Histopathology 5 - Gynaecological pathology Flashcards
1
Q
Common infectious organisms of the gynaecological tract
A
2
Q
What organisms cause PID?
A
Gonococci
Chlamydia
Enteric bacteria
3
Q
Complications of PID
A
- Peritonitis:
Inflammation can spread via the fallopian tubes → peritoneal cavity
- Intestinal obstruction due to adhesions:
When healing from inflammation → fibrosis → adhesion in the abdominal cavity → obstruction
- Bacteraemia:
Spread of infection via blood stream which → systemic spread of infection
- Infertility:
Due to adhesions
4
Q
Complications of salpingitis
A
- Infertility
- Fitz-Hugh Curtis
- Adhesions
- Chronic pelvic pain
- Ectopic pregnancy
- Plical fusion:
- The fimbrial ends of the fallopian tubes can start adhering together and to the ovary
- Hydrosalpinx:
- fallopian tubes are obstructed
- → fluid continues (inflammatory and biological fluids) to accumulate in the fallopian tube
- → tube can swell
- → enlarged fallopian tube filled with fluid
- Tubo-ovarian abscess
- Peritonitis
5
Q
Where does cervical cancer rank in the common cancers affecting women?
A
6
Q
What general pathology can affect the cervix?
A
Inflammation
Polyps
7
Q
Risk factors for cervical cancer
A
Human Papilloma Virus (HPV)- present in 95% of cases
Many sexual partners
Sexually active early
Smoking
Immunosuppressive disorders
8
Q
Which types of HPV cause which lesions?
A
High risk: 16 and 18- can cause low and high grade carcinoma.
Low risk: HPV 6 and 11. causes oral and genital warts.
9
Q
Difference between CIN and cervical cancer
A
CIN: abnormal cells have not invaded the basement membrane
10
Q
What is salpingitis?
A
Infection of fallopian tubes
11
Q
What are the possible complications of untreated salpingitis?
A
Adhesions
Abscesses
Peritonitis
Ectopic pregnancy
12
Q
What are the high risk forms of HPV for cervical cancer?
A
16 and 18
13
Q
Recall the stages of progression from normal cervical cells to cervical carcinoma
A
Normal
T positive HPV (abnormal cells)
CIN 1 (lower 1/3 of cells neoplastic)
CIN 2 (2/3 of cells neoplastic)
CIN 3 (full thickness neoplastic)
Carcinoma
14
Q
What do CIN and CGIN stand for, and what is the main difference between them?
A
CIN = cervical intraepithelial neoplasia
CGIN = cervical glandular intraepithelial neoplasia
CIN progresses to squamous cell carcinoma
CGIN progresses to adenocarcinoma
15
Q
How does HPV lead to neoplatic transformation of cervical cells?
A
E6 and E7 viral proteins deactivate p53 and Retinoblastoma (tumour suppressor genes)
16
Q
What age range is invited to cervical screening?
A
25-64
17
Q
Which HPV strains are included in the quadrivalent vaccine?
A
6,11,16,18
18
Q
What is leiomyoma of the uterus?
A
Smooth muscle cell tumour of the uterus
19
Q
What is a fibroid?
A
Leiomyoma
20
Q
How are fibroids classified?
A
As either intramural, submucosal or subserosal
21
Q
What is the biggest risk factor for endometrial hyperplasia?
A
Persistent oestrogen
22
Q
Which is the most common gynaecological cancer in developed countries?
A
Endometrial carcinoma
23
Q
WHo is at risk of endometrial hyperplasia?
A
- Occurs in perimenopausal women
- It can occur in women with persistent anovulation e.g. PCOS:Because in menstrual cycle:
- there is a surge in oestrogen then ovulation
- → oestrogen drops and progesterone rises
- No ovulation:
- oestrogen surge continues driving proliferation and hyperplasia of endometrium
- Women with polycystic ovary disease are at risk
- Granulosa cell tumours from the ovary can produce oestrogen which may result in this
- Oestrogen therapy (alone i.e. HRT) can also lead to this
24
Q
Risk factors for endometrial carcinoma
A
Nulliparity
Obesity
DM
Excessive oestrogen stimulation
25
What is the difference between type 1 and 2 endometrial carcinomas?
Type 1: adenocarcinomas (endometroid, mucinous and secretory adenocarcinomas)
- happen in younger patients
- are oestrogen dependent
Type 2: Serous/ clear cell carcinoma
- happen in older women (post menopausal)
- less oestrogen dependent
- happen in atrophic endometrium
26
What is the relative prevelance of type 1 vs type 2 endometrial carcinoma?
Type 1 = 80-85%
Type 2 = 10-15%
27
Recall the genetic associations of serous and clear cell endometrial carcinomas
Serous: p53 mutation
Clear cell: PTEN mutation
10 before 53
c before s
28
Which type of endometrial carcinoma is high grade and which is low grade?
Type 1 = low grade
Type 2 = high grade
29
Which type of endometrial carcinoma is most likely to arise in atrophic endometrium?
Type 2
30
Recall the FIGO stages of endometrial cancer
Stage 1: Confined to uterus
Stage 2: Spread to cervix
Stage 3: Spread to adnexa, vagina, local lymph nodes (pelvic/ para-aortic)
Stage 4: Distant metastases
31
Recall the different types of gestational trophoblastic disease
Partial/ complete mole
Invasive mole
Choriocarcinoma
32
How does gestational trophoblastic disease usually present?
As spontaneous abortion
33
Genetics of complete mole
Fertilisation of empty egg by:
1. one sperm that duplicates its genetic material once fertilised with the egg
2. 2 sperm
Possible genotypes: 46XX, 46XY (but for some reason not 46YY...)
34
Genetics of partial mole
Egg fertilised by 2 sperm or 1 sperm that hasn't split
Possible genotypes: 69XXY, 69XYY, 69XXX
35
Difference between invasive mole and choriocarcinoma
Invasive mole: partial or complete mole that invades the uterine wall and beyond
Choriocarcinoma:
* This is a malignancy of trophoblastic disease
* RARE: 1 in 20,000-30,000 pregnancies
* It is rapidly invasive, widely metastasising
* Responds well to chemotherapy
* 50% arise in moles
* 25% arise in previous abortion
* 22% arise in normal pregnancy
36
Describe the prognosis of choriocarcinoma
Very aggressive but also very responsive to treatment
37
What is endometriosis?
Presence of endometrial glands and stroma outside of the uterus - bleeding of ectopic material is painful
38
What is adenomyosis?
Ectopic endometrial tissue within the myometrium
39
What is the main symptom of adenomyosis?
Dysmennorhoea
40
What are the 3 layers of the ovary?
Surface epithelium
Germ cells (this is in the middle)
Sex cord stromal cells (this is what surrounds the germ cells)
41
Primary and secondary neoplastic tumours of the ovaries
Primary:
a) specific- epithelial, germ cell, sex cord stromal
b) non-specific- lymphoma, sarcoma
Secondary:
metastasis from intestines, stomach, breast, lymphoma, sarcoma
42
Epidemiology of primary ovarian tumours (\*\*from the lecture\*\*)
•Epithelial tumours:
–make up 65% of all ovarian tumours & 95% of malignant ovarian tumours
–50% found in 45-65 age group
•Germ cell tumours:
–have bimodal distribution; one peak 15-21 year olds and one peak at 65-69
•Sex cord stromal tumours:
–most commonly seen in post-menopausal women but some sub-types peak in 25-30 year age group (eg granulosa cell tumours)
43
What type of tumour are 95% of ovarian neoplasms?
Epithelial tumours
44
Describe the classification of ovarian epithelial tumours
SMEC
45
What type of epithelium are most ovarian carcinomas derived from?
Serous
46
Which types of ovarian carcinoma are associated with endometriosis?
Endometrioid and clear cell carcinoma (both types of Type 1 epithelial carcinomas)
47
Recall the 4 types of sex cord stromal tumours, and the malignant potential of each.
Which one is associated with endometrial hyperplasia?
Fibromas (from fibroblasts) = benign
Granulosa cell tumours = variable behaviour
Thecoma (thecal cells) = benign
Sertoli-Leydig cell tumours = variable behaviour
Granulosa cell tumours are associated with endometrial hyperplasia as they produce oestrogen
48
In what age group of women are germ cell tumours seen?
\<20s
49
Recall the different types of germ cell tumour in women
Undifferentiated germ cells: dysgermioma
Tumour of extra-embryonic tissue: endodermal sinus tumour
Trophoblast tumour: choriocarcinoma
Cancer of embryonic tissue: teratoma
50
Which is the most common malignant ovarian germ cell tumour?
Dysgerminoma
Associated with Turner's syndrome
51
Epidemiology of ovarian cancer
6th most common cancer affecting women
2nd most common cause of cancer death in women
52
Risk factors for ovarian cancer
and what decreases risk?
1) MOST significant risk factor is genetic predisposition:
Up to 10% of epithelial ovarian cancer cases are familial
10% with ovarian carcinoma are carriers of a breast/ ovarian cancer susceptibility gene
2) Increased oestrogen exposure:
Nulliparity/ Infertility
Early menarche
Late menopause
Hormone replacement therapy
3) Family history of ovarian and breast cancers
4) Endometriosis
5) Inflammation:
pelvic inflammation exposes the lining of the ovary to toxic mediators (lots of cytokines and growth factors)
and makes cells quickly turnover
Both may be mutagenic
RISK DECREASED BY: OCP, PREGNANCY
53
Two types of ovarian cancer
Type 1 (low grade) - 20% of tumours. Arise from precursor lesions. Mutations - k-ras.
Type 2 (high grade)- 80% of tumours. Mostly serous. Arise de novo (not from pre-cursor lesions). Mutations - p53
\*\*basc opposite of endometrial cancer
54
Which 3 familial syndromes are related to ovarian cancer?
– familial breast-ovarian cancer syndrome (BRCA1 and BRCA2)
– site-specific ovarian cancer
– cancer family syndrome (Lynch type II)
55
What is the significance of BRCA1 and BRCA2 with prognosis for ovarian cancer?
in HIGH GRADE serous carcinoma- having BRCA2 mutation confers survival advantage over having no BRCA mutations or BRCA1 mutation
\*\*low grade serous carcinoma doesn't show association with BRCA1 and BRCA2
56
Which ovarian tumour is lynch syndrome associated with?
endometroid and clear cell
\*\*same as those associated with endometriosis
57
Recall 2 types of cancer that commonly metastasise to the ovary
Krukenburg tumours- from gastric or breast mucosa
Colon cancer
58
Which site in female genital tract receives the most metastases?
Ovaries
59
Do most leiomyosarcomas arise de novo or from precursor lesions?
Usually de novo lesions rather than from fibroid precursor
60
Classification of ovarian tumours: path guide
1) epithelial (70%)
* endometroid
* serous
* mucinous
* clear cell
2) sex cord stromal (20%)
* fibroma
* thecoma
* sertoli-leydig cell tumour
* (granulosa)
3) germ cell (10%)
* dysgerminoma
* teratoma
* yolk sac
* choriocarcinoma
4) metastatic
* krukenburg tumour
61
Histopathology of serous cystadenomas
62
Mucinous cystadenoma histology
63
What is pseudomyxoma peritonei?
Presence of mucin in the peritoneal cavity
caused by mucinous cystadenomas
64
Which is the most common oestorgen secreting ovarian tumour?
Mucinous cystadenoma
65
Which mutation is found in mucinous cystadenoma of the ovary?
K-ras mutation in 75%
66
Serous vs mucinous cystadenoma of the ovary
**Serous:** columnar epithelium (mimics tubal), psammoma bodies, affects women in 30s-40z
**Mucinous:** mucin secreting cells (mimcis endocervical mucosa), no psammoma bodies, affects younger women
67
Which ovarian tumour is endometriosis a risk factor for?
Endometroid
68
Clear cell tumour of the ovary: histology
Abundant clear cytoplasm - intracellular glycogen
Hobnail appearance
69
What is the prognosis of clear cell tumours of the ovary?
Malignant with poor prognosis
70
What is dysgerminoma?
Female counterpart of testicular seminoma
\*rare, but most common ovarian malignancy in young women senistive to radiotherapy
71
What is the most common malignant germ cell tumour?
Dysgerminoma
72
What is the most common ovarian tumour in young women? (15-21)
Teratoma
73
Two types of teratomas
**Mature:** aka demroud cyst. 95% of teratomas. Benign, usually cystic. Differentiate into mature tissues (skin, hair, teeth). Usually bilateral, aasymptomatic.
**Immature:** malignant, usualy solid, contains immature, embryonal tissues. secrete AFP
74
What are the 4 sex cord stromal tumours and their distinguishing features?
75
What is normal vulval histology?
Squamous epithelium
76
Which HPV causes VIN?
HPV-16
77
Two types of VIN
1) usual type
- women aged 35-55y
- associated with warty/basaloid SCC
2) differentiated type
- common in older women
- higher risk of malignant transformation
78
Describe the normal cervical epithelium
Outer cervix covered by squamous epithelium; endocervical canal lined by columnar glandular epithelium. The squamocolumnar junction (SCJ) separates them.
79
What is the transformation zone?
Transformation zone (TZ): the area where columnar epithelium transforms into squamous cells (=squamous metaplasia). This is a normal physiological process. This area is susceptible to malignant change
80
81
How do you define CIN?
Dysplasia at the TZ as a result of infection by HPV 16 & 18.
82
Cytology vs histology of CIN
Graded **mild, moderate or severe dyskaryosis on cytology**, but graded CIN 1-3 on histology (from biopsy).
● CIN 1 = dysplasia confined to lower 1/3 of epithelium
● CIN 2 = lower 2/3
● CIN 3 = full thickness, but basement membrane intact
83
Cervical cancer epidemiology
2 peaks in incidence
one at 30-39 y
one at 70+ y
84
Which ovarian tumour is associated with Meig syndrome?
Fibroma
Meig syndrome: ascites + pleural effusion
85
Powder burn spots
Endometriosis
86
87
Which ovarian tumour has psammoma bodies?
Serous cystadenoma
88
What syndrome are fibromas associated with?
Meig's syndrome
Right sided pleural effusion + ascites + fibroma
