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6230 (Estimated new cases for 2020 in the United States)

Incidence of clear cell adenocarcinoma as a result of in utero diethylstilbestrol

(DES) exposure estimated at 1/1000

Stage at presentation
Localized 33.1%
Regional 35.5%
Deaths: Estimated 1450 in 2020 Distant 17.1%
Median age: Squamous cell cancer (60–65 years); DES-related adenocarcinoma/clear cell (19 years) Unstaged 14.3%

Daling JR et al. Gynecol Oncol 2002;84:263–270

Siegel R et al. CA Cancer J Clin 2020;70:7–30

Surveillance, Epidemiology and End Results (SEER) Program, available from [accessed in 2020]

Tedeschi C et al. J Low Genit Tract Dis 2005;9:11–18


Histologic Classification of Vaginal Neoplasia

VAIN (VAginal Intraepithelial Neoplasms)

These are pre-malignant lesions of the vaginal squamous epithelium that can develop primarily in the vagina or as an extension from the cervix. Histologically, VAIN is defined in the same way as cervical intraepithelial neoplasia (CIN). Classification includes three grades: Grade 1 (VAIN I = mild dysplasia); Grade 2 (VAIN II = moderate dysplasia); and Grade 3 (VAIN III = severe dysplasia or carcinoma in situ)

Invasive carcinoma:

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1. Squamous cell carcinoma


2. Adenocarcinoma


3. Other epithelial cell types (adenosquamous, adenoid cystic, undifferentiated)


4. Mesenchymal tumors (leiomyosarcoma, sarcoma botryoides, endometrioid sarcoma)


5. Mixed epithelial and mesenchymal tumors


6. Other histologies (melanoma, sarcoma, yolk sac tumors, lymphoma, carcinoid, small cell)


Higinia R et al. Vagina. In: Hoskins WJ et al (editors). Principles and Practice of Gynecologic Oncology. 4th ed. Philadelphia: Lippincott-Raven; 2005:707–742

Zaino RJ et al. Diseases of the vagina. In: Blaustein’s Pathology of the Female Genital Tract. 5th ed. New York: Springer-Verlag; 2002:178–195


VAIN (vaginal intraepithelial neoplasia):

  1. H&P, including bimanual examination, palpation, and colposcopic examination of the vagina, vulva, and cervix

  2. Multiple site-directed biopsies, including cervical and vulvar biopsies, to rule out invasive disease and metastatic lesions

Invasive carcinoma:

  1. H&P including bimanual examination and palpation of vagina

  2. Multiple site-directed biopsies, including cervical biopsies to rule out invasive disease and primary cervical cancer

  3. Studies allowable for staging as per FIGO guidelines: chest x-ray, cystoscopy, proctosigmoidoscopy, and intravenous pyelogram. Although not part of staging, pelvic MRI or CT scan may aid in planning of patient care

  4. If clinically warranted, barium enema and CAT scan or MRI

Staging is best performed by gynecologic and radiation oncologists with the patient under general anesthesia. Additional biopsies of the vagina should be done to determine the limits of abnormal vaginal mucosa


International Federation of Gynecology and Obstetrics (FIGO)

Hoskins WJ et al (editors). Principles and Practice of Gynecologic Oncology. 2nd ed. Philadelphia: Lippincott-Raven; 1997


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TNM Category FIGO Stage Primary Tumor (T)
TX   Primary tumor cannot be assessed
T0   No evidence of primary tumor
T1 I Tumor confined to vagina

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