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Annals of Surgical Oncology 9:840-846 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Sentinel Node Biopsy in Vulvar and Vaginal Melanoma: Presentation of Six Cases and a Literature Review

Liana Abramova, BSc, Jaysheree Parekh, MD, William P. Irvin, Jr, MD, Laurel W. Rice, MD, Peyton T. Taylor, Jr, MD, Willie A. Anderson, MD and Craig L. Slingluff, Jr, MD

From the Department of Surgery (LA, CLS), Division of Surgical Oncology; Department of Radiology (JP), Division of Nuclear Medicine; and Department of Obstetrics and Gynecology (WPI, LWR, PTT, WAA), Division of Gynecologic Oncology, University of Virginia Health Sciences Center, Charlottesville, Virginia.

Correspondence: Address correspondence and reprint requests to: Craig L. Slingluff, MD, Department of Surgery, University of Virginia Health Sciences Center, P.O. Box 800709, Charlottesville, VA 22906; Fax: 434-243-6844; E-mail: cls8h{at}virginia.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Urogenital melanoma is a rare neoplasm with poor prognosis. Its management in the past involved radical vulvectomy and complete bilateral inguinofemoral lymphadenectomy. Sentinel lymph node biopsy is an accurate low-morbidity procedure when used in the context of cutaneous melanoma. However, prophylactic lymphadenectomy has not been shown to improve survival of melanoma patients. We wanted to determine the feasibility of sentinel lymph node biopsy in patients with female urogenital melanoma as a staging procedure.

Methods: Six patients with vulvar or vaginal melanomas underwent preoperative lymphatic mapping with 99mTc-labeled sulfur colloid followed by sentinel lymphadenectomy. In addition, we reviewed the literature on the application of sentinel lymph node biopsy in urogenital tract melanomas.

Results: One or more sentinel nodes were identified in all six patients by lymphoscintigraphy. All patients underwent sentinel lymphadenectomy, except for one patient with a deep vaginal melanoma that drained to pelvic nodes. The five successful cases had unilateral drainage patterns. None of the sentinel lymph nodes excised had tumor invasion. Combined with five other patients from the published literature, the success rate of localizing sentinel lymph nodes in the patients with urogenital melanoma approaches 100%.

Conclusions: This experience, plus reports of a small number of patients from three similar studies, supports the impression that sentinel lymph node biopsy is feasible for vulvar and vaginal melanoma.

Key Words: Melanoma • Sentinel lymph nodes • Vulvar • Vaginal


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Vulvar and vaginal malignant melanomas are rare neoplasms, representing 2% to 4% of all external genital tract malignancies and 3% of all primary vaginal malignancies.1,2 A population-based study from the United States reported that the vulva was the most common site of occurrence for those neoplasms, comprising 1.3% of all melanomas, followed by vaginal melanoma, which accounts for .3%.3 Their incidence peaks between the sixth and seventh decades of life. As with cutaneous melanoma, prognosis is related to the tumor thickness and lymph node status. The overall 5-year survival rate for vulvar melanoma ranges from 25% to 85%, depending on the extent of involvement.4 Prognosis for vaginal melanoma is markedly more dismal, with a 5-year survival rate of 8.7%.5

Traditionally, vulvar melanoma was treated in the same manner as squamous vulvar carcinoma, with radical vulvectomy and bilateral inguinofemoral lymph node dissection.6 Considerable morbidity associated with the procedure led to the development of less radical, but more controversial, approaches, such as various modifications of radical vulvectomy and less extensive groin dissections. One of the largest studies on vulvar melanoma retrospectively reviewed 219 Swedish women and failed to reach a conclusion on the best surgical strategy that would optimize survival and reduce local recurrence.7 Therapy for vaginal melanoma also remains controversial, largely because of the rarity of lesions and the lack of a consistent strategy. Reid et al.,8 in a literature review of 115 patients, noted four different treatment modalities for vaginal melanoma: surgery only, radiotherapy only, surgery plus radiotherapy, and chemotherapy plus surgery and radiotherapy. None of those treatment regimens was associated with a significantly improved disease-free interval or overall survival. The role of elective lymph node dissection in vaginal melanoma is also controversial, because pelvic lymph nodes are most often involved, and their dissection leads to considerable morbidity, without a proven effect on survival.9,10

Intraoperative lymphatic mapping and sentinel lymphadenectomy, introduced in 1990 by Morton et al.,11 is now used routinely to map out lymphatic drainage of cutaneous melanomas and to locate the lymph node that drains the primary tumor. This approach evolved from the hypothesis that melanoma metastasis follows lymphatic drainage and spreads first to the primary lymph node, called the sentinel node, before spreading to other regional nodes.12 Recently this technique has been applied in localization of nodes in Merkel cell carcinoma, breast cancer, and thyroid and gastrointestinal cancers.13–15 Studies considering application of sentinel lymph node biopsy in urogenital cancers in women have largely been limited to squamous cell carcinoma of the vulva.16–23 This study assessed the applicability of this technique for vulvar and vaginal melanoma in six patients treated in our center in the past 2 years.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Clinical Cases
We reviewed the charts of all patients referred to the University of Virginia Cancer Center since 1999 with melanoma of the vulva or vagina. All patients were treated in a multidisciplinary fashion through the Cancer Center’s melanoma team. One patient who had clinically palpable lymph nodes did not undergo sentinel lymph node biopsy and was excluded from the study, leaving six patients. Patients were brought to the nuclear medicine suite on the day of surgery or on the day before surgery. Approximately 1 mCi (in a .5-mL volume) of 99mTc-labeled sulfur colloid (Mallinckrodt Medical Inc., St. Louis, MO) was injected intramucosally around the biopsy site of the tumor with a tuberculin syringe. This was well tolerated by patients. The 99mTc sulfur colloid was prepared in the radionuclear pharmacy by a 3-minute heating step. In one case, the patient had two primary lesions (urethral and vaginal), and both lesions were injected with the radiocolloid after administration of local or topical anesthetic. Immediately after injection, the patient was placed under the gamma camera, and images were taken to identify sentinel nodes. The skin overlying the "hot" spot was marked with indelible ink for intraoperative identification. Sentinel lymphadenectomy was always performed within 18 hours after lymphoscintigraphy. In one patient, immediately before the operation, 1 mL of isosulfan blue dye (Lymphazurin 1%; Hirsh Industries Inc., Richmond, VA) was also injected intradermally around the same site as the sulfur colloid. A handheld gamma probe (C-TrakTM; Care Wise Medical Products Corp., Morgan Hill, CA) was used to identify the location of the sentinel nodes during the procedures. All hot nodes were removed until residual counts in the node bed were <10% of the maximal count ex vivo of the hottest sentinel node. All the nodes removed were submitted for examination with conventional hematoxylin and eosin methods with three tissue sections and with immunohistochemical staining with S100, tyrosinase (Novacastra; distributed through Vector Labs, Burlington, CA), and HMB45 (Biogenics, San Ramon, CA) antibodies.

Literature Review
We reviewed the published medical literature on sentinel lymph node biopsy in urogenital melanomas by using the MEDLINE and PubMed databases. The following terms were used: sentinel lymph node biopsy, vulvar melanoma, vaginal melanoma, lymphoscintigraphy, lymphadenectomy, and mucosal melanoma.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Clinical Cases
Four patients with vulvar melanoma and two patients with vaginal melanoma were studied. Patient characteristics are listed in Table 1. Five patients were white, and one was Asian American. All of the tumors were mucosal lesions, except for a vulvar lesion that involved normal skin. Most lesions were >1 mm deep. One of the vulvar tumors was a thin .31-mm lesion in the radial growth phase, on the basis of the histological review, but because of the poor overall prognosis of vulvar melanoma, the young age of the patient, and the request of the family, the patient underwent sentinel lymph node biopsy. Only one primary lesion was identified with an exception of one patient, who had simultaneous vaginal and urethral primary lesions arising from a large area of extensive melanoma in situ.


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  		TABLE 1. Patient characteristics
 
In five out of six patients, the sentinel lymph nodes were successfully localized and excised from the medial aspect of a superficial inguinal basin. Results of sentinel lymph node biopsy for all patients are listed in Table 2. In one patient with vaginal melanoma, lymphoscintigraphy showed two deep pelvic nodes (patient 3; Fig. 1), and sentinel lymph node biopsy was not performed because of its expected morbidity. The patient was treated with postoperative radiation in accordance with our institution’s published experience.24 In the five remaining patients, an average of 2.2 sentinel nodes were excised. In one patient, three prominent hot spots were evident on the lymphoscintigraphy (patient 2; Fig. 2). A total of five sentinel nodes were removed from the right superficial groin to ensure that all hot nodes were removed and that residual counts in the node bed were <10% ex vivo of the maximal count. All five nodes were small (5 x 5 x 3 mm to 10 x 5 x 5 mm). They represented the three hot spots seen on lymphoscintigraphy plus two very small adjacent nodes.


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  		TABLE 2. Summary of sentinel node biopsy
 


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  		FIG. 1. Lymphoscintigraphy in patient 3 with vaginal melanoma showed two pelvic nodes (arrows). R, right; L, left.

 


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  		FIG. 2. Three prominent hot spots on the right were seen during lymphoscintigraphy in this patient (patient 2). They were classified as true sentinel nodes (SLNs); on delayed images, additional hot spots were seen (nonsentinel lymph nodes; NSLNs). R, right; L, left.

 
The sentinel node drainage observed was unilateral for all patients. In one patient (patient 5) with a right-sided vulvar lesion, lymphoscintigraphy revealed bilateral drainage to the groin: one in the right groin, which at first was obstructed by the shadow of radioactivity from the injection site, and one questionable spot in the left groin. Thirty minutes before the incision into the groin, 1 mL of isosulfan blue dye was injected intradermally at same sites injected with sulfur colloid, to confirm the drainage pattern outlined earlier. One node identified in the right groin was blue and was also the hot spot in that groin. There were no convincing hot spots demonstrated by the handheld probe in the left groin at the time of surgery. Nevertheless, the left groin was explored, but no blue nodes were identified, and no hot nodes were identified in the wound. In two other patients, early imaging revealed an ipsilateral drainage pattern, and delayed images showed additional hot spots in the contralateral groin (patients 2 and 4; Figs. 2 and 3). Because the first images showed unilateral drainage, those nodes were considered the sentinel nodes, and exploration of the contralateral groin was not performed.



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  		FIG. 3. Lymphatic channels and two prominent hot spots (sentinel lymph nodes; SLNs) are seen in the early images. On the delayed images, additional hot spots were classified as nonsentinel lymph nodes (NSLNs). R, right; L, left.

 
None of the patients had any complications related to the removal of sentinel lymph nodes. None had evidence of tumor in the sentinel lymph nodes on histological review, which was confirmed with immunohistochemistry. On follow-up, only the patient in whom sentinel lymph node biopsy was not performed developed metastatic melanoma, which presented as malignant ascites after 6 months of follow-up. Five other patients are alive and free of disease at a median of 9 months of follow-up.

Literature Review
We identified, through MEDLINE and PubMed database searches and cross-referencing bibliographies of related articles, more than 12 articles on vulvar malignancies, mostly squamous cell carcinoma. Only five of the reports included patients with urogenital melanoma who underwent sentinel lymph node biopsy for staging. One study reported 21 patients with vulvar cancer and sentinel lymph node biopsy, but there was no information on the breakdown of patients with melanoma versus squamous cell carcinoma, so this study was excluded from analysis.17 One study that reported six patients with vulvar melanoma and sentinel lymph node biopsy was in abstract form, and because of the format, no information on patient characteristics or sentinel lymph node biopsy outcome could be extracted.25 In the remaining articles, 16,26,27 five patients with sentinel lymph node biopsy for urogenital melanoma were identified, and their characteristics and outcomes are listed in Table 3.


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  		TABLE 3. Patient characteristics and SLN biopsy outcome from literature review and this study
 
A total of 11 patients, including 6 in this study, underwent lymphatic mapping. The success rate of the procedure approached 100%. Only in 1 of 11 patients was tumor invasion found at the examination of the sentinel lymph node. In all cases in which complete lymphadenectomy was performed, nonsentinel lymph nodes were never positive if the sentinel lymph node was negative, and in this study, no lymph node recurrences have been identified in the short-term follow-up.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Melanomas of the female urogenital tract are rare tumors with poor prognosis, presenting with mixed symptoms of bleeding, pain, and presence of mass. Studies published to date have found that at the time of the initial diagnosis, 60% to 65% of the patients have local disease only, approximately one third of patients have regional lymph node involvement, and 5% to 6% have evidence of distant metastasis.7,28 There is no consensus on the appropriate management of those tumors. Some patients undergo wide local excision only, and some have more radical resections of the primary lesions. In addition, there are different approaches to lymph nodes metastasis, such as prophylactic inguinal lymphadenectomy to various extents: bilateral or unilateral, superficial, or deep. This leaves some patients with a high risk for locoregional recurrences and leaves some patients with unnecessary morbidity associated with surgical operations and complete lymphadenectomy.

Intraoperative lymphatic mapping and sentinel lymph node biopsy were recently used to resolve some similar controversies in the management of squamous cell carcinoma of the vulva, with excellent results. This technique, based on the concept of sequential tumor metastasis, was first used in the context of the cutaneous melanoma.11 The success rate of identifying sentinel lymph nodes in squamous cell carcinoma of the vulva by using radiolabel and blue dye approached 100%, and studies that simultaneously removed and examined sentinel lymph nodes along with entire corresponding lymphatic basins found that in no case was the sentinel node negative when other nonsentinel nodes were positive.16–23

We evaluated the role of sentinel lymph node biopsy in six patients with melanoma of the female urogenital tract. In all but one patient, sentinel lymph nodes were successfully found and excised. The patient whose sentinel lymph node was not removed had primary melanoma located high in the proximal vagina, and lymphoscintigraphy performed before surgery revealed lymphatic drainage of the tumor to the pelvic nodes. The nodes were not removed because of the higher morbidity associated with the procedure. Thus, intraoperative lymphoscintigraphy identified sentinel lymph nodes consistently in all cases. Three similar studies reported five patients who underwent sentinel lymph node biopsy for vulvar or vaginal melanoma, and in all cases, the success rate of localizing and removing the sentinel node was similar and approached 100%. In one of those studies, both blue dye and radiocolloid were used to find the sentinel nodes.26

In our experience, use of radiocolloid alone, without blue dye, was sufficient to map out the drainage pattern of the tumor. In one case, blue dye was injected but did not add to the mapping obtained with radiocolloid. It was interesting to note that five of six patients had primary lesions that drained to the ipsilateral groin only. This would be expected because most of the primary tumors in our study were lateral, even though the female genital tract is a midline structure. Several retrospective studies in vulvar melanoma showed that contralateral spread from unilateral lesions is indeed very rare.29,30

Another surprising result was that in none of the sentinel lymph nodes examined was tumor invasion detected. Those findings, combined with results from published literature on sentinel lymph node biopsy for urogenital melanoma, revealed that out of 10 patients, only 1 had tumor invasion. In a large series of female urogenital melanomas, DeMatos et al.28 reported that 30% (13 of 43) of patients with urogenital melanomas had regional disease detected during initial staging. In the Swedish cohort of 198 patients with vulvar melanoma, reported rates were similar.7 However, both of those studies included in the analysis patients with clinically palpable nodes; these were excluded in our study. Also, the patient whose sentinel pelvic lymph nodes were not removed later developed metastatic ascites, leaving us to speculate on the status of those nodes. However, performance of prophylactic or elective pelvic lymphadenectomy is rarely indicated, because the presence of positive pelvic nodes usually signals a dismal prognosis, despite surgical intervention.9 In all other patients, there were no recurrences in any of the groins dissected, but the median follow-up is only 9 months, and it is too early to make definite conclusions. The low incidence of positive sentinel nodes in patients with urogenital melanomas, coupled with the high risk of systemic dissemination, argues against the routine performance of elective bilateral inguinofemoral lymphadenectomies in this population unless evidence of a survival advantage can be demonstrated.

One last note about the technique of lymphoscintigraphy should be mentioned. We recommend injecting radiocolloid overnight to account for the proximity of the primary tumor to the regional lymph node basin and to allow sufficient time for the background radiation to dissipate. In our experience, one patient in whom no clear hot spots were identified immediately or 1 to 2 hours after injection had scans obtained the next morning that showed prominent lymphatic drainage to sentinel nodes. This was confirmed during surgery with the handheld gamma probe. White et al.31 tested the accuracy of lymphatic mapping 18 to 24 hours after injection of the radiocolloid in 46 patients with cutaneous melanoma. They found that in at least two patients, overnight imaging helped in clarification of the nodal drainage and identification of nodal basins not clearly identified on initial imaging. We believe that this will be helpful even more often in patients with urogenital melanoma because of the proximity of the injection site to the sentinel nodes. However, we recommend lymphoscintigraphy immediately after injection and again on the morning before surgery so that the sequence of the nodal drainage can be defined.

In conclusion, sentinel lymph node biopsy is a feasible, low-morbidity operation that can identify the lymphatic drainage pattern in patients with urogenital melanoma. Longer follow-up will establish the accuracy of the sentinel lymph node biopsy in patients with early stages of the disease without subjecting patients to complete lymphadenectomy and the associated morbidity. Furthermore, our study included only six patients because of the rarity of urogenital melanomas in the population, and further investigation in multicenter studies with more patients is warranted to validate the outcome.


   Footnotes
 
This study supports the impression that sentinel lymph node biopsy for vulvar and vaginal melanoma is feasible.

Received for publication July 16, 2001. Accepted for publication July 15, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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