INVASIVE VULVAR CARCINOMAS
  The International Federation of Gynecology and Obstetrics (FIGO) has defined four clinical stages of vulvar carcinoma. In addition, many centers use the tumor, node, metastasis (TNM) classification. In 1988, the FIGO staging was modified to reflect lymph node status and the location of the tumor (

Table 100-2). In this classification, a tumor that is located on the perineum is no longer considered to be stage III. In 1995, FIGO instituted a subclassification of stage I into IA and IB, based on whether there is stromal invasion greater than 1 mm.

Squamous Cell Carcinoma   Squamous cell carcinomas comprise approximately 90% of primary vulvar malignancies. Grossly, these carcinomas usually appear as ulcerated or polyploid masses on the vulva. Biopsy reveals the characteristic histologic appearance: the tumor appears in nests and cords of squamous cells infiltrating the stroma, often with islands of keratin.

The pattern of spread for this carcinoma relates to the intricate lymphatic drainage of the vulva (

Figure 100-3). Tumors located in the middle of either labium initially drain to the ipsilateral inguinal femoral nodes, whereas midline perineal tumors can spread either to the left or right side. Using technetium 99m colloid, Iversen and Aas showed that when radioactivity was injected to one side of the vulva, 98% of it localized in the ipsilateral nodes and less than 2% in the contralateral nodes. Tumors along the midline in the clitoral or urethral areas may spread to either groin. From the inguinal-femoral nodes, lymphatic spread continues to the deep pelvic iliac and obturator nodes. Although there has been concern in the past that tumors in the clitoral-urethral area could spread directly to the deep pelvic nodes, current evidence indicates that this is rare.

Stage I Microinvasive Carcinoma
  There is no uniformly accepted definition regarding microinvasive carcinoma of the vulva, and this may result from confusion in measuring the depth of invasion. Microinvasion has been defined by some as a small lesion of the vulva less than 2 cm in diameter and invading less than 3 mm. The International Society for the Study of Vulvar Diseases has recommended that the term microinvasive be dropped and that stage IA be used for tumors less than 2 cm in diameter and invading less than 1 mm from the epidermal-stromal junction, the basement membrane.

Different clinical results have been reported with this definition. Spread to regional lymph nodes has varied from 0 to 10% in tumors with less than a 5 mm depth of invasion. For example, Hoffman and colleagues reported no nodal metastases in 43 patients whose tumor invaded less than 2 mm. Lesions that were at risk of spreading to inguinal nodes included tumors with confluent tongues rather than those with individual tongues merely extending into the stroma. Hacker and colleagues, however, reported that six of seven patients with invasion of less than 3 mm had regional node involvement.

The risk of nodal involvement may be decreased when carcinoma in situ is present in the lesion. Rowley and colleagues noted that only 1 of 35 cases with adjacent carcinoma in situ had nodal metastases. By contrast, 5 of 27 had positive lymph nodes when superficial stage I lesions penetrating 2.1 to 5.0 mm did not have adjacent carcinoma in situ.

For stage IA lesions, therapy may be less extensive than with invasive vulvar carcinoma. Different treatments have been reported, including wide local excision with or without ipsilateral node dissection, simple vulvectomy without node dissection, and radical vulvectomy without node dissection. In younger patients, especially those with tumors located at a distance from the clitoris, an operation that spares the clitoris should be considered. DiSaia and colleagues recommended an operative procedure in which the superficial inguinal lymph nodes are removed and sent for frozen section. If positive nodes are found, bilateral complete groin dissection and complete radical vulvectomy are performed; if the nodes are negative, wide local excision of the primary cancer is performed.

Iversen and colleagues reported an alternative approach, recommending a hemivulvectomy with ipsilateral groin dissection for lesions involving the labia. For medial lesions, they suggest conventional radical vulvectomy with bilateral groin dissection. Boyce and colleagues recommended that conservative therapy can be used with minimal risk. This recommendation appears to be advisable if invasion is greater than 1 mm and the tumor diameter is greater than 2 cm.

To identify patients who can be treated more conservatively, investigators have used intraoperative lymphatic mapping and sentinel node identification for squamous cell carcinoma. Investigators have improved the rate of identification of the sentinel node by combining blue dye with radiolocalization.

The feasibility of intraoperative lymphatic mapping with vulvar cancer has been demonstrated in 21 patients. In this series, the sentinel node was found in a variety of locations at the femoral vessels and at the medial border of Scarpa fascia. In no patients were the nonsentinel nodes positive if the sentinel nodes were negative.

Stage I, II, and III Invasive Carcinoma
  The prognosis of a patient with vulvar carcinoma relates to the stage of disease (

Figure 100-4) and to the nodal status. The presence of carcinoma in the regional lymph nodes correlates with the size and thickness of the primary lesion, the degree of tumor differentiation, and the involvement of vascular spaces by the tumor (

Table 100-3). In 272 women with invasive vulvar carcinoma reported by the Gynecologic Oncology Group (GOG), regional nodes were involved in 8.9% of stage I, 25.3% of stage II, and 31.1% of stage III lesions. If a lesion was less than 1 mm thick, there was a 3.1% incidence of positive nodes. With larger lesions, 4 mm or greater in thickness, 31% of nodes were positive. Hacker and colleagues reported an actuarial 5-year survival rate of 96% in those with negative nodes. Survival decreased to 94% with one positive node, 80% with two positive nodes, and 12% with three or more nodes involved by tumor.

Not only is the number of nodes important, but there also appears to be a correlation with the size of the metastases. Hoffman and colleagues noted that 14 of 15 patients with inguinal lymph node metastases measuring less than 36 mm survived free of disease for 5 years compared with 12 of 29 patients whose tumor metastases measured greater than 100 mm.

The grade of tumor related to the percentage of positive nodes in the GOG study. Patients with grade 1 lesions did not have positive nodes, yet in patients with grade 4 lesions, 47.7% of nodes were positive.

Vascular space involvement also was prognostic because 72% with vascular invasion showed tumor in regional nodes compared with 34% of those without vascular invasion. Nodal involvement also correlated with the location of the primary lesion. Lesions on the labia are associated with 7.4% positive nodes, whereas clitoral lesions have a higher incidence of positive nodes (27.4%). Boyce and colleagues reported that six tumors under 1 cm in diameter had no metastases to regional nodes but that the fraction of tumors with positive nodes rose to 55% for 29 cases with lesions over 4 cm.

Therapy for stage I and II and early stage III vulvar carcinoma is accomplished with radical vulvectomy and bilateral inguinal femoral node dissection. The deep pelvic nodes are rarely removed unless the inguinal nodes are involved. Most oncologists now remove only the inguinal and femoral nodes at the time of operation and treat the deep pelvic nodes with external radiation if superficial nodes are involved with tumor.

A wide variety of management options of the primary lesion have been proposed. In a unilateral lesion less than 1 cm from the midline, radical wide local excision with possible postoperative radiation has been used. This approach has been used for risk factors such as large tumor sites, positive capillary-lymphatic space invasion, or surgical margins that are less than 8 mm. For midline lesions, standard management has varied from use of surgery as primary treatment to use of radiation with possible chemotherapy.

Different surgical approaches to invasive vulvar carcinoma have been evaluated. Classically, an en bloc dissection has been performed. Radical vulvectomy and groin dissection have been carried out through a single suprapubic incision that extends between the left and right anterior iliac spines (

Figure 100-5). This operation removed the entire vulva, including the clitoris, subcutaneous tissue, and inguinal femoral nodes. If the lesion involved the distal urethra, this has often been removed without the loss of urinary continence. In this procedure, the major complication has been wound breakdown and infection (occurring in 50% of the patients). Recently, modifications have been introduced to decrease the incidence of wound breakdown. These modifications include performing the inguinal femoral node dissection through separate inguinal incisions and then completing the radical vulvectomy. Tumor recurrences rarely occur in the skin bridge when separate groin incisions are used.

Less mutilating procedures also have been reported in stage I disease. Rowley and colleagues reported using wide local excision and superficial inguinal node dissection in 20 patients with stage I lesions invading to a depth of less than 5 mm. The superficial and contralateral inguinal femoral nodes were removed only if the superficial nodes contained tumor. This approach seems to be reasonable if a unilateral lesion is present; however, with a midline lesion, bilateral inguinal node dissection seems to be appropriate. In a recent update of a series of 50 patients initially reported by DiSaia and colleagues, only 1 patient died because of recurrent carcinoma treated with the latter conservative approach.32 Six patients had only recurrent carcinoma in situ or minimally invasive carcinoma. Modifying the approach for these early-stage lesions appears to be effective and is associated with less morbidity than the standard radical vulvectomy. If the nodes are free from tumor in stage I and II carcinomas of the vulva, no further therapy is required. If the nodes (especially the femoral nodes) are involved, pelvic irradiation is required. From a randomized study, Homesley and colleagues reported an improved survival rate in 118 patients with positive lymph nodes who received 4,500 to 5,000 cGy of radiation (

Figure 100-6).