J. Donald Woodruff

Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone

OBJECTIVE We evaluated four oral combinations of conjugated estrogens (Premarin) and medroxyprogesterone acetate in preventing endometrial hyperplasia, which can occur with conjugated estrogens alone. STUDY DESIGN This was a 1-year prospective, double-blind, randomized, multicenter study in 1724 postmenopausal women. All five groups took conjugated estrogens (0.625 mg) daily. The respective medroxyprogesterone acetate dosages were 2.5 and 5.0 mg daily (groups A and B) and 5.0 and 10.0 mg for 14 days per 28-day cycle (groups C and D). RESULTS Among the 1385 patients with valid biopsy data, endometrial hyperplasia developed in 20% in the conjugated estrogens-treated group and < or = 1% in each of the four conjugated estrogens/medroxyprogesterone acetate-treated groups. The incidence of endometrial hyperplasia did not differ significantly between any of the conjugated estrogens/medroxyprogesterone acetate regimens. However, none of the patients receiving the two higher medroxyprogesterone acetate dosages (groups B and D) had endometrial hyperplasia. CONCLUSION The endometrial hyperplasia incidence was significantly lower in women treated with conjugated estrogens and medroxyprogesterone acetate than in women treated with conjugated estrogens alone.

Long-term follow-up of serous ovarian tumors of low malignant potential

The biologic behavior of serous tumors of low malignant potential (LMP) is of significant interest, yet most large series lack extended follow-up. This study consists of 200 patients: 106 patients were diagnosed with serous tumors of LMP at our institution between 1979 and 1984 and an additional 94 patients were identified in the referred tumor registry. The patients ranged in age from 6 to 98 years (median, 34 years). The stage distribution was Stage I in 135 patients (67.5%), Stage II in 24 patients (12%), and Stage III in 41 patients (20.5%). Follow-up information from 4 to 27 years (median, 10 years; mean, 11.2 years) revealed 155 patients (77.5%) were alive without further evidence of disease and 11 patients (5.5%) died of unrelated conditions without recurrent tumor. Thirty-four patients (17%) developed recurrent neoplasms at 6 to 145 months (median, 26 months). Patients with Stage III disease developed recurrent neoplasms more commonly (54%) than did patients with Stage I or II disease (6 and 17%, respectively). Following treatment of recurrence, 15 patients are free of disease, 6 patients are alive with disease, and 13 (6.5% overall) patients have died of disease 1 to 15 years (median, 5 years) after their initial diagnosis. Mortality was also stage dependent: 0.7, 4.2, and 26.8% of patients with Stages I, II, and III disease, respectively, died secondary to tumors of LMP. Clinical life table analysis demonstrated 5-, 10-, and 15-, and 20-year survival rates for all stages of 97, 95, 92, and 89%, respectively. These findings confirm the excellent prognosis for patients with serous tumors of LMP, even when long-term follow-up is extended to 20 years. Additionally, these data suggest that those with more advanced or recurrent disease can enjoy extended survival.

Possible etiologic heterogeneity of vulvar intraepithelial neoplasia : A correlation of pathologic characteristics with human papillomavirus detection by in situ hybridization and polymerase chain reaction

A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the β‐globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a “condylomatous” appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus‐16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV‐positive women were younger than HPV‐negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles.

Ovarian extraembryonal teratoma

Forty-one cases of pure endodermal sinus ovarian tumors are reported. The extraembryonal nature of this tumor is supported with comparative studies utilizing early human implantations. The clinical picture is one of a virulent malignancy occurring in young women, and although the tumor is commonly unilateral and encapsulated at the time of initial diagnosis, the outcome is almost always fatal. Experience with different therapeutic modalities is limited, but there is significant evidence that vigorous combination chemotherapy will improve the therapeutic outcome.

Ovarian extraembryonal teratoma: II. Endodermal sinus tumor mixed with other germ cell tumors

From the files of the Emil Novak Ovarian Tumor Registry, 18 cases of mixed ovarian germ-cell neoplasms containing endodermal sinus tumor as one element have been reviewed. The data regarding the patient age, presenting symptoms, gross appearance of the tumors, and response to therapy are similar to those reported in a previous series of pure endodermal sinus tumors. Response to all modes of therapy is disappointing but there is growing evidence that combination chemotherapy should be added to surgical excision as a routine part of therapy in such patients. The rarity of this lesion is such that meaningful data are likely to be available only if individual and institutional experiences are combined in central tumor registries.

Risk factors for gestational trophoblastic neoplasia.

A case-control study to determine the gynecologic and reproductive risk factors for gestational trophoblastic neoplasia was conducted in the Baltimore Metropolitan Area. All cases (N = 190) that were pathologically diagnosed from 1975 to 1982 as hydatidiform mole, invasive mole, or choriocarcinoma were ascertained. Slides were independently reviewed by two pathologists. Cases were matched by age, race, and last menstrual period to controls who were delivered of normal pregnancies at term. In the analysis of medical record and interview data, factors found to be positively associated with gestational trophoblastic neoplasia included professional occupations (odds ratio = 2.56, p less than 0.0001), prior spontaneous abortions (odds ratio = 2.32, p = 0.02), and the mean number of months from the last pregnancy to the index pregnancy (cases = 35.9, controls = 28.2; p = 0.03). Factors found not to be associated with disease included contraceptive history, irradiation, ABO blood group, and smoking factors of the male partner. The findings suggest that gestational trophoblastic neoplasia may be part of a continuum of early (first-trimester) reproductive abnormalities.

Early invasive carcinoma of the vulva

Abstract Early invasive and/or microinvasive carcinomas have presented problems in the areas of histopathologic interpretation and clinical management. The reported and anecdotal cases treated by less than radical procedures with rapid recurrences have increased in the past 5 years. As with cervical cancer, there have been multiple interpretations of “microinvasion.” This series of 58 cases of early invasive disease addresses these controversial issues.

Metastatic ovarian tumors.

Abstract This study of 120 metastatic tumors from the files of the Emil Novak Ovarian Tumor Registry of the American Gynecological Society describes the various patterns presented by these unorthodox lesions. Certain features that are patently characteristic of metastatic disease are emphasized. The recognition of these will often allow the observer to differentiate a secondary from a primary tumor. The association of endometrial and ovarian cancer is felt to represent multicentric foci of origin in many patients and the high salvage rate in this group substantiates this thesis.

Differential maternal-fetal response to androgenizing luteoma or hyperreactio luteinalis.

: Lacl of masculinization in female infants whose virilized mothers have h. luteinalis is in contrast to the common finding of fetal masculinization when maternal virilization occurs with luteoma of pregnancy. From the data at hand, this variation in fetal response cannot be explained by differences in the quantity of androgen production nor by the stage of pregnancy when maternal virilization becomes evident. Steroid analysis from cases of h. luteinalis suggests that the placenta may serve as an androgen barrier by aromatizing steroids before they reach the fetus. Testosterone conversion by the placenta of an anencephalic fetus confirms that conversion to estrogens occurs even without significant fetal adrenal activity. Understanding of the breakdown of this mechanism, with resultant fetal masculinization, will require careful evaluation of the steroid milieu in conditions like luteoma in which fetal masculinization often occurs. Both cystic and solid ovarian hyperplasia are recognized as are complications of pregnancy which require proper identification and conservative management. The significant difference in patients at risk for luteoma and h. luteinalis and the pathological and hormonal differences clearly indicate that these are distinct and separate entities.Lacl of masculinization in female infants whose virilized mothers have h. luteinalis is in contrast to the common finding of fetal masculinization when maternal virilization occurs with luteoma of pregnancy. From the data at hand, this variation in fetal response cannot be explained by differences in the quantity of androgen production nor by the stage of pregnancy when maternal virilization becomes evident. Steroid analysis from cases of h. luteinalis suggests that the placenta may serve as an androgen barrier by aromatizing steroids before they reach the fetus. Testosterone conversion by the placenta of an anencephalic fetus confirms that conversion to estrogens occurs even without significant fetal adrenal activity. Understanding of the breakdown of this mechanism, with resultant fetal masculinization, will require careful evaluation of the steroid milieu in conditions like luteoma in which fetal masculinization often occurs. Both cystic and solid ovarian hyperplasia are recognized as are complications of pregnancy which require proper identification and conservative management. The significant difference in patients at risk for luteoma and h. luteinalis and the pathological and hormonal differences clearly indicate that these are distinct and separate entities.

Endometrial adenocarcinoma arising in adenomyosis

Endometrial adenocarcinoma and adenomyosis are both common problems arising in the uterus. Interestingly, there are few reports of the combination of these two pathologic entities. A recent experience with eight cases found in the files of the Gynecologic Pathology Laboratory at The Johns Hopkins Hospital between the years 1955 and 1974 are reported. Of significance is the differential in prognosis between such cases with deep involvement and true invasive disease.