5. Vulva, Vagina, Cervix

Question 1

What is the structure of the vulva?

Answer 1

Vulva is lined with squamous epithelium and has labia major / minora

Question 2

What are vulvar conditions?

4

Answer 2

1. Bartholian cyst: cystic dilatation of Bartholian gland due to obstruction of the duct (unilateral cystic lesion)
2. Vulvar dystrophies: Lichen simplex, Lichen sclerosis
3. Vestibular adentitis: ulceration of mucosa and glands
4. Tumours: VIN, Paget’s disease, carcinoma

Question 3

How do vulvar conditions clinically present typically?

Answer 3

1. Leukoplakia

2. Vitiligo: loss of pigmentation (death of melanocytes)

Question 4

Describe the vulvar dystrophies:

1. Lichen sclerosis
2. Lichen simplex

Answer 4

1. Lichen Sclerosis:
   - Autoimmune inflammatory condition, occurring at any age (most usually post-meno women)
   - CP: leukoplakia followed by atrophy, scarring
   - Patho: thinning of epidermis, degeneration of basal layer, fibrosis (sclerosis) of dermis, and band-like lymphocytic infiltrate under sclerosis
   - Check for dysplasia and malignancy even though it is benign it can progress to SCC
2. Lichen Simplex:
   - Non specific dx —> benign = no risk of progression to SCC
   - CP: leathery vulvar skin, leukoplakia, chronic irritation (itch)
   - Patho (micro): hyperplasia of vulvar squamous epithelium, hyperkeratosis, ancathosis, variable inflammatory infiltrate of dermis

Question 5

List the benign and malignant vulvar neoplasms:
Benign: 2
Malignant: 3

Answer 5

Benign:

1. Papillary Hidradenoma
2. Condyloma Acuminatum

Malignant:

1. Carcinoma: VIN —> SCC + Paget’s Disease
2. Melanoma

Question 6

What is Papillary Hidradenoma?

Answer 6

Nodular lesion on the labia that can ulcerate
Papillary projections of the 2 cell layers - columnar and myoepithelial
* similar to intraductal papilloma of the breast

Question 7

What is Condyloma Acuminatum?

Answer 7

Warty neoplasm of vulvar skin (large)
Doesn’t progress to carcinoma
Histo: koilocytes (hallmark of HPV-infected cells)
Sexually transmitted, a/w with HPV 6+11 (low risk)
Acanthosis, hyperkeratosis, parakeratosis

Question 8

What is VIN?

What is differentiated VIN?

Answer 8

Vulvar Intra-Epithelial Neoplasia 
High risk HPV —> VIN —> Carcinoma 
Dysplastic precursor characterized by: 
1) Increase in mitotic activity 
2) Koilocytic change 
3) Nuclear atypia
4) Disordered cell maturation 
- Risk of invasive tumour increases with age and immunosuppression 

Differentiated VIN: not HPV related (TSG, p53) get leukoplakia

Question 9

What is Paget’s Disease?

Answer 9

Malignant epithelial cells of the epidermis of the vulva (carcinoma in-situ NOT invasive)
- CP: ulceratous, purifitic, red, crusted skin lesion
- Histo: clear halo, which separates from surrounding cells
PAS+, Keratin+, S-100- (separates from Melanoma which is the opposite)

Question 10

What are the types of SCC?

2

Answer 10

SCC have 2 types:

1) HPV related: from VIN (HPV 16 + 18)
2) Non-HPV related: from Lichen Sclerosis

Question 11

What are the vaginal conditions?

3

Answer 11

1. Congenital anomalies: adenosis —> persistence of columnar epithelium (failure of fusion of Müllerian ducts) - increase incidence with women exposed to DEC
2. Infection
3. Tumours
   —> SSC: precursor is VaIN (vaginal intraepithelial neoplasia), HPV associated // when spread to lymph node low 1/3 spread to inguinal nodes and upper 2/3 spread to iliac nodes
   —> Clear cell adenocarcinoma: malignant proliferation of glands with clear cytoplasm (due to DEC exposure)
   —> Embryonal Rhabdomyosarcoma: malignant mesenchymal proliferation of immature skeletal muscle
   - CP: bleeding and grape like protrusion from vagina aka Sarcoma Botyroids
   - Patho: Rhabdomyoblast = cytoplasmic cross striation and positive for desmin and myogenin

Question 12

What is the structure of the cervix?

Answer 12

Neck of uterus
Outer portion (exocervix) = non keratinizing squamous epithelium 
Inner portion (endocervix) = columnar epithelium
- junction between the 2 = squamo-columnar junction —> can get metaplasia and metaplastic squamous epithelium is susceptible to HPV infection

Question 13

What is HPV?

Answer 13

HPV: viral oncogene transmitted by sexual contact
- HPV enters vulnerable cell —> vulnerable cell either regresses or persists —> HPV E6+E7 proteins inactivate TSG (Rb and p53) which allows the cell to enter precancerous stage —> CGIN —> adenocarcinoma OR CIN3 —> SCC (risk of CIN depends on type of HPV = high risk: HPV 16, 18, 31, 33 / low risk: HPV 6, 11)

Question 14

Describe CIN

Answer 14

Cervical Intraepithelial Neoplasia

• Characterized by
  1. Nuclear atypia
  2. Increase in mitotic activity
  3. DISORDERED cellular maturation
  4. Koliocytic change
• Divided into grade based on the epithelial involvement with immature dysplastic cells (CIN1, CIN2, CIN3, CIS (carcinoma in situ) —> invasive carcinoma
• CGIN —> adenocarcinoma in situ

Question 15

Describe cervical cancer

Answer 15

Invasive carcinoma of the cervical epithelium
CP: vaginal bleeding, postcoital bleeding, cervical discharge
2nd most commonest cancer in women
CIN3 —> SCC
CGIN —> adenocarcinoma
Also: neuroendocrine carcinoma and adenosquamous carcinoma
Prognosis: based on depth of invasion
- Microinvasion: early SCC
- More than microinvasion: SCC
Dx: FIGO, TMN

Question 16

How do you control cancer?

4

Answer 16

1. Primary prevention
2. Secondary prevention
   A) Cervical screening: cytology / HPV testing —> PAP smear (scrapes cells from jxn and views it, dysplastic cells graded)
   - Cytology: assess for dyskaryosis
   B) Cervical examination (colonoscopy): done if PAP was abnormal —> direct visualization of cervix, biopsy, treatment, excise lesion before cancer develops
   C) Lesion excision: large bx, LLETZ, cone, hysterectomy , chemo / radio
3. Early diagnosis
4. Immunization: vaccine for HPV 6, 11 (Condylomas - benign vulvar neoplasms) and HPV 16,18 (CIN and carcinoma)

Question 17

What is an example of hereditary cancer syndrome?

Answer 17

Peutz Jeghers Syndrome: adenocarcinoma of cervix (not related to HPV)