
What are all the IN related to
A
HPV hence they often occur together
9
Q
What is dysplasis
A
The earliest morphological manifestation of neoplasia
It is in situ/non-incasive
If left significant change of progressing to invasive
10
Q
What are features of malignant cells
A
Nuclear pleomorphism
Mitoses not in the basal layer (where they usually are)
11
Q
How many early and late genes are there in HPV
A
7 early
2 late
12
Q
What are the low risk HPV types
A
6, 11
13
Q
What are the high risk oncogenic HPV types
A
16, 18
14
Q
What type of DNA is in HPV
A
Double stranded DNA
15
Q
What % of cancers have HPV/DNA
A
99.7%
But the vast majority of HPV infections resolve themselves
16
Q
What do the low risk HPV viruses cause
A
Lower genital warts
Condylomas = benign, squamous neoplasia
Low grade IN
17
Q
What is a condyloma
A
benign, squamous metaplasia
18
Q
What do the high risk HPV viruses causes
A
high grade IN’s, invasive carcinomas
19
Q
What does the cervavarix vaccine protect against
A
16, 18
20
Q
What does the gardasil virus protect agains
A
6, 11, 16, 18
21
Q
Who is vaccinated against HPV
A
12/13 - catch up till 18
22
Q
How does HPV cause cancer
A
Early genes expressed at infection onset - control viral replication
Late genes code for cashed proteins
High risk HPV integrates itself into the host chromosome
Upregulate E6, and E7
23
Q
What does E6 do
A
Binds to and inactivates p53
p53 is the fate keeper of the genome - mediates apoptosis in response to DNA damage
24
Q
What does E7 do
A
Binds to the RB1 gene product
RB1 is a tumour suppressor gene that arrests cells in the G1/S phase
25
What are the 2 forms of VIN
1) Classical
| 2) differentiated
26
Describe Classical VIN
Warty/baseloid
Related to HPV
Generally younger people
Graded VIN 1-3
27
Describe differentiated VIN
Not graded
not HPV related
Generally older people
OCCURS IN PEOPLE WITH CHRONIC DERMATSOSES especially lichen sclerosus
28
What is lichen sclerosus
Not curable
Affects vulva/penis
Can lead onto VIN
29
What makes progression in VIN more likely
Immunocomprised, post menopausal
| Often get spontaneous regression in younger and post partum
30
What is the most common vulval cancer
Squamous cell carcinoma
| Associated with VIN and inflammatory dermatoses (non HPV)
31
What is squamous cell vulval carcinoma
Erodes plaque or ulcer
Spreads locally to include vagina and distal urethra
Spreads to ipsilateral inguinal lymph nodes ,then contralateral, then depp iliofemoral
32
Treatment of squamous cell vulval carcinoma with less than 1mm invasion
Wide excision, rarely will metastasis
33
Risk of metastasis of squamous cell vulval carcinomas
1-3mm invasion - 10%
| Over 4mm = 40%
34
What age do malignant melanoma affcts
50-60 years old (5% of all vulval cancers)
35
Describe malignant melanomas
Local recurrent in 1/3, frequently spreads to the urethra
Lymph and haematogenous spread
Depth of invasion correlates with lymph node involvement
commonly pigmented but some aren't
Not sunlight related at all!
36
Who does Paget's disease usually affect
over 80
37
What type of cancer is page's disease
In situ adenocarcinoma of squamous mucosa
38
What happens in Paget's disease
Adenocarcinoma but usually no underlying tumours
| Can develop invasive adenocarcinoma - same prognosis as squamous cell vulval carcinoma
39
What other tumours can cause paget's
Bladder, cervix, primary rectal
40
What epithelium is the vagina
stratified squamous
41
what epithelium is the cervix
simple columnar
42
What is the acquired transformational zone
Physiological area of metaplasia in the vagina
Where squamous cell metaplasia has occurred
it is susceptible to HPV infection
43
What happens to the cervix in menopause
Decreased oestrogen
SCJ moves back up the cervix - but no metaplasia occurs
Difficult to swab here hence difficult to diagnose cancers post menopausal
44
What is CIN
The pre-invasive stage of squamous cell carcinoma - detect in the cervical screening programme
45
How do we treat grade I CIN
No treatment just observe as high rates of regression but low rates of regression
46
How do we treat grade II and III CIN
Treat these with cancer treatment etc.
47
Who do we test in the cervical screening programme
First call at age 25, every 3 years till 50, then every 5 years until 65
48
Why don't we screen under 25's in the cervical screening programme
High carriers of HPV - 70-80% will be eliminated
Relative changes due to normal reactions in young people produce confusing cytology
Unnecessary LLETZ can cause obstetric ocmplications
49
What is LLETS
Large loop excision of the transmission zone - to get rid of CIN
50
What do we do if the cervical screening test shows low grade change
HPV test
51
When do we do a colposcopy
If high grade cervical change or positive HPV test
52
What are the risk factors for cervical squamous cell carcinoma
HPV (most important)
Multiple sexual partners, male with multiple sexual partners, young age at first intercourse, high parity, low socioeconomic group, smoking (DNA adducts), immunosuppression
53
How do we treat cervical adenocarcinoma
CIN/SCC
54
Why is the stage for stage prognosis of cervical adenocarcinoma worse than cervical squamous cell carcinoma
Due to radioresistance
55
Where do cervical carcinomas metastasise too
Pelvic and para-aortic lymph nodes
| Via blood to lungs/bones
56
How do we stage cervical carcinomas
Use FIGO staging
57
What is endometriosis
Spread of the endometrium into the pelvis
58
What are the theories explaining endometriosis
Regurgitation theory
Metaplasia theory
Stem cell theory
Metastasis theory - lymphatic spread
59
How does endometriosis cause disease
Bleeding into tissues causing fibrosis
60
History of endometriosis
25% asymptomatic
Dysmennorhoea, dysparenunia, pelvic pain, subfertility
Late symptoms are pain on passing stool and dysuria
61
What investigations do you do for endometriosis
Laproscopy
62
Treatment of endometriossi
COCP, GnRH Agonists/antagonists, progesterone agents
| Surgical - ablation or TAH-BSO depending on wish to remain fertile
63
What is endometriosis linked to
Ectopic pregnancy, ovarian cancer, IBD
64
What is endometriris
Inflammation of the endometrium
65
What causes acute endometritis
Retained POC/placenta, prolonged ROM, complicated labour
66
What do we see in acute endometritis
Neutrophils
67
What causes chronic endometritis
PID, retained gestational tissues, endometrial TB, IUCD infection
68
What do we see in chronic endometritis
Lymphocyes/plasma cells
69
History of endometriris
Abdominal pain, pyrexia, discharge, dysuria, abdnormal vaginal bleeding
70
Investigations of endometritis
biochemistry/microbiology, USS
71
Treatment of endometritis
Analgesia to remove cause
72
What are endometrial polyps
Sessile/polypod oestrogen dependent uterine overgrowths
73
History of endometrial polyps
```
Often asymptomatic
Intermenstrual bleeding
Post menopausal bleeding
Menorrhagia
Dysmenorrhagia
```
74
Treatment of endometrial polyps
Expectant
Progesterone
GnRH agents
Surgical Cutterage
75
What % of endometrial polyps are malignant
Less than 1%
76
What investigations do we do of endometrial polyps
USS, hysteroscopy
77
What is a leimyomata
Benign myometrial tumours with oestrogen/progesterone dependent growth
78
Risk factors for leimyomata
Genetics, nullparity, obestiy, PCOS, HTN
79
Symptoms of leimyomata
Asymptomatic
Menometorrhagia (become iron deficient)
Sub-fertility/pregnancy problems
Pressure sx
80
Investigations of leimyomata
Bimanual examination
| USS
81
Treatment of leimyomata
NSAIDS, IUS, OCP/Fe2+
Or
Artery embolization, ablation, TAH
82
What is endometrial hyperplasia
Excessive endometrial proliferation
| High oestrogen but low progesterone
83
Types of endometrial hyperplasia
Atypical (unto 48% are carcinomas) or non-atypical (1-3% progress to carcinomas)
84
History of endometrial hyperplasia
Abnormal bleeding (IMB, PCB, PMB)
85
Investigations of endometrial hyperplasia
USS, hysteroscopy +/- biopsy
86
Treatment of endometrial hyperplasia
IUS, progesterone, surgical (TAH
87
How does malignant hyperplasia progress
Normal
Non-atypical hyperplasi
Atypical hyperplasia
Endometrial carcinoma
88
What do we see in atypical hyperplasia
Complex patterns of proliferating glands with nuclear atypia
89
What do we see in non-atypical hyperplasia
Whole overgrowth of the endometrium with simple tubular gland
Dilated and high gland to storm ratio
90
What is the most common cancer of the female genital trct
Endometrial carcinoma
91
History of endometrial carcinoma
PMB/IMB, pain if late
92
investigation of endometrial carcinoma
USS, biopsy, hyterescopy
93
Staging of endometrial carcinoma
FIGO (1-4)
94
Treatment of endometrial carcinoma
Progesterone
Surgery (TAH-BSO)
Adjuvant therapy (chemo/radio)
95
Prognosis of different stages of endometrial carcinoma
Stage 1 - 90%
| Stage 2 -3 :
96
What are the 2 types of endometrial carcinoma
Type 1 - endometrial
| Type 2 - serous
97
What % of cases are type 1 and type 2 endometrial carcinoma
Type 1 - 75%
| Type 2 - 25%
98
Age of type 1 endometrial carcinoma
Pre/peri menopausal
99
Age of type 2 endometrial carcinoma
Post menopausal
100
Pre-existing state of type 1 endometrial carcinoma
Endometrial hyperplasia
101
Pre-existing state of type 2 endometrial carcinoma
Ednometrial atrophy
102
Mutation in type 1 endometrial carcinoma
Kras, PTEN
103
Mutation in type 2 endometrial carcinoma
p53
104
Oestrogen status of type 1 endometrial carcinoma
Oestrogen +ve
105
Oestrogen status of type 2 endometrial carcinoma
Oestrogen -ve
106
Grades of type 1 endometrial carcinoma
1-3
107
Grades of type 2 endometrial carcinoma
3
108
What is polycystic ovary syndrome
A complex endocrine disorder
109
What is the rotterdam criteria
A set of 3 symptoms, of which you must have 2 to have polycystic ovary disease
110
What are the 3 rotterdam criteria
```
Polycystic ovaries (20% f women have this)
Hyperanddrogenism (hirsuitism/biochemical)
Menstrual abnormalities (cycles over 35 days)
```
111
Investigations of polycystic ovary disease
USS, bioschemical screen
112
Biochemical results of polycystic ovary disease
Low FSH
| High LH, testosterone, DHEAS
113
Treatment of polycystic ovary disease
Weight loss
Metformin, OCP, clomiphene
Ovarian drilling surgery
114
Links of polycystic ovary disease
Infertility, endometrial hyperpalsia, adenocarcinoma
115
What is primary gonadal failure
Hypertrophic hypogonadism
| High LH and FSH to try and stimulate the gonads
116
Congenital causes of primary gonadal failure
45XO
| 47XXY
117
Acquired causes of primary gonadal failure
Infection
Surgery
Chemo/radiotherapy
Toxins/drugs
118
What is secondary gonadal failure
Hypotrophic hypogonadism
119
Causes of secondary gonadal failure
Sheehans syndrome, pituitary tumour, brain injury, empty sella syndrome, PCOS
120
Presentation of gonadal failure
Amenorrhea/absent menarche
Delayed puberty
Decreased sex hormones
Increased LH/FSH in primary
121
Investigation of gonadal failure
Hormonal and karyotyping
122
What are the 3 origins of ovarian neoplasms
Surface epithelium
Germ cell tumours
Sex cord stromal stumours
123
What are the 3 types of surface epithelium ovarian tumours
Serous (tubular)
Mucinous (endocervical)
Endometrial (endometrial)
Each type can be benign or malignant
124
Name th benign tumours of surface epithelium ovarian neoplasm
Cystic - cystadenoma
Fibrous - adenofibroma
Cystic and fibrous - cystadenofibroma
125
Name the malignant tumour of surface epithelium neoplasia
Cystadenocarcinoma
126
What % of ovarian tumours are surface epithelium tumours
90%
127
What % of ovarian tumours are germ cell tumours
15-20%
128
What are the two types of germ cell tumours
Germinatous or non-germinatous
129
Name the type of germinatous germ cell tumours of the ovary
Dysgerminosa - differentiate towards again
Malignant
Respond to chemo
130
Do dysgerminosas respond to chemo
Yes
131
Name the type of non-germinatous germ cell tumours of the ovary
Teratomas
Yolk Sac
Choriocarcinomas
132
What do teratomas differentiate towards
Differentiated towards multiple germ layers
133
What do yolk sac tumours differentaite towards
The extramembryonic yolk sac
134
What do choriocarcinomas differentiate towards
Placenta
135
Describe mature teratomas
Benign, dermatoid cysts
| Only 1% malignant
136
Describe immature teratomas
Malignant
| Often contain immature fetal/embryonic tissue
137
Are yolk sac tumours responsive to chemo
Yes
138
Are choriocarcinomas responsive to chemo
No
139
Are choriocarcinomas malignant
Yes
140
Treatment of germ cell tumours of the ovary
Surgery +/- chemo if they are malignant
141
Where do sex cord stromal tumours arise from
They are rare but arise from ovarian stroma which was derived from the sex cord of an embryonic gonad
142
What are the types of sex cord stromal tumours
Thecomas/fibromas/fibrothecomas
Granulosa cell tumours
Sertoli/Leydig Cell tumours
143
What do thermos and fibrothecomas produces
Oestrogen and also rarely androgens
144
What do fibromas produce
Nothing they are hormonally inactive
145
What are thecomas/fibrothecomas/fibromas comprised of?
Comprised of spindle cells with lipid droplets - thecoma appearance
146
What is Meig's syndrome
Ovarian tumour (thecoma/fibroma) with RS hydrothorax and ascites
147
What are granulosa cell tumours
Sex cord stromal cell tumours
They are low grade malignant
Produce oestrogen
148
What do granulosa cells do
Convert testosterone to oestrogen (thecoma cells also help)
149
What do setoli/leydig cells do
Produce androgen
150
What happens in sertoli/leydig cell tumours
Produce androgens and 10-25% of them are malignant
151
What increases your risk of ovarian cancer
FH, Elderly, PMH Breast cancer, oestrogen only HRT, Lynch II syndrome
Weak - obestiy and nullparity
152
What is protective from ovarian cancer
OCP, breast feeding, hysterectomy
153
History of ovarian cancers
```
Non-specific symptoms (difficult to diagnose)
Pain
Bloating
Weight Loss
PV bleeding
Urinary frequenct
Anorexia
```
154
What is the staging for ovarian tumours
FIGO
155
Treamtnet for ovarian tumours
Stage 1 - TAH/BSO
Amenectomy, appendectomy, lymphadenectomy and adjuvant chemom
Chemo in sensitive germ cell tumours
156
Prognosis of ovarian tumours
5 years survival - 43%
157
What are the metastatic mullerian tumours of ovarian cancer (most common)
Uterus
Fallopian tubes
Pelvic peritoneum
Contralateral ovary
158
What are the metastatic extra mullerian metastatic tumours of ovarian cancer
Haematogenous and lymphatic spread to:
GI Tract: large bowel, stomach (called Krukenburg Syndrome), pancreatobilliary
Breast, melanoma (kidneys and lungs less common)
159
Direct extension of ovarian tumours to where
Bladder and rectal
160
Prognosis of ovarian metastatic tumours
generally poor prognosis
161
Where do the majority of breast malignancies arise from
Epithelial cells hence carcinomas
| Sarcomas are relatively rare
162
What type of tissue to tumours have more of
Fibrous tissue - makes them hard and lumpy/radioopaque so we can see them more
Fat is soft and translucent
163
What are the main priniciple ingredients of breast tissue
Fat
Fibrous tissue
Epithelial cells
164
What diffference in structure is there in younger breasts
Have more fibrous tissue
| More opaque and lumpy therefore more difficult to find tumorus
165
What increaeses the risk of breast cancer
```
Alcohol
Oestrogen containing pills
Body fatness
Height
Digoxin
Shiftwork - it disrupts the circadian rhythm
Smoking
```
166
What is protective against breast cancer
Breastfeeding
| Physical activity
167
When do you get invited to the breast screening programm
Every 3 years once you are 50
| Some areas extended it from 47 to 73
168
How can breast cancer present
```
Lumps
Puckered skin/indrawn nipple
Pain (rare)
Inflammation
Nipple discharge
Abnormal/sore nipple
Radiologically
```
169
What is the triple assessment of breast abnormatlities
Clinical - examination/palpation
Radiological
Pathological - cytology or hystopathoogy
Discuss results in MDT meeting
170
What do we look for in radiology of breast abnormalities
Calcifications
171
What is fibrocystic change
Almost physiological group of changes
Ductal hyperplasia, apocrine metaplasia and cysts
Can mimic cancer clinically and pathologically
May present as a lump and associated with micro calcifications - hard for histopathologists to identify
172
Is fibrocystic change linked to breast cancer
Unlikely to be a precursor
| BUT some statistical link to breast cancer - probably as both are associated with high levels of oestrogen
173
What is a fibroadenoma
Common/mobile lumps - BENIGN
| Biosy them - if fine leave them alone
174
What are fibroadomas aka Fibroepithelial neoplasma
Coordinated growth of glandular and connective (stromal) tissue
175
What are phyllodes tumours
Rare fibroepithelial neoplasms - form a spectrum of lesions
One end of spectrum - looks like firoadomas
Other end of spectrum - may show overgrowth of stromal element - sarcomas so may recur
176
Can benign tumours be moved about
Yes as they do not invade - may have sharp edges
177
What colour does cancer appear
White
178
Why do we get puckered skin/indrawn nipples
Due to fibrous tissue with fibroblasts in
| Fibroblasts contract
179
What is Peau D'orange
a pitted or dimpled appearance of the skin, especially as characteristic of some cases of breast cancer or due to cellulite.
It is an inflammatory carcinoma blocking the lymphatic capillaries causing oedema
180
Causes of inflammation/infection in the breast
Mastitis during breast feeding
Breast abscesses and fistulae
TB
Carcinoma/sarcoma
181
Causes of nipple duct discharge
Duct ectasia (dilation/distension)
Intraductal papilloma
In situ papillary carcinoma
INtracystic papillary carcinoma
182
What is Paget's disease of the nipple
Ductal carcinoma in situ
| Due to cancer cells growing up through ducts and colonising the skin - looks red
183
Describe pain in best
Can be cyclical and difficult to treat
| Not a common presentation of breast cancer
184
Why do calcium crystals form in cancer
Necrosis in centre of tumour
| Causes influx of calcium and formation of calcium crystals (but other benign causes also are linked to cancer)
185
What should pathology reports of malignancy tell you
1) in situ/invasive
2) type
3) Grade
4) Vascular Invasion - stage related
5) relationship to margins - close margins and lymph node involvement affect treatment
6) Nodal status
7) Size
8) ER, PR and HER2 status
186
What type of carcinomas produce mucin
Mucinous carcinomas
187
What do lobular carcinomas look like
Indian files of cancer cells
188
What are the most common type of cancer
Ductal - 75%
Lobular - 12%
Tubular/cribiform - 3%
189
What is stage
how far a tumour has progressed
190
What is grade
How fast a tumour is progressing
191
What are two key stage indicators
Nodal status and size
192
If a tumour is oestrogen positive what does this mean
Can respond to oestrogen targeting agents
193
Why is HER2 status important
Overexpression of HER2 on the membrane means they are likely to respond to Herceptin
