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Female Reproductive System Pathology Flashcards

1
Q

Define adenomyosis

A

The abnormal presence of endometrial tissue in the uterine wall (myometrium).

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2
Q

What features of adenomyosis do you see under the microscope?

A

Irregular shaped endometrial glands and stroma within myometrium
Glands may be enlarged, or irregularly shaped (not ovale)
Glands tend to be interconnected.
Surrounding myometrium (smooth muscle histology) is often undergoing hyperplasia and hypertrophy.

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3
Q

What are the clinical symptoms of adneomyosis?

A

Painful periods (dysmenorrhoea)
Heavy periods (menorrhagia)
Pain during intercourse (dyspareunia)
May also present with infertility or pregnancy-related complications.
Examination - enlarged and tender uterus - softer than a fibrotic uterus

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4
Q

What features of endometriosis are seen on a microscope slide?

A

The presence of endometrial glands and stroma
With or without hemosiderin laden macrophages.
Glands may be enlarged and irregular shaped.

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5
Q

Haemosiderin laden macrophages are frequently seen in endometriosis - what could be the reason for this?**

A

Increased iron metabolism
Endometrial tissue responds to hormone changes - will undergo menses - rbcs taken up by macrophages.

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6
Q

Define endometriosis

A

Presence of endometrial glands and stroma outside the uterus

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7
Q

What does the normal uterus/endomterial lining look like in histology?

A

Outermost - perimetrium - connective tissue
Myometrium - smooth muscle fibres
Endometrium - simple columnar epithelium, simple tubular glands, highly cellular and vascularised stroma.

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8
Q

What are some common sites for endometriosis to occur?

A

Ovary
Broad ligament
Uteroscaral limagenet
Peritoneal surface of the rectum
Cul-de-sac (pouch of douglas)
The peritoneal surface of the sigmoid colon
The peritoneal surface of the bladder.
Laparotomy scats
Serosa of the large, small bowel and appendix
Mucosa of the cervix, vagina and fallopian tubes

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9
Q

How common is endometriosis?

A

Affects around 10% of women in reproductive age groups
Commonly diagnosed at 30-40yrs.

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10
Q

What are the clinical features of endometriosis?

A

Dysmenorrhea (painful mesntraution)
Dyspareunia (pain with intercourse)
Pelvic pain - intrapelvic bleeding and periuterine adhesions
Menstrual irregularities
Infertility - 30 to 40% of women.
These symptoms are often associated/worse with menstraution due to the oestrogen-dependent nature of the tissue.

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11
Q

What are the different theories underpinning the pathogenesis of endometriosis?

A
  1. Regurgitation theory - retrograde menstraution
  2. Benign metastasis theory - spead through blood vessels and lymphatic channels
  3. Metaplastic theory - coelomic epithelium (mesothelium) undergoes metaplatic changes triggered by local stimuli.
  4. Extrauterine stem/progenitor cell theory - progenitor from bone marrow differentiate into endometrial tissue.
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12
Q

What are some key points of the pathophysiology of endometriosis?

A

Ectopic endometerial tissues causes a local inflam response - macro, pro-inflam, GF, prost -> promotes growth, angiogenesis, fibrosis and adhesions
Lesions may produce own oestrogen and retinoic acid from stromal cells and become progesterone resistance - promote growth
Display increased adhesion and invasiveness (inc MMPs) to grow with surrounding tissue.
Angiogenesis = high vascularised
Mutations in TSG and oncogenes
Pain - may be due to inflam, nerve infiltration or sensitizing peripheral receptors.

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13
Q

What are some complications/risks of endometriosis?

A
  1. Periodic/cyclical bleeding - extrinsic cyclic (ovarian) and intrsinsic hormonal stimulation - (has red/blue or yellow/brown appearance)
  2. Organising hemorrhage -> extensive fibrous adhesions -> obliterate pouch of dougals/ovaries
  3. Ovaries - large and cystic - brown fluid from previous hemorrhage
  4. RIsk of malignancy - endometrioid and clear cell carcinoma
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14
Q

What complication of endometriosis is shown in this image?

A

Chocolate cyst or endometriomas
Brown fluid from previous bleeding from ectopic endometrial tissue.

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15
Q

What is the purpose of cervical cancer screening?

A

Screening of non-symptomatic population to identify pre-cancerous changes to allow early treatment or interventions to reduce the incidence of cervical cancer.

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16
Q

Who is the NHS cervical cancer screening programme offered to?

A

Women and people with a cervix aged 25 to 64yrs in England
Between 25-49 offered every 3 years
Between 50-64 - offered every 5 yrs.

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17
Q

What is the strongest risk factor for cervical cancer?

A

Human Papilloma Virus

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18
Q

What is the role of HPV in cervical cancer?

A

HVP is a DNA oncogenic virus - express HPV E7 and HPV E6 proteins
Hig risk subtypes - HPV16 60% of cases and HPV 18 for 10% of cases
Can also cause cancer of the vagina, vulba, penis, anus, tonsil and other oropharyngeal locations

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19
Q

What are low risk HPV strains?

A

Sexually transmitted
Can cause ano-genital warts (Condyloma acuminatum)

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20
Q

What is the role of HPV E6 and HPV E7 in cancer?

A

Are proteins expressed by HPV 16 and HPV18 high risk strains for cancer.
E6 - activates TERT causing increased telomerase expression, and inhibits p53
HPV E7 - inhibits p21 leads to increased CDK4/Cyclin D, leads to inhibition of RB
Leads to immortalisation, increased cell proliferation and genomic instability
Increased risk of cancer.

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21
Q

What are the different stages in the cervical cancer screening programme?

A

Cervical Smear Taking
HR HPV testing (PCR)
Cervical cytology
Colposcopy with biopsy +/- cervical loop

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22
Q

What is meant by cervical cytology?

A

Examine cells brushed from the cervix under the microscope to detect pre-cancerous changes in both squamous and glandular cells.

‘Pap smear or Papanicolaou’

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23
Q

What do normal cervical cells look like under the microscope?

A

Endocervix - lining links to uterus - is simple columnar epithelium with mucus-secreting cells - thick lamina propria with lots of cervical glands.
Ectocervix - lings to vagina - stratified squamous epithelium

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24
Q

What is the transformation zone?
Why is this linked to cervical cancer?

A

Contains the squamocolumnar junction between the endo and ecto cervix
This junction can move at different times of a woman life to due with oestrogen: puberty, pregnancy, oral contraceptive pill.
This exposes new simple columnar epithelium to the acidic vaginal pH, undergoes metaplastic changes, this new immature sqaoumous epithelium is more vulnerable to HR-HPV infection, these changes put at high risk of later cancerous changes.

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25
Comment on the results of this pap smear
This is a normal cervical smear - no pre/cancerous changes The nucleus are small and surrounded by an abundant cytoplasm
26
Comment on the results of this pap smear
Abnormal pap smear Cells show dyskaryosis (between normal and malignant) Note cells are smaller than normal, with a larger nuclear to cytoplasmic ratio. Would require further escalation
27
Comment on the results of this pap smear
Abnormal It shows that carcinoma cells are smaller, have a larger nuclear-to-cytoplasm ratio, and have abnormal chromatic distribution.
28
How is cervical smear taken?
Conventional smears take cells from the whole transformation zone with a 360-degree sweep using an Ayres or Aylesbury spatula and smeared onto a glass slide. New liquid based methods use a plastic spatula/endocervical brush/broom like device - sweep cervical os and ectocervix 5 times - this is the recommended method.
29
What is the UK is considered the primary method of testing for cervical cancer.
Cervical smear for HR HPV testing
30
What is the primary screening for cervical cancer pathway like in the NHS?
1. hrHOV testing - if negative routine call -if positive - undergoes cytology 2. If cytology is negative should be re-screen in 12 months If positive colposcopy referral. 3. If re-screen in 12 months has positive for hrHPV then colposcopy referral.
31
What is the escalation process from an abnormal cervical smear?
Cervical punch biopsy may be taken Cervical loop (if high grade smear)
32
What is colposcopy?
When the cervix is visualised by a binocular microscope colposcope
33
What changes of the cervix can be viewed by colposcopy and can indicate pre(malignant changes)?
CIN - increased amount of protein anad lower levels of glycogen than normal epithelium. Apply acetic acid to the cervix - protein coagulates and abnormal cell appear aceto-white. A mosaic pattern may appear if separated by areas of red blood vessels.
34
What is shown in this colopscopic image of the cervix?
Aceto white cervix - cancerous cells mixed with acetic acid - have more protein and less glycogen - gives white appearance of coagulatnes with acid
35
What is shown on this colposcopy of the cervix?
Sqaoumous cell carcinoma Abnormal growth or lesion on the cervix, often white in appearance Easily bleeding on irritation May occlude the external os may initially appear red and ulcerated
36
What is meant by CIN (cervical Intraepithelial Neoplasia)?
Sqaoumous cervical precurosr lesion (carcinoma in situ) Can develop into sqaoumous cell carcinoma UK three grades: 1 - mild dysplasia 2 - moderate dysplasia 3 - severe dysplasia CIN2 and CIN3 are high grade - risk of progression to invasive carcinoma - require treatment.
37
Describe the normal appearance of the cervix on histology? How does this change with CIN
Normal - gradual transiion from basal to sqaoumous cells CIN 1 - affects lower 1/3 2 - 2/3 3 - more than 2/3 Looks for abnormal chromatin patterns, hyperchromatic, inc nuclear size, loss of differentiation, and increased mitotic index
38
What is the treatment for CIN1?
Not treated Spontaneously resolves Only a small proportion progress Patient will have increased surveillance.
39
What is the treatment for CIN2 and CIN3?
Large loop excision of the transfromation zone Test of cure - six months later - for HPV and cytology
40
What is cervical glandular intraepithelial neoplasia?
Precursor lesion to cervical adenocarcinoma (less common cervical cancer) High grade by definition and requires treatment
41
What is seen under the microscope in these images?
A = normal B = CGIN - precursor to an adenocarcinoma Note nucleus stacking, hyperchromatic, enlargement.
42
Who is the HPV vaccine offered to? What does it protect against?
Protects against cervical cancer, some mouth and throat cancers, some anus and genital area cancer Gardasil in UK is offered to all girls and boys in year 8.
43
What is the most common type of cervical cancer?
Sqaoumous cell carcinoma - 80%
44
What are the different types of cervical cancer? How common?
Sqaoumous cell carcinoma = 80% Adenocarcinoma and mixed adenosqaoumous carcinoma = 15% Small cell carcinoma <5%
45
What are some risk factors for endometrial cancer?
Unoppsed eostrogen action - PCOS, early menarche and late menopause, HRT, metabolic syndrome (Obsseity and T2DM) Lynch syndrome - AD mutation Note Combined oral contraceptive pill is protective as opposes oestrogen with progesterone
46
What is the typical patient profile for a type 1 endometrial cancer?
55-65yrs Obesity, Hyperoestrogenic states, DM, HTN Precursor = hyperplasia
47
What is the morphology of a type 1 endometrial cancer?
Endometerioid adenocarcinoma
48
What is the basic pathophysiology underpinning a type 1 endometrial cancer?
Linked to prolonged uncontested oestrogen exposure Endometerial tissue responsids to oesotrgen and progesterone Oestrogen in proliferative phase - cause thickening of lining and proliferation of glands. Luteal phase - progesterone - glands sweel and increase blood supply Drop in prog - menses When oestorgen remains dominant proliferation is not stooped - becomes abnormal
49
What is the most common type of endometrial carcinoma?
Adenocarcinoma
50
What is the basic physiology of type 2 endometrial cancers?
Rare and have a non-endometerioid histology Made up a serous and clear cell carcinomas Tend to be oestrogen independent and associated with genetic predispositions (p53)
51
What are the clinical features of a type 2 endometrial cancer?
65-75yrs usually in atrophic endomterium Pre cursor - serous endometrial intraepithelial carcinoma
52
Compare the behavious of type 1 and type 2 endometerial cancers
Type 1 - indolent, spread via lymphovascular system Type 2 - aggressive, intraperitoneal and lymphovascular spread
53
What are the stages of development of endometrial cancers?
54
Give a clinical overview of endometrioid endometrial adenocarcinoma
Closely resemble normal endometrium Gland forming tumour Usually express oestrogen and progesterone receptors Grade 1 and 2 - mild to moderate cytologic atypia - low grade Grade 3 = high grade
55
How to differentiate between grade 2 and grade 3 endometrial carcinoma histologically?
2 - mod differentialted - glandular architecture mixed with solid areas (>5 <50%) 3 - poorly diff - predominantly solid growth (more than 50%)
56
What is a serous endometrial adenocarcinoma?
Papillary architecture (may have glandular) Display high grade cytological atypica Tumours have mutations in TP53 genes.
57
What is a clear cell endometrial adenocarcinoma?
Can have solid, papillary and glandular architecture Presence of 'clear cells' Oestrogen receptor negative High grade aggressive tumour
58
What is the link between endometrial cancer and lynch syndrome?
Cause 2-5% AD - germline mutation in DNA mismatch repair genes Gives a 40-60% lifetime risk of developing endometerial cancer Also affects - colorectal, gastric, ovarian, pancrea, ureter, renal pelvis and biliary tract
59
What is the treatment for endometrial cancer?
Standard surgery - total hysterectomy with bilateral salpino-oophorectomy High grade serous carcinoma - omentectomy High grade carcinomas - sentinel lymph node biopsy, pelvic/para-arotic lymphadenectomy Post surgery - adjuvant radio or chemotherapy
60
What are the three cell types in the normal ovary?
Epithelial Germ cells (pluripotent germ cells) Sex cord stromal cells
61
What is the most common cell type in ovarian cancers?
Epithelial (905)
62
What are the main different types of ovarian neoplasms?
Epithelial - serous, mucinous, endomteriod, clear cell etc Germ cell - teratoma, dysgerminoma Sex-cord stromal - fibroma, thecoma Metastatic - commonly from the colorectal, breast, stomach, cervix or endometrium
63
What are the three major histological tumour types of epithelial ovarian tumours?
Serous Mucinous Endometriod
64
What are the different classifications of epithelial ovarian tumours based on risk?
Bening (cystadeoma) Borderline - recurrence or progression risk Malignant
65
What is the most common type of ovarian cancer?
High-grade serous ovarian cancer
66
What are the risk factors for high grade serous ovarian cancer?
Germline BRCA1/2 mutations Lynch syndrome HRT Smoking Obesity/overweight Asbestos exposure Early menarch and late menopause
67
What are some protective factors against ovarian cancer?
Combined contraceptive pill Breast feeding children (compared to non-breast feeding any children, not to not having children) Hysterectomy and sterilisation
68
What are some signs and symptoms for ovarian cancer?
'Silent killer' Bloating Abdominal pain Loss of appetite/feeling full Change in bowel habit Tiredness Weight loss
69
How can ovarian cancer be diagnosed?
Tumour markers - CA125 is raised in 90% of advanced ovarian cancer Suspected germ cell tumour - betaHCG, AFP, LDH Imaging - US,CT scan, PET scan (staging FIGO) Biospy
70
What is meant by the tubular origin of ovarian cancers?
Ovarian carcinomas are suspected to start in the fallopian tubes then seed to the ovary via the fimbriae, useful as early cancerous changes may be identified in the tubes before ovarian cancer occurs.
71
What is the treatment for HG serous ovarian carcinoma?
Surgical debulking - cytoreduction Cytotoxic chemotherapy - cisplatine-paclitaxel - 70% respond favourably but 80% will recur Targeted therapies - PARP inhibitors - Olaparib.

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