Twenty-one cases of clear cell adenocarcinoma of the cervix and vagina have been reviewed. Fifteen cases occurred in females under 25 years of age and four in women over 45 years. In seven cases, a positive history of maternal ingestion of diethylstilbestrol (DES) was obtained. One mother gave a history of medication with conjugated estrogens and ethisterone. Of the 13 patients with a negative history, three were born during the time period when DES was commonly used to prevent abortion. Fifteen carcinomas were cervical in origin; seven of these also involved the vagina. In six cases the carcinoma was entirely vaginal. Vaginal involvement of the carcinomas was more common in the estrogen-related group. Two non-estrogen-related cases had coexisting congenital malformations with double uterus and vagina and unilateral renal agenesis. The histopathologic appearance was similar in both groups. In most cases, a mixture of papillary, microcystic, tubular, and solid features was seen. Vaginal adenosis was found in nine cases, six of which were estrogen-related. Surgical therapy was employed in most cases and was generally superior to radiation therapy. Five patients had lymphatic involvement. All died from carcinoma. The survival rate among sixteen patients followed for 2 years or more was 62.5%. The probable müllerian origin of clear cell adenocarcinoma is discussed. It is suggested that DES, by virtue of being an estrogen, interferes with the normal process of differentiation and degeneration of müllerian epithelium in the fetal vagina. The persistence of müllerian cells altered at the subcellular level could form the basis for development of carcinoma in later life. However, a similar sequence of events must also be accepted to occur "spontaneously" since clear cell adenocarcinoma can develop in women without a history of maternal estrogens.

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Chemotherapy is used primarily to treat advanced or recurrent cervical cancer. There are three major applications: primary therapy, as a radiation sensitizer, and neoadjuvant therapy. Primary chemotherapy is employed in advanced and disseminated cervical carcinoma (Stage VB). The four best single drugs with moderate activity against cervical cancer are: cisplatin, ifosfamide, dibromodulcitol (mitolactol), and Adriamycin (doxorubicin). Cisplatin and ifosfamide appear to be the best combination therapy: they provide an objective response rate of 33%. However, because the overall survival was not significantly improved with combination therapy, single‐agent therapy with one of the above active drugs is acceptable. For stages IIB, III and IVA, the primary therapy is still radiation. Concomitant chemotherapy with hydroxyurea or a combination of cisplatin and 5‐fluorouracil (5‐FU) have been shown to enhance radiation response in several randomized trials. Hydroxyurea is the preferred radiation sensitizer because it offers less toxicity, ease of administration, and equivalent results. Chemotherapy in neoadjuvant setting produces promising results. Various cisplatin combinations of mitomycin C, 5‐FU, vincristine, and bleomycin have been employed to shrink locally advanced cervical cancer and permit safe, radical excision. Early results with these combinations in small trials are encouraging but further studies are needed to fully evaluate their potential. Semin. Surg. Oncol. 16:247–250, 1999. © 1999 Wiley‐Liss, Inc.

SUMMARY Twenty-five endometrial carcinomas and three non-endometrial carcinomas were studied for the influence of various steroid hormones on the synthesis of DNA and RNA in short-term incubations in vitro. Endometrial carcinomas showed a dose-dependent sensitivity to progesterone in vitro, the response in both nucleic acids sometimes exceeding that of normal endometria. The mean reduction in DNA synthesis was to 46% and in RNA synthesis to 39% of the control values. Poorly differentiated carcinomas showed higher values of DNA synthesis than highly differentiated ones, as did carcinomas from younger women compared with those from older women. The response in vitro to progesterone was not correlated with these factors. Pregnenolone and a synthetic progestogen were less effective in vitro than progesterone. Oestradiol at a high concentration (20 μg/ml) in some cases significantly reduced the synthesis of both nucleic acids, possibly because of a specific 'toxic' action on the cells. No hormonal effects were observed in non-endometrial carcinomas.

The Bethesda Pap Smear system and its 1991 revisions aim to simplify Papanicolaou (Pap) smear reporting and make it more reproducible. It redefines the Pap smear request as a medical consultation. The pathologist consultant is required not only to provide the smear reading but also its clinical recommendation. The Bethesda system insists on a detailed Pap smear report assessing specimen adequacy and types of epithelial changes. Squamous cell abnormalities are grouped according to their biologic potential. Both cervical intraepithelial neoplasia, grade I (CIN I) (mild dysplasia) and human papillomavirus (HPV) lesions are grouped together as low-grade squamous intraepithelial lesions (LGSIL), while moderate and severe dysplasia (CIN II and III) belong to the high-grade squamous intraepithelial lesion (HGSIL) category. Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGCUS) need further qualification as to whether they favor either a reactive or neoplastic process. Guidelines for management of abnormal Pap smears are discussed in detail. Semin. Surg. Oncol. 16:217-221, 1999.