In the early part of the 20th century, patients with vulvar cancer usually died of disease. The overall survival rate for vulvar cancer after simple surgical excision was less than 25%. Attempts to improve outcomes for patients with vulvar cancer by performing more radical surgery were first described by Basset in 1912. Way described an improved survival rate using an en bloc dissection radical vulvectomy with an inguinal and pelvic lymphadenectomy. The Bassett-Way operation resulted in a 5-year survival rate of 74% as reported by Morley.This success rate convinced most surgeons to use this operation for all patients with vulvar cancer regardless of tumor size. Major morbidity from this procedure included poor wound healing and long-term lymphedema.
Fred Taussig collected a large series of vulvar cancer cases from 1911-1940. He initially started his series with a radical excision of the primary tumor with an en bloc dissection of the inguinal lymph nodes. Later, he modified his technique for patients with small lesions in an attempt to decrease operative morbidity. He used separate incisions for the groin dissection and the vulvar excision. This less radical operation for small lesions was not routinely used until Hacker reported his experience with 100 patients in 1981.5 He reported using 3 separate incisions, as described by Taussig, for patients with clinical stage I disease. The 5-year survival rate was 97%.
Vulvar carcinoma encompasses any malignancy that arises in the skin; glands; or underlying stroma of the perineum, including the mons, labia minora, labia majora, Bartholin glands, or clitoris. Tumors can also arise in ectopic breast tissue that can be located in the vulva along the milk line. Metastatic tumors have also been described but occur relatively infrequently.
For related information, see eMedicine's article on Malignant Vulvar Lesions.
Cancer of the vulva is the fourth most common malignancy of the female genital tract. The American Cancer Society estimates 3,460 women will be diagnosed with vulvar cancer in 2008.Currently, approximately 75% of patients with vulvar carcinomas will be cured, making vulvar carcinoma responsible for approximately 900 deaths annually in the United States.
Unfortunately, the incidence of preinvasive disease of the vulva has almost doubled over the past decade, and this may translate into a marked increase in the incidence of invasive vulvar carcinoma in the future. Since vulvar cancer is rare and is not monitored by the World Health Organization, the global incidence of this disease is not precisely known.
The incidence of vulvar carcinoma has a bimodal peak. Currently, development of vulvar carcinoma in situ in young women is suggested to correlate to human papillomavirus (HPV) infection. In older women, the etiology of the carcinoma is attributed to chronic irritation or other poorly understood cofactors. Estimates indicate that women who smoke cigarettes have a 4- to 5-fold increase in the incidence of carcinoma in situ of the vulva and a 20% increase in vulvar carcinoma. The incidence of vulvar carcinoma in situ and vulvar carcinoma is higher in women with multiple sexual partners and in women with a history of HPV infection. For women who report a history of genital warts or HPV-related disease, the relative risk for carcinoma in situ is 18.5 and for invasive cancer is 14.5.
The development of vulvar dysplasia and cancer in most patients is related to HPV infection. Certain strains of HPV are known to be more oncogenic than others. HPV types 16, 18, 31, 33, 35, 45, and 54 are more likely to be associated with cervical neoplasia and cancer and are suspected to also be responsible for vulvar cancers. The DNA from HPV 16 and 18 has been detected in up to 60% of patients with vulvar cancer.
The mechanism of HPV transformation into dysplasia and cancer is not well understood. Two gene products from HPV are known to immortalize cells in culture and are probably responsible for malignant transformation. The HPV E6 protein does have the ability to bind the host p53 protein. The HPV E7 protein binds the Rb gene product. The oncogenic viral types are thought to have a greater affinity for these cellular proteins, which would explain the increased risk of malignant transformation. Some infections may lead to integration of the viral DNA into the host, with disruption of the normal regulation of the E6 and E7 oncoproteins. This increased production of the E6 and E7 gene products could then result in oncogenic transformation.
Diagnosis of vulvar carcinoma is often delayed. Women neglect to seek treatment for an average of 6 months from the onset of symptoms. In addition, a delay in diagnosis often occurs after the patient presents to her physician. In many cases, a biopsy of the lesion is not performed until the problem fails to respond to numerous topical therapies. A biopsy should be performed when any discrete lesion of the vulva is discovered. The most common presentation is a pruritic lesion of the vulva or a mass detected by the patient herself. However, early vulvar cancer may be asymptomatic and recognized only with careful inspection of the vulva. A biopsy should be performed on all visible lesions on the vulva. More advanced vulvar carcinomas present with bleeding, pain, or discharge.
Choosing the proper surgical procedure for vulvar cancer is important. Patients with vulvar dysplasia can have a wide local excision. The advantage of this procedure is that the removed tissue is sent for pathologic examination. Pathologic examination allows for assessment of surgical margins and assures the absence of invasive disease. Ablative procedures can be used for dysplastic lesions if vulvar cancer can be excluded with reasonable certainty.
Patient with biopsy-proven squamous cell carcinoma of the vulva are usually candidates for surgical excision. Patients with a lesion involving the upper urethra or anus or is fixed to the pelvic bone can be treated with neoadjuvant radiation and chemotherapy prior to surgical intervention.7 This type of therapy can allow future resection with preservation of the urethral or rectal sphincter in most cases. Radiation can also be used in an attempt to spare the clitoris.
Relevant Anatomy The vulva includes all external genital structures, including the mons pubis, labia majora, labia minora, clitoris, vaginal vestibule, perineum, and supporting structures exterior to the urogenital diaphragm. The femoral triangle is bounded by the inguinal ligament superiorly, the adductor longus medially, and the sartorius laterally. The superficial groin nodes lie above the cribriform fascia in the femoral triangle. Careful dissection generally reveals 5 vessels in the femoral triangle above the cribriform fascia, the largest of which is the saphenous vein. Often, a lateral accessory saphenous vein can be identified. The other vessels include the superficial circumflex, the superficial epigastric, and the external pudendal. Below the cribriform fascia are the deep inguinal nodes. Three to 4 nodes can be found medial to the femoral vein. The most superior of these is the sentinel node to the pelvic lymphatics and is known as the node of Cloquet.
The lymphatics of the vulva and distal third of the vagina drain into the superficial inguinal node group and travel through the deep femoral lymphatics and the node of Cloquet to the pelvic nodal groups Direct spread to the deep nodal groups without metastasis to the superficial group has been documented using lymphatic mapping. This type of direct spread is uncommon and represents fewer than 5% of cases.
Lymphatic mapping studies have also demonstrated that radioactive colloid injected into the vulva can accumulate more readily in the lateral external iliac nodes than in the medial group, which suggests that not all lymphatics flow to the medial pelvic nodes through the node of Cloquet. Studies suggest that 10-20% of lymphatic flow from the superficial node group travels directly to the pelvis without passage through the deep inguinal nodes. A direct pathway from the clitoris or vulva to the pelvic nodes has not been identified.
Because few alternatives to surgery are available for vulvar carcinoma, resection of the primary lesion should be attempted in most cases. Regional or general anesthesia can be used for this type of surgery. A combination of radiation and chemotherapy is an alternative to surgery. However, this regimen can have significant morbidity. For this reason, women who are not candidates for surgery are generally poor candidates for chemoradiation. The use of radiation alone can be used for palliation but should not be considered a curative treatment.
Treatment Medical Therapy
Neoadjuvant therapy for vulvar cancer may be considered for tumors that manifest with bowel or bladder involvement that would require extensive or exenterative surgery. The Gynecologic Oncology Group (GOG) reported its experience with a combination of cisplatin and 5-fluorouracil with hyperfractionated radiation for patients with unresectable stage III or stage IV squamous cell carcinoma of the vulva. After chemotherapy and radiation, 71 of 73 women were candidates for surgery and almost half had no visible disease. Urinary and fecal continence was preserved in all but 3 of these women.
Except in the neoadjuvant setting, chemotherapy for vulvar carcinoma is palliative and often ineffective. Only bleomycin has been reported to produce a complete clinical response. In a series of 11 patients, Trope and colleagues administered bleomycin at a dose of 15 mg twice weekly and noted 2 complete responses (19%) and 3 partial responses (27%), for a total response rate of 46%.
The only other agent that has been reported to be effective in recurrent vulvar cancer is doxorubicin. Deppe et al reported a partial response in 3 of 4 patients treated at a dose of 45 mg/m2. Cisplatin and 5-fluorouracil (5-FU) have been used in the neoadjuvant setting but have not been studied extensively in recurrent vulvar cancer. However, due to a lack of effective chemotherapy agents, these drugs are often used in recurrent vulvar cancer.
Great effort has been devoted to decreasing the morbidity of surgery for vulvar carcinoma. Traditional surgery has been a large en bloc resection of the vulva with the superficial and deep inguinal nodes through a single incision with at least 2-cm margins around the tumor and deep resection to the genitourinary diaphragm (see Media files 3-4). This procedure resulted in significant surgical morbidity and distressing change in body image for the patient.
Refinements to surgery include (1) a definition for microinvasive carcinoma that does not require radical vulvar dissection or inguinal node dissection, (2) unilateral inguinal node dissection for small ipsilateral tumors, (3) using a triple-incision technique instead of an en bloc approach, (4) using radical local resection with 1-cm margins instead of complete vulvectomy, and (5) sparing the saphenous vein in an attempt to prevent lymphedema. Many gynecologic oncologists omit dissection of the deep inguinal lymph nodes, although this is controversial. In an attempt to decrease the morbidity from inguinal node dissection, radiation alone has been used to treat the groin lymph nodes but was shown to be inferior to groin node dissection.
Sentinel lymph node (SLN) dissection may eventually replace routine groin node dissection.This idea assumes metastasis occurs first to the SLNs, followed by metastasis to the other inguinal lymph nodes. This orderly metastasis has been validated in breast cancer and cutaneous melanoma. Confirmation of this technique in patients with vulvar cancer continues to be examined.
he results of lymphoscintigraphy and blue dye used in 59 patients with vulvar cancer was reported by de Hullu. All 37 SLNs interpreted as positive on frozen section were confirmed on final pathologic examination, resulting in a positive predictive value of 100%. A more recent study examined the use of identification of the SLN in patients with squamous cell carcinoma. Patients were divided into 2 groups. Of the women, 28 had a vulvectomy and lymphadenectomy with identification of the SLN using lymphoscintigraphy with technetium-99 colloid albumin and 27 women had a vulvectomy and lymphadenectomy with no attempt to identify the SLN. SLN identification failed in 1 case. There was 1 false-negative SLN. The average number of SLNs identified was 2.2. Recurrent disease was similar in both groups. The authors did not report which patients developed recurrent disease in the inguinal area.
The initial proposal for microinvasive lesions was a depth of 5 mm for tumors smaller than 2 cm. However, the risk of groin node metastasis in lesions with 3-5 mm of invasion was noted to possibly be as high as 20%. It was later determined that women with 1-mm invasion or less had a negligible chance of node metastasis and could be treated with wide local excision with a 1-cm clinical margin around the tumor. A GOG study suggested that women with well-differentiated tumors up to 2 mm in depth had a very low risk of lymph node metastasis.
A study by Yoder and colleagues identified 3 features most important in predicting tumor recurrence: depth of invasion, presence of squamous cell carcinoma at the surgical margins, and the histologic grade.Omitting the groin node dissection in women with 1-2 mm of invasion can be considered if the tumor is well differentiated and the patient is elderly, debilitated, or at significant risk of lymphedema.
The risk of lymph node metastasis based on the depth of invasion
- Invasion to less than or equal to 1 mm - 0% (n = 34)
- Invasion to 1.1-2 mm - 10% (n = 19)
- Invasion to 2.1-3 mm - 12% (n = 17)
- Invasion to 3.1-5 mm - 14% (n = 7)
- Invasion to deeper than 5 mm - 43% (n = 7)
In stage I lesions, 0 of 177 patients had positive findings from contralateral groin nodes when the ipsilateral node findings were negative and the lesion was not located in the midline. Therefore, contralateral groin node dissection has been omitted when patients present with a primary lesion smaller than 2 cm and have negative ipsilateral lymph node findings.
Since the early part of the 20th century, the traditional surgery has been a radical dissection of the primary lesion with a bilateral groin node dissection performed through a single incision. Although this technique was later modified to remove less skin, the primary wound breakdown rate exceeded 50%. Taussig eventually adopted a triple-incision technique in response to the high wound breakdown rate. Concern was raised over the triple-incision technique because of the possibility of residual disease in the "skin bridges" due to cancer cells in the lymphatics between the primary tumor and the lymph nodes. Hacker et al reported a series of 100 patients who had undergone surgery with a triple-incision technique and reported a 56% primary healing rate. Although 2 patients had metastasis in the skin bridge, neither of these instances were isolated metastasis.
Helm et al reported findings when comparing the cases of 32 women treated with a single incision with 32 similar patients treated with a triple incision. Patients with a triple incision had a significantly shorter operative time, less blood loss, and a shorter hospital stay. No difference was observed in the overall survival or recurrence rate between the 2 groups, and none of the women in the triple-incision group developed skin bridge metastasis. The biggest difference in the 2 groups was that the single-incision group had a 19% complete wound-breakdown rate, compared to only 3% for the triple-incision group. Similar results have been noted for women with larger lesions.
A less-radical approach was adopted following the discovery that the local recurrence risk was low when the pathologic margin around the primary lesion was 8 mm. When taking into account the shrinkage during tissue fixation, this translates to a 1-cm clinical margin. Deep dissection to the urogenital diaphragm is performed, but most of the vulva can be spared if the primary lesion is small.
The traditional description of a groin node dissection includes ligation of the saphenous vein during removal of the superficial groin lymphatics. A review of 139 cases of groin node dissection demonstrated that when the saphenous vein was preserved, the incidence of wound cellulitis and acute and chronic lymphedema was significantly lower. Only one patient in this series with saphenous vein preservation developed chronic lymphedema. This occurred in a patient who received postoperative radiation therapy. No evidence indicated that an attempt to save the saphenous vein significantly increased blood loss or operative time.
The idea to implement radiation therapy to treat the groin lymphatics without surgery has been studied by the GOG. The GOG performed a study on the efficacy of groin irradiation compared to surgery. Women with clinically negative findings from groin nodes were randomized to radiation alone or lymphadenectomy with radiation when the groin nodes were pathologically positive. The study was discontinued prematurely as an interim analysis demonstrated a significant decrease in survival in women receiving only groin irradiation.
This study has been criticized due to the radiation dosage. The prescribed dose of radiation was at 3 cm, regardless of body habitus or the actual groin node location. Studies of CT scan data have demonstrated that this technique delivers 100% of the prescribed dose to only 18% of women, and fewer than half the women would have received more than 60% of the prescribed dose to the entire groin lymphatic area. Many physicians now omit deep groin node dissection. Opening the femoral sheath and removing the deep nodes is not without morbidity. Deep lymph node dissection may increase the incidence of lymphedema. In addition, infection of the groin over the femoral vessels after deep groin dissection can result in catastrophic bleeding. The sartorius muscle historically was transferred to the inguinal ligament to cover the exposed femoral vessels. Judson reported this technique is not beneficial based on a randomized control trial and increased the risk of lymphocyst formation.
Several authors have examined the incidence of unexpected groin failure in the presence of pathologically negative superficial lymph node findings. The incidence rate of unanticipated failure is approximately 0-5%.These percentages match those of an older series by Stanley Way, in which he examined both nodal groups separately and found that the deep nodes (deep femoral and pelvic) were involved in only approximately 3% of cases when the superficial lymph node findings were negative. He later adopted a technique of using the deep inguinal nodes to predict the need for pelvic lymph node dissection but continued to remove both the superficial and deep inguinal nodes. A survey of a group of gynecologic oncologists found that fewer than 25% of respondents still perform deep inguinal node dissection.
Surgery for vulvar carcinoma is often performed with the woman's legs in adjustable stirrups to facilitate both the groin node dissection and the perineal phase of the operation. A surgical team can greatly reduce operative time. After the patient is prepared and draped, make an incision approximately 2 cm below the inguinal ligament. The tissue is undermined below the Scarpa fascia. Carry the dissection down to the tensor fasciae latae. Then, dissect the superficial inguinal nodal group off the cribriform fascia, taking care to not injure the great saphenous vein.
If the deep nodes are to be dissected, open the cribriform fascia laterally and take it as part of the specimen. Then, dissect the femoral vein free and remove the nodes from the medial portion of the femoral vein. After a deep groin node dissection, the sartorius muscle can be divided at its insertion on the anterior iliac spine and sutured to the inguinal ligament to cover the femoral vessels. Bring closed suction drains in through a separate incision and suture to the skin. Close Scarpa fascia with 3-0 absorbable sutures, and close the skin with mattress sutures or with staples.
For the vulvectomy, outline the lesion and make an incision to encompass 1-cm margins around the tumor. In contrast to a simple vulvectomy, the dissection is carried deep to the perineal membrane. Care must be taken at the posterior aspects of the incision where the pudendal vessels enter the vulva. The lower portion of the bulbocavernosus muscle should be clamped and ligated to prevent bleeding. Once the lesion is removed, the vagina and vulvar skin can be mobilized to reduce the tension on the incision. It is closed in layers with absorbable suture, and the skin is closed with horizontal or vertical mattress sutures. The authors' preference is to use 2-0 polyglycolic acid for the mattress sutures and to reinforce the incision with a running 3-0 polyglycolic acid suture.
After surgery, recommend frequent sitz baths. Patients should dry the vulva completely after each sitz bath. A Foley catheter may be needed for a prolonged period after surgery around the urethra. Low molecular weight heparin or pneumatic compression stockings should be used in all women to prevent postoperative venous thrombosis. A Jackson-Pratt or similar type of drain should be placed in the inguinal space at the time of lymphadenectomy. Leave this drain in place until drainage is approximately 25 mL or less per day. In many cases, this may take more than 2 weeks.
Although surgery for vulvar carcinoma is often curative, it can be disfiguring and may significantly impact sexual function. This type of surgery can have serious psychological sequela, even in the absence of a functional problem after surgery. Sexual dysfunction seems to be related to a disturbance in body image, leading to hypoactive sexual disorder and aversion disorder. Depression and increasing age are risk factors for sexually active women to discontinue intercourse after surgery. Interestingly, few studies have been able to correlate sexual dysfunction with extent of surgery if the clitoris was preserved.
Women who have positive findings from more than one node are likely to benefit from adjuvant radiation therapy to the inguinal and pelvic nodes. The GOG studied the use of pelvic node dissection instead of pelvic and groin radiation and found that radiation was superior. A clear benefit for radiation has not been proven in women with positive microscopic findings from one node, but, because groin recurrence is almost universally fatal, adjuvant radiation is often recommended.
Monitor patients closely after treatment for vulvar carcinoma. Examinations every 3 months for the first 2 years are often recommended because more than two thirds of recurrences are in this time period. Detection of local recurrence of vulvar carcinoma is important because it can be treated by radical surgical excision.
The long-term survival rate after radical excision of a vulvar recurrence has been reported as 50-60%. Survival is better in women who originally presented with early-stage disease. Other factors that diminish the cure rate after local recurrence include disease at sites other than the vulva and a short interval from initial treatment to recurrence. For a large recurrence, an exenterative procedure can be attempted. A long-term survival rate of 38% has been reported after exenterative surgery for vulvar carcinoma.
Resection of a groin recurrence is not usually recommended. Often, this area heals slowly if radiation has already been used. Generally, the procedure should not be considered curative. The only situation in which resection of a groin node recurrence should be attempted is if the groin node is an isolated recurrence and the patient has not been previously irradiated.
Positive groin nodes at the time of initial surgery increase the risk of recurrence in the groin in the first 2 years. After the first 2 years, the risk of groin recurrence is low, regardless of the status of the nodes at the time of the initial surgery. It has been noted that the risk of local failure on the vulva is elevated for many years after the surgery. A report from the Mayo clinic showed that up to 10% of patients treated for vulvar cancer had a local recurrence more than 5 years after the original diagnosis. For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Procedures Center. Also, see eMedicine's patient education articles Colposcopy and Cervical Cancer.
Lymphocyst formation is noted in 7-19% of patients after groin lymphadenectomy. Although cellulitis after vulvectomy has been associated with an increase in the incidence of lymphedema, it has not been associated with an increase in lymphocyst formation. Do not remove drains after inguinal node dissection until the daily output of the drain is less than 25 mL.
Lymphocysts usually manifest as an asymptomatic mass in the groin. To exclude a groin recurrence, aspirate fluid from the cyst and send for cytologic evaluation. Multiple aspirations are often required and may not be curative. If the mass is symptomatic, the lymphocyst can be removed surgically. However, in one small series, lymphocysts were successfully treated by placing a drain in the groin until the output was less than 25 mL/d. The drain was then removed and a pressure dressing was placed to prevent reaccumulation of the fluid. Sclerosis of lymphocysts with Betadine solution has also been described.
Cellulitis and lymphangitis can occur after groin node dissection. The incidence rate of cellulitis requiring antibiotics ranges from 20-40%. Often, patients who develop lymphocysts are at increased risk of lymphangitis. The etiologic agent is most often a streptococcal species, and treatment with penicillin is adequate. If drains are still in place, first-generation cephalosporins may be more appropriate to treat Staphylococcus aureus.
Chronic lymphedema has been reported in 10-20% of women after groin node dissection. This can be a disabling problem and is more common if radiation is required after groin dissection. Limiting groin node dissection in women with early cancers and preserving the saphenous vein decreases the incidence of this problem. The use of graduated compression stockings after lymphadenectomy can help prevent lymphedema. If edema does develop, the use of compression stockings, massage therapy, and limb wraps can help control the accumulation of fluid. However, lymphedema can be chronic and disabling in severe cases. Many major centers offer lymphedema treatment programs.