Vulva

INTRODUCTION

According to the American Cancer Society (1) statistics, in 2010 there were 3,900 estimated new cases of vulvar cancer in the United States, with an estimated death toll of 920 (1).

ANATOMY

The vulva consists of the mons pubis, clitoris, labia majora and minora, vaginal vestibule, and their supporting subcutaneous tissues, and blends with the urinary meatus anteriorly and the perineum and anus posteriorly.
The Bartholin’s glands, two small mucus-secreting glands, are situated within the subcutaneous tissue of the posterior labia majora.
Lymphatics of the labia drain into the superficial inguinal and femoral lymph nodes, located anterior to the cribriform plate and fascia lata; they penetrate the cribriform fascia and reach the deep femoral nodes. There are usually three to five deep nodes, the most superior of which, located under the inguinal ligament, is known as Cloquet’s node (4). From these, the lymph drains into the pelvic lymphatics (external and common iliac lymph nodes).
Lymphatics of the fourchette, perineum, and prepuce follow the lymphatics of the labia.
Lymph from the glans clitoris drains not only to the inguinal nodes but also to the deep femoral nodes. Some lymphatics originating in the clitoris may enter the pelvis directly, connecting with the obturator and the external iliac lymph nodes and bypassing the femoral area (Fig. 39-1).

NATURAL HISTORY

Over 70% of vulvar malignancies arise in the labia majora and minora, 10% to 15% in the clitoris, and 4% to 5% in the perineum and fourchette. The vestibule, Bartholin’s gland, and the clitoral prepuce are unusual primary sites, each accounting for less than 1% of vulvar cancers (24).
Carcinomas arising in the vulvar area ordinarily follow a predictable pattern of spread to the regional lymphatic nodes. Superficial inguinofemoral lymph nodes are involved first, followed by the deep inguinofemoral nodes. Metastasis to the contralateral inguinal or pelvic lymph nodes is very unusual in the absence of ipsilateral inguinofemoral node metastasis.
Although lesions arising in or involving the glans clitoris or urethra theoretically can spread to pelvic lymph nodes through the channels that bypass the inguinal areas, such metastases without inguinal node involvement occur infrequently.

The incidence of inguinal lymph node metastasis in surgically staged patients is 6% to 50%, depending on the depth of tumor invasion (3, 33).

FIGURE 39-1 Lymphatic drainage of female pelvis in area of vulva. (From Agur AM R, Dalley, AF, eds. Grant’s atlas of anatomy, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:244, with permission.)

Approximately 20% to 30% of patients with histologically proven involvement of the femoral nodes show deep pelvic lymph node involvement if pelvic lymphadenectomy is performed (3).
Hematogenous dissemination is unusual and is a manifestation of late disease.
The most common metastatic sites are lung, liver, and bone.

CLINICAL PRESENTATION

Mass in the vulva is the most common complaint of patients with vulvar carcinoma; pruritus, bleeding, and pain also are noted. Up to 20% of patients are asymptomatic.
Some women present with advanced disease, with local pain, bleeding, and surface drainage from the tumor.
Metastatic disease in the groin lymph nodes or at distant sites may also be symptomatic.

DIAGNOSTIC WORKUP

Clinical history and a complete physical examination are essential. In addition to assessment of the vulvar and anal area, the perineum, vagina and cervix should be thoroughly inspected.

A Papanicolaou (Pap) smear of the cervix and vagina should be performed.

TABLE 39-1 Diagnostic Workup for Vulva Tumors

*General*
	History
	Physical examination, including careful bimanual pelvic examination
*Special Studies*
	Exfoliative cytology of cervix and vagina
	Colposcopy and directed biopsies (including Schiller’s test)
	Biopsies and examination under anesthesia to determine tumor extent
	Cytoscopy
	Proctosigmoidoscopy (as indicated)
*Radiographic Studies*
	Standard
		Chest radiographs
		Intravenous pyelogram
	Complementary
		Barium enema
		Lymphangiogram
		CT or MRI scans of pelvis and abdomen, PET-CT scan (optional)
*Laboratory Studies*
	Complete blood cell count
	Blood chemistry
	Urinalysis
Source: From Perez CA, Grigsby PW, Chao KSC, et al. Vulva. In: Perez CA, Brady LW, eds. Principles and practice of radiation oncology, 3rd ed. Philadelphia, PA: Lippincott-Raven, 1998:1915-1942, with permission.

Careful bimanual pelvic examination is mandatory.
Besides careful determination of the extent and depth of the primary lesion (size, fixation, etc.), assessment of the regional lymph nodes is critical. Because of frequent inflammatory lymphadenopathy in the inguinal area, lymph node assessment in vulvar tumors has a substantial rate of error.
Chest radiographs should be routinely obtained.
Other studies include cystoscopy, proctosigmoidoscopy, barium enema, and intravenous pyelogram, when indicated.
Computed tomography (CT) or magnetic resonance imaging (MRI) may aid in the outline of tumor extent and in evaluating the inguinal and pelvic/periaortic lymph nodes.
Radiographic evaluation of regional lymphatics is of limited value and is rarely used.
Preoperative lymphography correlated with the surgical specimens showed an overall accuracy of 54.5%, with a sensitivity of 15.7% and a specificity of 66.1% (34).
The standard workup for these patients is shown in Table 39-1.

STAGING

The International Federation of Gynecology and Obstetrics (FIGO) adopted a modified surgical staging system for vulvar cancer in 1989 (5, 29).
A microinvasive substage (IA) was defined at the most recent FIGO meeting for tumors less than 2 cm in diameter with depth of invasion less than 1 mm.
Tumor assessment is based on physical examination with endoscopy in cases of bulky disease.
Nodal status is determined by surgical evaluation of the groins.
The American Joint Committee on Cancer and FIGO staging systems are shown in Table 39-2.

TABLE 39-2 TNM and FIGO Staging Categories for Cancer of the Vulva

*AJCC*		*FIGO*
*Primary Tumor*
TX			Primary tumor cannot be assessed
T0			No evidence of primary tumor
Tis		^a	Carcinoma in situ (preinvasive carcinoma)
T1a		IA	Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤ 1.0 mm^b
T1b		IB	Lesions >2 cm in size or any size with stromal invasion >1.0 mm, confined to the vulva or perineum
T2^c		II	Tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement)
T3^d		IVA	Tumor of any size with extension to any of the following: upper/proximal 2/3 of urethra, upper/proximal 2/3 vagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone
*Regional Lymph Nodes (N)*
NX			Regional lymph nodes cannot be assessed
N0			No regional lymph node metastasis
N1			1 or 2 regional lymph nodes with the following features
	N1a	IIIA	1 or 2 lymph node metastases each 5 mm or less
	N1b	IIIA	1 lymph node metastasis 5 mm or greater
N2		IIIB	Regional lymph node metastasis with the following features:
	N2a	IIIB	3 or more lymph node metastases each <5 mm
	N2b	IIIB	2 or more lymph node metastases 5 mm or greater
	N2c	IIIC	Lymph node metastasis with extracapsular spread
N3		IVA	Fixed or ulcerated regional lymph node metastasis An effort should be made to describe the site and laterality of lymph node metastases.
*Distant Metastasis (M)*
M0			No distant metastasis (no pathologic M0; use clinical M to complete stage group)
M1		IVB	Distant metastasis (including pelvic lymph node metastasis)
^aFIGO staging no longer includes stage 0 (Tis). ^bThe depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. ^cFIGO uses the classification T2/3. This is defined as T2 in TNM. ^dFIGO uses the classification T4. This is defined as T3 in TNM.
Source: Staging from Edge SB, Byrd DR, Compton CC, et al., eds. AJCC cancer staging manual, 7th ed. New York, NY: Springer Verlag, 2009, with permission.

PATHOLOGIC CLASSIFICATION

Preinvasive forms of vulvar malignancy include carcinoma in situ (Bowen’s disease or erythroplasia of Queyrat and Paget’s disease).
Paget’s disease is equivalent to the same entity in the breast and is associated with invasive apocrine carcinoma in approximately 20% to 30% of cases (31).
Squamous cell carcinoma comprises over 90% of invasive lesions of the vulva. Histologically, most squamous cell carcinomas are well differentiated with keratin formation; 5% to 10% are anaplastic.
Two variants of squamous cell carcinoma that are infrequently described are adenosquamous and basaloid carcinoma. These tumors may be exophytic and well differentiated and may invade locally, but they rarely metastasize.
Verrucous carcinoma of the vulva is extremely rare. The incidence of lymph node metastasis is very low. The preferred treatment is wide surgical excision.
Basal cell carcinoma of the vulva is occasionally reported (22).
Adenoid cystic carcinoma of Bartholin’s gland constitutes approximately 10% of all carcinomas of this gland and approximately 0.1% of all vulvar malignancies (20).
Adenocarcinomas may originate from the periurethral Skene’s glands, but most arise either in Bartholin’s gland or from bulboadnexal structures associated with Paget’s disease (16).
Bartholin’s gland carcinoma may occasionally be squamous cell when it originates near the orifice of the duct, papillary if it arises from the transitional epithelium of the duct, or adenocarcinoma when it arises from the gland itself.
Melanoma represents 2% to 9% of vulvar malignancies; nodular and superficial spreading melanoma varieties are described. As in other locations, the depth of invasion correlates with patterns of spread and prognosis (5).
Sarcomas of the vulva are extremely rare; leiomyosarcoma is the most common. Neurofibrosarcoma, rhabdomyosarcoma, fibrosarcoma, and angiosarcoma have been reported (31).
Metastatic carcinomas to the vulva from the uterine cervix (most common), the endometrium, or the ovary, as well as extension or metastases from the urethra or the vagina, have been reported.