Lecture 23- Reproductive tract tumours Flashcards
1
Q
Tumour-
A
any clinically detectable lump or swellingTumour- any clinically detectable lump or swelling
2
Q
Neoplasm –
A
an abnormal growth of cells that persists after the initial stimulus is removed
3
Q
Malignant neoplasm-
A
an abnormal growth of cells that persists after the initial stimulus is removed and invades surround tissue with potential to spread to distant sites
4
Q
Metastasis-
A
malignant neoplasm that has spread to a distant site
5
Q
Dysplasia-
A
a potentially pre- neoplastic alteration which cells show disordered organisation and abnormal appearances. May be reversible
6
Q
Metaplasia-
A
conversion in cell type
7
Q
features of vulval tumours
A
- External vagina
- Rare – 3% of female cancers
- Older people (peak onset 80-84)
- Skin cancer
8
Q
vulval cancer is most commonly
A
squamous cell carcinoma (skin cancer)
- Can also see basal cell carcinoma or malignant melanoma less commonly
- Rarely see soft tissue tumours
- From fat cells, blood vessels and nerves
9
Q
Precursor to vulval squamous cell carcinoma =
A
Vulval intraepithelial neoplasia (VIN)
10
Q
Vulval intraepithelial neoplasia (VIN)
A
- In Situ precursor of vulval squamous cell carcinoma
- In situ= atypical cells which doesn’t invade basement membrane
- May or may not progress to SCC
11
Q
presentation of vulval tumours
A
- Lumps, bumps, ulceration, skin changes (pigmentation, sensation, pain)
- May be delayed presentation (due to it being in older patients and also due to the intimate nature of the cancer)
12
Q
are VIN and Vulval SCC related to HPV?
A
30% of cases are/ 70% are not
- usually HPV 16
- mostly in pre-menopasual women
13
Q
Vin and vulval SCC are usually asscoiated with
A
longstanding inflammtory conditions
- Lichen sclerosus
- Squamous hyperplasia
14
Q
what are the layer sof skin from outr to inner
A
epidermis
dermis
subcutaenous
15
Q
Squamous cell carcinoma histology
A
- Loss of architecture
- Cannot distinguish between dermis and epidermis
- Atypical squamous cells
- Keratin formation by squamous cells
16
Q
How does vulval cancer spread? Locally
A
-
Direct extension
- Anus
- Vagina
- Bladder
-
Lymph nodes
- Inguinal (predominantly)
- Iliac
- Para-aortic
-
Distant metastases via blood vessels
- Lungs
- Liver
17
Q
Vulval cancer histology
A
- Normal tissue laterally and medially
- Cancer in the middle
- Architecture completely loss- no distinction between dermis and epidermis
- Cell look very abnormal
- Formation of keratin (pink)
18
Q
Vulval intraepithelial neoplasia (VIN) histology
A
- Cells look abnormal- no maturation
- Pleiomorphic
- Large nuclei (immature)
- irregular nuclear outline
- No breaking though basement membrane (IN SITU)
- May develop into SCC
19
Q
Vulval cancer treatment
A
- Definitive surgery would include removing the primary tumour and nodes, with a higher survival rate in smaller lesions.
- Excision affects cure
20
Q
before the onset of menstruation the cervix is divisible into 2 parts
A
the ectocervix
endocervix
21
Q
ectocervix
A
- communicates with vagina (low pH)
- Stratified squamous
22
Q
endocervix
A
- not in contact with vagina
- Simple columnar (doesn’t need protecting from acidic vagina)
23
Q
At menstruation, oestrogen causes an anatomical change in the cervix-
A
eversion of the cervix
24
Q
eversion of the cervix
A
- Simple columnar epithelium of the endocervix is now exposed to acidic environment of the vagina –> not v appropriate to cope with acidic environment
- Inflammation
25
overtime (e.g. women in her 30s) what will happen to the columnar cells of the endocervix
) these columnar cells will undergo metaplasia and become squamous cells, which are better adapted to cope with acidic environment – transformation zone
26
transitional zone of the cervix
risk of dysplasia - cells undergoing metaplasia are at
27
risk factors for cervical cancer
* Sexual partners with HPV
* Multiple partners
* Early age of first intercourse
* Early first pregnancy
* Multiple births
* Smoking
* Low socio-economic status
* immunosuppression
28
**Human Papilloma Virus**
* DNA virus
* Sexually transmitted
* High risk subtypes cause cancer
29
high risk subtypes of HPV
HPV 16 and 18
30
HPV and cervical cancer MOA
* In the cervix they infect the transformation zone
* Produces viral proteins (E6 and E7)
* Inactivates tumour suppressor genes (E6- p53 and E7- Rb)
* Uncontrolled cellular proliferation (hallmark of cancer)
31
percursor condition of cervical cancer
cervical intraepithelial neoplasia (CIN)
32
cervical intraepithelial neoplasia (CIN)
* Dysplasia
* Confined to cervical epithelium (in situ- doesn’t breach basement membrane )
* Caused by HPV infection (95%)
33
CIN can be divided into
CIN 1/2/3 --\> SCC
* Defined by the thickness of the cervical epithelium
* **If CIN breaches basement membrane – invasive squamous cell carcinoma**
34
**CIN histology**
* Abnormal cells
* Loss of maturation
* Pleomorphic
* Irregular nuclear membrane
* Clumps of chromatin within nucleus
* Abnormal mitosis
* Full thickness abnormality – CIN3 (hasn’t broken. Through basement membrane
35
**Treatment of CIN**
* **CIN1**
* Often regresses spontaneously
* Follow up cervical smear in 1 year
* **CIN 2 and**
* Needs treatment
* Colposcopy
* **Large loop excision of transformation zone (LLETZ)**
36
prevention of cervical cancer
- screening
- vaccination
37
**Cervical cancer screening programme**
* aged 25-49= eveyr 3 years
* age 50-64= every 5 years
* over 65 only if recent abnormality
brush used to scrape cells from transformation zone- tested for HPV
if positive= cells looked at under microscope
38
what is the HPV vaccine called and which subtypes does it cover
Gardasil
* Recombinant vaccination
* HPV subtypes 6/11/16/18
39
who receives the HPV vaccine
girls ages 12-13
- now being given to boys (oral and anul cancer)
- homosexual sex
- protect girls
40
gardasil protects from
* from cervical, vulval, oral and anal cancers
* lasts 10 years
41
**Invasive cervical cancer**
* Squamous cell carcinoma
* Adenocarcinoma
* Less common/ arises from endocervical glandular cells
42
presentation of cervical cancer
**Presentation**
* Bleeding
* Post coital
* Inter menstrual
* Post menopausal
* Mass
* Screening
43
**Cytology: squamous cell carcinoma**
* Large nuclei
* Pleiomorphism
* Irregular nuclear outlines
Less commonly endocarcinomas
44
spread pf cervical carcinoma
45
stage 0 cervical cancer
carcinoma in situ
100% survival
46
stage 1 cervical cancer
confided to cervix
85% 5 year survival
(most people at this stage at presentation 47%)
47
stage 2 cervical cancer
disease beyond cervix but not pelvic wall or lower 1/3 of vagina
65% survival
48
stage 3 cervical cancer
disease to pelvic wall or lower1/3 of vagina
36% 5 year survival
49
stage 4 cervical cancer
invades bladder, rectum or metastasis
7% survival
50
**Treatment of invasive cervical cancer**
* **If advanced:**
* Hysterectomy
* Lymph node dissection
* Chemoradiotherapy +-
51
**Endometrium is composed of**
* Glands- adenocarcinoma
* Stroma – supporting cells
52
Endometrial hyperplasia
* Increased gland: stroma ratio
* Thickened endometrium \>7mm (biopsy taken)
* Can be precursor to invasive endometrial cancer
53
**Presentation of endometrial hyperplasia**:
intermenstrual/ postmenopausal bleeding
54
cause of endometrial cancer
excessive oestrogen
55
endogenous cause of excessive oestrogen
* Obesity
* Fat cells convert androgens --\> oestrogen
* Early menarche/late menopause
* Increased lifetime amount of oestrogen
* Oestrogen secreting tumours
56
Exogenous cause of excessive oestrogen
* Unopposed oestrogen hormone replacement therapy (manage symptoms of menopause)
* Tamoxifen
57
Tamoxifen
* Drug used to treat oestrogen receptor positive breast cancer (blocking oestrogen receptors)
* Stimulates oestrogen receptors in the endometrium
58
excessive oestrogen caused by irregular cycle
PCOS
59
**Invasive endometrial cancer**
* Most common gynaecological tract cancer
* Typically presents between 60/70
* Most commonly **adenocarcinoma**
60
presentation of invasive endometrial cancer
* **Bleeding**
* Post menopausal
* Intermenstrual
* **Mass (palpable if progressed)**
61
types of invasive endometrial cancer
* Endometroid adenocarcinoma
* Serous adenocarcinoma
62
endometrioid adenocarcinoma features and histology
* Most common
* Resembles normal endometrial glands
* Commonly arises from hyperplasia
* Grow back-to-back into each other- cells look atypical
* Pleiomorphic
* Irregular nuclear membranes
* Hyperchromatic
63
spread of endometrioid adenocacrinoma
direct invasion
* Spreads to the cervix, bladder and rectum, through the peritoneal cavity and to regional lymph nodes
64
serous adenoacrinoma features and histology
* Less common
* More aggressive- worse prognosis
* Poorly differentiated endometrial gland
* Big nuclei
* Hyperchromatic
* Irregular outlines
* psammona bodies
65
psammona bodies
serous adenocarcinoma feature- assoicates with collections of calcium
66
serous adenocarcinoma spread
**exfoliates**
* Cells break off from main tumour
* Travels through fallopian tubes
* Deposits on peritoneal surface (transcoelomic spread- across serous cavities e.g. peritoneum)
67
normal endometrium histology
* Glands are spaced out
* Not too tightly packed
68
**Endometrial cancer**
* Glands growing into one another
* Too tightly packed
* Cells of glands look atypical
* Pleiomorphic
* Irregular nuclear outline
* Hyperchromatic
69
**another Serous adenocarcinoma histology**
*
* Projections of tissues- papillae--. LINED BY ABNORMAL CELLS
* Pleiomorphic
* Nuclear look abnormal
* Cells breaking off- can spread- exfoliate
70
**Management of endometrial cancer**
* Hysterotomy- removal of cervix and uterus
* Bilateral salpingo-oophorectomy- removal of fallopian tubes and ovaries
* +- lymph node dissection
* +- chemo radiotherapy
71
myometrial tumours can be
benign or malignant
72
benign tumour of myometirum
fibroids
73
fibroids are more medically known as
leiomyoma
74
Fibroid(leiomyoma) features
* Most common tumour of myometrium
* Benign tumour of connective tissue
* Pale homogenous, well circumscribed mass
* Their growth is oestrogen dependent and usually regress after the menopause
75
**Presentation of leiomyoma depends on size**
*
* Asymptomatic
* Pelvic pain
* Heavy periods
* Infertility
* Urinary frequency (bladder compression)
* Multiple leiomyomas can cause massive uterine enlargement and results in pressure symptoms of the pelvis
76
fibroid histology
* Made up of smooth muscle cells
* Arranged in fascicles which intersect in a 3 dimensional nature
77
**Leiomyosarcoma** features
* Malignant tumour of smooth muscle
* **Atypical cells**
* Pleiomorphic cells
* Irregular nuclear
* Doesn’t arise from leiomyoma
* Metastasis to lungs and then systemically
* Similar symptoms to fibroids
78
types of cells within the ovary and associated tumours
* Lined by epithelium
* **Epithelial tumours**
* Contains germ cells
* **Germ cell tumours**
* Contains stromal cells
* **Sex cord stromal tumours**
79
the ovaries are a good site for
80
**Ovarian cancer presentation**
*
* Early symptoms
* Vague and non-specific
* Delayed diagnosis
* Later symptoms (mass effect)
* Abdominal pain
* Abdominal distension
* Urinary symptoms
* GI symptoms
* Hormonal disturbances
81
**Risk factors for ovarian cancer**
* Number of pregnancy
* COCP
* Family history
* BRCA 1/ 2
* Tumour suppressor genes
* Associated with high grade serous cancers
* Prophylactic salpingo-oophrectomy
82
BRCA 1/2
* Tumour suppressor genes
* Associated with high grade serous cancers
* Prophylactic salpingo-oophrectomy
83
**Serum marker for ovarian cancer**
*
* Ca-125
* Diagnosis
* Monitoring recurrence
84
ovarian epitheilal tumours
* Most common ovary cancers- often present as cystic masses
85
histological subtypes of obvarian epitheilial tumours
* **Serous adenocarcinoma**
* **Mucinous adenocarcinoma**
* **Endometroid adenocarcinoma**
86
ovarian epitheil tumours can be further divided based on being
* Benign (top photo)
* Borderline- increased atypia, no stromal invasion
* Malignant (bottom photo- complex architecture)
87
Ovarian serous adenocarcinoma histology
* Highly atypical cells
* Often shows Psammoma bodies (calcium collections)
* Spreads to the peritoneum due to exfoliation of cells
* Common first presentation of serous andeocarcinoma- can constrict the intestine
88
89
**Ovarian mucinous adenocarcinoma**
* Atypical epithelial cells
* Look like goblet cells- produce mucin (push nuclei to the side of the cell)
90
**Ovarian endometrioid adenocarcinoma**
* Glands resembling endometrium
* May arise in endometriosis
* May have synchronous endometrial endometrioid adenocarcinoma
* **In both the endometrium and the ovary**
91
germ cell tumours
dysgerminoma
yolk sac
embryonal carcinoma
choriocarcinoma
teratoma
92
most common type of germ cell tumour
teratoma
93
teratoma subtypes
* Three subtypes
* **Mature** (benign)- the scarier it looks
* **Immature** (malignant)
* E.g. primitive neuroepithelium
* Risk for intra-abdominal spread
* **Monodermal** (highly specialised)
94
mature teratoma
benign
* Contain fully mature, differentiated tissue from all 3 germ cell layers
* GI tissue
* smooth muscle
* hair shafts and keratin
* cartilage
* Can be bilateral
* Often contains skin and hair structures
95
**Sex cord stromal tumours of the ovary**
**testes**
- sertoli cells
- leydig cells
**ovaries**
- granulosa cells
- theca cells
96
sex cord stromal tumour- can sertoli and leydig cells tumours occur in women
Tumours resemble all the above cell types can arise in the ovary (e.g. you can get Sertoli or Leydig cells in the ovary)
These are derived from the ovarian stroma, which in turn is derived from the sex cords of the embryonic gonad.
97
**Theca and granulosa cell tumours**
* Produce oestrogen
* Symptoms depend on age of development
* Patient pre-puberty = Precocious puberty
* Patient post puberty
* Breast cancer
* Endometrial hyperplasia
* Endometrial carcinoma
98
**Sertoli-Leydig tumours**
* Produce testosterone
* Rare
* Symptoms depend on age
* Pre-puberty
* Prevents normal female pubertal changes
* Post puberty
* Infertility
* Amenorrhoea
* Hirsutism
* Male pattern baldness
* Breast atrophy
99
metastases to the ovary
* breast cancer
* GI cancers
* Krukenberg tumour
* other gynae tumours (endometrial, other ovary, fallopian tube)
100
krueknberg tumour
metastatic GI tumour
- ofte gastric
- signet cells
101
. Most common origin of ovary metastases
they are from tumours derived from Müllerian epithelium, i.e., from the uterus, Fallopian tubes, contralateral ovary or pelvic peritoneum.
102
**Testicular cancer is the most**
Most common tumour in men aged 15-34
103
classification of testicular tumours
* Germ cell tumour
* Seminomatous
* Non seminomatous
* Non germ cell
* Sex cord stromal
* Others .e.g lymphoma or metastases
104
**Risk factors**
**Risk factors**
* Cryptorchidism (undescended testicles)
* even more likely if both testicals havent descended
105
presentation of testicualr cancer
Mass +- pain (usually no pain)
106
investigations for testicular cancer
scan tumour markers
107
testicular tumour markers are useful in monitoring and diagnosisn
germ cell tumours
- BhCG
- Alpha fetoprotein (AFP)
108
* **BhCG (****beta-human chorionic gonadotropin (hCG)**
**positive**
choriocarcinoma
109
* **Alpha fetoprotein (AFP)**
* **Yolk sac tumours**
* Not specific – also produced in liver cancer
110
subtypes of testicular cancer
111
112
non germ cell tumours
sex cord stromal tumours
other
113
**Sex cord-stromal tumours**
are a type of non-germ cell tumour, and the most common types seen in the testes are Sertoli or Leydig cell tumours. These are uncommon and are benign.
114
other non germ cell tumours
lymphoma and metastases
115
**Germ cell tumours features**
In postpubertal males, 95% of testicular tumours arise from germ cell tumours and all are malignant. The aetiology of germ cell tumours is unknown, although a familial predisposition is well recognised and furthermore cancer in one testis is associated with an increased risk of cancer in the other testis. In addition, there is a three to five times increased risk of testicular cancer in cryptorchidism (failure of testicular descent into the scrotum). In 10% of cases of testicular cancer there is a history of cryptorchidism. This increased risk affects both the descended and the undescended testis. Orchiopexy (surgical placement of the undescended testis into the scrotum) before puberty decreases this risk of cancer.
116
types of germ cell tumours
Seminomas
## Footnote
**Nonseminomatous germ cell tumours (NSGCTs)**
117
**Seminomas**
Approximately 50% of germ cell tumours are seminomas. The peak age for development of a seminoma is 40-50 years. Seminomas often remain confined to the testis for long periods of time. When they do metastasise it is by the lymphatics, most commonly to the iliac and paraortic lymph nodes. Further spread is rare.
118
**Nonseminomatous germ cell tumours (NSGCTs)**
Pure NSGCTs are classified as yolk sac tumours, embryonal carcinomas, choriocarcinomas and teratomas. However many NSGCTs are mixed tumours and contain at least two of the pure NSGCT components.
119
NSGCTs metastasises
**NSGT metastasise early and do so both via lymphatics and blood vessels- sometimes metastasised before mass even apparent**
120
**NSGTs- yolk sac tumour**
Yolk sac tumours occur in young children and have a very good prognosis. Almost all of them produce alpha fetoprotein (AFP) which can be detected in the blood as a tumour marker
121
NSGCTs- Embryonal carcinomas, choriocarcinomas and mixed NSGCTs occur in
young adults. All choriocarcinomas are associated with elevated serum concentrations of the tumour marker beta- human chorionic gondatropin (hCG). Most mixed NSGCTs are associated with elevated serum concentrations of both AFP and hCG.
122
NSGCTs- Teratomas
Teratomas occur in men of all ages. If they arise in prepubertal men they are usually benign, however if they occur in postpubertal men they are malignant. Of note approximately 10% of seminomas are also associated with raised serum concentrations of hCG. In these seminomas syncytiotrophoblastic cells that produce hCG are present.
123
management of testicular cancer
* Radical orchiectomy
* Further treatment depends on whether the tumour is a seminoma or NSGCT
124
seminomas management
* very radiosensitive and treated with radiotherapy
* Best prognosis
125
NSGCTs management
after surgery treated with aggressive chemo
