Review of the granulosa-theca cell tumors from the emil Novak ovarian tumor registry.

OBJECTIVE: Our purpose was to review patients with granulosa and theca cell tumors as filed in the Emil Novak Ovarian Tumor Registry. STUDY DESIGN: Our study was a descriptive, retrospective study of 454 case records. RESULTS: The reviewed diagnoses were for 97 patients with granulosa cell tumors, 116 with theca cell tumors, and 97 with granulosa-theca cell tumors. The remaining cases (n = 144) were reclassified as "nonspecific" gonadal stromal tumors (n = 61), luteomas of pregnancy (n = 7), and 76 "other" cases. These included poorly differentiated cancer, metastatic cancer, mixed mesodermal tumors, and sarcomas. The tumor-related mortality rate for the 310 patients with granulosa, theca, and granulosa-theca cell tumors was 7% (37.3% for granulosa cell tumors only). The surgical stage of disease was the most significant prognostic factor, with a mortality rate of at least 40%, given that the tumor had spread beyond the ovary. CONCLUSION: Because the differential diagnoses of particularly granulosa cell tumors included several conditions with an extremely poor prognosis, an accurate histologic diagnosis is crucial.

Granulosa and theca cell tumors in children: a report of 17 cases and literature review.

The files of the Emil Novak Ovarian Tumor Registry (ENOTR) were searched for granulosa and theca cell tumors in children aged 12 years and less. In addition, an extensive literature search was done for English publications on children with these tumors aged 10 years or less. Of the 17 children from the ENOTR, 5 had adult-type granulosa cell tumors, 6 had juvenile granulosa cell tumors, and 1 had a luteinized granulosa cell tumor. In addition, there were three cases with gonadal stomal tumors, one theca cell tumor, and one granulosa-theca cell tumor. Precocious pseudopuberty was present in 70 percent of the children, abdominal pain in 24 percent, and ascites in 18 percent. The literature review revealed a tumor-related mortality rate of 9 percent (based on 163 cases with granulosa cell tumors, including the juvenile type). Some of these tumors are large with acute pain, but nevertheless, the prognosis is good, particularly in cases with precocious puberty. Treatment can be conservative.

Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group.

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 stage I cervical adenocarcinoma treated by radical surgery.

From 1972 to 1988 55 patients underwent radical abdominal hysterectomy, pelvic lymph node dissection for treatment of FIGO Stage I cervical adenocarcinoma. A minimum of 60 months follow-up was available on all surviving patients. A detailed retrospective analysis was conducted to determine the influence of radical surgery on survival and to identify prognostic factors for recurrence. A bilateral salpingo-oophorectomy was included as part of the primary surgery in 52 the patients. Histologic subtypes included endocervical adenocarcinoma (44), papillary carcinoma (5), clear cell carcinoma (3), and adenosquamous carcinoma (3). The 5- and 10-year disease-free survival was 85.5%. The median follow-up of the surviving patients was 78.5 months (range, 60 to 240 months). Eight patients recurred, all but 1 of whom died of disease. Median time to recurrence was 28 months (range, 6 to 47 months). Five patients recurred beyond 24 months. One patient recurred locally, 5 recurred regionally, and 2 developed distant recurrences. Lymph node metastases (P < 0.0001), histologic grade (P < 0.0001), depth of invasion (P = 0.0001), presence of paracervical disease (P = 0.0034), and size of the lesion (P = 0.0059) were shown to be significant determinants of recurrence. Two of the 3 patients with a single involved lymph node recurred. Age, parity, history of oral contraceptive use, histologic subtype, and lymph vascular space involvement were not statistically significant determinants of recurrence. Adjuvant whole pelvic radiotherapy did not influence regional recurrence or survival but may decrease local recurrence. Radical abdominal hysterectomy pelvic lymph node dissection is an appropriate treatment of patients with Stage I cervical adenocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcutaneous injection of triamcinolone acetonide in the treatment of chronic vulvar pruritus.

OBJECTIVES: We studied the efficacy of subcutaneous corticosteroid injection as therapy for chronic vulvar pruritus. STUDY DESIGN: Adult women with symptoms of vulvar pruritus > 6 months were studied. After appropriate biopsies and cultures were performed, patients were included in the study group if they experienced limited relief with topical triamcinolone cream. Triamcinolone acetonide (15 to 20 mg) was injected subcutaneously and massaged into the affected vulvar tissue. RESULTS: Seventy-eight percent of patients (35/45) experienced relief of vulvar pruritus for > 1 month (mean duration 5.8 months). CONCLUSIONS: We found that subcutaneous injection triamcinolone acetonide provided relief of symptoms of chronic vulvar pruritus.

Time-related effects of RU486 treatment in experimentally induced endometriosis in the rat.

OBJECTIVE: To evaluate the time-dependent effect of the progesterone antagonist RU486 on experimentally induced endometriosis in the rat. DESIGN: Endometriosis was induced by implanting endometrium onto the peritoneal side wall. Size of the implants was measured before and after treatment. PARTICIPANTS: Fifty-two adult female Sprague-Dawley female rats weighing 200 to 225 g. SETTING: Departmental research laboratory of university hospital. INTERVENTION: Animals treated with RU486 or vehicle only for 2, 4, 6, or 8 weeks. MAIN OUTCOME MEASURES: Size of the implant was measured before and after treatment; relative change in size of the implants was calculated. RESULTS: There was not a statistically significant difference between the treatment groups and the control groups. There was no regression of endometriosis in any of the treatment groups. CONCLUSIONS: RU486 administered for 8 weeks in the rat model was not effective therapy for endometriosis.

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.

Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential.

A comprehensive understanding of retroperitoneal lymphatic involvement is lacking in tumors of low malignant potential. This study was undertaken to evaluate retroperitoneal lymphatic involvement in patients with ovarian tumors of low malignant potential. One hundred seventy-one patients were diagnosed with epithelial ovarian tumors of low malignant potential between 1979 and 1989. Thirty-four (20%) of these patients underwent surgical staging which included lymph node sampling. The stage distribution was Stage I in 17 patients (50%), Stage II in 4 patients (12%), and Stage III in 13 patients (38%). The histology of the tumors was serous in 26 patients (76%), mucinous in 7 patients (21%), and seromucinous in 1 patient (3%). The incidence of retroperitoneal lymphatic involvement was 21%. The occurrence of positive pelvic and para-aortic nodes was 17 and 18%, respectively. Patients with localized intraperitoneal disease were upstaged in 22% of the cases based on retroperitoneal lymphatic involvement. Four of twenty-one patients (19%) with intraperitoneal disease confined to the ovary and two of six patients (33%) with intraperitoneal disease confined to the pelvis were upstaged to Stage III as a result of retroperitoneal lymphatic disease. Although the nodal status of patients did not significantly affect survival, those patients with localized intraperitoneal disease and nodal involvement had a higher incidence of recurrence which was statistically significant (P = 0.025). Accordingly, retroperitoneal lymph node sampling at the time of initial laparotomy may provide valuable prognostic information regarding recurrence in patients with tumors of low malignant potential.

Placental site trophoblastic tumor in a postmenopausal woman.

Placental site trophoblastic tumor is a rare neoplasm that arises in the trophoblastic tissue of the placental bed. This case report is unusual because of the patient's advanced age at the time of diagnosis and the favorable response of the disease to chemotherapy. Although the clinical course is benign for most patients with placental site trophoblastic tumor, the malignant variant of the disease is characterized by recurrence, relative insensitivity to radiation and chemotherapy, and death. To the authors' knowledge, the 53-year-old woman reported is the oldest patient with histologically confirmed placental site trophoblastic tumor. Initially, surgery, radiation, and multiagent chemotherapy failed to control vaginal and pulmonary metastatic disease. After administration of four treatment cycles of a "second-line" chemotherapeutic regimen consisting of cyclophosphamide and cisplatin, complete clinical and radiologic remission was achieved. The patient's serum level of human chorionic gonadotropin has remained undetectable, and she has been without measurable evidence of disease for 16 months.

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 beta-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.

Investigation of ovarian neoplasia of low malignant potential for human papillomavirus.

Recent in situ hybridization studies have suggested the presence of human papillomavirus type 6 (HPV-6) DNA in ovarian cancer cells. An association between HPV and ovarian neoplasia of low malignant potential (LMP) has not been previously identified. Paraffin-embedded tissue blocks from 24 patients with LMP ovarian tumors were screened for human papillomavirus DNA. The patients ranged in age from 18 to 73 years. Corresponding microscopic slides from each tissue block were reviewed to confirm the histopathologic diagnosis. For identification of HPV genome, deparaffinized sections were subjected to the polymerase chain reaction to achieve amplification of DNAs of HPV types 6, 11, 16, and 18. For each HPV type, a 120-base-pair region of the E6 gene was targeted for amplification. Human papillomaviral DNA was not detected in the tissue specimens subjected to polymerase chain reaction. These results suggest that HPV types 6, 11, 16, and 18 are not likely to play a role in LMP ovarian tumors. These results do not totally exclude possible contributions of other HPV types.

Primary ovarian malignant amelanotic melanoma arising in cystic teratoma.

A case of primary ovarian malignant amelanotic melanoma arising in a cystic teratoma is presented with the histology, immunohistochemistry, and ultrastructure of the tumor.

Analysis of false negative cytology by a chromosome study.

Forty-two cases of pre-invasive and invasive cancer of the cervix diagnosed by histology were studied cytologically and cytogenetically. Preinvasive lesions showed a good correlation between cytologic impression and the histologic diagnosis. However, among 17 patients with invasive cancer, there were 2 completely negative cytologic impressions. These were in cases having modal chromosome counts of 47 and 48, respectively. This study demonstrates that some invasive cancers of the cervix are resistant to cytologic diagnosis because of their peridiploid chromosome counts and lack of anisokaryosis.

Human papillomavirus and epithelial ovarian neoplasia.

In contrast to the strong association between human papillomavirus (HPV) and squamous cell carcinoma of the lower female genital tract, no viral DNA had been found in epithelial ovarian carcinoma. Recently, however, R. H. Kaufman, J. Bornstein, A. N. Gordon, E. Adam, A. L. Kaplan, and K. Adler-Storthy [Gynecol. Oncol. 27, 340-349 (1987)] reported the detection of HPV-6 DNA by in situ hybridization in 10 of 12 patients with advanced epithelial ovarian carcinoma. To further investigate the possible association between HPV and epithelial ovarian neoplasia, tumor from 12 patients with epithelial ovarian adenocarcinoma, 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian adenomas was examined for HPV DNA by the Southern hybridization technique. All the tissues were tested under low stringency for HPV-6 and under high stringency for HPV-6, HPV-16, HPV-18, HPV-31, and HPV-35. In addition, all tissues were tested by polymerase chain reaction for the presence of HPV-6 and HPV-11. Of the 12 patients with adenocarcinoma, 5 were poorly differentiated, 4 serous, 1 endometrioid, 1 mucinous, and 1 mixed. The neoplasms were of grades 2-4 with a predominance of stages III and IV (83%). Of the 3 patients with tumors of low malignant potential, all were serous and stage I. Of the 3 patients with adenomas, 1 was mucinous, 1 serous, and 1 Brenner. We were unable to detect HPV-related sequences in any of the specimens. On the basis of these findings, there appears to be no association between HPV and epithelial ovarian neoplasia.

Vulvitis circumscripta plasmocellularis. A report of four cases.

Four women were treated for erythematous lesions of the vulva, which vary from acute dermatitis to invasive cancer. Often a positive diagnosis can be made only with biopsy, and interpretation of the tissue is very important.

Leiomyoma of the uterus with multiple extrauterine smooth muscle tumors: a case report suggesting multifocal origin.

A 17-year-old woman underwent hysterectomy for removal of a "mitotically active" (six to seven mitoses per 10 high-power fields) yet otherwise benign-appearing cellular smooth muscle tumor. Eleven years later, she developed multiple histologically benign smooth muscle tumors in the posterior mediastinum, deep soft tissues of the neck, paravertebral region, incisional scar, and mesentery. The distribution and histologic appearance of the tumors, as well as the protracted clinical course, suggest multifocal origin rather than widespread metastases from a low-grade uterine leiomyosarcoma. This case raises the possibility that some similar cases reported as so-called benign metastasizing leiomyoma may be more satisfactorily explained by the concept of multifocality.

The predominance of human papillomavirus type 16 in vulvar neoplasia.

Southern transfer analysis for human papillomavirus genomic sequences was conducted on 152 vulvar and vaginal tissue specimens obtained from 86 patients. Histopathologic diagnoses included condyloma acuminatum, intraepithelial neoplasia, and invasive cancer. In six patients, lesions of more than one pathologic type were identified. Vaginal lesions constituted less than 5% of tissues examined. Distribution of lesions was as follows: condyloma, 93 lesions from 57 patients; intraepithelial neoplasia, 47 lesions from 29 patients; and invasive carcinoma, 12 lesions from six patients. Seventy-five percent of the patients were white. The mean age of the patients increased from 25 years for condyloma to 38 years for vulvar intraepithelial neoplasia III to 56 years for invasive cancer. A viral diagnosis was made in 81% of condylomas, 84% of vulvar intraepithelial neoplasia III, and 58% of invasive carcinomas. Distribution of viral types differed markedly for the various histopathologies. Types 6/11 accounted for 77% of condylomas and 0% of vulvar intraepithelial neoplasia III. Type 16 was recovered from 12% of condylomas and 81% of vulvar intraepithelial neoplasia III. Type 18 was identified in a small proportion in both categories; type 31 was seen in a few vulvar intraepithelial neoplasia III lesions. In invasive carcinomas, type 16 was the predominantly identified virus. Papillomavirus type 16 emerges as the dominant oncogenic virus in vulvar neoplasms. Its presence in a large percentage of condylomas raises the issue of an "atypical condyloma" as a precursor of neoplasia.