Pathology

V. Diethylstibestrol (DES) - Related Lesions

Objectives

After completing this tutorial the student will be able to:

• list various lesions associated with maternal use of DES during pregnancy
• describe the epidemiology of DES-related lesions
• describe clinical features
• describe/recognize histologic features
• state clinical behavior/outcome

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1. Background

DES is a drug that was administered frequently to pregnant women who were at high risk for early pregnancy loss during the 1940’s through the 1960’s.

Multiple developmental, neoplastic epithelial changes, as well as malignancies of the female genital tract have been linked to in utero exposure to DES.

2. Developmental abnormalities

About 20% of DES-exposed women have gross structural abnormalities of the vagina or cervix. These are in the form of transverse vaginal ridges, narrowing of the vaginal apex, cervical hypoplasia, portio vaginalis completely covered by columnar epithelium, and anterior cervical lip protuberances.

3. Vaginal Adenosis

Vaginal adenosis refers to the replacement of the normal squamous epithelium of the vagina by glandular epithelium. It is asymptomatic and presents as red, granular patches on the vaginal mucosa.

Epidemiology.

It is common in DES-exposed women but rarely, can also present in women who have not been exposed to DES.

Histology.

The lesion comprises glandular epithelium, usually endocervical type, which may or may not merge with metaplastic squamous epithelium.


Glands in chronically inflamed lamina propria and merging with metaplastic squamous epithelium on the surface.

Clinical behavior

Benign but rarely, may give rise to clear cell adenocarcinoma.

4. Clear cell adenocarcinoma


Clear cell adenocarcinoma of the vagina is a rare tumor that is associated with in utero DES-exposure.

Epidemiology.

It affects young women, average 17 years old. Two thirds of patients have history of in utero DES exposure. The risk in exposed population is 1 in 1000.

Clinical appearance.

The tumor develops most frequently in the upper, anterior vaginal wall as a polypoid mass or flat lesion.

Histology.

It is composed of tubules, nests, and papillae lined by "hobnail" cells with clear cytoplasm (hence the name "clear cell") due to the presence of glycogen.


Clear cell adenocarcinoma showing papillae and nests lined by "hobnail" cells with clear cytoplasm.

Clinical behavior.

Prognosis is good with 80% 5-year survival.