• First described in 1877 by Cruveilhier
• Vaginal intraepithelial neoplasia was first described by Hummer in 1933
• Primary invasive vaginal carcinoma has a frequency of 1-2% of all genital malignancies
• Intraepithelial carcinoma is even more rare
• Neoplastic lesions of the vagina are far less frequent than corresponding lesions in either the vulva or cervix

INCIDENCE

• The age adjusted incidence of primary squamous carcinoma of the vagina is one in 100,000 black women, and 0.6 in 100,000 white women
• Squamous vaginal carcinoma is typically a disease of older women. Seventy percent of cases occur in women past the age of 50. The peak incidence is between age 60 & 70.
• In women who have had a surgically created neovagina, the incidence peaks at a much younger age - between 25 and 35.
• While little is known about the Epidemiology of vaginal carcinoma, there is evidence that radiotherapy given earlier for other gyn malignancies may increase the risk. If the period between application of radiation to the development of vaginal cancer is greater than 10 years, the prognosis is much improved.
• Factors that may increase the risk of vaginal carcinoma may include - - chronic irritation from pessary use - immunosuppression - papilloma virus infection - lower genital tract neoplastic syndrome
• Primary carcinoma of the vagina must be differentiated from vaginal extension from either the vulva or the cervix, and from metastatic extension of other tumors.
• A valid diagnosis of a primary vaginal cancer necessitates that there be no cancer of the vulva or the cervix for at least 10 years or more prior to that diagnosis
• Figo staging of vaginal carcinoma
  
  

  Stage	Clinical Status
  0	Intraepithelial
  I	Limited to vaginal wall
  II	Extends to the subvaginal tissue, but not to the pelvic sidewall
  III	Extends to the pelvic sidewalls
  IV	Extends beyond the true pelvis or involves the mucosa of the bladder or rectum (bullous edema does not consign the patient to stage IV)
  IVa	Adjacent organs involved
  IVb	Distant organs involved

  
  

PATHOLOGY

• Only 10-20% of vaginal carcinomas are primary
• Squamous cell carcinoma is the most common malignant tumor of the vagina
• Clear cell adenocarcinoma is found in women who had exposure to diethylstilbesterol in utero and to a lesser degree in post menopausal individuals
• Metastatic tumors are the most common cancer found in the vagina
• Classification of intraepithelial neoplasias of the vagina parallels that of the cervix eg VaIN 1, VaIN2, and VaIN3.
• VaIN is usually asymptomatic and is diagnosed by abnormal cytologic testing. Infrequently women complain of postcoital staining or unusual vaginal discharge
• VaIN usually occurs in the upper third of the vagina on the posterior wall
• VaIN lesions may be either single discrete or multifocal

COLPOSCOPIC EVALUATION

• VaIN is most frequently diagnosed by colposcopy
• Care must be exercised to make sure the entire surface area of the vagina is examined, including that behind the blades of the speculum
• In post hysterectomy patients, the lateral invagination of the vaginal vault must be carefully evaluated. The rugate pattern must be flatted out so that complete inspection can be done.
• 3-5% acetic acid is applied to the vaginal walls for 3 minutes to detect acetowhitening.
• Lugol’s iodine solution is then applied. Normal tissue will stain mahogany while tumor cells will not retain the color.
• Areas of VaIN are typically discrete with slightly elevated borders and are pinkish or white in color
• VaIN has typically the same patterns as those of CIN, but after the application of acetic acid the appearance of the lesion is often more subtle and less easily detected.
• VaIN appears as an area of acetowhite epithelium
• VaIN may have a well established vascular pattern characterized by punctation and mosaicism
• The vascular pattern associated with high grade VaIN occurs late in the neoplastic process and s characterized by bizarre vascular forms
• Careful biopsy of suspicious areas is necessary to finalize the diagnosis.
  

TREATMENT OF VaIN

• VaIN tends to be multifocal and associated with HPV (by contrast, most invasive cancers are unifocal and are not often associated with HPV)
• VaIN tends to occur in younger patients
• Response of VaIN is unpredicatable - in some cases it regresses, in some it persists, while in some it progresses (probably less than 10%) to invasive cancer.
• Minor lesions probably can be carefully followed and are probably viral in origin
• High grade lesions should be promptly treated.

TREATMENT

• Treatment options should take in consideration the following data - age of the patient
  • sexual activity of the patient
  • extent of the lesion
  • previous history of radiotherapy
  • presence or absence of the cervix
  • grade of the lesion
  • site of the lesion
• If invasion is suspected or if the patient is beyond child bearing years, surgical excision, with or without skin grafting is the treatment of choice. Cure rates approach 90%.
• In post menopausal women with low grade lesions, local application of estrogen cream for 3-4 weeks frequently results in conversion of the epithelium and reversion of the PAP smear to normal
• 5-Fluorouracil cream locally applied to a low grade lesion is frequently effective
• CO2 laser can be used to vaporize discrete lesions but care must be exercised
• Cure rates with CO2 laser and 5-FU approach 85-90%
• Vaginal invasive carcinoma is usually managed with radiotherapy.

OTHER VAGINAL EPITHELIAL TUMORS OF LESSER SIGNIFICANCE

• Verrucous carcinoma - very rare - resembles condylomata. May recur after surgical excision but distant metastases are rate
• Basal cell carcinoma - very rare - similar to vulvar basal cell carcinoma
• Adenocarcinoma - was an extremely rare lesion prior to the DES exposure era. Can occur in any area of the vagina, but is most common in the upper third on the anterior or posterior wall.

SARCOMA

• Sarcomas comprise less than 2% of all malignant neoplasms. Of these embryonal rhabdomyosarcoma (sarcoma botryoides) is the most common type in infants and young adolescent girls
• The most common neoplasms of the lower genital tract in girls
• Many occur prior to the age of 5, 2/3 within the first 2 years
• Infiltrates the vaginal wall and pelvis, and presents as a polypoid mass of tissue resembling grapes
• The five year survival is between 10 and 35%
• Pelvic extenteration is the treatment of choice

MELANOMA

• Is the second most common cancer of the vagina - 3% of vaginal malignancies (0.3% of all melanomas)
• Usually occurs in the lower third of the vagina
• Frequently black or blue pigmentation.
• Lesions are frequently ulcerated
• Amelanotic lesions can occur. Immunoperoxidase staining for S-100 protein can facilitate the diagnosis
• Electron microscopic evaluation may be necessary.

METASTATIC TUMORS TO THE VAGINA

• Endometrial and cervical are the most common metastases
• Tumors of the ovary, rectum, and kidney can also spread to the vagina
• Choriocarcinoma can also metastasize to the vagina

REFERENCES

1. Aho M, Ves Terinen E, Meyer B et al: Natural history of vaginal intraepithelial neoplasia. Cancer 1991; 68:195-7.
   
   
2. Audet-Lapointe P, Body G, Vauclair R et al: Vaginal intraepithelial neoplasia. Gynecol Oncol 1992; 36:232-9.
   
   
3. Heinzl S: the value of colposcopy in assessment of intraepithelial neoplasia of the lower genital tract. Arch Gynecol Obstet 1995; 257:425-30.
   
   
4. Krebs HB: Treatment of vaginal intraepithelial neoplasia with laser and topical 5-Fluorouracil. Obstet Gynecol 1989; 72:657-60.
   
   
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7. Minucci D, Cinel A, Insacco E et al: Epidemiological aspects of vaginal intraepithelial neoplasia (vain). Clin Exp Obstet Gyencol 1995; 22:36-42.
   
   
8. Petrelli ES, Townsend DE, Morrow CP et al: Vaginal intraepithelial neoplasia: biologic aspects and treatment with topical 5-FU and carbon dioxide laser. Am J. Obstet Gynecol 1980; 38:321.
   
   
9. Stillman FH, Fruchter RG, Chen YS et al: Vaginal epithelial neoplasia: risk factors for persistence, recurrence, and invasion and its management. Am J Obstet Gynecol 1997; 176: 93-99.
   
   
10. Van Burden M, Kate FJ, Smits HL et al: Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcipritionally active HPV. Cancer 1995; 75:2879-84.
    
    
11. Wharton JT, Tortolero-Luna G, Linares AC et al: Vaginal neoplasia and vaginal cancer. Obstet Gynecol Clin North Am 1996; 23:325-45.
    
    
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13. Novak and Woodruff, Gynecologic and Obstetric Pathology, 1974.
    
    
14. Kurman RJ: Blaustein’s pathology of the female genital tract -3 rd edition, pp 113-120.