" MD Consult - Book Text Rakel: Conn s Current Therapy 1999, 51st ed., Copyright © 1999 W. B. Saunders Company



Emory University School of Medicine Atlanta, Georgia

Vulvar neoplasias are the fourth most common genital tumor in women, accounting for 3 to 5% of genital tumors and 0.3% of all female malignancies. The majority of patients present in the sixth decade of life. Unfortunately, vulvar disease and its treatment have altered the psychosocial well-being of women. The surgery is frequently disfiguring and is fraught with complications such as leg edema, vaginal stenosis, dyspareunia, wound separation, and lack of a cosmetic vulva. Recent changes in treatment protocols have helped to decrease the procedural morbidity and improved the patient s self-image.


The Ninth Congress of the International Society for the Study of Vulvar Disease (ISSVD) in 1987, in conjunction with the International Society of Gynecological Pathologists (ISGYP), changed the nomenclature for preinvasive vulvar disease (Table 1) . Non-neoplastic epithelial disorders of the skin and mucosa is the new term for vulvar dystrophies. Hyperplastic dystrophy is classified as squamous cell hyperplasia, and atypical hyperplastic dystrophy is categorized as vulvar intraepithelial neoplasia (VIN) (Table 2) . Mixed dystrophies will be reported as lesions containing both lichen sclerosus and squamous cell hyperplasia.


On gross examination, lichen sclerosus and squamous cell hyperplasia manifest as white plaques (leukoplakia), the former being an atrophic lesion with the microscopic appearance of a thin squamous epithelium and flattened rete ridges. In squamous cell
TABLE 278-1 -- Non-neoplastic Epithelial Disorders of the Skin and Mucosa
Old Terminology New Terminology
(ISSVD 1987)
Lichen sclerosus et atrophicus Lichen sclerosus (LS)
Hyperplastic dystrophy (without atypia) Squamous cell hyperplasia (SCH)
Mixed dystrophy LS and SCH
Abbreviations: ISSVD = International Society for the Study of Vulvar Disease-1987.

TABLE 278-2 -- Vulvar Intraepithelial Neoplasia (VIN)
Old Terminology New Terminology
(ISSVD 1987)
Mild atypia (dysplasia) VIN I
Moderate atypia (dysplasia) VIN II
Severe atypia (dysplasia) VIN III
Carcinoma in situ VIN III
Abbreviations: ISSVD = International Society for the Study of Vulvar Disease-1987.

hyperplasia, microscopically the squamous epithelium has a thick superficial layer of parakeratosis or hyperkeratosis and elongated rete ridges. Mixed lesions demonstrate the histologic features of both lesions. Occurring in 20% of non-neoplastic epithelial disorders, mixed lesions are more difficult to treat. Early studies have suggested that mixed lesions have a predisposition to transform into vulvar malignancies. However, this issue continues to be debated and should not alter treatment protocols.


Patients with non-neoplastic epithelial disorders frequently present with pruritus and vulvodynia. Often, patients are treated by practitioners for atrophic vulvitis and/or monilial vulvitis, only to have their symptoms persist. The hallmark to making a correct diagnosis is a thorough medical history followed by a comprehensive inspection of the genitalia, including the cervix, anus, and vagina. Non-neoplastic epithelial disorders and intraepithelial neoplasia are multifocal and may be present on all anogenital mucosal surfaces. On completing visual and digital examination, 3% acetic acid is placed on the vulva, anus, vagina, and cervix, and a colposcopic evaluation is performed. Raised white plaques and increased vascularity, punctation, and mosaicism should be biopsied to identify histologic changes. If colposcopy is not available or additional diagnostic tests are warranted, the vulva and anus are painted with a 1% aqueous solution of toluidine blue, which is allowed to stain for 3 minutes. The epithelium is then decolorized with 1% acetic acid for 1 minute. Surface nuclei of dysplastic or anaplastic lesions will retain the blue stain and should be biopsied. Biopsies are easily performed using 1% lidocaine injected circumferentially around the lesion with a 25-gauge needle. A Keyes punch enables the physician to circumscribe the lesion and incise the epidermis. Forceps and scissors are then required to free the remainder of the specimen from the underlying tissue. The vagina and cervix also can be evaluated with Schiller s or Lugol s solution, which will not stain intraepithelial neoplasia.


Lichen sclerosus is treated primarily with high-potency topical steroids such as betamethasone dipropionate

(Diprosone), 0.05% daily for 1 month, then twice weekly as needed. In the past, testosterone or progesterone creams were first-line treatment. Two percent testosterone propionate cream is made by adding testosterone propionate, 3 mL of 100 mg per mL in sesame oil, with 12 mg of petroleum. The cream is applied to the vulva three times daily for 6 to 8 weeks, followed by a daily application for 1 week and then weekly application. Testosterone s androgenic side affects such as clitoromegaly, hirsutism, voice changes, acne, and dermal hypertrophy may not be accepted by all patients. Alternatively, 1% or 2% progesterone cream has been substituted in patients who could not tolerate testosterone. Results have been comparable but without the androgenic side affects. Seventy-five to 90% of patients treated with either regimen have reported symptomatic relief.

Squamous cell hyperplasia is best treated with medium potency topical steroids such as triamcinolone acetamide 0.1% (Aristocort) and desoximetasone 0.25% (Topicort) twice daily for 1 month or when symptoms decreased. The patient is then weaned to daily, twice weekly, and as needed administration. Non-neoplastic epithelial disorders frequently recur and require chronic administration of topical agents as described previously. Surgical procedures such as laser vaporization, ultrasonic surgical aspiration, loop excision, simple lesion excision, and cryotherapy have also been utilized in treating non-neoplastic epithelial disorders but should be reserved as second-line therapy after the patient has failed treatment with topical compounds. Unless all conservative measures have failed, vulvectomy and skinning vulvectomy should be avoided in these patients because of the recurrence rate and disfiguring secondary to the procedure. The pruritus and vulvodynia that plague patients with non-neoplastic epithelial disorders can be controlled by administering benzocaine or lidocaine ointment topically during the initial steroid therapy. Patients with more severe and recalcitrant disease can be given palliative treatment with triamcinolone diacetate (Aristocort) injections in a grid distribution on the vulva. Intradermal alcohol injections were previously used in recalcitrant cases. Recent advances in treating these patients with topical medium- and high-potency steroids have essentially eliminated the use of intradermal alcohol injections.


Granular cell tumors (GCTs) were initially described in 1854. Over a 31-year period, 20 patients presented with GCT of the vulva at my institution. Two patients presented with additional lesions not on the vulva. Patients with localized disease were treated successfully with wide local excision. Although benign, GCT may resemble an invasive lesion grossly and histopathologically to the untrained eye. If surgical margins are positive, additional resection is required. A minimum of 1- to 2-cm margins are required to decrease the risk of recurrence.


Mild and moderate dysplasias of the vulvar epithelium are designated VIN I and II. Bowen s disease, erythroplasia of Queyrat, and carcinoma simplex have been classified as VIN III, which also includes in situ disease and severe dysplasia. VIN is multifocal, with 50% of the patients presenting in the third and fourth decades of life. An association has been found between VIN and human papilloma virus (HPV) subtypes 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, and 61. HPV 16 and 18, however, are responsible for the majority of VIN III and invasive neoplasias. Patients presenting with atypical or flat condylomata acuminata should have their lesions biopsied before conservative chemical desiccation to rule out intraepithelial neoplasia. Twenty to 30% of patients with VIN III also have associated genital tract neoplasias, with the preponderance being intraepithelial neoplasia of the anus, vagina, and cervix, followed by cervical, vaginal, and endometrial carcinoma. The diagnostic evaluation of VIN is identical to that described for non-neoplastic epithelial disorders of the skin and mucosa.


Small focal lesions of VIN may be treated with local excision, cryotherapy, ultrasonic surgical aspiration, loop excision, or laser vaporization. Extensive and multifocal lesions, however, are best treated with laser vaporization, skinning vulvectomy, or simple vulvectomy. Laser vaporization is performed under regional or general anesthesia with a carbon dioxide laser attached to a colposcope and microslad. The laser is set with a 2.0-mm spot size, power of 20 to 30 watts superpulse, and vaporization performed to a depth of 2 to 3 mm. On completing vaporization of the lesion, the operative field is dressed with 1% silver sulfadiazine (Silvadene) cream and 5% lidocaine mixture. Ample quantities of analgesic medications must be prescribed postoperatively, as the patient may experience excruciating discomfort. Unfortunately, many physicians frequently forget that laser vaporization results in a third-degree burn and requires special care. Ultrasonic aspiration of these lesions does not result in a third-degree burn and heals faster without much discomfort.

Skinning vulvectomy may be partial or complete; unlike with laser vaporization, a specimen can be sent for histologic evaluation. Unfortunately, this procedure carries increased morbidity when compared with laser therapy. Split-thickness skin grafts are also required on completion of the skinning vulvectomy. Carbon dioxide laser vaporization, ultrasonic surgical aspiration, electroloop excision, and skinning vulvectomy offer cosmetic and functional results without mutilation of the female genitalia. Hair dryers and heat lamps provide valuable assistance in keeping the surgical field dry after either procedure.


Local chemotherapeutic regimens such as 5% fluorouracil cream * (Efudex), bleomycin sulfate * (Blenoxane), and interferon * have met with limited success.


Paget s disease of the breast was first described by James Paget in 1874. Its manifestation on the vulva was reported in 1901 by W. Dubrewilh. Twenty percent of patients with Paget s disease of the vulva have an underlying adenocarcinoma versus more than 90% of patients with a Paget s breast lesion who have occult carcinomas. Grossly, Paget s has an eczematoid scaly appearance, is well demarcated, and frequently presents as a raised velvety lesion. The most common symptoms, as with most vulvar lesions, are pruritus and vulvodynia. It is imperative to obtain a vulvar biopsy to make a definitive diagnosis. Microscopically, cells are large and round with abundant cytoplasm, few mitotic figures, and hyperchromatic or vesicular nuclei.


After diagnosis is confirmed, a thorough evaluation should be made to rule out breast, vaginal, cervical, bladder, or gastrointestinal adenocarcinoma. Wide local excision with 2- to 3-cm margins is suggested in treating Paget s disease. This affords the surgeon the opportunity to evaluate the surgical specimen for an underlying adenocarcinoma. In addition, Paget s disease spreads laterally beyond the lesion and requires extensive resection with 2- to 3-cm margins. As a result of this lesion s behavior, its mode of spread, and the frequency of occult carcinomas, Paget s disease should not be treated primarily with laser vaporization or ultrasonic surgical aspiration. Recent studies using monoclonal cytokeratin antibodies have enabled pathologists to distinguish Paget s disease of the vulva from Bowen s disease (VIN-III) and superficial spreading melanoma (Table 3) .


All patients treated for preinvasive disease of the vulva require a minimum follow-up 1 month postoperatively, quarterly for 1 year, and then semiannual
TABLE 278-3 -- Cytokeratin Expression
Histology 54 kDa 57 kDa 66 kDa
Paget s disease Positive Variable Negative
Bowen s disease (VIN III) Negative Positive Positive
Melanoma Negative Negative Negative
Modified from Shah KD, Tabibzadeh SS, Germa MA: Immunohistochemical distinction of Paget s disease from Bowen s and superficial spreading melanoma with the use of monoclonal cytokeratin antibodies. Am J Clin Pathol 88:689-695, 1987.

TABLE 278-4 -- TNM Classification for Vulvar Carcinoma (FIGO October 1988)
(Not Available)
Modified from Shah KD, Tabibzadeh SS, Germa MA: Immunohistochemical distinction of Paget s disease from Bowen s and superficial spreading melanoma with the use of monoclonal cytokeratin antibodies. Am J Clin Pathol 88:689-695, 1987.

evaluations. Patients with procedure morbidity or recurrence require more comprehensive and frequent evaluations.


Vulvar carcinoma accounts for 3 to 5% of all female genital cancers, with approximately 90% being squamous cell carcinoma. The most common presenting signs and symptoms are pruritus and pain, followed by vulvar lesions, bleeding, and dysuria. The International Federation of Gynecology and Obstetrics (FIGO) clinical staging for vulvar carcinoma is based on the TNM classification (Tables 4 (Table Not Available) and 5) (Table Not Available) . This system evaluates lesion size, location, and inguinal node spread and metastasis. Clinical staging includes physical examination, chest radiograph, vulvar biopsy, node biopsy, serum chemistries, hematologic profile, intravenous pyelogram, cystoscopy, and sigmoidoscopy (the last three if required by location
TABLE 278-5 -- FIGO Clinical Staging
(Not Available)
Modified from FIGO News: Int J Gynecol Obstet 28:189, 1989, with permission from Elsevier Science.

*Not FDA approved for this indication.

of the lesion). Additional studies obtained but not used for staging are magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and lymphangiography. Lymphangiography has not proven efficacious in vulva disease, with a sensitivity of less than 20% and specificity of less than 70%. DNA hybridization has revealed the presence of HPV 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, and 61 in VIN and invasive carcinoma.

The majority of the anaplastic lesions are HPV subtypes 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, and 61. Traditional treatment for vulvar carcinoma had been en bloc resection of the vulva, including the clitoris and a bilateral superficial and deep inguinal femoral lymphadenectomy. This has been replaced with vulvectomy and lymphadenectomy through separate incisions. In the past, more extensive lymph node dissections including pelvic lymphadenectomy were performed in patients with positive inguinal lymph nodes. Presently radiation therapy rather than lymphadenectomy is the preferred therapy to treat the pelvic nodes, as demonstrated by a recent Gynecologic Oncology Group study. Inguinal femoral lymphadenectomy is evaluated surgically. Primary radiation of groins is not as efficacious. Some surgeons report up to a 90% incidence of wound separation in patients undergoing an en bloc resection of the vulva and inguinal nodes. Recent modifications advocate a radical vulvectomy or radical hemivulvectomy with inguinal femoral lymphadenectomy through separate incisions. This has resulted in decreased wound separations, infections, and hospital stays. The number of positive inguinal nodes is a prognostic factor in determining survival (Table 6) (Table Not Available) . Radiation therapy, however, has been successful in obtaining local control in advanced disease. Surgery is more efficacious than primary radiation in the treatment of vulvar carcinoma. Radical vulvectomy and bilateral inguinal femoral lymphadenectomy have resulted in 5-year survivals of 60 to 65% versus 25 to 30% in patients treated with definitive radiation therapy. Teletherapy and iridium needle placement in large tumors have been used to decrease tumor burden and permit a less radical procedure. This has helped to decrease the number of exenterations for lesions extending into the urethra and/or anus. The vulva unfortunately has a poor tolerance to high doses of radiation, and therefore this results
TABLE 278-6 -- Correlation of Positive Inguinal Lymph Nodes and Survival
(Not Available)
Modified from Homesley HD, Bundy BN, Sedlis A, Adcock L: Radiation in therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 68:733, 1986, with permission from the American College of Obstetricians and Gynecologists.

in marked skin toxicity, especially in the menopausal patient.

Stage I and II Lesions

Stage I lesions are defined as being less than or equal to 2 cm in largest diameter with no inguinal nodes palpable. Several studies have not found positive inguinal nodes in patients with less than 1 mm of invasion, and therefore many gynecologic oncologists have advocated not doing lymphadenectomies in patients with less than 1 mm of invasion. Superficial lymphadenectomy in patients with less than 5 mm of invasion carries a nodal positivity of 10 to 30%. This has enabled us to alter therapy by performing radical local excisions of the primary lesion to the inferior fascia of the urogenital diaphragm and ipsilateral superficial inguinal lymphadenopathies. The lymph nodes are then sent for frozen section, and, if positive, a more thorough dissection of the deep femoral lymph nodes below the cribriform fascia and adjacent to the femoral vessels is performed. Superficial lymphadenectomy consists of the removal of the nodal tissue above the cribriform fascia and adjacent to the greater saphenous and superficial epigastric veins.

Recently treatment protocols have been modified in patients with lateralizing lesions 2 cm or less in greatest diameter. Radical hemivulvectomy and ipsolateral inguinal femoral lymphadenectomy are performed rather than a complete vulvectomy and bilateral inguinal femoral lymphadenectomy. This modification has markedly decreased the morbidity of wound separation and bilateral lymphedema. In addition, a hemivulvectomy frequently preserves the clitoris, thereby improving sexual function postoperatively. Midline and stage II lesions (>2 cm) are treated with a radical vulvectomy and bilateral inguinal femoral lymphadenectomy through separate incisions to decrease morbidity. The perineal defects can be closed in a multitude of fashions, including primary closure, secondary granulation, Z-plasty (rhomboid flap), gracilis myocutaneous graft, and tensor fascia lata myocutaneous graft. If two or more nodes are positive, the patient should receive radiation therapy to the ipsilateral groin, ipsilateral pelvis, and contralateral groin. Alternatively, the patient can choose to have a radical vulvectomy and bilateral inguinal femoral radiation consisting of 45 to 50 cGy over a 5-week interval rather than lymphadenectomy. In addition, radiation therapy is used to provide a perineal boost in patients with positive surgical margins. Complications of a radical inguinal femoral lymphadenectomy can be divided into immediate postoperative and delayed complications (Table 7) (Table Not Available) .

Stage III and IV Vulvar Disease

Stage III tumors can be lesions of any size with adjacent spread to the urethra, anus, or vagina (T3 lesions) and/or unilateral lymph node metastasis


TABLE 278-7 -- Complications of Radical Vulvectomy and Inguinal Lymphadenectomy
(Not Available)
Modified from Podratz KC, Symmonds RE, Taylor WF, Williams TJ: Carcinoma of the vulva: Analysis of treatment and survival. Obstet Gynecol 61(1):63-74, 1983, with permission from the American College of Obstetricians and Gynecologists.

(N1). Patients with T1 or T2 lesions with N1 nodes are treated as described previously with a radical vulvectomy and bilateral inguinal femoral lymphadenectomy. As with stage I and II lesions, the patient undergoes pelvic radiation if inguinal nodes are positive. Stage III lesions with minimal spread to organs adjacent to the vulva can be treated by extending the surgical margins of the vulvectomy to include the distal one third of the urethra, distal vagina, or anus as long as the lesion does not involve the anal sphincter. For extensive T3 lesions and T4 (stage IV lesions) invading the bladder or bowel mucosa, treatment consists of an exenterative procedure, radiation, or a combination of radiation and surgery. Recent studies have advocated the combination of chemotherapy and teletherapy to treat cervical and vulvar carcinomas.


Recurrence and survival are directly correlated with lesion size and the number of positive lymph nodes. Table 8 summarizes the gynecologic oncology literature for the last 2 decades, as well as the 1985 FIGO Annual Report. Small local recurrences can be treated with wide local excision or radiation therapy. Extensive recurrences, however, require exenterative procedures and/or a combination of radiation therapy and extensive resection of the perineum. Chemotherapy thus far has limited use in the treatment of vulvar carcinoma. Chemotherapeutic agents such as doxorubicin * (Adriamycin), cisplatin * (Platinol), ifos
TABLE 278-8 -- 5-Year Survival in Patients Treated for Vulvar Carcinoma
FIGO Stage 5-Year Survival
I 70-90%
II 45-80%
III 30-50%
IV 10-20%
Abbreviations: FIGO = International Federation of Gynecology and Obstetrics.

* (Ifex), bleomycin sulfate * (Blenoxane), methotrexate, * mitomycin-C * (Mutamycin), 5-fluorouracil, * and etoposide * (VePesid) have had minimal success in controlling recurrent or systemic disease.


Unlike invasive squamous cell carcinoma of the vulva, verrucous carcinoma is an indolent, locally invading, cauliflower-like tumor that rarely metastasizes. The verrucous lesion is frequently mistaken for a giant condyloma of Buschke-Lowenstein; therefore it is imperative that the surgeon obtain multiple biopsies to ensure the diagnosis. Treatment consists of radical local excision for small lesions and radical vulvectomy for larger lesions. In light of the tumor s indolent nature, lymphadenectomy is rarely required unless palpable and suspicious lymph nodes are present. If lymph nodes are positive on frozen section, the patient should undergo a radical vulvectomy and bilateral inguinal femoral lymphadenectomy. Radiation therapy may transform this lesion into a more anaplastic lesion and is contraindicated in its treatment.


Melanomas are the second most common vulvar malignancy. Two thirds of the patients presenting with melanomas are postmenopausal and fair skinned. There are three histologic types of melanomas: superficial spreading, lentigo maligna, and nodular. The most aggressive is the nodular melanoma. Unlike squamous lesions, melanomas are not staged by the FIGO classification but by the depth of invasion (Table 9) . Preoperative evaluation should include a chest radiograph and a CT or MRI of the abdomen and pelvis to rule out retroperitoneal, hepatic, or pelvic disease.


Treatment is tailored to the depth of invasion. Melanotic level I or II lesions (<1 mm) can be treated with wide local excision without lymphadenectomy. No studies have reported level I or II lesions with positive inguinal lymph nodes. Patients with level III small lateralizing lesions can be treated with a radical hemivulvectomy and ipsilateral inguinal femoral lymphadenectomy. Larger lesions and level IV and V lesions require radical vulvectomy and bilateral inguinal femoral lymphadenectomy. Occasionally large lesions necessitate perineal resection, vaginectomies, or exenterations to adequately resect the tumor. Poor results have been obtained using radiation and chemotherapy to control this disease. Responses to tamoxifen citrate (Nolvadex) have been reported but require prolonged administration as long as the patient s condition is stable. The prognosis of melanoma patients depends on the depth of

*Not FDA approved for this indication.


TABLE 278-9 -- Staging Systems for Vulvar Melanoma
Level Clark Breslow Chung
I Intraepithelial <0.76 mm Intraepithelial
II Into papillary dermis 0.76-1.50 mm <1 mm superficial penetration
III Filling dermal papillae 1.51-2.25 mm 1-2 mm into subepithelial tissue
IV Into reticular dermis 2.26-3.0 mm Penetration >2 mm
V Into subcutaneous fat >3 mm Into subcutaneous fat

invasion, tumor volume, and lymph node metastasis, with an overall 5-year survival rate of 30%.


Bartholin s gland carcinomas account for 3 to 5% of all vulvar carcinomas, with a mean age of 57 years and a range of 14 to 85 years of age. Ninety percent of the histologic cell types are equally divided between adenocarcinoma and squamous cell carcinoma, with the remaining 10% consisting of adenoid cystic, transitional, and mixed cell types.


Treatment consists of radical hemivulvectomy or radical local excision and an ipsilateral inguinal femoral lymphadenectomy. Postoperative pelvic and contralateral groin irradiation should be performed if ipsilateral groin nodes are positive. If the tumor is adherent to the pubic ramus, preoperative radiation may permit future surgical resection. Occasionally large Bartholin s gland carcinomas invading the rectum require exenterative procedures to obtain adequate surgical margins.


Basal cell carcinoma accounts for approximately 2% of all vulvar lesions and usually presents with vulva pruritus and/or ulceration. This tumor is locally invasive and is treated with a wide local excision of the lesion. Basal cell carcinomas rarely metastasize to lymph nodes and therefore do not require lymphadenectomy unless suspicious lymph nodes are palpated.


Vulvar sarcomas account for 1 to 3% of all vulvar malignancies. The most common histologic type is leiomyosarcoma, which occurs in the third and fourth decades of life. The patient frequently presents with a rapidly growing tumor. Prognostic features include lesion size, contour, and mitotic figure index.


Treatment consists of a radical local excision, with lymphadenectomy required only if a suspicious lesion is present. Recurrences are treated with a wide local excision. More aggressive rhabdomyosarcomas can also manifest on the vulva. Treatment consists of radical local excision followed by chemotherapy with VAC (vincristine sulfate (Oncovin), actinomycin D (Dactinomycin), and cyclophosphamide (Cytoxan), with or without doxorubicin (Adriamycin)). In patients with positive surgical margins, nodal metastasis, and recurrence, radiation therapy can be helpful in controlling central disease.


Although rare, several nongynecologic primary tumors have been reported to metastasize to the vulva. They include non-Hodgkin s lymphoma and melanoma as well as breast, pulmonary, gastric, and renal carcinomas. The primary tumor is treated and the metastatic lesions are excised.

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