Human papillomavirus testing for triage in a referral population.

OBJECTIVE: This study evaluated the Digene HPV Assay Hybrid Capture System(R) as a triage method. METHODS: Results of an HPV assay were compared with a final tissue diagnosis of cervical intraepithelial neoplasia 2 (CIN2) or greater. These results were stratified based on Pap smear diagnosis and evaluated in 4 triage algorithms. RESULTS: Of the 4 algorithms evaluated, the highest savings came from not performing colposcopy for patients with repeat atypical squamous cells of undetermined significance (ASCUS), but that resulted in missing nine patients with CIN2 and CIN3 histology. HPV testing failed to diagnose 67% (6 out of 9) to 48% (10 out of 21) of patients with underlying CIN2 and CIN3. CONCLUSIONS: Although HPV high-risk positive results correlate with high-grade histology, it is associated with significant false negatives. The HPV low-risk test is not clinically useful. These tests were poor methods to triage patients in our population.

Endometriosis-associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature.

This clinicopathologic study of primary Mullerian tumors of the bowel arising in foci of endometriosis is based on six new cases and an analysis of 17 previously reported cases. Varieties of Mullerian tumors occur in the bowel; the most common types are endometrioid carcinoma, followed by various mixed Mullerian tumors and stromal sarcomas. Seventy-eight percent develop in the rectosigmoid colon, the remaining in the cecum or ileum. Those in the latter area tend to be sarcomas or mixed Mullerian tumors. Certain architectural growth characteristics, derived from precursor endometriosis, are common to most endometriosis-associated intestinal tumors (EAITs). Seventy percent of EAITs occur in the outer bowel wall. Transmural tumors tend to form luminal polyps and assume an hourglass shape. Metachronous or synchronous Mullerian tumors occur in 39% of cases. Seventy percent of women with EAITs are in their mid 30s to early 50s. Common presenting symptoms are abdominal or pelvic pain, melena, and an abdominal or pelvic mass. Documented in 26% of patients is a history of prolonged unopposed estrogen therapy. Only 28.5% of cases die of their tumors, but follow-up is less than 5 years in all but 2 patients.

Chronic plasma cell cervicitis simulating a cervical malignancy: a case report.

BACKGROUND: Only one case of plasma cell cervicitis, a rare variant of chronic cervicitis, has been reported. We report a second case and present data supporting the detection of human papillomavirus (HPV) outside of epithelial tissues. CASE: A 67-year-old woman was found to have a large cervical tumor. Extensive diagnostic evaluation failed to reveal a suspected cervical cancer; subsequently, a hysterectomy was performed. Light microscopic studies confirmed plasma cell cervicitis. Standard virologic tests were used to confirm the presence of HPV 16 in cervical sections. Retrospective study of the first reported case also demonstrated HPV. CONCLUSION: Fulminant cases of chronic cervicitis, presenting with clinical features similar to cervical cancer, are unusual. Even more interesting is the detection of HPV outside of the epithelium; this is the first case that clearly demonstrates HPV in plasma cells.

Hyperthecosis of the ovaries in a woman with a placental site trophoblastic tumor.

Rapidly increasing testosterone levels were observed in a patient presenting with sudden onset of virilization. Exploratory laparotomy revealed a placental site trophoblastic tumor in the uterus. Wedge biopsies of the ovaries showed extensive luteinization of the ovarian stroma in both ovaries. Concentrations of testosterone, dihydrotestosterone, and androstenedione were markedly increased in the ovarian vein serum, indicating ovaries as the source of these steroids. The serum concentration of hCG was 69 mIU/mL. Pulsatile secretion of LH persisted in spite of elevated hCG levels. Follicle-stimulating hormone levels were low or undetectable. Elevated hCG levels and low FSH levels resulted in a hormonal environment similar to that seen in polycystic ovary disease (high LH to FSH ratio), resulting in extensive stromal luteinization. Decline in hCG levels after removal of the tumor resulted in the return of androgen levels to normal.

Steroid biosynthesis in the Sertoli-Leydig cell tumor: effects of insulin and luteinizing hormone.

In vitro steroid production by a virilizing Sertoli-Leydig cell tumor of the ovary was studied. For comparison, stromal tissue from the opposite normal ovary was also incubated under similar conditions. The tumor fragments secreted significantly more testosterone (527 +/- 168 versus 48 +/- 29 pg/mg tissue, p less than 0.001), androstenedione (1188 +/- 400 versus 40 +/- 10 pg/mg tissue, p less than 0.001), and dehydroepiandrosterone (419 +/- 132 versus 73 +/- 25 pg/mg tissue, p less than 0.004) than that of normal ovarian stroma. Measurement of steroids in the ovarian venous serum draining the tumor indicated a peripheral ovarian gradient for both delta 4 and delta 5 steroids. Incubation of tumor fragments with luteinizing hormone alone resulted in a significant increase in the secretion of androstenedione and dehydroepiandrosterone (p less than 0.05). Addition of insulin to luteinizing hormone resulted in significantly greater release of androstenedione than that of treatment with luteinizing hormone alone (p less than 0.04). Addition of insulin had no effect on the release of dehydroepiandrosterone. Luteinizing hormone and insulin, either alone or in combination, failed to produce any change in the secretion of testosterone. We conclude that (1) increased testosterone secretion by Sertoli-Leydig cell tumor resulted from increased availability of precursors from both delta 4 and delta 5 pathways; (2) the tumor was responsive to luteinizing hormone with an increase in the secretion of androstenedione and dehydroepiandrosterone; (3) insulin acts synergistically with luteinizing hormone to increase secretion of androstenedione; (4) the tumor has specific binding sites for insulin; and (5) the increased levels of insulin and luteinizing hormone in polycystic ovarian disease may play a role in the pathogenesis of Sertoli-Leydig cell tumor.

A rapid DNA probe test for detecting human papilloma virus types 6/11 and 16 in biopsy specimens.

A simple, rapid and sensitive non-radioactive in situ hybridization assay for human papillomavirus (HPV) has been developed and used to detect HPV 6/11 and HPV16 DNA in ano-genital biopsy specimens. A comparative study to determine the sensitivity and the specificity of this assay relative to Southern blot hybridization assays was performed using one hundred biopsy specimens. The sensitivity of the in situ hybridization assay was 88% for HPV type 6/11 and 89% for HPV type 16. The specificity of the test was 99% for both virus types. In addition to its high sensitivity and specificity, this in situ hybridization assay for HPV uses a non-radioactive detection system. The assay is faster and easier to perform than the Southern blot method. Also, in situ hybridization assays permit the simultaneous evaluation of the histology, as well as the DNA content of biopsy tissues because they do not result in the destruction of tissue or cell morphology. This prototype HPV DNA assay was developed using DNA probes for HPV 6/11 and HPV 16 DNA in anogenital biopsy specimens. However, the protocol developed in these studies can easily be extended to include the use of probes for detecting other HPV types in a variety of tissues.

Ovarian steroid secretion in postmenopausal women with and without endometrial cancer.

The concentrations of testosterone (T), androstenedione (A), estradiol (E2), and estrone (E1) were measured in peripheral and ovarian venous serum obtained at the time of bilateral oophorectomy from 15 postmenopausal women with endometrial cancer and 9 without cancer. The cancer and noncancer (control) patients were matched for age, weight, and years since menopause. In women with endometrial cancer, significantly higher ovarian than peripheral venous concentrations were found for all hormones measured [T, 3781 +/- 1255 (+/- SE) vs. 213 +/- 43 pg/ml (P less than 0.01); A, 5352 +/- 1845 vs. 1299 +/- 187 pg/ml (P less than 0.04); E2, 52 +/- 11 vs. 23 +/- 3 pg/ml (P less than 0.02); E1, 81 +/- 12 vs. 32 +/- 2 pg/ml (P less than 0.001)], but in the control patients, only the concentration of T was significantly higher (623 +/- 108 vs. 156 +/- 21 pg/ml; P less than 0.001). Ovarian venous concentrations of T and A were significantly higher in thin women with cancer than in obese women with cancer. These results suggest that the ovaries of postmenopausal women with endometrial cancer secrete significantly more T and A than do the ovaries of women without cancer, while secreting only minimal amounts of E2 and E1. This increase in ovarian steroid secretion might play a role in the pathogenesis of endometrial cancer.

Hyperinsulinemia in hyperthecosis of the ovaries.

Fasting insulin concentrations and the insulin response to an oral glucose tolerance test were measured in six virilized women with ovarian hyperthecosis and six weight-matched normal women. For comparison, six women with polycystic ovarian disease were also studied. The diagnosis of hyperthecosis was confirmed in all six virilized women by histologic examination of the ovaries. The fasting insulin concentrations were increased in all of the hyperthecosis patients (84 +/- 32 microU/ml). Insulin response to an oral glucose tolerance test was greatly increased (p less than 0.01) in comparison to normal women and women with polycystic ovarian disease. Significant positive correlations were found between peripheral insulin concentrations and ovarian vein testosterone (r = 0.879, p less than 0.02), dihydrotestosterone (r = 0.866, p less than 0.03), and androstenedione (r = 0.992, p less than 0.01) levels. Insulin resistance persisted after removal of the ovaries even though androgen levels returned to normal. These results suggest that a significant degree of insulin resistance exists in women with hyperthecosis and that insulin stimulates ovarian stromal androgen synthesis and thus may play a role in the pathogenesis of ovarian hyperthecosis.

Diagnosis of herpes simplex virus in routine smears by an immunoperoxidase technique.

Routine Papanicolaou-stained cervicovaginal smears from 59 patients were cytologically screened for herpetic infection. Forty-one of the smears were positive for herpes, 2 were suspicious and 16 were negative. All 59 slides were then destained and restained by a commercial immunoperoxidase kit for the detection of herpes simplex virus (HSV). The immunoperoxidase stain was positive in 23 of the 41 cytologically positive slides. One of the 2 cytologically suspicious slides was also immunoperoxidase positive, as was 1 of the 16 cytologically negative slides. This study indicates that immunoperoxidase staining is very specific but not quite as sensitive as routine Papanicolaou-stained smears in the detection of HSV. The immunoperoxidase method is thus recommended for the confirmation of HSV cases rather than for the routine diagnosis of HSV infection.

Adenoid cystic and adenoid basal carcinomas of the cervix.

Adenoid basal and adenoid cystic carcinomas of the cervix are uncommon and differ from each other in their histology, treatment, and prognosis. Whereas adenoid basal carcinoma is a slow-growing, locally invasive lesion amenable to simply hysterectomy, adenoid cystic carcinoma is an aggressive tumor associated with regional lymph node involvement and late pulmonary metastases. This study, based on the evaluation of nine cases of adenoid cystic and five cases of adenoid basal carcinoma of the cervix, reviews the literature and formulates a program for the management of these rare lesions.

XY gonadal dysgenesis with gonadoblastoma and dysgerminoma.

We present the clinical and endocrine findings in the case of a phenotypic woman with XY karyotype and gonadal dysgenesis. An examination of the gonads revealed bilateral gonadoblastomas, the right one almost completely replaced by a massive dysgerminoma.

Leiomyosarcoma of the uterus.

A series of 43 cases of uterine leiomyosarcoma was reviewed. Forty-one of the 43 patients were followed up 2 or more years. The overall 5-year survival was 73%. Favorable prognostic features included the premenopausal status of the patient, the confinement of the tumor within a myoma, the low mitotic count (less than four mitotic figures in any one high-power field or less than four mitotic figures per 10 high-power fields), the absence of necrosis, and the presence of hyalinization in the adjacent tissue suggesting confinement. Special cases such as those in which only myomectomy was performed and those receiving adjunctive chemotherapy are discussed. The differential in survival between patients with primary myosarcoma and those with lesions arising in a leiomyoma is stressed.

Verrucous carcinoma of the vulva: study of 24 cases.

The clinicopathologic features of 24 cases of vulvar verrucous carcinoma were reviewed. Based on the absence of lymph node metastasis in 27 patients who underwent radical vulvectomy with lymph node dissection (10 in previous series, 17 in present series), a conservative approach consisting of wide local excision is suggested. Radiotherapy did not aid in prolonging survival.