Vulva

Question 1

Lichen Sclerosus

Answer 1

• Immune mediated
• Fibroinflammatory condition
• Male version: Balanitis xerotica obliterans

Clinical:
* Commonly postmenopausal
* Intensly pruritic
* Can become excoriated

• Increased risk of:
• Differentiated VIN (HPV independant)
• SCC

Macro:
* Irregular, ill-definied, hypopigmented patches
* Multiple, bilateral, sometimes symmetrical
* Advanced stages: skin is shiny and wrinkled (Cigarette paper)
* Atrophic labia

Micro:
* Lichenoid inflammatory reaction
* Hyalinasation and homogenisation of superficial dermal collagen.
* Displacement of inflammatory cells downwards
* Atropic epidermis

IHC:
* p53 +ve
* p16 -ve (HPV stain)

Question 2

Bartholin Gland Cyst

Answer 2

• Vagina
  *** Posteriolateral **
• Inferior thrid

Clinical:
* Blockage of gland
* Inflammation
* Trauma
* Childbirth
* Infection - Chlamydia, Gonorrhoea

Micro:
* **Transitional or squamous **epithelium
* Adjacent mucinous Bartholin glands are present in cyst wall
* Surrounding inflammation

Question 3

Gartner Duct Cyst

Answer 3

• Vaginal cyst in children
• Anteriolateral
• 11 o’clock and 1 o’clock

Cause:
* Remnant of mesonephric duct (Wolffian Duct)
* Fails to regress —> forms Gartner duct cyst

Micro:
* ** Cuboidal to low columnar** non-mucinous epithelial

Question 4

Aggressive Angiomyxoma

Answer 4

• Rare
• Locally aggressive
• Mesenchymal neoplasm

Clinical:
* Unique to soft tissues of the lower genital tract, pelvis and perineum
* Often large, >10cm
* Rapid growth may occur during pregnancy
* Most commonly in women of reproductive age

• Local recurrance in 30-40%
• Distant mets/death rare
• GnRH agonist therapy –> recurrent or unresectable disease.

Macro:
* Poorly circumscribed/Infiltrative
* Gelatenous cut surface
* Recurrent tumours may be more fibrotic

Micro:
* Poorly marginated
* Hypocellular
* Copious myxoid matrix
* Bland spindled cell
* Medium to large sized, hyalinised blood vessels
* Condensation of fibrillary collagen around vessels

IHC:
Myogenic markers:
* Desmin
* SMA
* Calponin
* MSA

• May be focal
• Highlight perivascular myoid bundles
• ER, PR
• HMGA2 (90%) –> highly sensitive but not specific

Question 5

Angiomyofibroblastoma

Answer 5

• Rare benign tumour
• Painless mass
• <5mm
• Occasionally pedunculated
• No potential for recurrence

Macro:
* Well-circumscribed
* Non-encapsulated
* Tan-white cut surface

Micro:
* Alternating zones of hyper and hypocellularity
* Abundant thin-walled blood vessels
* Blank spindled, plasmacytoid and epithelioid stromal cells.
* Variable oedematous to collagenous matrix.
* Scattered lymphos and mast cells

IHC:
* Vimentin +
* Desmin +
* ER, PR +
* SMA variable
* CD34 variable

Question 6

Hidradenoma Papilliferum

Answer 6

• Benign
• Often an asymptomatic nodule
• Almost always found in the vulva/perianal region
• Virtually identical to intraductal papilloma of the breast.

Micro:
* Sharply circumscribed
* Maze-like glandular and papilary architecture
* No connection to overlying epithelium
* Glands: Inner layer of cuboidal cells, outer layer of myoepithelial cells.
* Mitotic figures are rare

IHC:
Myoepithelial cells:
* S-100
* SMMS
* P63

Question 7

Extramammary Paget’s Disease

Answer 7

• Vulva is the most common site
• Local recurrences are common
• Pruritic, erythematous lesions
• Considered to be in-situ adenocarcinoma
• Probably arises from multipotential cells located in the basal layer of epidermis

Micro:
* Large, pale tumour cells
* Often ,istalen for melanoma

IHC:
Intracytoplasmic mucin:
* Mucicarmine +ve
* PAS
* Alcian blue

Three types:

Primary cutaneous VPD (Type 1)
* CEA+
* CK7+
* GCDFP-15+

Secondary to intestinal malignancy (Type 2)
* CEA+
* CK20+
* CDX2+
* MUC2+

Secondary to urological malignancy (Type 3)
* CEA+
* p63+
* CK7 +/-
* CK20 +
* Uroplakin-III +ve
* GATA-3 +

Question 8

Condyloma Acuminatum

Answer 8

• Benign
• Verrucous papillary lesion
• Caused by HPV
• Usually low risk types –> HPV6 and HPV11 are most prevalent types

Micro:
* Acanthosis
* Papilomatosis
* Parakeratosis
* Hypergranulosis
* Hyperkeratosis
* Thick rete ridges
* Koilocytic change

Question 9

Squamous Intraepithelial Lesion (SIL) / Vulval Intraepithelial Neoplasm (VIN)

Answer 9

• Precursor lesion of HPV-associated Vulvar carcinoma
• Reproductive age women
• High Grade SIL is most frequent type
• More common in people with HIV

Risk factors:
* Smoking
* Oral contraception
* Herpes infection
* HPV infection elsewhere

Aetiology:

• HSIL: high risk types –> HPV 16 and **18, 31, 33, 45 **
• LSIL: low risk types –>** 6, 11** and **High risk types **

Prognosis:
* most LSIL regress spontaniously
* 9% HSIL progress to SCC if untreated

Question 10

LSIL (VIN1)

Answer 10

• Low risk HPVs –> 6, 11

Micro:
* Koilocytosis/HPV cytopathic effect in upper two thirds of epithelium
* Proliferation of basal/parabasal-like cells –> lower third if epithelium
* Mitotic figures limited to lower third of epithelium

Question 11

HSIL (VIN2 and 3)

Answer 11

• High risk HPV –> 16, 18

Micro:
* VIN 2 –> loss of maturation lower two thirds
* VIN 3 –> loss of maturation full thickness
* Atypical mitotic figures are readily identifiable
* Koilocytosis –> within or adjacent

IHC:
* P16 –> strong, block-like
* P53 –> scattered suprabasally, lack of staining in basal layer

Basaloid/Warty SCC

Imiquimod and other antivirals

Question 12

Differentiated Type Vulvar Intraepithelial Neoplasia (dVIN)

Answer 12

• Precursor lesion of HPV independent vulvar squamous cell carcinoma.
• Post-menopausal women

Cause:
* Chronic inflammatory dermatoses
* Lichen sclerosis
* Lichen simplex chronicyus

Micro:
* Mild to moderate atypical cells in basal and parabasal layers.
* Lacks full thickness atypia
* Enlarged squamous cells with eosinophillic cytoplasm
* Vesicular nuclei, prominent nucleoli
* Acanthosis, parakeratosis, anastomosis of rete ridges

Molecular:
* HPV ISH negative
* Mutations in TP53 - basal/parabasal over expression or absent
* Also can have TP53 wildtype variant - scattered expression

• More likely to progress to invasive carcinoma than usual VIN
• Shorter latency to become invasive

IHC:
* P53 overexpression in lower third of epithelium
* Ki67 confined to basal levels
* p16 -ve

Keratinising SCC

Role of immune checkpoint inhibition

Question 13

Vaginal Polyp

Answer 13

• Women of childbearing age
• Often found during pregnancy

Macro:
* Soft, polypoid/papillary mass
* Usually lower third of vagina
* Usually <4cm

Micro:
* Squamous epithelium
* Plump, cytologically atypical myofibroblasts
* Bizarre multinuclei giant cells may also be present
* Mitotic activity is generally low.

IHC:
Stromal cells:
* Vimentin
* Desmin
* ER
* PR