Case Of Clear Cell Adenocarcinoma Research Articles

Epidemiologic aspects and factors related to survival in 384 Registry cases of clear cell adenocarcinoma of the vagina and cervix

Three hundred and eighty-four cases of clear cell adenocarcinoma of the vagina and cervix accessioned into the Registry as of December 31, 1978, have been analyzed. The annual incidence of these tumors has been found to correspond closely to the estimated usage of diethylstilbestrol (DES) for pregnancy support in the United States. The annual incidence of the DES-associated cases appears to have dropped in the United States in the past 2 years in comparison to 1973 to 1975. The risk of tumor development appears to be higher in young women exposed to DES early in intrauterine life than in those exposed later. The carcinomas are rare before the age of 14 years and an irregular peak in the age-incidence curve appears between 17 and 21 years followed by a decline. The 5-year survival rate is better for women over the age of 19 years than for younger patients, and a higher frequency of the tubulocystic histologic pattern of the tumor is observed in the former age group. Oral contraceptive usage did not appear to influence the behavior of the tumor and the improved survival in those using this medication appears to be related to greater medical surveillance.

DES-associated clear cell adenocarcinoma of the vagina and cervix.

Epidemiologic, clinical and pathologic data on all cases of clear cell adenocarcinoma of the genital tract in women born in 1940 and later are collected by the Registry for Research on Hormonal Transplacental Carcinogenesis. Other cases of genital cancer are also recorded if there is a history of prenatal hormone exposure. Evidence strongly suggest a mullerian nature for clear cell adenocarcinomas. Of the 333 cases accessioned between 1970 and 1976, about 2/3 of the completely investigated cases had histories of prenatal exposure to stilbestrol (DES) or similar compounds. Estimated risk of clear cell adenocarcinoma ranges from 0.14 to 1.4 per 1000 DES-exposed, with age-incidence peaking at age 19. Cytology and a thorough pelvic examination are important tools for accurate diagnosis. Surgery and radiation are used to treat these tumors, but follow up in most cases has been limited to 5 years. Several cases of small or superficial tumors have been observed to spread to regional pelvic nodes, with recurrences in the lungs or supraclavicular areas. For inquiries, contact the Registry for Research on Hormonal Transplacental Carcinogenesis, 5841 S. Maryland Ave., Chicago, Ill 60637. Analysis of pathologic specimens should be directed to Robert E. Scully, MD, Dept of Pathology, Massachusetts General Hospital, Boston, Mass 02114.

An analysis of 346 cases of clear cell adenocarcinoma of the vagina and cervix with emphasis on recurrence and survival

Three hundred and forty-six cases of clear cell adenocarcinoma of the vagina and cervix have been accessioned into the Registry for Research on Transplacental Carcinogenesis. In the early 1970s these cancers reached a peak incidence which has continued on the same level up to the present. Two-thirds of the patients with a maternal history had been exposed to diethylstilbestrol (DES) or related compounds in utero. Follow-up for the periods up to 15.3 years (mean, 4.0) yielded an actuarial 5-year survival of 78%. The survival figures in cases of Stage I carcinomas of the vagina and cervix were 87 and 91%, respectively. Local excision of Stage I appeared to carry an increased risk of recurrence. The overall rate of recurrence for all cases was 23% at 5 years. Recurrences were most frequent in the pelvis and lungs. Surgical therapy, and less often, radiotherapy, resulted in the survival of 12 of the 58 patients with recurrent tumor for 3 or more years. Various cytotoxic chemotherapeutic agents were administered to 34 patients with four objective responses, but no total remissions. The details of these findings will be presented.

Complications of Prenatal Therapy With Diethyistilbestrol

Cancer of the vagina is a rare type of genital malignancy that usually occurs as squamous cell carcinoma in postmenopausal women. Vaginal clear cell adenocarcinoma (Fig. 1), which used to be termed "mesonephroma," is an extremely rare type of genital cancer and was almost never encountered in younger patients until recently. In 1970, a clinical and pathologic study of seven cases of clear cell adenocarcinoma of the vagina in females between the ages of 14 and 22 years was published; all of them had been seen or treated in the late 1960s. These seven cases exceeded the total number of this type of cancer that had been previously reported in this age group.1 The next year, a retrospective epidemiologic study was conducted that included an additional case, and this cohort of eight was compared to 32 controls. It was found that the risk of development of these carcinomas was significantly associated with intrauterine exposure to diethylstilbestrol.2 Diethylstilbestrol therapy for high-risk pregnancy to reduce fetal wastage had been very popular in the late 1940s and 1950s. However, its use was stated to be contraindicated in 1971 by the Food and Drug Administration after the results of the initial epidemiological studies were confirmed.3 Clear cell adenocarcinoma of the cervix has also been associated with intrauterine exposure to diethylstilbestrol.4,5 In addition, other similar nonsteroidal synthetic estrogens such as dienestrol and hexestrol have also been implicated in the association. Studies of the clinical, epidemiological, and pathologic aspects of these neoplasms have been centralized in the Registry for Research on Hormonal Transplacental Carcinogenesis (formerly the Registry of Clear Cell Adenocarcinoma of the Genital Tract in Young Females).

In utero exposure to DES. Evaluation and followup of 199 women.

Among 199 women from 12 to 30 years of age who had been exposed to DES in utero, the colposcopic evaluation of the vagina and cervix was considered normal for only 13.6%. The incidence of colposcopically detected lesions was not related to the trimester of DES exposure, the patient's age, use of oral contraceptives, or presenting symptoms. Areas of punctation, mosaic patterns, white epithelium, and keratosis were not considered areas of adenosis. Cervical bands, hoods, cock's combs, etc., were considered as part of the cervix. Under this definition adenosis of the vagina was diagnosed in only 14.1% of the patients. Eight (4.0%) women were found to have cervical intraepithelial neoplasia (CIN), Grade 3 lesions, and an additional 36 (14.1%) women were found to have CIN, Grade 1 lesions based on the light microscopy evaluation of directed biopsies. There were no cases of clear cell adenocarcinoma. It appears that women with in utero DES exposure may be at a higher risk of developing squamous neoplasia compared with non-DES-exposed women.

Cytologic feature of the clear cell adenocarcinoma, coexisting with early invasive squamous cell carcino ma of the uterine cervix

One case of clear cell adenocarcinoma of the uterine cervix is reported in this paper. Detailed analysis of cytologic specimens was performed, and we found somedifferent cytologic features from that of endocervical adenocarcinoma. Case Report.A forty-eight-year old woman, G. 7P.2, with complaints of vaginal bleeding and low abdominal tenderness, visited our clinic in 1974. This patient's case was diagnosed as myomata uteri and cervical erosion. Leukoplakia, punctation, and mosaic were found on colposcopic examination. Two different types of atypical cells were observed on cytologic examination, one suggesting adenocarcinoma and the other, carcinoma in situ of the uterine cervix. Histologic examination (punch biopsy, cone biopsy, and D & C) revealed early invasive squamous cell carcinoma, mesonephric adenocarcinoma of the uterine cervix, and clear cell adenocarcinoma of the endometrium. Radical hysterectomy, followed by chemotherapy and postoperative radiation, was performed, and the patient was followed up in the out-patient clinic. But she died of pulmonary metastasis and cancerous peritonitis 16 months after the operation.Histologic FindingsThe uterine corpus, child head sized, was elastic and hard. On the cross-section were found microcystic lesions, including bloody mucinous materials in the myometrium and cervical stroma. Bilateral ovaries were normal in appearance. Microscopically, early invasive squamous cell carcinoma was found in the uterine cervix, and tubular adenocarcinoma, suggesting hobnail pattern in some part, was also found in the deep cervical stroma which was situated at 10-12 o'clock and 2-7 o'clock positions of the cervix. Solid clear cell adenocarcinoma was also found in the myometrium penetrating in to the endometrium. These two types of adenocarcinoma had transitional parts in the upper cervical area. Right internal iliac, external iliac, and It parametral lymphnodes were involved by the solid clear cell adenocarcinoma. Staining reaction of these adenocarcinoma was weakly positive with P.A.S. and mucicarmin, but negative with.Sudan-III. Mitosis was rarely found. We thought that these tumors were mesonephric adenocarcinomas arising from the uterine cervix, involving the corpus and lymphnodes, and coexisting with early invasive squamous cell carcinoma of the uterine cervix.Cytologic FeaturesCervical swab smears and touch smears of the hysterectomized specimen were analysed. In the cervical swab smear, many glandular atypical cells were detected, arranged in sheet or isolated (70%). Tumor diathesis was seen. These cells had more abundant cytoplasm, finerchromatin pattern, and more macronucleoli than endocervical adenocarcinoma cells. In the touch smears, tumor diathesis was not seen, and polygonal cytoplasm and irregular chromatin pattern were predominant.DiscussionMany mesonephric adenocarcinomas of the ovaries have been reported since the first description of Schiller's mesonephroma. Mesonephric remnant or cyst in several parts of the female genital tract were often found; therefore, the extraovarian mesonephric adenocarcinoma may be expected to be more often found. But mesonephric adenocarcinoma of the uterine cervix was rarely reported. Schiller pointed out the glomerulus-like structure as diagnostic criterion of mesonephroma. But Saphir, not agreeing to it, suggested clear cell patterns of the tumor as diagnostic criteria. Many authors used the term of clear cell adenocarcinoma and that of mesonephric adenocarcinoma synonymously. But some of adenocarcinomas and squamous cell carcinomas suggested the clear cell pattern; therefore, only the clear cell adenocarcinoma, suggesting hobnail pattern, peg-like pattern or glomerulus-like structure, should be diagnosed as mesonephric adenocarcinoma.

Clear cell adenocarcinoma of the cervix and vagina. A clinicopathologic study of 21 cases with and without a history of maternal ingestion of estrogens.

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.