Pathology of the Cervix, Vulva and Vagina Flashcards
What are the layers of the normal ectocervix?
Exfoliating cells Superficial cells Intermediate cells Parabasal cells Basal cells Basement membrane
What is present on the surface of the normal endocervix?
Cilia
What is the transformation zone?
Squamo-columnar junction between ectocervical (squamous) and endocervical (columnar) epithelia
When does the position of the TZ alter during life? (physiological)
Menarche Pregnancy Menopause
What is cervical erosion?
Exposure of delicate endocervical epithelium to acid environment of vagina, leading to physiological squamous metaplasia.
What are nabothian follicles?
Mucus producing gland on surface of the cervix
What are the inflammatory pathologies of the cervix?
Cervicitis Cervical polyp
What are the neoplastic pathologies of the cervix?
Cervical intraepithelial neoplasia (CIN) Cervical cancer
How does cervicitis present?
Often asymptomatic, can cause infertility due to simultaneous silent Fallopian tube damage
What is follicular cervicitis?
Sub-epithelial reactive lymphoid follicles present in cervix
What are the causes of cervicitis?
Chlamydia trachomatis Herpes simplex viral infection
What is a cervical polyp?
Localised inflammatory outgrowth
What can cervical polyps cause?
Bleeding if ulcerated
What are the types of cervical cancer?
Squamous carcinoma Adenocarcinoma
HPV has a ______, _____ stranded DNA, protected by ____ proteins.
HPV has a circular, double stranded DNA, protected by capsid proteins.
More than __ HPV subtypes are known, HPV __ & __ cause 70% of all cervix cancers.
More than 100 HPV subtypes are known, HPV 16 & 18 cause 70% of all cervix cancers.
How does HPV infection cause cancer?
Infection by HPV infects epithelial cells in the cervical mucosa. HPV DNA integrates into the cellular genome when causing cancer.
What increases risk of CIN?
Many sexual partners
How does the vulnerability of SC junction in early reproductive life contribute to CIN/cervical cancer?
Age at first intercourse Long term use of oral contraceptives Non-use of barrier contraception
What are the risk factors for CIN/cervical cancer?
Persistence of High risk HPV types (16, 18) Vulnerability of SC Junction in early reproductive life Smoking: 3x risk Immunosuppression
Describe the appearance of HPV 6 and 11 infection?
Genital warts Conduloma acuminatum: thickened papillomatous squamous epithelial with cytoplasmic vacuolation (koilocytosis)
Describe infection with HPV 16 & 18
Infected epithelium remains flat, but may show koilocytosis- which can be detected in cervical smears
HPV infection –> High grade CIN (_ _____- _ ____)
HPV infection –> High grade CIN (6 months- 3 years)
High grade CIN –> Invasive cancer ( _ to __ years)
High grade CIN –> Invasive cancer ( 5 to 20 years)
What is CIN?
Cervical intraepithelial neoplasia- pre-invasive stage of cervical cancer
Where does CIN occur?
Transformation zone. Can involve large area
What is seen in CIN?
Dysplasia of squamous cell
How can CIN be detected?
Asymptomatic- detected by cervical screening
What is the progression from Normal squamous epithelium to CIN 3?
Normal squamous epithelium Koilocytosis CIN 1 CIN 2 CIN 3
What is seen in histology of CIN?
- delay in maturation/differentiation
- nuclear abnormalities
- excess mitotic activity
What is seen as a result of delay in maturation/differentiation in CIN?
Immature basal cells occupying more of epithelium
What nuclear abnormalities are seen in CIN?
- hyperchromasia
- Increased nucleocytoplasmic ratio
- pleomorphism
What is seen as a result of excess mitotic activity in CIN?
Situated above basal layers
Abnormal mitotic forms
Often _______ (indicating HPV infection) also present.
CIN is graded I-III depending on _____ of;
- delay in ______/_________
- ______ abnormalities
- excess ______ activity
Often koilocytosis (indicating HPV infection) also present.
CIN is graded I-III depending on severity of;
- delay in maturation/differentiation
- nuclear abnormalities
- excess mitotic activity
What is CIN I?
Basal 1/3 of epithelium occupied by abnormal cells.
- Raised numbers of mitotic figures in lower 1/3*
- Surface cells quite mature but nuclei slightly abnormal.*
What is CIN II?
Abnormal cells extend to middle 1/3
- mitoses in middle 1/3
- abnormal mitotic figures*
What is CIN III?
Abnormal cells occupy full thickness of epithelium
Mitosis, often abnormal present in upper 1/3
What percentage of CIN III progress to invasion?
12%
What cancer makes up 75-95% of malignant cervical tumours?
Invasive squamous carcinoma
What does invasive squamous carcinoma develop from?
Pre-existing CIN
What are the stages of invasive squamous carcinoma?
- Stage 1A1- depth up to 3mm, width up to 7mm
- Stage 1A2- depth up to 5mm, width up to 7mm
- Stage 1B- confined to cervix
- Stage 2- spread to adjacent organs (vagina, uterus etc)
- Stage 3- involvement of pelvic wall
- Stage 4- distant metastases or involvement of rectum or bladder
What are the symptoms of invasive carcinoma?
- Usually none at microinvasive and early invasive stages (Detected at screening)
- Abnormal bleeding
- post coital
- post menopausal
- brownish or blood stained vaginal discharge
- contact bleeding- friable epithelium
- pelvic pain
- haematuria/urine infections
- ureteric obstruction/renal failure
Describle local spread of squamous carcinoma
Uterine body, vagina, bladder, ureters, rectum
Describe lymphatic spread of squamous carcinoma
Pelvic, para-aortic nodes
Describe haematogenous spread of squamous carcinoma?
Liver, lungs, bone
How does squamous carcinoma spread?
Local
Lymphatic
Haematogenous
How is squamous carcinoma graded?
Well differentiated
Moderately differentiated
Poorly differentiated
Undifferentiated/anaplastic
What is cervical glandular intraepithelial neoplasia?
Preinvasive phase of endocervical adenocarcinoma
What is the origin of CGIN?
Endocervical epithelium
Why is CGIN missed?
More difficult to pick up on smear
Describe the prognosis of endocervical adenocarcinoma?
Worse than squamous carcinoma
Endocervical carcinoma are responsible for _-__% of cervical cancer
Some are _____ (________) arise from a common cell of origin
Endocervical carcinoma are responsible for 5-25% of cervical cancer
Some are mixed (adenosquamous) arise from a common cell of origin
What is the epidemiology of adenocarcinoma?
Higher S.E class
Later onset of sexual activity
Smoking
HPV- particularly 18
What diseases are driven by HPV?
- vulvar intraepithelial neoplasia- VIN
- Vaginal intraepithelial neoplasia- VaIN
- Anal intraepithelial neoplasia, AIN
What is VIN also known as?
Paget’s disease
unusual kind of skin cancer that arises from glandular cells. This disease appears as a red, velvety area with white islands of tissue on the vulva.
What is the epidemiology (age) of VIN?
- bimodal
- young women: often multifocal, recurrent or persistent causing treatment problems
- older women: greater risk of progression to invasive squamous carcinoma
CIN often presents with?
synchronus CIN & VaIN
What is vulvar invasive squamous carcinoma?
Arises from normal epithelium or from VIN
Usually presents in elderly women, ulcer or exophytic mass
Vulvar invasive squamous carcinoma are usually ____ differentiated (______ are an extremely painful well differentiated type)
Vulvar invasive squamous carcinoma are usually well differentiated (verrucous are an extremely painful well differentiated type)
What is the most important prognostic factor for vulvar invasive squamous carcinoma?
Spread to inguinal lymph nodes
What is the treatment for vulvar invasive squamous carcinoma?
Radical vulvectomy and inguinal lymphadencetomy
What is the prognosis for vulvar invasive squamous carcinoma?
90% 5 year survival- node negative
<60% 5 year survival- node positive
Descreibe the presentation of vulvar paget’s disease?
Crusting rash
What does tumour arise from in vulvar paget’s disease?
Sweat gand in skin
Tumour cells in epidermis, contain mucin
What are some infectious vulval diseases?
- Candida (Particularly diabetics)
- Vulvar warts (HPV 6 & 11)
- Bartholin’s gland abscess (blockage of gland duct)
What are some non-neoplastic epithelial disorders of the vulva?
- lichen sclerosis
- other dermatoses
- lichen planus
- psoriasis
What causes atrophy of the vulva?
Post-menopause
- VaIN :Vaginal intraepithelial neoplasia.
- May also have _____ and _____ lesions.
- VaIN :Vaginal intraepithelial neoplasia.
- May also have cervical and vulval lesions.
Squamous carcinoma: Less common than _____ and _____ counterparts. A disease of the _____.
Squamous carcinoma: Less common than cervical and vulval counterparts. A disease of the elderly.
Melanoma is ____ and may appear as a ______
Melanoma is rare and may appear as a polyp
