Premenopausal (75%)

Premenopausal (75%)

• Premenopausal (75%)

• No racial predisposition

Vulvovaginal / perianal intraepithelial neoplasia is more prevalent in HIV infected women (9 % & 1 %)

• Vulvovaginal / perianal intraepithelial neoplasia is more prevalent in HIV infected women (9 % & 1 %)

• 7% HIV positive with vulvovaginal or perianal condylomata acuminata  high-grade intraepithelial lesions

Table 2

• Table 2

Basaloid– thickened epi. with flat, smooth surface, composed of atypical immature parabasal type cells with numerous mitotic figures and enlarged hyperchromatic nuclei

• Basaloid– thickened epi. with flat, smooth surface, composed of atypical immature parabasal type cells with numerous mitotic figures and enlarged hyperchromatic nuclei

• Warty(condyloma) – undulating or spiking surface, condyloma appearance, cellular proliferation with numerous mitotic figures and abnormal maturation

• Differentiated (simplex) – thicked and parakeratotic epi. with elongated and anastomosing rete ridges, abnormal cells confined to parabasal and basal portion of the rete pegs with little or no atypia above the basal layers, basal cell positive to P53 which extend above the basal layers to epidermis, a precursor of HPV-negative vulvar cancer

Embryonic cloaca anogenital epithelium

• Embryonic cloaca anogenital epithelium

• (cervix, vagina, anus, lower 3cm of rectal mucosa up to the dentate line)

• Susceptible to similar exogenous factors HPV !!

• CIN, VIN, VAIN, PAIN may multifocal !!

• The risk of neoplastic progression of VIN to invasive cancer :lower than CIN !!

• Genetic instability risk to invasive Dz.

Unifocal

• Unifocal

• Postmenopause

• No relationship to HPV

• Histology: differentiated type

Pruritus

• Pruritus

• Altered appearance of the vulva

• Palpable abnormality

• Perineal pain or burning

• Dysuria

• 50% asymptomatic !!

Physical examination

• Physical examination

• --inspection & palpation (mass, color, ulcer)

• --most multifocal, non-hairy part

• --raised/verrucous white, red, brown, pink, gray, macular lesion

Acetic acid

• Acetic acid

• -- 2-5% acetic acid, several minutes, dense acetowhite, punctation or vascular abnormality (may be a sign of invasive cancer)

Biopsy

• Biopsy

• -- local anesthetic

• -- Punch Bx & Excisional Bx.

• Differential diagnosis

• -- Invasive squamous cell cancer, lichen sclerosis, planus

• -- difficult to distinguish esp. occur concurrent

Prevent development of invasive vulvar cancer and relieve symptoms

• Prevent development of invasive vulvar cancer and relieve symptoms

• Preserve vulvar anatomy and function

• Based on biopsy results, extent of disease and symptom

Wide local excision

• Wide local excision

• -- individual lesion with a 1 cm margin

• -- removal of epidermis

• -- satisfactory cosmetic result

• # remove small amount of dermis to insure invasive disease

Laser ablation

• Laser ablation

• -- multi-focal or extensive

• -- cosmetic advantages

• -- effective in multiple small lesions (VIN I, II)

• -- evaluate the coexistent invasive cancer previously

• -- use colposcopy to control depth (1 mm)

• -- cure rate: 70% (1st), 1/3 need 2nd, 3rd

Imiquimod

• Imiquimod

• -- topical immune response modifier

• -- FDA-proved to treat anogenital warts

• -- treat multifocal VIN II or III…

Natural Hx. without Tx

• Natural Hx. without Tx

• -- high grade: varies from persistence, progression to remission

• -- 9% untreated VIN III invasive cancer ( 8 yrs 內)

4th common GYN cancer

• 4th common GYN cancer

• Postmenopause

• 65 y/o

Unifocal vulvar plaque, ulcer or mass (most labia majora)

• Unifocal vulvar plaque, ulcer or mass (most labia majora)

• 5% multifocal (evaluate vulvar and perianal skin, cervix, vagina)

• Synchromous second neoplasm (most cervical neoplasm): 22%

• Pruritus (vulvar bleeding, discharge, dysuria, enlarged groin LN…)

Biopsy !!

• Biopsy !!

• -- Determine the depth and nature of stromal invasion

• -- Taken from the center of the lesion

• -- If multiple abnormal areas: multiple biopsies to map

• -- Use acetic acid & colposcopy if not sure !

Squamous cell carcinoma

• Squamous cell carcinoma

• -- Variant: verrucous carcinoma

• Melanoma

• Basal cell carcinoma

• Sarcoma

• Extramammary Paget’s disease

• Bartholin gland adenocarcinoma

Keratizing, differenrtiated or simplex type

• Keratizing, differenrtiated or simplex type

• -- More common

• -- Older p’ts

• -- No related to HPV infection

• -- Associated with vulvar dystrophy

Squamous cell carcinoma of the vulva, keratinizing type. The multiple pearl formations consist of laminated keratin.

• Squamous cell carcinoma of the vulva, keratinizing type. The multiple pearl formations consist of laminated keratin.

Early invasive carcinoma of vulva originating from vulvar intraepithelial neoplasia.

• Early invasive carcinoma of vulva originating from vulvar intraepithelial neoplasia.

• An irregular nest of malignant cells extend from the base of rete pegs. Desmoplastic stromal reaction and chronic inflammation are useful diagnostic signs of stromal invasion. The depth of stromal invasion is measured from the base of the most superficial dermal papilla vertically to the deepest tumor cells.

Verrous configuration

• Verrous configuration

• Papillary fronds without central connective tissue core (typical of condyloma acuminata)

• Rarely metastasis to LN

• May local destructive

2nd common, 5% of primary, 3~7% of all melanomas

• 2nd common, 5% of primary, 3~7% of all melanomas

• Postmenopause, white, nonHispanic

• 68 y/o

• Pigmented lesion

• Most clitoris or labia minora

Vulvar melanoma. Spindle-shaped melanoma cells form interlacing bundles, and some contain melanin pigment (right upper corner). Epidermal invasion is evident in the form of Pagetoid migration (left upper corner).

• Vulvar melanoma. Spindle-shaped melanoma cells form interlacing bundles, and some contain melanin pigment (right upper corner). Epidermal invasion is evident in the form of Pagetoid migration (left upper corner).

Basal cell carcinoma

• Basal cell carcinoma

• -- 2% / 2%

• -- postmenopausal Caucasian women

• -- locally invasive

• -- rodent ulcer with rolled edges and central ulceration

• -- high incidence of antecedent or concomitant malignancy

Intraepithelial adenocarcinoma

• Intraepithelial adenocarcinoma

• < 1%

• 60~70 y/o

• Pruritus (70%), eczematoid appearance, well-demarcated, slightly raised edges with a red background, dotted with small pale islands

• Dx.: Bx. Histopathology !

• Persistent pruritus with no response to antieczema therapy within 6 weeks Bx. !!

• Invasive adenocarcinoma may be beneath or within the surface lesion synchronous neoplasm !!

Rare, 57 y/o

• Rare, 57 y/o

• Duct lined by stratified squamous epi. which changes to transitional epi. as the terminal ducts are reached

• If squamous lesion related to HPV infection !!

• Bartholin gland tumor in a postmenopausal women or > 40 y/o Bx. to survey the malignancy !!

• Metastasis is common (due to rich vascular and lymphatic network)

Direction extension to adjacent structure

• Direction extension to adjacent structure

• Lymphatic embolization: may occur early, begins at superficial inguinal LN drainage to deep inguinal and femoral LN pelvic lymphatics

Hematogenous dissemination

• Hematogenous dissemination

• -- typically late in the course

• -- rare in p’ts without inguinofemoral LN involvement

Clinical staging

• Clinical staging

• -- PE (palpate LN: inguinal, axillary, supraclavicular )

• -- PV (Cx. Cytology, colposcopy of Cx, vagina & vulva due to multifocal lesions)

• -- Radiographic and endoscopic studied in large tumor or suspected metastasis

Surgical staging—FIGO

• Surgical staging—FIGO

• -- Inguinofemoral LN status: the most important predictor of overall prognosis (clinical assessment of groin LN: false negative)

• -- Inguinofemoral lymphadenctomy (except stage IA)

• # Unilateral: unilateral lesion, distant from the midline

• # Bilateral: midline or bilateral lesions or unilateral lesion with positive ipsilateral LN

Less invasive means to assess LN status

• Less invasive means to assess LN status

• Sentinel node biopsy (unilateral)

• Reduce acute and long-term complications

• (1)Lymphoscintigraphy using radiolabeled human albumin and an intraoperative γ-detecting probe

• (2)Peritumor injection of isosulfan blue dye

•  Bilateral groin involvement is common in midline vulvar cancers  not suggest !!

Goal

• Goal

• -- Cure the cancer

• -- Minimize perioperative morbidity

• -- Maximize long-term psychosexual and physical well-being

Stage IA

• Stage IA

• Radical local excision without LN dissection

• Inguinofemoral LN metastases : <1 %

• Wide, deep excision of the lesion down to the inf. fascia of the urogenital diaphragm

• Clear margin: 2 cm (at least 1 cm)

Stage IB

• Stage IB

• Inguinofemoral LN metastases : >8 %

• Radical local excision + ipslateral inguinofemoral LN dissection ( lateralized lesion) or bilateral inguinofemoral LN dissection (central lesions)

Stage II

• Stage II

• Modified radical vulvectomy + ipslateral / bilateral inguinofemoral lymphadenectomy

• Clear margin: at least 1 cm

Small (T1) vulvar carcinoma at the posterior fourchette.

• Small (T1) vulvar carcinoma at the posterior fourchette.

Adjuvant R/T ?

• Adjuvant R/T ?

• -- appears benefit those with two or more positive inguinal LN or positive/closes surgical margin

• -- The minimum number of nodes that should be examined is unclear !!

• -- GOG study: adjuvant R/T to high risk p’ts (> 4.1 cm tumor, positive margins, lymphovascular space invasion) with negative LN reasonable to consider !!

Stage III and IV

• Stage III and IV

• Radical vulvectomy combined with pelvic exenteration high morbidity !!

• Preoperative radiation therapy: downstage the tumor, allow a more conservative surgery

• Chemoradiotherapy: locally advanced vulvar cancer (cisplatin + 5-FU, Mitomycin + 5-FU

Stage III and IV

• Stage III and IV

• Neoadjuvant chemotherapy—for recurrent or locally advanced disease

• --Decreased tumor bulk and permit later resection

• --Result is inf. to chemoradiotherapy

Radical local excision

• Radical local excision

• Bx. suspicious LN, if positive inguinofemoral lymphadenectomy

• RT: contraindication !! (induce anaplastic transformation and increase the likehood of metastases)

• Recurrence: surgical excision

Sarcomas

• Sarcomas

• -- Wide local excision

• -- Lymphatic metastases: uncommon

• # Exception: Rhabdomyosarcoma primary C/T + surgery

Local excision or vulvectomy depend upon the extent of disease

• Local excision or vulvectomy depend upon the extent of disease

• Poor prognostic markers: greater depth of invasion and lymphovascular involvement

• Moh’s micrographic surgery: lower recurrence rate

• RT or C/T ?

• Long-term F/U (high risk of recurrence)

• Annually inspection of vulva & survey tumors at other site (breast, lung, colorectum, gastric, pancreas, ovary)

Bartholin gland cancer

• Bartholin gland cancer

• -- radical vulvectomy + bilateral groin & pelvic LN dissection

• --Extensive deep dissection

stage, tumor size, depth of invasion, capillary lymphatic space, older age, degree of nodal involvement

• stage, tumor size, depth of invasion, capillary lymphatic space, older age, degree of nodal involvement

Twice yearly

• Twice yearly

• Inspection, palpation of vulva, skin bridge and inguinal nodes

• Colposcopy & Bx. If suspicious

Local, inguinal or distant

• Local, inguinal or distant

• 5-yr survival rate: according to location

• -- Perineal : 60 %

• -- Inguinal and pelvic : 27 %

• -- Distant : 15 %

• RT add to surgery or C/T or a sole modality

• Salvage cytotoxic C/T: for distant metastases

• -- most active agents: those against squamous cell tumors at other sites ( Cisplatin, MTX, bleomycin, mitomycin C, cyclophosphamide)

• --duration of response usually low and short

Anti-EGFR tyrosine kinase inhibitors…

• Anti-EGFR tyrosine kinase inhibitors…