A large number of reports have been published over the past 25 years on sentinel lymph node detection in various cancers. The concept relies on the presumption that the sentinel lymph node is the initial site of metastatic disease and that lack of metastatic involvement of the sentinel lymph node reflects an absence of metastasis in the rest of the lymph nodes in the basin. Lymphatic mapping is the standard of care in the United States for the surgical treatment of patients with clinically early-stage melanoma and breast cancer.

In the case of invasive squamous cell carcinoma of the vulva, interest in sentinel lymph node was driven by the high incidence and significant morbidity of complications following full inguinal-femoral lymphadenectomy. Though the incidence of groin wound complications has been reduced by separate incisions, it still may occur in up to 30% of patients, and the risk is increased by patient comorbidities and adjuvant chemotherapy or radiation. Therefore, the use of a lesser surgical procedure such as sentinel lymph node dissection is particularly relevant to vulvar cancer.

The concept of sentinel lymph node dissection applies well to vulvar cancer as the tumor location is easily accessible to injection of both radiocolloid and blue dye, and the lymphatic drainage is predictable for most tumors. With lymphatic mapping, the pathologist has only a few lymph nodes to examine, allowing a more detailed examination. Techniques such as serial sectioning, immunohistochemical staining, and reverse transcriptase-polymerase chain reaction analysis can be applied, increasing the sensitivity of the examination and allowing the detection of micrometastases.

When using the combined technique for vulvar cancer patients, lymphatic mapping is nearly always successful in identifying sentinel lymph nodes (Fig. 49.10). Further, the false-negative rate (based on standard pathology) is very low. A meta-analysis by Hassanzade and colleagues showed that pooled sensitivity of 27 studies was 92% and a negative predictive value of 97%. A phase III trial by the GOG including tumors from 2 to 6 cm showed a sensitivity of 92.1% and a negative predictive value of 97.4% when a combination of blue dye and radiocolloid was used. Another multiinstitutional observational study by van der Zee et al. revealed a sensitivity of 94.1% and negative predictive value of 97.1%. A full inguinal-femoral lymph node dissection is reserved for those patients in which the sentinel node is positive or has not been successfully identified.

Sentinel lymph node mapping is a promising method to substantially reduce the morbidity of inguinal lymphadenectomy. It is widely used in the management of vulvar cancer today. However, many unanswered questions remain, including who the best candidates are for the technique, the role of frozen section, the role of immunohistochemistry, the role of lymphoscintigraphy, the reliability of an isolated lymphoscintigraphy-directed unilateral negative sentinel node with a midline lesion, the role of ultrasound, management of a patient with a microscopically positive sentinel lymph node, the incidence of “skip” metastases, the reliability of lymphatic mapping after prior excisional biopsy, and the optimal lymphatic mapping methodology for vulvar cancer patients.

Various modifications on the extent of lymphadenectomy have been examined. Before the introduction of sentinel lymph node biopsies, a technique involving limited resection of the inguinal lymph nodes in the management of superficially invasive vulvar cancer was reported by DiSaia and coworkers in 1979. The dissection they described is aimed at removal of the superficial lymph nodes above the cribriform fascia, mainly associated with the great saphenous and superficial epigastric veins. These lymph nodes were sent for frozen section analysis. If results were positive, a complete bilateral inguinofemoral lymphadenectomy was performed. In the 1979 study, DiSaia and colleagues also reported 79 cases of invasive squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. In these cases, it was noted that the deep femoral lymph nodes were never positive in the absence of positive superficial inguinal lymph nodes. The purpose of a superficial dissection only is to reduce the morbidity of the groin lymphadenectomy. The dissection is less radical and resulted in only one groin breakdown in the 18 patients in the series of DiSaia and associates. The series was updated in 1989, and they reported no groin recurrences in 50 patients, 42 of whom had been followed for a median of 36 months.

A GOG study specifically studied the issue of superficial inguinal lymphadenectomy in patients with early carcinoma of the vulva. The study group included clinical stage I patients with tumor invasion of 5 mm or less and no capillary or lymphatic space involvement. A modified radical vulvectomy
and ipsilateral superficial inguinal lymphadenectomy were performed, and 121 patients were evaluable. These were compared with a historical control group in the GOG registry who had undergone radical vulvectomy with bilateral inguinofemoral lymphadenectomy. Nine patients in this study, or 7.3%, experienced groin recurrences versus no recurrence in the control group. Six of the groin recurrences were in the ipsilateral groin, and 5 of the 9 patients died of the recurrent vulvar cancer. The interpretation from this study was that superficial inguinal lymphadenectomy may not be adequate treatment even for early vulvar carcinoma. However, in a number of patients in this study, the tumors approached the midline; there is evidence that more medial tumors may have direct drainage to the deep inguinal lymph nodes. Another area of concern in this study is the high percentage of poorly differentiated tumors—almost twice as many as in the control group. Six of the nine groin recurrences in this study were from the poorly differentiated tumors. Whether poorly differentiated tumors are more likely to metastasize to deep inguinal or contralateral inguinal lymph nodes deserves further study. Subsequent additional retrospective data from large cancer centers also report a 5% to 10% incidence of groin relapse in patients with negative nodes from superficial inguinal lymphadenectomy.

The technique of superficial lymphadenectomy of the inguinal nodes above the cribriform fascia has been largely replaced by sentinel lymph node biopsy, but the occurrences of groin recurrences after apparently negative superficial nodes in these studies remains concerning.

The benefit of sparing versus sacrificing the saphenous vein remains unclear. Various studies have found conflicting results on the reduction of the incidence of lymphedema. A randomized trial by the GOG showed that application of fibrin sealant at time of lymphadenectomy also did not reduce the incidence of lymphedema.

Unilateral lymphadenectomy only on the side of a unilateral vulvar tumor has been another modification of surgical treatment that has been used for selected patients (Fig. 49.11). In 1981, Iversen reported on 53 women with unilateral tumors and lymph node metastases. Eighty-three percent of these patients had only one positive ipsilateral node, 15% had bilateral positive nodes, and one patient had contralateral positive lymph nodes only. Other retrospective studies have confirmed these results. It has been the opinion of a number of authors that capillary or lymphatic space involvement by tumor may increase the
risk of contralateral nodal metastases. Patients with tumors approaching the midline or involving more medial structures (perineum, clitoral hood or clitoris, vagina, and labia minora) are at increased risk for contralateral lymph node metastases. The issue of unilateral groin lymphadenectomy was studied to some extent in 1992 by Stehman and associates in a GOG study. Patients with early disease and negative ipsilateral superficial inguinal lymph nodes were treated with ipsilateral superficial inguinal lymphadenectomy and a modified radical vulvectomy. A few patients in this study did have a bilateral inguinal lymphadenectomy because of midline involvement. A total of 121 patients were in the study, and 3 experienced contralateral inguinal lymph node recurrences. The vulvar lesions of these 3 patients ranged from 0.6 to 2.5 mm in depth of invasion, and all were poorly differentiated. Although lesion location was not given for these 3 cases, a large percentage of patients included in this study had lesions approaching the midline, as defined by involvement of the labia minora. Tumors with capillary or lymphatic space involvement were excluded from this study.

At present, unilateral inguinal-femoral lymphadenectomy appears to be a reasonable approach in a patient with a welllateralized early tumor that is well differentiated, with no capillary or lymphatic space involvement and with negative ipsilateral inguinal lymph nodes.

During the late 1970s and early 1980s, several studies were published showing that carcinoma of the vulva metastasizes to the inguinofemoral lymph nodes before spreading to the pelvic lymph nodes. Extension of the groin lymphadenectomy to include removal of the pelvic lymph nodes continued to be performed in selected patients with positive inguinofemoral lymph nodes. A number of studies also showed that the 5-year survival rate of vulvar cancer patients with positive pelvic lymph nodes is less than 20%. A 1986 study by the GOG directed by Homesley compared pelvic lymph node dissection with groin and pelvic radiotherapy in patients with positive inguinofemoral lymph nodes. The study included 114 patients and showed no difference in morbidity between the two treatment arms and a better 2-year survival rate in the radiotherapy group (68% vs. 54%). The improved survival was seen in those patients with suspicious or grossly positive lymph nodes or those with more than one positive groin lymph node. There was no evidence that groin radiation therapy was beneficial to those patients with occult metastases and only one positive groin node. Review of the pattern of recurrence in that study suggested that adjuvant radiation was more effective largely because groin recurrences were reduced. The value of removing positive pelvic lymph nodes before radiotherapy is unknown. Pelvic lymphadenectomy is now rarely indicated in the treatment of vulvar cancer.

Extensive data support the contention that a subset of early vulvar carcinomas (carefully studied pathologically) can be identified that have an extremely low risk of nodal involvement. In a GOG study reported by Sedlis and associates, a subgroup (63 of 272) of patients with early disease was identified as having a zero incidence of lymph node metastases. This subset included nonmidline tumors with no capillary or lymphatic space involvement that were well differentiated or were grade 2 and limited to 2 mm in thickness. Other factors that have been studied for the purpose of identifying a low-risk group include tumor volume (which does not appear to have received further attention since Wilkinson’s report in 1985), tumors that are largely carcinoma in situ with very early stromal invasion and with a pushing rather than an infiltrative pattern, tumor diameter, squamous cell type, the presence of an inflammatory response, and tumor ploidy.

There seems to be general agreement that the patients for whom it would be most reasonable to omit the lymphadenectomy are those with tumor invasion less than or equal to 1 mm and less than 2 cm in diameter. However, certain tumors with less than 1 mm of invasion should still be considered for lymphadenectomy. As reported in the literature, three of nine patients with nodal disease or nodal recurrence in association with tumor invasion less than or equal to 1 mm had poorly differentiated cancers (Table 49.2). Thus, women with suspicious lymph nodes, poorly differentiated tumors, tumors with capillary or lymphatic space involvement, and perhaps those with multiple foci or broad areas of invasion or aneuploidy should still undergo lymphadenectomy. It is important to remember that even with superficial invasion, metastases to the nodes do occur. In the report by Sedlis and colleagues of 272 patients with invasion of 5 mm or less, the groin nodes were positive in approximately 20%.

Sentinel lymph node detection is currently accomplished using two methods of lymphatic mapping: blue dye and radiocolloid. One to two milliliters of isosulfan blue dye (Lymphazurin) is injected superficially around the periphery of the primary tumor, and the blue-dyed lymphatic channels are followed. An incision is made over the anticipated location, and the dyed lymph node or nodes that have been stained by accumulating the blue dye are removed. Alternatively, the periphery of the tumor is injected with 400 mCi of technetium-labeled sulfur colloid 2 to 4 hours before surgery. A preoperative technetium scan (lymphoscintigraphy) is done, which may be helpful in confirming lymph node uptake, localization of target lymph nodes, unilateral versus bilateral lymphatic drainage, and identification of the unusual case of predominant drainage to pelvic lymph nodes. An intraoperative gamma counter is used to identify one or more sentinel lymph nodes (Fig. 49.15). The removed lymph nodes are checked with the gamma counter, and complete removal is assured when the radioactivity in the inguinal area returns to background levels. In practice, the two techniques are complementary and are frequently used together. The removed nodes are sent for frozen section, and the small skin incision in the groin is closed with absorbable sutures. Drains are not required. If the frozen section is negative, no further lymphadenectomy is required. However, if metastatic disease is detected, a complete inguinal-femoral lymphadenectomy is indicated.

An incision is made starting about 2 to 4 cm medial and about 2 cm caudal to the anterior superior iliac spine. The incision gradually curves downward just above the superior border of the inguinal ligament medially to the inguinal ring or about 2 cm below and 2 cm medial to the pubic tubercle. Unless there is a large clitoral lesion or palpably suspicious nodes, the mons pubis is spared, and separate incisions with a skin bridge are made as illustrated in Figure 49.16. For anterior lesions, such as those involving the clitoris, a portion of the mons pubis is included in the resection and the lymphadenectomy on one or both sides may be done en bloc with the radical vulvectomy as illustrated in Figure 49.12. From the lateral points, caudal incisions are carried medially so as to excise a strip of skin (optional) 2 to 4 cm in width. Excising an ellipse of the skin may reduce the likelihood of skin necrosis and facilitate more complete dissection of the groin. This incision is designed to extend from just below the fossa ovalis (this can generally be identified clinically as the area just medial to the femoral pulsation in the groin) to the top of the labiocrural fold above a point just medial to the external inguinal ring. In the presence of grossly positive inguinal lymph nodes, a wider resection of both the groin skin and fat is necessary to help ensure adequate tumor clearance. The separate groin skin incision may also be done vertically (with the leg), centered across the fossa ovalis, and about halfway between the femoral artery and pubic tubercle.

Leaving a layer of subcutaneous tissue with the skin, the superior incision is undermined so that the lymph node-bearing adipose tissue above the inguinal ligament and around the superficial circumflex iliac, as well as the superficial epigastric vessels, are included with the resection. These vessels are ligated or electrocoagulated as they are encountered. The superior dissection over the groin area is carried down to the superior border of the inguinal ligament (Fig. 49.17A and B). The midline aspect of the superior flap can be mobilized off the pubic bone and rectus fascia at this point to facilitate later closure of the wound without tension. Dissection of the block of inguinal tissue is carried inferiorly off of the inguinal ligament. The lateral corner is dissected medially off of the sartorius fascia. The inferior flap of the lower incision is also mobilized, especially medially, and the saphenous vein is identified as it enters the region of the femoral triangle (Fig. 49.17C). Accessory saphenous veins can also be seen entering this area. If it is to be sacrificed, the long saphenous vein is isolated and ligated with a free-tie and a transfixion ligature of 2-0 polyglactin (Vicryl). The vein with its surrounding block of lymph node-bearing tissue is dissected superiorly off of the sartorius and adductor fascia. Dissection of the block of inguinal tissue is continued from the three sides toward the fossa ovalis. As this area is approached, the overlying cribriform fascia is recognized, and the femoral artery pulsation can be palpated in the lateral aspect. En bloc dissection continues and includes the contents of the fossa ovalis (Fig. 49.17D). The area under the fascia lateral to the femoral artery should be left undisturbed as the femoral nerve lies lateral. There are no lymph nodes of consequence here, and avoidance of this area prevents injury to the femoral nerve and possibly reduces subsequent
lymphedema. Rather, resection of the cribriform fascia begins over the area of femoral pulsation, exposing the underlying femoral vessels. A few small branches of the femoral nerve are sacrificed during this dissection. The sheath of the femoral artery is incised along its anteromedial aspect from somewhere between the base of the fossa ovalis and the apex of the femoral triangle to its emergence from under the inguinal ligament. Branches, such as the external pudendal artery, are ligated as they are encountered. There is no purpose in dissecting under the artery or between the femoral artery and vein. Rather, the dissection that has been performed over the top of the artery is continued over the top of the vein, mobilizing the specimen to the medial aspect of the femoral vein. During this process, the saphenofemoral venous junction is identified, ligated with a 2-0 silk free-tie followed by a suture ligature for security, and transected, thus removing several centimeters of the saphenous vein with the specimen (Fig. 49.17E).

An alternative method, as long as there are no adherent suspicious lymph nodes, is to dissect the saphenous vein free of the specimen so that it can be preserved, potentially reducing the risk of subsequent lymphedema. Complete dissection of the space medial to the vein is important because this is where most of the femoral groin nodes are located. The specimen is freed from the femoral vein medially, from the inguinal
ligament superiorly, and from the underlying pectineal fascia. Dissection is continued toward and off of the adductor longus fascia until the labiocrural fold is reached (Fig. 49.17F).