Carcinoma of the vulva represents 3% to 5% of malignancies of the female genital tract. Ninety-five percent of both preinvasive and invasive lesions of the vulva are squamous. There is some consensus regarding the behavior and the staging, treatment, and prognosis of squamous cancers. The experience regarding the management of less common lesions such as Paget's disease, sarcomas, adenocarcinomas (including those of Bartholin's gland), and melanomas is limited.

Squamous cell carcinoma of the vulva affects postmenopausal women, occurring primarily in the fifth and sixth decades. In the last 10 years, there has been a trend for multifocal lesions associated with vulvar intraepithelial neoplasia (VIN) in younger premenopausal patients.¹ These lesions are associated with human papillomavirus (HPV) infections. Most epidermoid (squamous) carcinomas of the vulva are of low histologic grade and exhibit a predictable clinical course, with progressive local extension and then extension to the regional lymph nodes. A clear understanding of the prognostic factors and natural history of this disease allows for individualization of treatment. A common “standard” approach to treatment is no longer acceptable in the management of carcinoma of the vulva. Earlier detection of the malignant lesions of the vulva is an important factor that makes individualization of treatment possible. Statistics indicate that about half of patients presenting with vulvar carcinoma are International Federation of Gynecology and Obstetrics (FIGO) stage I. In the last decade, less radical surgical interventions have been possible. Improved preoperative and postoperative management of high-risk patients has resulted in improved survival.

VIN, including dysplasia and carcinoma in situ (CIS), is seen with increasing frequency in younger women. This reflects a changing pattern of contemporary sexual behavior with increased frequency of HPV infection of the lower reproductive tract. CIS is considered a precursor lesion, but the rate of progression to invasive carcinoma is only 4% to 6% with a median progression time of 5 years.^2,3 Although VIN frequently is present adjacent to invasive squamous carcinoma lesions, its presence or absence has no prognostic significance. Immunosuppresion related to HIV infection or transplant medications is an important factor that has increased the incidence of vulvar dysplasia.

Multiple sexual partners and previous genital warts are strongly associated with the development of CIS. Smoking is an important risk factor. Patients who smoke and have a history of genital warts exhibit a 35-fold increase in the risk of CIS and subsequent invasive carcinoma.⁴ Both invasive and intraepithelial carcinoma of the vulva frequently are associated with prior, concurrent, or subsequent neoplasia of the vagina and cervix. Between 13% and 40% of patients with vulvar lesions have epithelial carcinomas elsewhere in the lower reproductive tract. Complete screening of the entire anogenital tract is indicated before final staging and treatment planning, and it must be included in the follow-up of the patient treated for carcinoma of the vulva. There is no evidence for the association with hypertension, diabetes, or obesity that had been considered in the past. The association between chronic vulvar inflammatory conditions and invasive carcinoma is unclear. Lichen sclerosus areas can be described in up to 30% of invasive squamous carcinoma specimens.⁵ It is not known if lichen sclerosus areas are precursor lesions.

Human papillomavirus type 16 (HPV-16) has been the strain of virus most frequently associated with intraepithelial and invasive carcinoma of the lower genital tract, including the vulva. HPV-16 DNA can be isolated in 70% to 80% of intraepithelial lesions and in 10% to 50% of invasive lesions.^6,7 The differences in HPV DNA detection rates may be related to decreased retrieval of the virus in the vulvar lesions.

Vulvar Intraepithelial Neoplasia

As already noted, there has been a substantial increase in the prevalence of VIN in young patients. VIN usually is multifocal, and the most common sites are the hairless skin of interlabial folds, the posterior fourchette, and the perineum. Lesions may be macular or papular with a keratotic rough surface. White lesions are caused by hyperkeratosis, whereas red ones represent hypervascularity. Gray or brown lesions are produced by melanocytic overactivity and pigment incontinence. Vulvoscopy and punch biopsies are the most important tools in the diagnostic approach. The use of a colposcope is of benefit in the evaluation of these lesions, but grading of the lesion is limited because of the keratin layer. Unlike the cervix and vagina, the histologic abnormality may extend beyond the area of a lesion visible with colposcopy.

A more conservative approach for the treatment of VIN has been followed recently.

Wide local excision, removing a full thickness of skin encompassing epidermis and dermis with a 2-cm lateral margin, is sufficient treatment. The histologic abnormality may extend beyond the clinically or colposcopically apparent lesion. Frozen-section evaluation of the margins has been advocated by some authors to trim an additional margin and achieve complete excision. Nevertheless, a more conservative approach can be followed for microscopically positive margins waiting for the development of clinical lesions before proceeding with re-excision procedures. The use of CO₂ laser ablation is an effective nonmutilating alternative that is particularly useful for multifocal lesions. Proper application minimizes thermal damage to the underlying normal tissues. This property makes the CO₂ laser an excellent tool for management of intraepithelial neoplasia of the anogenital epithelium. Super-pulse technology allows high-intensity output and short duration of the laser beam to dissect through the layers of the epithelium with extreme precision and ensures complete removal of the atypical epithelium. Use of the CO₂ laser results in minimal scarring, excellent function preservation (anal sphincter), and low recurrence rates. The only disadvantage for the use of the CO₂ laser is the loss of tissue for pathologic examination. Proper evaluation with biopsies to rule out the presence of invasive carcinoma before therapy is essential. CO₂ laser ablation is an excellent alternative to the more traditional superficial or “skinning” vulvectomy.

Planning of appropriate therapy for invasive carcinoma begins with clinical evaluation of the lesions and an assessment of the patient to determine her risk as an operative candidate. Vulvar carcinoma has a propensity to remain locally confined. Metastases occur by way of the lymphatics to the groin, a site amenable to clinical evaluation and successful treatment by inguinal lymphadenectomy. Treatment failures primarily result from failure to ensure adequate margins during excision of the primary lesion or from recurrence within the lymphadenectomy site. The latter should not occur with proper surgical technique for removal of microscopic clinically occult metastases. It is, however, a more frequent problem when extensive metastases associated with clinically suspicious or positive nodes are present before surgery. In addition to an increased frequency of local (incisional) recurrence, positive groin nodes also are associated with an increased frequency of pelvic lymph node metastasis and progression of disease to distant sites.

Squamous carcinoma of the vulva usually proceeds in a predictable fashion through its regional lymphatics, first to the inguinofemoral nodes and only then to pelvic and distant sites. Therefore, the superficial inguinal lymph nodes are the most common site for detecting metastasis. Metastasis to the contralateral nodes in the absence of involvement of the ipsilateral nodes is rare.⁸ Midline lesions involving the clitoris may have spread to bilateral inguinal nodes. Direct metastasis of invasive squamous carcinoma of the vulva to the pelvic lymph nodes is rare, occurring with a frequency of 0% to 3%.⁹

One of the most important recent developments in the treatment of vulvar carcinoma has been the individualization of treatment. Less radical surgery for early stage disease does not compromise survival. No lymphadenectomy is needed for patients with microinvasive tumors (stage IA). For unilateral lesions less than 2 cm in diameter, contralateral lymphadenectomy is not required unless lymph node metastasis is found in the ipsilateral side at the time of surgery. Performing separate incisions for inguinal lymph node dissection results in better wound healing with a reduced rate of infection.¹⁰

Another important development is the use of preoperative radiation therapy. It reduces the need for primary exenteration in advanced cancer, therefore leading to conservation of urinary and defecatory functions. It also is useful for the management of enlarged fixed and ulcerated nodes. Preoperative radiation has not been associated with significant healing problems or fistula formation. Planning of therapy should be individualized to define the least radical surgical intervention possible for achieving control of the primary lesion and the immediate regional lymphatics (the groin) while recognizing the potential for distant spread.

Staging

Clinical criteria for staging of carcinoma of the vulva were formulated and adopted in 1970 by the FIGO. A modified surgical staging system was adopted in 1989 and revised in 1995¹¹ (Table 1). The definition of microinvasive carcinoma follows the recommendations of the International Society for the Study of Vulvar Disease and the International Society of Gynecologic Pathologists.¹² The staging emphasizes definition of the primary tumor by size and location, including the involvement of structures contiguous with the vulva. Status of the nodes is based on surgical evaluation of the groin. The presence or absence of distant metastasis also is considered, including cystoscopic or proctoscopic evaluation. The survival results for stages I and II are similar and excellent, approximately 90% when no positive groin nodes are present.¹³ Stage III lesions have a 50% 5-year survival rate, although successful treatment of 60% to 70% of patients has been reported.

TABLE 1. FIGO Staging of Vulvar Carcinoma (1995)

Size and location of the lesion are the primary parameters in deciding what procedure to perform. Early stage lesions are treated surgically. Advanced stage lesions are treated preferentially with chemoradiation. Pelvic exenteration with radical vulvectomy and inguinal lymph node dissection is a surgical option with significant physical and psychological morbidity as well as mortality. This procedure is rarely indicated. Treatment recommendations are summarized in Table 2. Microinvasive tumors (less than 1 mm of invasion, stage IA) may be treated by wide local excision with low risk of groin lymph node or vulvar recurrence.^14,15 A 1-cm lateral margin is recommended. Lesions less than 2 cm in diameter (stage IB) may be treated successfully by wide radical excision. A 2-cm lateral margin is obtained, and dissection is carried down to the fascia of the urogenital diaphragm for the deep margin.¹⁶ When the invasion of the lesion is greater than 1 mm, ipsilateral groin lymph node dissection is recommended. This approach of radical local excision and ipsilateral node dissection works best for lesions that are lateral or posterior. Stage II lesions (greater than 2 cm in diameter) are treated by radical vulvectomy with inguinal-femoral lymph node dissection. Certain stage III lesions with extension to the lower urethra or proximal vagina may be treated the same way. Lymph node dissection is done by the separate incision technique rather than the en bloc resection performed years ago (Figs. 1 and 2). This results in decreased rate of wound separation and infection. The cosmetic results also are satisfactory for the patient. Early complications of radical vulvectomy are wound separation in up to 14% of patients and seromas of the femoral triangle in 10% to 15% of patients.¹⁷ Medical complications are significant and occur in up to 15% of patients. These include deep vein thrombosis, pulmonary embolism, and myocardial infarction. Urinary tract infections also are common. Late complications are less common. Chronic edema of the extremities and recurrent cellulitis are related to inguinal lymphadenectomy. Urinary incontinence and pelvic prolapse may require further reconstructive surgery. Osteitis pubis is rare but results in significant morbidity for the patient. Sexual dysfunction with dyspareunia from stenosis of the vagina should be managed conservatively. Poor self-esteem should be explored because the patient is not likely to express her feelings in this area. A sense of mutilation is common.

TABLE 2. Approach to the Treatment of Vulvar Cancer

Careful evaluation of both the clinical and the pathologic status of the inguinal nodes is important. In the absence of inguinal node metastases, most patients with lesions smaller than 2 cm should be cured, particularly if their primary lesion is excised with wide margins negative for disease. A close surgical margin is a powerful predictor of local recurrence. Deep or lateral margins greater than 8 mm are associated with no recurrence in the study of Heaps and colleagues.¹⁸ The risk of regional lymph node metastasis is related to the primary lesion, depending on lymphatic and vascular invasion, clinical stage (tumor size), and depth of stromal invasion.^18–20 When the stromal invasion exceeds 2 mm, the risk of node metastasis has been reported to be greater than 20%, whereas the risk is 40% when the thickness or invasion exceeds 4 mm.²¹ Although it is possible to anatomically and experimentally demonstrate the presence of pathways of direct lymphatic communication from the vulva to the pelvis, particularly in the area of the clitoris, such direct pelvic metastases have not been of clinical significance, occurring in squamous carcinoma in only up to 3% of cases.⁹

Clinical evaluation of the status of inguinal nodes has been subject to widespread misunderstanding and criticism because of variability in correlation between clinical impression and histologic status of the lymph nodes. In nodes that are not clinically suspicious, the frequency of metastasis varies from 12% to 43%. This wide range is not simply a reflection of variable clinical acumen, but also a statistical function. First, there is a significant variability in the frequency of metastatic inguinal lymphadenopathy reported within any series, varying from 37% to 68%. This is an uncontrollable variable reflecting the character of the population being evaluated. From review of large reported series, between 68% and 87% of the patients with clinically positive nodes will have metastatic cancer. Conversely, two thirds to three fourths of patients who have positive nodes will have palpable suspicious or clinically positive nodes before surgery. This implies that 25% to 30% of the lymph node metastases are present in unsuspicious lymph nodes. During lymphadenectomy of clinically suspicious nodes, only the enlarged nodes are removed. If frozen section confirms the presence of carcinoma, it is not necessary to proceed with full dissection of the femoral triangle. These patients require postoperative radiation. The least possible disruption of the femoral triangle results in decreased radiation complications, particularly lymphedema and wound breakdown. In a reported series of 40 patients with inguinal node metastasis, 20% had thigh or groin recurrence.²² Such recurrence occurred only in patients who had clinically suspicious or positive groin nodes before surgery. No patient with microscopic node disease, that is, metastases in nonpalpable or unsuspicious nodes, experienced recurrence in the groin.

Intraoperative lymphatic mapping and sentinel node identification has the potential to improve detection of lymph node metastasis and decrease morbidity by minimizing radical lymph node dissections. The technique of sentinel node biopsy was originally developed for selecting patients with melanoma for regional node dissection. Vital blue dye or a radioactive tracer is injected close to the tumor. The sentinel node can be identified by lymphoscintigraphy in the case of the radioactive tracer. Use of ^99mTc-labeled sulfur colloid is technically feasible and may be sensitive for detecting subclinical metastasis in regional lymphatics.²³ The blue dye is identified during dissection in surgery. The predictive value of intradermal injection of patent blue dye has been found to be low.²⁴ Multicenter studies evaluating the utility of these techniques are needed.

Pelvic Lymphadenectomy

Although pelvic lymphadenectomy formerly was emphasized as an essential component of “adequate” treatment of invasive carcinoma of the vulva, this is no longer the case. First, it has been documented that direct metastasis of squamous carcinoma of the vulva to the pelvic lymph nodes bypassing the inguinal lymphatics rarely occurs.⁹ Second, the clinical status of the inguinal nodes does reflect the probability of pelvic node metastasis. Pelvic node involvement is not seen in the absence of ipsilateral groin metastasis. Clinically positive groin nodes are associated with pelvic node metastases in 33% of cases. Based on collected data, 19% of patients with microscopic groin metastasis also have pelvic node metastasis. This number increases with three or more microscopically positive nodes.^20,22,25,26 The overall risk of pelvic node metastases is between 8.5% and 16%.²⁷ Basically, only the patient with clinically apparent metastases in the groin nodes or in Cloquet's node is at risk for pelvic metastases. The other indication for pelvic lymphadenectomy is the presence of enlarged nodes in computed tomography scan of the pelvis. An extraperitoneal approach should be used. The absolute survival rate after positive pelvic lymphadenectomy has been reported to vary from 12.5% to 25%. Patients with positive groin lymph nodes currently are treated with postoperative radiation, which includes the pelvic nodes in the radiation field.

Radiation Therapy

The effective use of radiation therapy for the treatment of vulvar carcinoma has been demonstrated in recent prospective and retrospective studies. Relatively high doses of radiation can be delivered safely to the vulva. Locoregional control, survival rates, and complications may be improved by the use of radiation in advanced vulvar cancer. In particular, the need for exenterative surgery can be reduced with the utilization of preoperative radiation. Extrapolation from the results of chemoradiation in carcinoma of the anus has lead investigators to explore the use of cisplatin, mitomycin C, and 5-fluorouracil as radiosensitizers.^28,29 Small retrospective series suggest that response rates to radiation are improved by the addition of concurrent chemotherapy. Nevertheless, the role of radiation and chemoradiation in the treatment of advanced vulvar cancer is not well defined.

The use of postoperative radiation in decreasing regional recurrences is better defined. A prospective randomized study by Homesley and associates examines the use of radiation after radical vulvectomy with inguinal and pelvic lymphadenectomy in patients who had positive groin nodes.²² For patients with clinically positive nodes, the 2-year survival rates were 59% for the group that received radiation and 31% for the group that had lymphadenectomy only. The patients with clinically positive nodes or multiple microscopically positive nodes benefited the most. For clinically negative nodes, there seems to be no significant difference in groin recurrence rates between radical lymphadenectomy and groin radiation.³⁰

Recurrence of Disease

The number of positive nodes is the most important predictor for recurrence. Patients with one microscopically positive node have an excellent prognosis, with an overall survival rate of 90%. The presence of three or more positive nodes carries a poor prognosis with, a 5-year survival rate of 50%, even after radiation to the groin and pelvis.^31,32 Recurrence localized to the vulva may be treated by local resection. Local resection may achieve disease control for an extended period or may be only palliative. Lesions limited to the vulva that can be resected with a negative margin can result in recurrence-free survival in up to 75% of cases.³³ Radiation is another alternative to treat these recurrences. Central recurrence to the vagina with no evidence of inguinal node involvement may be treated by exenteration. Groin recurrence may be treated with radiation if the patient did not get radiation after the primary surgery. Groin recurrence is not associated with long-term survivors. Both local and systemic dissemination of disease occasionally have been treated successfully with chemotherapy.

Although squamous cell carcinoma of the vulva is an infrequent entity, it represents most malignancies of the vulva (95%). The remaining 5% of cases include metastatic and rare primary lesions, which may arise from the accessory structures or specialized cells of the anogenital epithelium. Metastatic lesions are rare and represent hematogenous emboli or retrograde lymphatic flow. Frequent primary sites are the cervix, endometrium, and rectum, followed by the urethra, ovary, and breast. Such metastases always reflect the adverse prognosis of the disseminated primary lesion; treatment is primarily palliative and is coordinated with treatment of the primary malignancy.

Carcinoma of Bartholin's Gland

The diagnosis of primary malignancy of Bartholin's gland can be made only when there is an area of apparent transition from normal Bartholin structures to a neoplastic focus or a tumor that occupies the area of Bartholin's gland with no evidence of a primary tumor arising elsewhere.

The presenting symptoms of the malignancy usually are nonspecific. The incidence increases after the age of 40 (median age, 50 years). Conservative therapy may have been instituted for a lesion thought to be cystic or inflammatory. The diagnosis usually is made when the lesion fails to respond to conservative therapy, including possible incision and drainage or marsupialization. Further delay may follow these procedures because of complications like poor healing, infection, or induration with edema. Such delay in diagnosis and institution of therapy may explain the adverse prognosis associated with these lesions. The emphasis of management of the primary lesion must be on complete excision. Therefore, patients older than 40 years of age presenting with a Bartholin's gland abscess or mass (even if cystic) should have an excision procedure. Radical local excision, hemivulvectomy, or radical vulvectomy seem to be appropriate procedures, depending on the size of the primary lesion.³⁴ The incidence of groin node metastasis is about 30%, so lymphadenectomy should be performed. Radiation therapy may have some role in improving local control for patients with large lesions.

Verrucous Carcinoma

Another infrequent malignancy occurring throughout the anogenital tract, possibly involving vulva, vagina, or cervix, is verrucous carcinoma. Verrucous carcinoma is a distinct variant of squamous cell carcinoma that occurs in wet mucosae. It is most commonly found in the oral cavity. This carcinoma also develops in anogenital mucosae with similar behavior. An association with HPV-6 has been reported. The tumor is locally aggressive and extends into the underlying tissues. Typically, the tumor is extensive with a “cauliflower-like” appearance. Metastasis to lymph nodes is rare. Radiation is contraindicated in the treatment of verrucous carcinoma. The tumor is reported to be resistant to radiation therapy and may become more aggressive and invasive after radiation therapy because of anaplastic transformation. Aggressive primary surgery to ensure adequate excision is curative.³⁵ Radical local resection is adequate treatment because the tumor is locally destructive. Enlarged groin lymph nodes should be evaluated preoperatively by fine-needle aspiration because they usually are inflammatory.

Malignant Melanoma of the Vulva

The anogenital tract, particularly the vulva, is a preferred site for melanoma. These lesions represent only 0.5% to 5.0% of malignancy of the female genital organs. Melanoma is the second most common malignancy of the vulva. The disease presents predominantly in white postmenopausal patients. The most common location of the lesions is the clitoris and labia minora. Most vulvar melanomas arise de novo or from junctional nevi. The behavior of vulvar melanomas is similar to that of melanomas found elsewhere on the body. In contrast to the relatively predictable behavior of squamous carcinomas of the vulva, which spread in a stepwise fashion to regional lymph nodes, melanomas may present with early distant metastasis. Melanomas spread through the regional lymphatics, but they also penetrate the surrounding dermal lymphatics. This explains their greater propensity to disseminate elsewhere in the body at an early stage of disease by both hematogenous and lymphatic pathways. Early lesions with less than 1 mm of invasion have an excellent 5-year prognosis with survival rate greater than 90%. All other lesions have dismal outcomes, with 5-year survival rates between 21% and 54%.³⁶ Depth of invasion is the most important prognostic factor. Three classification systems for depth of invasion exist (Table 3). Chung and coworkers modified Clark level definitions to account for the variation in the histologic features of the subepithelial tissue of the clitoris and labia majora and labia minora.³⁷ They conclude that it was possible to demonstrate a prognostic value in such a classification, with a clear-cut necessity for regional lymphadenectomy for lesions with invasion for stage III or greater. The classic recommendation has been for radical vulvectomy. Recent studies indicate that a more conservative approach does not compromise survival. Lesions with less than 1 mm of invasion may be treated by radical local excision.³⁸ For lesions with more than 1 mm of invasion, radical vulvectomy with bilateral inguinofemoral lymph node dissection is advocated. Recommendations for selection of high- and low-risk patients have been formulated with proposals for less radical surgery.³⁹ As with the treatment of melanoma elsewhere on the body, the necessity for adjunctive therapy with chemotherapy or immunotherapy to complement surgery is critical, but it has limited success.

TABLE 3. Staging Systems for Vulvar Melanomas

Paget's disease occurs infrequently in the anogenital area, but when present, it is associated with distressing symptoms of itching. The origin of the lesion continues to be unclear. Paget's disease is an intraepithelial lesion with occasional in situ involvement of the skin appendages. Paget's disease is associated with synchronous and metachronous adenocarcinomas. The lesions are associated with an underlying adenocarcinoma component in 15% of cases.⁴⁰ These adenocarcinomas arise from the skin appendages. Also, about 30% of patients have or develop adenocarcinomas of nonvulvar locations.⁴¹ The most common locations are breast, colon, and rectum. Screening for these cancers is important for patients with Paget's disease.

Metastasis to regional lymphatics is rare. Only lesions associated with invasive underlying adenocarcinomas may present with metastasis to inguinal lymph nodes, and the prognosis is poor. Paget's disease may be extensive. Microscopic margins commonly extend well beyond the clinical lesion. This presents a problem for adequate excision of the primary lesion. Wide local excision is adequate treatment.⁴² The excised primary lesion can be examined intraoperatively to determine whether there is invasion into the underlying tissue or an associated adenocarcinoma of an accessory gland. If underlying invasion is suspected, a radical local excision should be performed with deep margins extending to the urogenital diaphragm fascia. Some authors advocate review of the margins by frozen section at the time of surgery.⁴³ Nevertheless, this approach may not avoid recurrence. Repeat local excision of a recurrence usually is effective treatment. There is a greater propensity for the malignancy to metastasize if an invasive adenocarcinoma is present. Inguinal lymphadenectomy can be performed later once such diagnosis has been established.

The authors thank Ernest W. Franklin, MD, for his contribution and Thomas Heffernan, MD, for the excellent drawings.

1. Carter J, Carlson J, Fowler, J et al:Invasive vulvar tumors in young women: A disease of the immunosuppressed? Gynecol Oncol 51: 307, 1993

2. Roy M: VIN: Latest management approaches. Contemp Obstet Gynecol 32: 170, 1988

3. Hording U, Junge J, Poulsen H et al: Vulvar intraepithelial neoplasia: III. A viral disease of undetermined progressive potential. Gynecol Oncol 56: 276, 1995

4. Brinton LA, Nasca PC, Mallin K et al: Case-control study of cancer of the vulva. Obstet Gynecol 75: 859, 1990

5. Hart WR, Norris HJ, Helwig EB: Relation of lichen sclerosus et atrophicus of the vulva to development of carcinoma. Obstet Gynecol 45: 369, 1975

6. Kurman RJ, Trimble CL, Shah KV: Human papillomavirus and the pathogenesis of vulvar carcinoma. Curr Opin Obstet Gynecol 4: 582, 1992

7. Ansink AC, Krul MRL, DeWeger RA et al: Human papillomavirus, lichen sclerosus, and squamous cell carcinoma of the vulva: Detection and prognostic significance. Gynecol Oncol 52: 180, 1994

8. Hoffman JS, Kumar NB, Morley GW: Prognostic significance of groin lymph node metastasis in squamous cell carcinoma of the vulva. Obstet Gynecol 66: 402, 1985

9. Franklin EW, Rutledge FD: Prognostic factors in epidermoid carcinoma of the vulva. Obstet Gynecol 37: 892, 1971

10. Hacker NF, Leuchter RS, Berek JS et al: Radical vulvectomy and bilateral inguinal lymphadenectomy through separate groin incisions. Obstet Gynecol 58: 574, 1981

11. Creasman WT: New gynecologic cancer staging. Gynecol Oncol 58: 157, 1995

12. Microinvasive cancer of the vulva: Report of the ISSVD task force. J Reprod Med 29:454, 1984

13. Kosary CL: FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: An analysis of 1973-87 SEER cases of cancers of the endometrium, cervix, ovary, vulva and vagina. Semin Surg Oncol 10: 31, 1994

14. Kelley JL III, Burke TW, Tornos C et al: Minimally invasive vulvar carcinoma: An indication for conservative surgical therapy. Gynecol Oncol 144: 240, 1991

15. Magrina JF, Gonzalez-Bosquet J, Weaver AL et al: Squamous cell carcinoma of the vulva stage IA: Long-term results. Gynecol Oncol 76: 24, 2000

16. Stehman FB, Bundy BN, Dvosretsky PM et al: Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: A prospective study of the Gynecologic Oncology Group. Obstet Gynecol 79: 490, 1992

17. Figge CD, Gaudenz R: Invasive carcinoma of the vulva. Am J Obstet Gynecol 119: 382, 1974

18. Heaps Jm, Fu YS, Montz FJ et al: Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 38: 309, 1990

19. Binder SW, Huang I, Fu YS et al: Risk factors for the development of lymph node metastasis in vulvar squamous carcinoma. Gynecol Oncol 37: 9, 1990

20. Boyce J, Fruchter RG, Kasambilides E et al: Prognostic factors in carcinoma of the vulva. Gynecol Oncol 20: 364, 1985

21. Homesley HD, Bundy BN, Sedlis A et al: Clinical and surgicopathologic findings in squamous cell carcinoma of the vulva: A Gynecologic Oncology Group study. Proceedings of the Second Meeting of the International Gynecologic Cancer Society 2: 60, 1989

22. Homesley HD, Bundy BN, Sedlis A et al: Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 68: 733, 1986

23. Terada KY, Shimizu DM, Wong JH: Sentinel node dissection and ultrastaging in squamous cell cancer of the vulva. Gynecol Oncol 76: 40, 2000

24. Ansik Ac, Sie-Go DM, van der Velden J et al: Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: A multicenter study. Cancer 86: 652, 1999

25. Podratz KC, Symmonds RE, Taylor WF et al: Carcinoma of the vulva: Analysis of treatment and survival. Obstet Gynecol 61: 63, 1983

26. Hacker NF, Berek JS, Lagasse LD et al: Management of reguional lymph nodes and their prognostic influence in vulvar cancer. Obstet Gynecol 61: 408, 1983

27. Rutledge F, Smith JP, Franklin EW: Carcinoma of the vulva. Am J Obstet Gynecol 106: 1117, 1970

28. Berek JS, Heaps JM, Fu YS et al: Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva. Gynecol Oncol 42: 197, 1991

29. Han SC, Kim DH, Higgins SA et al: Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva. Int J Radiat Oncol Biol Phys 47: 1235, 2000

30. Petereit D, Mehta M, Buchler D et al: A retrospective review of nodal treatment for vulvar cancer. Am J Clin Oncol 16: 38, 1993

31. Farias-Eisner R, Cirisano FD, Grouse D et al: Conservative and individualized surgery for early squamous carcinoma of the vulva: The treatment of choice for stage I and II (T1-2 N0-1 M0) disease. Gynecol Oncol 53: 55, 1994

32. Figge DC, Tamimi HK, Greer BE: Lymphatic spread in carcinoma of the vulva. Am J Obstet Gynecol 152: 387, 1985

33. Hopkins MP, Reid GC, Morley GW: The surgical management of recurrent squamous cell carcinoma of the vulva. Obstet Gynecol 75: 1001, 1990

34. Copeland LJ, Sneige N, Gershenson DM et al: Bartholin gland carcinoma. Obstet Gynecol 67: 794, 1986

35. Japaze H, Dinh TV, Woodruff JD: Verrucous carcinoma of the vulva: Study of 24 cases. Obstet Gynecol 60: 462, 1982

36. Jaramillo BA, Ganjei P, Averette HE et al: Malignant melanoma of the vulva. Obstet Gynecol 66: 398, 1985

37. Chung AF, Woodruff JM, Lewis JL: Malignant melanoma of the vulva: A report of 44 cases. Obstet Gynecol 45: 638, 1975

38. Sim FH, Taylor WF, Pritchard DJ: Lymphadenectomy in the management of stage I malignant melanoma: A prospective randomized study. Mayo Clinnic Proc 61: 697, 1986

39. Tasseron EWK, van der Esch EP, Hart AA et al: A clinicopathologic study of 30 melanomas of the vulva. Gynecol Oncol 46: 170, 1992

40. Parmley TH, Woodruff JD, Julian CG: Invasive Paget's disease. Obstet Gynecol 46: 341, 1975

41. Hart WR, Millman RB: Progression of intraepithelial Paget's disease of the vulva to invasive carcinoma. Cancer 40: 2333, 1977

42. Bergen S, DiSaia PJ, Liao SY et al: Conservative management of extramammary Paget's disease of the vulva. Gynecol Oncol 33: 151, 1989

43. Stacy D, Burrell MO, Franklin EW: Extramammary Paget's disease of the vulva and anus: Use of intraoperative frozen-section margins. Am J Obstet Gynecol 155: 519, 1986