I. What every physician needs to know.
Vulvar cancer is malignancy affecting the mons pubis, clitoris, labia majora or minora, or the vaginal vestibule. Pathology is almost always squamous cell carcinoma, although the verrucous carcinoma variant of squamous cell carcinoma, melanomas, cloacogenic, adenocarcinoma, neuroendocrine, and sarcoma histologies are also seen. Typical management is surgery for smaller lesions, although lesions whose resection would require significant impairment of function are candidates for chemotherapy and radiation.
Vaginal cancer is seen most often in the upper portion of the vagina, with a predominance in posterior wall lesions. Histology is classically squamous cell carcinoma, although adenocarcinomas, melanomas, sarcoma, lymphomas, small cell carcinomas, and carcinoids can also occur. Cancers that encompass a portion of the vagina but also extend to the urethra or cervix are classified as urethral cancers or cervical cancers, respectively. Surgical resection for smaller, upper-third lesions is effective treatment, although lower lesions and larger lesions are better treated with radiation, with the addition of concurrent chemotherapy for locally advanced lesions. Vaginal cancers can be obscured by the speculum during examination, so rotation of the speculum and careful examination are critical in diagnosis.
II. Diagnostic Confirmation: Are you sure your patient has vulvar or vaginal cancer?
Tissue confirmation is required to establish the diagnosis of vulvar orvaginal cancer, but a high index of suspicion should be held for women with even a small vulvar mass persisting beyond six weeks, or any vaginal mass. Women over age forty with a bartholin’s gland area mass should have a biopsy, as inflammatory conditions in this area at this age are rare. More than two-thirds of vulvar cancer occurs in the labia majora or minora.
A. History Part I: Pattern Recognition:
The typical patient with vulvar cancer experiences pruritus, pain, spotting, discharge, and/or bleeding, often in conjunction with a noticeable mass. When lesions are located close to the anus, there may be difficulty with defecation, and patients with lesions close to the urethra may have difficulty with urination. Dyspareunia may be present in many patients, depending on the proximity to the vaginal vestibule. A long history of pruritus secondary to lichen sclerosis may antedate the vulvar carcinoma. Although less common, bulky inguinal or pelvic adenopathy can cause lower-extremity swelling. The mean age at diagnosis is sixty-five years.
The typical patient with vaginal cancer will experience vaginal discharge, bleeding, or pelvic pain if the mass extends beyond the pelvis. Dyspareunia, as well as hematuria or hematochezia in advanced cases, can also be present. The median age at diagnosis is sixty years.
Masses in both these areas can present as fleshy exophytic masses, necrotic purulent masses, or ulcers.
B. History Part 2: Prevalence:
Vulvar cancer is associated with human papillomavirus infection, typically serotypes 16 and 33. Vulvar cancer represents only 1-2% of all cancers in women, and only 3-4% of all gynecologic cancers. Cigarette smoking, vulvar or cervical intraepithelial neoplasia, northern European ancestry, prior history of cervical cancer, and immunodeficiency have elevated rates of vulvar cancer.
Vaginal cancer comprises about 3% of all gynecologic malignancies, and there are just over 2,000 cases in the United States per year. Vaginal cancer has historically been associated with disethylstilbesterol exposure. Clear cell adenocarcinoma is the histology most reported in this cohort. DES came off the market in 1971, and in 2004 most DES daughters reached age thirty-three. As many cases are expected to occur prior to this age, it is expected that the incidence of clear cell carcinoma will steadily decrease. The other group in which vaginal cancer is prevalent is those with HPV exposure, typically serotypes 16 and 18. Women with diagnoses of CIN 3 (cervical intraepithelial neoplasia) are at higher risk of vaginal cancer.
C. History Part 3: Competing diagnoses that can mimic vulvar and vaginal cancer.
Benign inflammatory masses, such as abscess and bartholin gland cyst, can mimic vulvar or vaginal cancer. A high index of suspicion is needed to avoid misdiagnosis, as the clinical findings can be similar.
D. Physical examination findings.
Detailed physical examination will include pelvic examination with rectovaginal exam, speculum exam, and cervical cytology. Colposcopy can be considered in some cases to examine the vagina for multifocal lesions and to exclude concurrent cervical dysplasia, given the disease’s association with HPV. Inguinal lymph node examination should be performed, although the reader is cautioned that clinical examination of the groin should be interpreted with caution. In vulvar carcinoma, false positive and false negative clinical examinations of the groin are both approximately 30%.
E. What diagnostic tests should be performed?
Biopsy is essential to make the diagnosis. Complete blood count should be performed, and consideration of HIV testing should be considered in patients who have risk factors or particularly advanced disease. Computed tomography (CT) of the pelvis with intravenous contrast should be performed to search for pelvic lymph node metastasis and to evaluate the groin.
Pet scan has no clearly defined role at this time.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
There are no useful tumor markers in this disease.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Vulvar cancer tends to follow an orderly pattern of spread: first to the superficial inguinofemoral nodes, then to the deep inguinofemoral nodes. Involvement of the pelvic nodes without the involvement of the inguinofemoral nodes is rare. In patients with clinically palpable lymph nodes, 62% have lymph node metastasis. The most common metastatic sites are lung (most common), liver, and bone. Distant metastases are rare without lymph node metastases, but patients with three or more positive lymph nodes should have systemic staging with chest CT.
Vaginal cancer typically drains first to the pelvic lymph nodes, although those located in the lower third of the vagina may have direct drainage to the inguinofemoral lymph nodes as a first site of metastasis. Although rare, hematogenous metastasis to the lungs can occur. Pelvic magnetic resonance imaging (MRI) may be helpful in determining the thickness of the vaginal lesion for planning treatment with radiation.
The role of PET scan in vulvar and vaginal cancer is poorly defined.
F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
Failure to biopsy a vulvar of vaginal lesion that persists beyond a reasonable amount of time (4-6 weeks) and prescribing multiple courses of antibiotics is the most wasted step in diagnosis of this cancer.
III. Default Management.
Following tissue confirmation, patients require evaluation with gynecologic oncology for potential resection. For vulvar cancer, typical management is wide local excision of the lesion with groin evaluation for any lesion with 1mm or more of stromal invasion. Groin evaluation is inguino-femoral lymph node dissection, although sentinel lymph node biopsy is being tested by the gynecologic oncology group in a prospective manner.
A. Immediate management.
There is no emergency management of this diagnosis other than blood transfusion with significant hemorrhage, which is rare with either of these conditions.
B. Physical examination tips to guide management.
Presence of groin adenopathy indicates more advanced disease, and combined modality therapy with surgery and radiation is required for patients with positive lymph nodes.
C. Laboratory tests to monitor response to and adjustments in management.
Complete blood counts should be monitored during chemotherapy or radiation.
D. Long-term management.
Long-term management depends on stage of the cancer.
E. Common Pitfalls and Side Effects of Management.
Lymphedema can occur in about 16% of patients managed with surgery alone, and 22% of patients managed with surgery and radiation. Vaginal cancer complications include the small potential for rectovaginal or vesicovaginal fistulas, radiation cystitis or proctitis, rectal and vaginal strictures, vaginal necrosis, vaginal stenosis, or pubic bone pain. A high number of premenopausal women treated with pelvic radiation will have premature menopause.
Acute surgical complications include wound seroma, urinary tract infection, wound cellulitis, temporary anterior thigh anesthesia from femoral nerve injury, thrombophlebitis, and pulmonary embolus. Surgical chronic complications include leg edema, genital prolapse, urinary stress incontinence, temporary weakness of the quadriceps muscle, introital stenosis, pubic osteomyelitis, femoral hernia, and rectoperineal fistula.
Acute complications of radiation therapy to the pelvis include diarrhea, fatigue, skin desquamation, and nausea. Excessive mucosal or skin reaction during vulvar or vaginal cancer radiation may indicate subclinical co-infection with candida; patients should be treated empirically with oral diflucan if this occurs. Patients will have significant irritation in the vulvar region for treatment of vulvar cancer, for which sitz baths with half-strength domeboro (aluminum acetate) solution is often helpful. Loose clothing should be worn to prevent physical irritation of this tender area. Narcotic analgesia can be required, especially to help with sleep.
IV. Management with Co-Morbidities.
Patients who are not surgical candidates can receive primary radiation for cure.
A. Renal insufficiency.
Cisplatinum is renal toxic, so patients with impaired baseline renal function are unlikely to tolerate concurrent cisplatinum, which is often chosen for concurrent therapy.
B. Liver insufficiency.
No change in standard management.
C. Systolic and diastolic heart failure.
No change in standard management.
D. Coronary Artery Disease or Peripheral Vascular Disease.
No change in standard management.
E. Diabetes or other Endocrine issues.
No change in standard management.
Multiple synchronic primaries should be managed in order of the most life-threatening malignancy.
G. Immunosuppression (HIV, chronic steroids, etc).
Chemotherapy doses may require adjustment. Such patients should have tight regulation of HIV disease if present, as immunosuppression predisposes to recurrence.
H. Primary Lung Disease (COPD, Asthma, ILD).
No change in standard management.
I. Gastrointestinal or Nutrition Issues.
No change in standard management.
J. Hematologic or Coagulation Issues.
Dose adjustments in chemotherapy may be required.
K. Dementia or Psychiatric Illness/Treatment.
Patients who are unable to make their own decisions need a health-care proxy to consent to surgery, radiation, or chemotherapy.
V. Transitions of Care.
A. Sign-out considerations while hospitalized.
Patients with vulvar or vaginal cancer are predominantly managed as outpatients.
B. Anticipated Length of Stay.
Vulvar and vaginal cancer patients are typically managed as outpatients.
C. When is the Patient Ready for Discharge.
Patients who are admitted for acute symptoms during radiation or chemoradiation are ready for discharge when hematologic counts show signs of recovery, when diarrhea is controlled, and when adequate oral pain management is achieved.
D. Arranging for Clinic Follow-up.
In early-stage disease, follow-up should be given with a gynecologic oncologist alone. In advanced-stage disease, follow-up should be given with a radiation oncologist and medical oncologist as well.
1. When should clinic follow-up be arranged and with whom?
2. What tests should be conducted prior to discharge to enable best clinic first visit?
Tissue biopsy and pelvic computed tomography.
3. What tests should be ordered as an outpatient prior to or on the day of the clinic visit?
Complete blood count and renal function.
E. Placement Considerations.
Hospice can be considered for patients with metastatic disease.
F. Prognosis and Patient Counseling.
Stage I and Stage II vulvar cancer (node-negative and involving only lower involvement of the vagina, anus, or urethra) have excellent survival rates of 80-100%. Stage IIIA/B vulvar cancer (positive lymph nodes) has a survival rate of 75-80%. Stage IIIC vulvar cancer (nodal metastasis with extracapsular extension) has a poor survival rate of 25% at 5 years. Stage IVA vulvar cancer (fixation to pelvic bone, ulcerated inguinal nodes, involvement of upper urethra, bladder, or rectal mucosa) has a 5-year survival rate of 30%. Stage IVB vulvar cancer (distant metastases) has a 0% survival rate at 5 years.
Vaginal cancer has a worse prognosis. Stage I (confined to the vagina, negative nodes) has a 5-year survival rate of 61%, Stage II (invading paravaginal tissues but not pelvic wall, negative nodes) has a 5-year survival rate of 48%, Stage III (extending to pelvic wall and/or node-positive) has a 5-year survival rate of 34%, Stage IVA (invades bladder or rectum or extends beyond true pelvis) has a 5-year survival rate of 22%, and Stage IVB (distant metastases) has a 5-year survival rate of 11%.
VI. Patient Safety and Quality Measures.
A. Core Indicator Standards and Documentation.
There are no NCCN guidelines for either of these diseases.
B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.
Aggressive management of diarrhea with antimotility agents and low residue diet is appropriate.
VII. What's the evidence?
Montana, G, Kang, S, Halperin, Perez, C, Brady, L. “Carcinoma of the vulva”. Principles and Practice of Radiation Oncology. 2008.
Plentl, AA, Friedman, EA. “Lymphatic system of the female genitalia: The morphologic basis of oncologic diagnosis and therapy”. Major Probl Obstet Gynecol. vol. 2. 1971. pp. 1-223.
Zacur, H, Genadry, R, Woodruff, JD. “The patient-at-risk for development of vulvar cancer”. Gynecol Oncol. vol. 9. 1980. pp. 199
de Koning, MN, Quint, WG, Pirog, EC. “Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma”. Mod Pathol. vol. 21. 2008. pp. 334
Grigsby, PW. “Role of PET in gynecologic malignancy”. Curr Opin Oncol. vol. 21. 2009. pp. 420-4.
Kunos, C, Simpkins, F, Gibbons, H, Tian, C, Homesley, H. “Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial”. Obstet Gynecol. vol. 114. 2009. pp. 537-46.
van der Steen, S, de Nieuwenhof, HP, Massuger, L, Bulten, J, de Hullu, JA. “New FIGO staging system of vulvar cancer indeed provides a better reflection of prognosis”. Gynecol Oncol. vol. 119. 2010. pp. 520-5.
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- I. What every physician needs to know.
- II. Diagnostic Confirmation: Are you sure your patient has vulvar or vaginal cancer?
- A. History Part I: Pattern Recognition:
- B. History Part 2: Prevalence:
- C. History Part 3: Competing diagnoses that can mimic vulvar and vaginal cancer.
- D. Physical examination findings.
- E. What diagnostic tests should be performed?
- F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
- III. Default Management.
- A. Immediate management.
- B. Physical examination tips to guide management.
- C. Laboratory tests to monitor response to and adjustments in management.
- D. Long-term management.
- E. Common Pitfalls and Side Effects of Management.
- IV. Management with Co-Morbidities.
- A. Renal insufficiency.
- B. Liver insufficiency.
- C. Systolic and diastolic heart failure.
- D. Coronary Artery Disease or Peripheral Vascular Disease.
- E. Diabetes or other Endocrine issues.
- F. Malignancy.
- G. Immunosuppression (HIV, chronic steroids, etc).
- H. Primary Lung Disease (COPD, Asthma, ILD).
- I. Gastrointestinal or Nutrition Issues.
- J. Hematologic or Coagulation Issues.
- K. Dementia or Psychiatric Illness/Treatment.
- V. Transitions of Care.
- A. Sign-out considerations while hospitalized.
- B. Anticipated Length of Stay.
- C. When is the Patient Ready for Discharge.
- D. Arranging for Clinic Follow-up.
- 1. When should clinic follow-up be arranged and with whom?
- 2. What tests should be conducted prior to discharge to enable best clinic first visit?
- 3. What tests should be ordered as an outpatient prior to or on the day of the clinic visit?
- E. Placement Considerations.
- F. Prognosis and Patient Counseling.
- VI. Patient Safety and Quality Measures.
- A. Core Indicator Standards and Documentation.
- B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.
- VII. What's the evidence?