Pathology of the Female Reproductive Tract Part 1 Flashcards
What type of epithelium is found in the vulva?
keratinizing squamous epithelium
What type of epithelium covers the vaginal mucosa?
non-keratinsing squamous epithelium
Which part of the vulva contains sweat and sebaceous glands?
Labia majora
Where are bartholin glands situated?
posterior part of the labia, either side of the bestibule
What are bartholin glands composed of?
acini lined by columnar mucous secreting cells
Where do bulbourethral glands open?
posterolaterally at the level of the hymen
Labia minora are devoid of adipose tissue
Labia minora has an epidermal rete ridge system
Labia minora contains elastic fibers
Which of these statements are true?
All
epidermal rete ridges are protective during childbirth and sexual interaction
Lymphatic drainage of the vulva
inguinal nodes then to external iliac nodes
As the vaginal opening is approached the ————- epithelium is reduced as mentioned above. This reduction continues to the —–, which is fibrous membrane between the vagina and vulva. Although the membrane itself is rarely intact (it can break from minor trauma) the external, vulval part of the hymen reflects the vulval microanatomy – that being —————- epithelium and the vaginal, inner part of the hymen reflects the vaginal microanatomy – that being ————–epithelium.
- keratinised, stratified squamous epithelium is - hymen
- keratinised stratified squamous epithelium -
and non-keratinised, stratified, squamous
epithelium.
Layers of the Vagina:
- stratified squamous epithelial mucosa
- sub-epithelial layer with elastic tissues +
venules - fibromuscular layer with some skeletal
muscle - tunic adventitia
Before puberty and after menopause epithelium thickness?
- thin
- during reproductive years, basal cell mitosis,
superficial cells increase in size and number
in response to glycogen, which peaks at
ovulation
The vagina is a series of
mucosal folds
Microanatomy of the vulva and vagina
insert diagrams
Non-neoplastic epithelial disorders of the vulva are
- disorders that cause hyperkeratosis
- manifest as white areas on vulval skin
- uncertain aetiology
- 5% develop into squamous carcinoma
Squamous hyperplasia:
- what classification of neoplasia/
- causes?
- non-neoplastic epithelial disorder
- hyperkeratosis, irregular thickening of rete
ridges, inflammation of the dermis
Linchen Sclerosis:
- what classification of reproductive
neoplasia?
- causes?
- non-neoplastic epithelial disorders
- hyperkeratosis, thinning and flattening of the
rete ridges, oedema, hyalinzed connective
tissue in the dermis
Neoplastic Epithelial Disorders of the Vulva:
- associated with HPV
- younger people
- undifferentiated form = warty
- differentiated form = Lichen’s Sclerosis
- basaloid, warty, mixed type
Squamous Carcinoma of the Vulva:
- predominantly elderly people
- lymph node metastases common
- grading as well differentiated, moderately
differentiated and poorly differentiated (grade
3) - nodal deposits larger than 5mm -> poor
survival
Paget’s Disease of the Vulva:
- mucin-containing adenocarcinoma cells in
squamous epithelium - analogous to Paget’s disease of the breast
- 25% underlying invasive adenocarcinoma
Basal Cell Carcinomas vs Malignant Melanomas of the Vulva:
- curative
- poor outcomes
Vaginal Adenosis:
- uncommon
- subepithelial connective tissue of the vagina
- embryological development issue
- change creates cells that are mucinous and
cuboidal, hence more likley to undergo
squamous metaplasia
Vaginal Intraepithelial Neoplasia:
- analogous to cervical intraepithelial
neoplasia - very rare
- generally with both vulva and cervical lesions
Squamous Carcinoma of the Vagina:
- rare
- older people
- similar to cervical squamous carcinoma,
invades locally, radical surgery needed
Different Classifications of Neoplasia of the Vulva and Vagina:
Vulva:
- non-neoplastic epithelial disorders
- neoplastic epithelial disorders
- squamous carcinoma
- Paget’s disease
- others: basal cell carcinoma etc
Vagina:
- vaginal adenosis
- vaginal intraepithelial neoplasia
- squamous carcinoma
Microanatomy of the Uterus:
insert diagrams
- uterus is muscular
- consists of fundus, body, and cervix
- layers of the uterus:
- outer parametrium (epithelial cells)
- middle myometrial layers (smooth muscles)
- endometrium (simple columnar epithelium)
Endometrial Polyps:
- common in peri/menopausal women
- single/multiple
- oestrogen stimulated endometrial reactions
- often cystic with thick walled blood vessels
- metaplasia is common + associated with
inflammation - BENIGN -> can lead to neoplastic changes
Endometrial Hyperplasia:
- hyperoestrogenism and exposure to
unopposed oestrogen eg in PCOS - classified into simple, complex and atypical
hyperplasias
Endometrial Hyperplasia: Simple Hyperplasia:
- abnormal hyperplastic/metaplastic changes
- dilation of glands + increased mitotic activity
- no cellular atypia/risk of malignancy
Endometrial Hyperplasia: Complex Hyperplasia:
- focal rather than global
- crowded glands
- irregular branched glands
- architectural abnormalities
- non cytological abnormalities hence
neoplastic change is low
Endometrial Hyperplasia: Atypical Hyperplasia:
- aka endometrial intraepithelial neoplasia
- both architectural and cytological changes
- nuclear polymorphism + cellular atypia
- high risk of malignancy
Endometrial Adenocarcinoma:
- due to unopposed oestrogenic acitivity and
atrophy of endometrium post-menopause - common invasion into myometrium
- spreads lymphatically and venously to cervix,
vagina and pelvis - two types:
- endometroid adenocarcinoma
- non-endometroid adenocarcinoma
Endometroid Adenocarcinoma:
- unopposed oestrogen stimulation
- atypical hyperplasia
- younger women + perimenopausal
- prognosis is good
- higher rates of molecular mutations with
oestrogen and progesterone receptors than
non-endometroid adenocarcinoma
Non-endometroid Adenocarcinoma:
- affects older women
- not directly associated with oestrogen
exposure - include clear cells, serous tumours
- poor prognosis
- p53 mutation
Endometrial Stromal Sarcoma
- rare
- incidental finding on hysterectomy
- low grade = locally, low mitotic activity,
recurrence - high grade = malignant, invasion of
myometrium, poor prognosis
Endometrial Carcinosarcoma:
- monoclonal origin
- include endo/myometrial tissue
- tissue foreign to the uterus
- affects elderly people and are highly
malignant - poor outcome
Endometriosis:
- presence of endometrial tissue outside the
endometrium - undergo atypical change with potential
associations including endometroid cancers
of the ovary and endometroid
adenocarinoma
Myometrium: Neoplasias:
- adenomyosis
- uterine fibroids
Adenomyosis:
- endometrial tissue within the myometrium
- aetiology uncertain
- affects perimenopausal people
- neoplastic changes is unusual
Uterine fibroids:
- most common benign tumours of the uterus
- affect older people
- aetiology is uncertain
- associated with infertility
- whorled appearance + large
- oestrogen dependent
- benign but neoplastic capability
Fallopian Tube Cysts:
- common and benign
- fimbrial and paratubual cysts
- lined by tubal-like epithelium
Adenocarcinoma of the Fallopian Tube Epithelium:
- rare
- potential BRCA1 inheritance
- spreads via lymphatics and peritoneum
- poor outcomes
Microanatomy of the Cervic:
- cervix meets uterine body at the internal
cervical os - cervix composed of stroma
- ectocervix is continuous with vagina = non-
keratinised, stratified, squamous epithelium - endocervix line lumen of the cervix = tall,
columnar epithelium that secretes mucous
Microanatomy of the Cervic:
insert diagrams
figure 1 = stroma
figure 2 = ecotocervix = non-keratinsing
stratified squamous
figure 3 = endocervix = tall columnar
What meets at the squamocolumnar junction?
endocervical columnar epithelium and ectocervical squamous epithelium
usually located at the external cervical os between the cervix and the vagina
The clitoris is analogous to
- male penis
- contains 2 ischiocavernosa, erectil tissue
- pacinian nerve endings
What does the endometrium consist of before puberty?
scanty, spindle-celled stroma
During the reproductive years and under the influence of gonadotrophins the uterus is differentiated into
2 layers
- deep basal layer at junction of myometrium
- superficial functional layer, sensitive to
hormonal changes and undergoes the
menstrual cycle
Secretory cells are found at which ends of the fallopian tubes?
uterine ends
smooth muscle content of the wall increases composed of inner circular and outer longitudinal layer
at the junction with the uterus a third muscular layer is added
How do hormonal changes during puberty create a metaplastic environment in the cervical transformation zone?
- hormonal changes driven by
gonadotrophins - columnar cells of endocervix migrate into
the ectocervix and are exposed to acidic
pH in the vagina during reproductive years - ectropion transforms cell type through
metaplasia as it heals, with squamous cells
now overlying the ectropion - erosion of aligned crypts can also at this
point form Nabothian cysts due to mucous
trapping -> physiological cysts - metaplastic environment is an increased
opportunity for pathology to arise
What is the most common site for the carcinoma of the cervix?
the cervical transformation zone
What is the most common cause of cervical cancer?
HPV (Human Papilloma Virus)
What is the most important risk factor for cervical cancer and why?
- sexual activity
- increased likelihood of transmission of
HPV - virus integration affects tumor suppressor
p16 and p53
What does Cervical Intraepithelial Neoplasia describe?
a spectrum of cervical disease up to the point of cervical cancer
Cervical Intraepithelial Neoplasia Grading:
- Grade 1,2,3
- low grade to high grade
- epithelial cytoplasmic maturation,
abnormal nuclei - high grade = breaching the basement
membrane
Invasive Squamous Carcinoma of the Cervix:
- small neoplastic foci
- breach basement membrane of cervix
Stages of Cervical Cancer:
- 0-4
insert diagram
Cervical Screening Program:
- HPV testing + cervical cytology
- Over 25, every three years
- cells are tested for grade of dyskaryosis
including disproportionate nuclear size,
irregular shape - grades of dyskaryosis (CIN1-3) are not
always linearly related to neoplasia
A patient presents to their GP with a change to their vulva. The skin on the patient’s vulva has become thinner, with a white appearance and it is very itchy. If scratched it bleeds and this is very painful.
What is the likely diagnosis?
Lichen Sclerosis
A patient presents to their GP with a change to their vulva. The skin on the patient’s vulva has become thinner, with a white appearance and it is very itchy. If scratched it bleeds and this is very painful.
- Patient has Lichen Sclerosis
What is the patient at risk of?
Differentiated VIN (Vulval Intraepithelial Neoplasias) and Vulval Squamous Carcinoma
A patient presents to their GP with postmenopausal bleeding for the last 3 months and abdominal bloating. The patient is referred to the gynaecology department at their local hospital and undergoes an endometrial biopsy. The biopsy shows both cytological and architectural changes with nuclear polymorphism and significant cellular atypia.
What is the likely diagnosis?
- endometrial hyperplasia with atypia
A patient presents to their GP with postmenopausal bleeding for the last 3 months and abdominal bloating. The patient is referred to the gynaecology department at their local hospital and undergoes an endometrial biopsy. The biopsy shows both cytological and architectural changes with nuclear polymorphism and significant cellular atypia.
- endometrial hyperplasia with atypia
What is the patient at risk of?
Endometroid adenocarcinoma
A patient presents to their local practice nurse for a smear test as part of the national cervical screening program. Cytology is obtained from the patient. The result is sent to the practice and the patient a few weeks later. The results shows borderline/ low grade CIN.
What is the main aim of the cervical screening program?
to detect pre-invasive disease in order to avoid neoplastic changes occurring
A patient presents to their local practice nurse for a smear test as part of the national cervical screening program. Cytology is obtained from the patient. The result is sent to the practice and the patient a few weeks later. The results shows borderline/ low grade CIN.
What would be the next step in management of this patient?
- HPV blood test
- if positive, patient referred to colposcopy
for further assessment - if negative, return to normal recall
