Malignant diseases of the vulva account for an estimated 3% to 5% of gynecologic neoplasia. The pathologic variants are many (Table 1). Squamous cell cancers account for 85% to 90% of these neoplasms. Melanoma, Bartholin gland cancer, Paget’s disease, and the various sarcomas are the other principal neoplasms. The preinvasive forms of the squamous cancer tend to occur in younger women and may be associated with in situ lesions of the cervix, vagina, perineum, and anus.
Malignant diseases of the vulva account for an estimated 3% to 5% of gynecologic neoplasia. The pathologic variants are many (Table 1). Squamous cell cancers account for 85% to 90% of these neoplasms. Melanoma, Bartholin gland cancer, Pagets disease, and the various sarcomas are the other principal neoplasms. The preinvasive forms of the squamous cancer tend to occur in younger women and may be associated with in situ lesions of the cervix, vagina, perineum, and anus.
Detection of the disease simply requires a minimal level of awareness on the part of the patient and examination with a significant level of suspicion on the part of the physician.
Patients with vulvar cancer frequently will be aware of a long-standing pruritus vulvae before they may be aware of a mass or lump. Localized vulvar complaints may include pain, burning, and discomfort of the vulva when voiding. Discharge and bleeding may develop. Although some patients come to the physician because of increasing size of a mass, delay is a more common feature.
The delay in diagnosis often occurs because a physician may write a prescription for symptoms without having performed a physical examination. Careful vulvar inspection and biopsy of any new lesion or suspicious area are mandatory.
To the experienced clinician, the diagnosis of a frankly malignant process will be evident. A high level of suspicion of any new lesion is appropriate. The clinician is well-advised to biopsy any new growth or suspicious change in the vulvar epithelium.
The TNM descriptive material and the International Federation of Gynecology and Obstetrics (FIGO) staging are displayed in Table 2. The purpose of staging, whether clinical or surgical, is to allow a common international vocabulary for comparison of data and to reasonably reflect clinical extent of disease. It will also identify subsets of patients with worrisome prognostic factors.
Therapy is obviously influenced by stage of disease, but other factors in addition to those that are included in the FIGO staging criteria (TNM) must be considered. These considerations include not only the size but also the location of the lesion. Histologic features include grade, depth of invasion, and the presence or absence of lymph-vascular space invasion. Equally important is the evaluation of the patients health status and ability to undergo various procedures.
While the current trend in vulvar cancer therapy reflects greater emphasis on individualization and more conservative treatment, the clinician must remember the events that led to the standardization of radical vulvectomy and groin dissection routinely for vulvar cancer. The move to decrease the radicality, thereby decreasing morbidity and major alteration of body image, may be associated with an increase in problems by failure of local control. Thus, caution when considering conservatism is of utmost importance.
The following discussion refers to the decision tree (Table 3) and treatment options for vulvar cancer (Table 4).
Carcinoma in Situ (CIS) and Vulvar Intraepithelial Neoplasia (VIN)The first decision is whether or not to treat. The progression of the various grades of intraepithelial neoplasia to invasive cancer is generally considered to be a very slow and protracted process, except in immunocompromised patients. Opinion is divided as to whether mild and moderate grades of dysplasia (VIN I and II) require therapy. If symptomatic, treatment is certainly justified. VIN III (severe dysplasia and carcinoma in situ) should be treated, but there are instances in the very debilitated patient where surveillance may be permitted.
The extended resections listed in Table 4 depend on the extent of disease. Gross surgical clearance should be the goal, and with the major thrust toward conservative resection, limited excisions rather than more radical (prophylactic) surgical resection may now be performed. Vulvar laser therapy and topical fluorouracil (5-FU) are selectively employed. Both are associated with significant pain. The latter is associated with a substantial relapse rate.
Microinvasive Vulvar CancerThe International Society for the Study of Vulvar Disease (ISSVD) and FIGO define stage IA carcinoma of the vulva as a single lesion measuring 2 cm or less in diameter and with a depth of invasion of 1 mm or less. Cases with more than one site of invasion were excluded, but the definition did include cases that have lymph-vascular space involvement.
There seems to be a consensus that wide local excision is adequate if the invasive process is 1 mm or less, a T1 lesion (2 cm or less), and without lymph-vascular space invasion. Some also feel that a highly undifferentiated lesion should not be considered for local resection only. If the local excision reveals features less favorable than those noted on the initial biopsy, a more radical excision should be performed. Groin dissection is not necessary for this lesion but may be considered if significant unfavorable features are found.
Clearly Lateral T1 and T2 LesionsRadical local excision with ipsilateral groin dissection to include the superficial and deep groin nodes is commonly employed for these presentations. The separate incision technique is often employed. The other approach is a radical hemivulvectomy with en bloc ipsilateral groin dissection, which keeps in continuity soft tissue and lymphatics between the primary and the groin dissection.
There is general agreement that the laterality be clearly defined, and a good guideline is that the margin of surgical clearance around the lesion should be 2 cm and the lesion be at least 2 cm from the introitus, the urethra, the posterior fourchette, or clitoris. Some modification is reasonable for more anteriorly or more posteriorly situated lesions. With the lymphatic drainage primarily anterior to the groin, posterior dissection might be omitted with a more anteriorly situated lesion. Clitoral sparing is permissible in selected posterior lesions. The dissection should involve the full thickness of the vulva down to the muscular fascia of the urogenital diaphragm.
Recent evaluation of radical local excision with superficial groin dissection without clearance of the deep groin nodes has reflected a higher than anticipated groin relapse and should be employed only in the most selected circumstances. Until data from clinical series using more conservative approaches have matured more fully, many oncologists still favor radical vulvectomy with bilateral groin dissection, especially for T2 lesions.
T1 and T2 Midline Lesions or Bilateral LesionsThe two most commonly employed surgical techniques are the standard radical vulvectomy with en bloc bilateral groin dissection, and the radical local excision with bilateral groin dissection. As in the previous section, individual surgeon preferences favor either the en bloc one incision or separate incisions with intervening skin bridges. Wound healing and morbidity may be slightly more favorable with the latter approach. Larger, more anterior lesions are probably not suitable for consideration of the separate incision approach.
Lesions With Clinically Positive Groin NodesThe radical vulvectomy with bilateral groin dissection is the basic surgical approach. The options at that point include pelvic node dissection or pelvic node exploration to remove any enlarged nodes clinically or radiographically identified.
Postoperative radiation therapy with or without chemotherapy should be added in all but the most exceptional case. Occasionally, preoperative pelvic and groin radiation therapy will be employed followed by a modified groin dissection and vulvectomy. The groin dissection in this instance can be modified with thicker skin flaps and limited to a more conservative dissection when preceded by radiation for occult disease control.
Lesions With Fixed/Ulcerative Groin NodesThere are two ways to treat the groins in this setting. One is primary radical surgery, and the second is primary radiation therapy. Primary radical vulvectomy with groin dissection to clear groin disease may be employed but is frequently a debulking exercise with residual disease intimately involving the femoral vessels. Titanium clip localization can provide a target for an electron-beam boost when postoperative radiation therapy is employed. If preoperative radiation therapy to the vulva, pelvis, and groin is employed with or without chemotherapy, it is followed by more conservative surgery to the vulva and groin. If complete resection was not possible, the residual field could be boosted with electron-beam therapy. Occasionally, the use of myocutaneous flaps or sartorius transposition is considered to cover the femoral vessels as a technique to reduce the risk of vascular blowout.
Vulvar T3 LesionsMinimal involvement of the distal urethra, the vagina, or the anus may lend itself to an extended viscera-preserving radical vulvectomy with bilateral groin dissection. Postoperative radiation therapy may or may not be added. The differences between early T3 lesions and T4 lesions as defined are quite obvious, but clinical expressions of disease are not always neatly distal urethral vs upper urethral or bladder mucosa. Vaginal extension may be quite significant, and anal involvement might be prominent even in the absence of rectal mucosal invasion. Therefore, the significant impact on relapse and survivorship of urethral, vaginal, and anal involvement must not be overlooked. Preoperative pelvic radiation therapy with or without brachytherapy and with or without chemotherapy followed by conservative surgery has produced good results. Exenterative surgery or modification, such as anovulvectomy, may be necessary in selected instances.
Vulvar T4 LesionsFor massive involvement of bladder and/or vagina and/or rectum, selective exenterative surgery with radical vulvectomy and groin dissection may offer the only hope of clearance. A modification would be the radical anovulvectomy for posterior lesions. A note of caution is the virtually nonexistent survivorship with exenterative surgery in the presence of positive nodes. Preoperative pelvic and groin radiation therapy with or without brachytherapy and with or without chemotherapy may produce sufficient regression to allow debulking surgery tailored to the disease presentation or to a modified exenterative procedure.
Postoperative TreatmentNode-Negative Lesions With Pathologic Findings Justifying Consideration of Postoperative TherapyMany surgeons would not consider any additional therapy in node-negative and margin-free resections. In some instances, various features, such as poorly differentiated cancers, large bulky tumors, those with diffusely infiltrative growth patterns, those with lymph-vascular space invasion, or those with very small surgical margins (< 1 cm), may be selected for postoperative therapy based on concern for local relapse. With regard to radiation therapy options, one choice would be whole-pelvic radiation therapy centered low to include the vulva and the soft tissues of the medial groins. The other would be a vulva-only field.
Lesions With Clinically Negative but Histologically Positive Groin NodesIf a unilateral dissection has been carried out, the contralateral groin may be dissected, radiated, or observed. If the positivity is confirmed intraoperatively, one may consider pelvic node dissection or pelvic retroperitoneal exploration to remove any enlarged or suspicious nodes. Opinion is divided over this surgical approach, with some feeling that pelvic node dissection is no longer indicated. In skilled hands, either approach is acceptable.
The Gynecologic Oncology Group (GOG) has documented, and others have confirmed, that the addition of pelvic radiation therapy to patients with positive groin nodes is associated with survival equal to or better than that achieved with the addition of pelvic node dissection. Virtually all agree that metastatic disease in the groin deserves consideration for postoperative radiation therapy.
Vulvar melanoma is the second most frequent neoplasm of the vulva. It is found predominately in the Caucasian geriatric population, with the majority of lesions involving the clitoris or labia minor.
ScreeningThere is no screening technique for vulvar melanoma aside from careful visual inspection, and it has been common gynecologic teaching to recommend excision of any pigmented vulvar nevi.
StagingThe FIGO staging system for vulvar cancer is not helpful for vulvar melanoma. In this disease, prognosis is significantly influenced by the two microstaging techniques that have been described (the Breslow system that measures the thickness of the invasive portion of the neoplasm and the Clark scheme that measures the depth of invasion in terms of descriptive histology of the skin). Both systems are outlined, along with the Chung et al modification, in Table 5.
TreatmentThe pigmented lesion should be excised with a 1- to 2-cm margin. If melanoma is confirmed, and if it is in the intraepithelial or superficial categories of either of the three microstaging classifications, wide local excision is probably adequate. If any lymph-vascular space invasion is noted, however, groin dissection may be considered. If the lesion is thicker or more infiltrative, radical wide local excision with bilateral groin dissection or radical wide local excision and ipsilateral groin dissection would be employed in most instances, pending careful assessment of location of the lesion. For the anterior lesion or clitoral lesion, the posterior vulva does not require resection.
Larger lesions also require radical surgical clearance with the option of unilateral or bilateral groin dissection. If the groins are suspect or clinically positive, pelvic node dissection may be considered. It is acknowledged, however, that the prognosis for patients with metastatic nodes is grave indeed. Patients should be considered a candidate for a research protocol of combination chemotherapy or immunotherapy.
When vaginal or urethral extension is evident, local control is felt to be improved if the surgery is extended to resect the entire vaginal cylinder and the uterus. In rare instances, anterior exenteration may be considered. The prognosis for patients with these more advanced lesions is extremely unsatisfactory, however.
While prognosis is perhaps more a function of the pathology than the surgery, one should not undertreat locally; local relapse, difficult to manage, occurs frequently. Radiation therapy has been underemphasized and therefore underutilized in this disease. Sufficient experience suggests that it may be worth considering postoperatively in cases, particularly, those with close surgical margins.
Bartholins Gland Cancer
Bartholins gland cancers may be either adenocarcinoma (arising from the gland per se) or transitional or squamous type cancers (arising from the Bartholin's duct system). Adenosquamous and adenoid cystic variants have also been reported. Bartholin's cancer represents the vast majority of adenocarcinomas of the vulva and are seen in women a decade or so younger than most invasive squamous cell carcinomas of the vulva.
ScreeningA firm mass in the area of the Bartholin's gland, particularly in the postmenopausal patient, should give rise to suspicion. Persistence of a noncystic mass in this area demands biopsy. In young patients the remote possibility of a sarcoma should be considered.
Diagnosis, of course, is established by biopsy. In the smaller lesions, freely moveable, the diagnosis is not likely to be in doubt. However, in the more locally advanced lesions, the anorectum should be inspected carefully, as occasional anal squamous cancers (the old cloacogenic designation) have infiltrated into the rectovaginal septum and may be mistakenly considered to be primary Bartholin's gland cancers. Treatment principles would be similar for either, however, so this distinction may not be critical. Unequivocal Bartholin's gland origin can be confirmed in the surgical specimen only if apparent transition from benign to malignant Bartholin's gland or duct epithelium can be demonstrated.
StagingSince the lesion arises in a subepithelial location rather than from the epithelium itself, the FIGO staging system is not particularly helpful for this disease.
TreatmentRadical vulvectomy with bilateral groin dissection and pelvic node dissection has been the standard approach. Radical hemivulvectomy with ipsilateral groin and pelvic node dissection may be equally valuable. Particularly because of the deep-seated location, the depths of the radicality into the ischial rectal fossa should be expanded beyond the scope of the usual radical vulvectomy. Similarly, because of this unique location, the old rule about the reliability of groin node metastasis as a predictor of the risk of pelvic node metastasis may not be entirely valid. In this context it may be well to consider postoperative pelvic radiation therapy for bulky tumors.
For the more locally advanced lesions, preoperative treatment with external-beam therapy with or without infusion chemotherapy may allow more conservative surgical clearance of disease and preservation of the anus and rectum.
Pagets disease of the vulva is predominately an intraepithelial adenocarcinoma. While there are histologic similarities with Pagets disease of the breast, Pagets disease of the vulva is uncommonly associated with an underlying invasive adenocarcinoma, presumably of apocrine gland origin. The disease occurs predominately in the menopausal Caucasian population.
ScreeningThere is no screening test. Attention to changing symptoms is essential. A long-standing history of vulvar discomfort and itching is often reported. The classic lesion is an eczematoid weeping lesion. In neglected cases, the process may be very extensive.
DiagnosisExcisional biopsy of a small lesion will establish the diagnosis and will confirm whether the process is intraepithelial or invasive. Biopsy from the center of a process suspicious for invasive disease may confirm an invasive Pagets cancer. From a more diffuse and apparently intraepithelial process, a random biopsy may establish the intraepithelial nature of the disease, but until all of the disease is excised, the presence or absence of the invasive component will not be known. While most invasive disease is clinical rather than occult, this is not universally true.
StagingPagets disease of the vulva may be staged according to the FIGO system.
TreatmentIn the absence of a preoperative biopsy-confirmed diagnosis of an invasive component, the clinician is faced with two concerns. The first is to establish whether or not an invasive component is present; the second is to adequately excise the intraepithelial component. The multifocal nature of the disease is well-documented, and pagetoid cells within the epithelium are frequently found well beyond the perimeter of the grossly abnormal epithelium. Indeed, the usual 0.5-cm margin employed with VIN lesions will usually be inadequate. Nevertheless, the move has been away from more radical surgery for this intraepithelial process as long as an invasive component is excluded.
Most feel that reexcisions of small reactive areas of intraepithelial Pagets is far more preferable than an extensive primary vulvar resection. Particularly troublesome, however, are the weeping eczematoid changes that extend into the urethra and anus. The use of intraoperative frozen-section studies of proposed margins can be time-consuming and may literally exhaust the frozen-section capabilities of even the best of surgical pathology laboratories.
Another approach is a surgical staging exercise in which multiple biopsies are taken from the target lesion and apparently normal skin and the vulva literally mapped. This is done as an outpatient exercise, and then permanent sections can be reviewed to help tailor the subsequent resection. The rare invasive lesion is treated like an invasive vulvar cancer.
In general, a radical vulvectomy with groin dissection is the treatment of choice using guidelines similar to those discussed in the section on squamous cell cancer of the vulva.
The management of recurrent squamous cancer of the vulva is a dismal therapeutic challenge. Management decisions turn on: (1) location and extent of the recurrence, and (2) modalities available.
With regard to the first consideration, recurrence may be: (1) local in the vulvar area, (2) in the groin, (3) in the pelvis, (4) more distal, and (5) combinations. Relapses (particularly early relapse) in the surgical field, whether vulvar or groin, tend to imply inadequate radicality of the surgery (late focal relapses may represent new primaries or field cancers). However, large bulky tumors, poorly differentiated tumors, and tumors with prominent lymph-vascular space invasion have a tendency to relapse in the surgical field (groin and/or vulva) notwithstanding adequate surgery. Such failures imply a therapeutic opportunity lost; that is, such cases might, at the time of the initial treatment, be given consideration for postoperative radiation therapy with or without chemotherapy to the treatment field. The same might be said for pelvic relapse with healing of the vulva and groins; again, surgical pathologic features that might well have suggested the high risk of relapse and the advisability of pelvic and/or groin and vulvar radiation therapy.
For relapse in the vulva and groin, the particular anatomic features of the recurrence would suggest either the advisability to operate or the advisability not to operate and whether or not to add radiation therapy to the field at risk, provided radiation therapy had not been used initially. Infusion chemotherapy as a radiation sensitizer would be a reasonable consideration.
Exenterative surgery will occasionally salvage a local recurrence, and combined-modality therapy with radiation therapy and more conservative surgery have recorded salvages as well. Experience with chemotherapy for recurrent vulvar cancer has been disappointing, but an occasional response will be observed.
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