Vulva

Disclaimer

This manual is not a substitute for consultation with an appropriate specialist.
The contents of this manual have been developed through consensus of a Provincial Tumour Group. Please note the various update dates for each section as some of the content of the manual may not be up to date.

1. Diagnosis

Revised November 2020

Predisposing Factors/Prevention

Vulvar Intraepithelial Neoplasia (VIN), is a precursor lesion in some cases:

Usual type VIN (warty, basaloid and mixed)

HPV-related

Differentiated VIN

Not HPV-related
Generally preceded by chronic inflammatory conditions of the vulva (lichen sclerosis, squamous hyperplasia)

In 2004, the International Society for the Study of Vulvovaginal Diseases (ISSVD) developed a new classification of VIN. The term VIN1 is no longer used, and VIN2 and VIN3 are now both called VIN.

VIN can be treated with wide local excision, and/or laser therapy. The use of topical imiquimod has also shown good response rates in women with usual type VIN.

Screening/Early Detection

There is no screening program for vulvar cancer. However, due to similar risk factors, women with a past history of HPV related cervical or vaginal cancer should have a careful inspection of their vulva as part of their regular follow-up. Women with lichen sclerosis, or with a past history of VIN should also have routine surveillance.

Vulvar cancer can be asymptomatic, but the majority of patients present with a vulvar lump or a vulvar ulcer. There is often pain associated with the lesion, along with a long-standing history of vulvar pruritus, bleeding or discharge. Most squamous cell carcinomas of the vulva occur on the labia majora, but the labia minora, clitoris, and perineum may also be primary sites. Advanced cases may present with an enlarged inguinofemoral node.

Diagnosis

The diagnosis needs to be confirmed with a biopsy prior to definitive management. The biopsy should include underlying stroma in order to assess for the depth of invasion. An office wedge or Keyes punch biopsy is usually sufficient.

Preferably, the entirety of the lesion should not be excised in order to obtain a tissue diagnosis, as this can make it challenging to plan the definitive excision.

Histological Classification:
Squamous cell carcinoma
Malignant Melanoma
Verrucous carcinoma
Paget's disease of the vulva
Adenocarcinoma
Basal cell carcinoma
Bartholin’s gland carcinoma

2. Staging

The staging of vulvar cancer is based on surgical findings.

FIGO 2021

FIGO Stage		Description
I		Tumour confined to the vulva, no nodal metastasis
	IA	Lesion < 2cm in size, confined to the vulva or perineum and with stromal invasion <1mm
	IB	Lesion >2cm in size or with stromal invasion >1mm, confined to the vulva or perineum
II		Tumour of any size with extension to adjacent perineal structures (lower third urethra, lower third vagina, anus), with negative nodes
III		Tumour of any size with extension to upper part of adjacent perineal structures or with positive inguinofemoral nodes
	IIIA	Tumour of any size with disease extension to upper two-thirds of the urethra, vagina or anus Or regional lymph node metastases <5mm
	IIIB	Regional lymph node metastases >5mm
	IIIC	Regional lymph node metastases with extracapsular spread
IV		Tumour invades other regional (upper 2/3 urethra, upper 2/3 vagina) or distant structures
	IVA	Disease fixed to pelvic bone or fixed to ulcerated inguinofemoral lymph nodes
	IVB	Any distant metastasis including pelvic lymph nodes

^* The depth of invasion is defined as the measurement of the tumour from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion

3. Management

The management of invasive vulvar cancer must be individualised. When considering treatment options, it is imperative to independently consider the management of

The primary vulvar lesion
The inguinofemoral lymph nodes

Microinvasive Vulvar Cancer (Stage IA)

1. The primary vulvar lesion

This lesion can be management with wide local excision, aiming for clear margins of 5mm.

2. The inguinofemoral lymph nodes

Groin evaluation is not necessary for microinvasive vulvar cancer.

Early Stage >Stage IA

1. The primary vulvar lesion

The vulvar lesion should be managed by a radical excision (radical vulvectomy or radical wide local excision). Aim for fresh surgical margins of >1cm which translates into >8mm formalin fixed margins.

The local recurrence risk increases as the disease free margin decreases, with up to 50% recurrence risk if the margin is <4.8mm¹. Other predictors of local recurrence are the depth of tumour invasion, the size of the tumour and the presence of lymphovascular space invasion.

If the margin is close, the patient should be re-evaluated for further local treatment with either re-excision or adjuvant radiation.

2. The inguinofemoral lymph nodes

Click on image below to enlarge.

The inguinofemoral lymph nodes need to be evaluated for all patients whose primary tumour is greater than 2cm in diameter or invades the stroma to a depth of greater than 1mm.

Studies have shown the feasibility and safety of a sentinel node procedure in lieu of a full inguinofemoral lymph node dissection in carefully selected patients, with a false negative rate of approximately 2%².

Appropriate candidates for a sentinel lymph node (SLN) assessment are patients with:

Unifocal tumour
Lesion <4cm in size
No palpably enlarged lymph nodes
No history of radical vulvar surgery that may interfere with the lymphatic drainage of the vulva

Patients who have vulvar lesions that are greater than 2cm away from the midline can have a unilateral lymph node assessment, while those with lesions within 2cm from the midline, or lesions that involve the anterior labia minora need a bilateral lymph node assessment.

If a patient has a negative SLN, they do not require any further nodal treatment. The isolated groin recurrence risk is 2.5%³.

Management of a positive SLN will depend on the size of the lymph node metastasis. For patients with one micrometastasis (≤2mm) they have the option of either having a full inguinofemoral lymph node dissection in the groin with the positive sentinel node or adjuvant radiation. Both options have a low risk of groin recurrence (around 2%) but the toxicity is higher with a full inguinofemoral lymph node dissection compared to adjuvant radiation⁴. Patients with one macrometastasis (>2mm) must undergo a full inguinofemoral lymph node dissection in the groin with the positive sentinel node. Radiation is not a safe alternative to full inguinofemoral dissection in patients with a macrometastasis⁴.

The current consensus is that for midline lesions (<2cm from the midline), it is reasonable to omit a full inguinofemoral lymph node dissection in the contralateral side to a positive sentinel node when that sentinel node was negative in that contralateral groin. Lateral lesions (>2cm from the midline) only need assessment of the ipsilateral groin⁵.

If a patient is found to have more than one metastasis of any size or there is extracapsular spread⁶, they should receive adjuvant radiation to both the groins and the pelvic nodes. The risk of pelvic nodal metastasis if there is a positive groin node is 20%.

A recurrence in a previously un-dissected groin is almost universally fatal.

Advanced Stage >= Stage 3

1. The primary vulvar lesion

Locally advanced vulvar cancer refers to FIGO stage III or IV carcinoma of the vulva, with local extension that infiltrates the urinary and or digestive tract or when the tumour is fixed to bone. If primary surgery would result in the need for a bowel or urinary stoma, it is preferable to have these women treated with primary radiation with chemosensitization (chemoradiation) followed by a more limited resection of the residual tumour bed if it is still persistent.

2. The inguinofemoral lymph nodes

a. Clinically normal nodes:

Patients with locally advanced vulvar cancer should have a Pelvic CT or PET/CT to evaluate for any suspicious nodes on imaging. If there are no suspicious nodes on the scan, bilateral full inguinofemoral lymphadenectomy can be performed. If final pathology reveals positive nodes, adjuvant radiation should be given to the groins and pelvis, as per early stage disease.

Alternatively, women with locally advanced disease can be treated with primary chemoradiation to the groins and pelvis.

The decision on whether or not women should have surgical nodal evaluation as compared primary nodal and pelvic radiation should be individualized. On one hand, having a full groin dissection followed by adjuvant radiation places the women at an extremely high risk of chronic lymphedema, however on the other hand, performing a full groin dissection may spare node-negative women (40%) the toxicities of radiation.

b. Bulky, but mobile groin nodes:

Bulky nodes should be biopsied in order to confirm the diagnosis. If there is no ability to biopsy the node preoperatively, an intraoperative frozen section should be performed. If the bulky node is metastatic, surgery should solely entail removal of the bulky nodes as all of these women will require adjuvant groin and pelvic radiation. If the bulky node is inflammatory, a full inguinofemoral lymph node dissection should be performed.

c. Fixed or ulcerated groin nodes:

After having a biopsy to confirm the diagnosis, patients with fixed or ulcerated groin nodes should receive primary chemoradiotherapy to the groins and the pelvis.

Prognosis:

FIGO Clinical Stage			5 Year Survival
1			90%
2			77%
3			51%
4			18%

Lymph node status is the most important prognostic factor. Patients with one microscopically positive node have a prognosis similar to FIGO stage 1. In women with 3 or more positive nodes, the 5 year survival is below 50%⁷.

Vulvar Melanoma:

This is the second most common malignancy of the vulva, with the majority of lesions involving the clitoris or the labia minora. The Clark or Breslow staging systems should be used in this disease rather than the FIGO staging criteria.

Primary Vulvar Lesions:

The preferred primary treatment of vulvar melanoma is surgery if feasible and not requiring an exenterative procedure.
A wide local excision of the primary tumour with a clinically negative margin should be attempted.
The exact minimal excision margin for melanomas is not entirely proven, but it is recommended that a clinical gross 1-cm margin circumferentially be achieved for a melanoma with a Breslow thickness of less than or equal to 2 mm and 2 cm for a Breslow thickness greater than 2 mm.
These margins correlate to pathologic negative margins of 0.8 and 1.6 cm, respectively.
Margin status is prognostic of locoregional control, but there seems to be no impact on overall survival.
For those tumours that are not resectable, radiotherapy combined with chemotherapy and immunotherapy is a consideration.

Inguinofemoral Lymph Nodes:

Sentinel Lymph Node mapping is now considered a standard approach in staging patients with newly diagnosed vulvar melanoma.
The SLN mapping seems most beneficial and accurate in patients with intermediate-thickness melanomas (Breslow thickness of 1- 4 mm).
The benefit in thin melanomas (<1 mm in Breslow thickness) seems not to be as great but may be considered in thin melanomas with higher risk features such as presence of ulceration or mitotic rate of 1/mm² or greater
SLN mapping may still be recommended for thick melanomas (Breslow thickness of >4 mm) despite less data specific to this group
Completion lymphadenectomy is not required in patients with a negative SLN
Completion lymphadenectomy is not required in patients with a positive SLN or in who the SLN could not be identified.
A full inguinofemoral lymphadenectomy can be considered in cases of clinically apparent nodal disease.

Locally Advanced / Unresectable Disease:

Referral to Systemic Melanoma Group

Vulvar Basal Cell Carcinomas:

These are slow growing, locally invasive tumours with rare reports of lymph node metastasis. Management includes wide local excision, without lymphadenectomy.

Vulvar Verrucous Carcinomas:

Grossly, this tumour has an exophytic, cauliflower-like appearance. These are slow growing and locally invasive tumours. Management consists of radical local excision of the primary tumour. Radiation therapy is contraindicated as it may induce anaplastic transformation with subsequent regional and distant metastasis.

Vulvar Bartholin Gland Carcinoma:

The diagnostic criteria of primary Bartholin's gland carcinoma were established by Honan in 1897:

Correct anatomic location of the tumour, with a primary location deep in the labia, with the overlying skin intact and the histologic presence of some elements of glandular epithelium

Histological Types

90% Squamous cell carcinoma or adenocarcinoma
10% Adenoid Cystic
Rarely: melanoma, sarcoma

Management:

If the tumour is not locally advanced, these lesions should be treated by radical resection of the primary tumour in addition to an ipsilateral inguinofemoral lymph node dissection.

4. Follow-up

Patients should be reminded that it is their responsibility to keep their recommended follow-up appointments. The objectives of the follow-up visits are as follows:

To determine the patient's immediate response to the treatment employed
Early recognition and prompt management of treatment related complications
Early detection of persistent or recurrent disease
Collection of meaningful data regarding the efficacy of existing treatment policies and their complications so that any appropriate modifications can be instituted

These objectives are best met by having the initial follow-up examination performed by BC Cancer medical staff. When appropriate, arrangements will be made for follow-up by the referring physician.

Post-Surgical

Year 1			every 4 months
Years 2-5			every 6 months
Years 5+			annually

Post-Radiotherapy

Year 1			first visit at 1 month, then every 2 months
Years 2-5			every 6 months
Years 5+			annually

Note: follow-up consists of general exam, pelvic exam and annual Pap smear screening.

References

Heaps JM, Fu YS, Montz FJ, Hacker NF, Berek JS. Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol. 1990;38(3):309-314.
Levenback CF, Ali S, Coleman RL, et al. Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: A gynecologic oncology group study. J Clin Oncol. 2012;30(31):3786-3791.
Van der Zee AG, Oonk MH, De Hullu JA, et al. Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol. 2008;26(6):884-889.
Slomovitz B, Oonk M, Monk B, et al. Radiotherapy as an alternative treatment for inguinofemoral lymphadenectomy in vulvar cancer patients with a metastatic sentinel node. Results of GROINSS-V II/GOG270 presented at SGO 2020
Covens A, Vella ET, Kennedy EB, et al. Sentinel lymph node biopsy in vulvar cancer: Systematic review, meta-analysis and guideline recommendations. Gynecol Oncol. 2015; (137):351-361.
Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol. 1986; (6): 733-40
Hacker NF, Eifel PJ, van der Velden J. Cancer of the vulva. Int J Gynecol Obstet. 2012;119 Suppl 2:S90-6.