Deborah E. Powell

Transition from benign to malignant epithelium in mucinous and serous ovarian cystadenocarcinoma

The slides of all patients with ovarian cystadenocarcinoma treated at the University of Kentucky Medical Center from 1966-1990 were reviewed. Fifty-four serous tumors and 42 mucinous neoplasms were identified for further study. Benign epithelium adjacent to an area of borderline or malignant epithelium was observed in 74 tumors (79%) and a site of epithelial transition was noted in 38 cases (40%). The presence of associated benign epithelium was more common in borderline or well-differentiated lesions and in patients with early-stage disease. These findings are consistent with epidemiologic and molecular genetic data and suggest that certain benign serous or mucinous ovarian tumors have the potential for malignant transformation. Removal of these tumors, particularly in postmenopausal women, should result in a subsequent reduction in the frequency of ovarian cancer.

Transvaginal sonography as a screening method for ovarian cancer a report of the first 1000 cases screened

From November 1987 to April 1989, 1000 women 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center (Lexington, KY). Patients included in this investigation were all asymptomatic and had no known pelvic abnormalities. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in postmenopausal women. In patients with normal scans, mean ovarian volumes decreased from 6.8 cm3 to 3.0 cm3 with menopause. Thirtyone patients (3.1%) had abnormal vaginal sonograms and 24 underwent exploratory laparotomy. All patients undergoing surgery had ovarian or fallopian tube tumors with dimensions identical to those predicted by ultrasound. Histologic diagnoses of these tumors included the following: adenocarcinoma, one; serous cystadenoma, eight; endometrioma, six; and cystic teratomas, two. Vaginal sonography was performed easily and without complications, and was well accepted by patients. All patients with normal sonograms have been rescreened annually and none have subsequently developed ovarian cancer. Further clinical trials to determine the efficacy of vaginal sonography as a screening method for ovarian cancer are indicated.

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA‐125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well‐accepted by patients. Currently, there are more than 3000 patient years of follow‐up in the screened population, and there have been no deaths due to ovarian cancer. A multi‐institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer.

Surgical specimens from 111 patients with Stage I endometrial cancer were reviewed for the presence of lymph‐vascular space invasion by tumor cells. Lymph‐vascular space invasion was noted in 16 cases, and occurred most frequently in poorly differentiated tumors with deep myometrial penetration. Tumor recurrence developed in 44% of patients whose tumors demonstrated lymph‐vascular space invasion as opposed to only 2% of patients without this finding (p < 0.001). Of seven patients with lymph‐vascular space invasion who experienced tumor recurrence, five developed extra‐pelvic metastases. Discriminant function analysis of these data revealed a statistically significant correlation between lymph‐vascular space invasion and tumor recurrence, independent of histologic differentiation of myometrial penetration. These findings suggest that lymph‐vascular space invasion by tumor cells is an important prognostic variable in Stage I endometrial cancer which should be considered in treatment planning.

Small cell carcinoma of the uterine cervix

From 1962 to 1985, 2201 patients with invasive cervical cancer were staged, evaluated, and treated at the University of Kentucky Medical Center. After a thorough evaluation, 25 cases (1.1%) fulfilled the histologic criteria for small cell cancer defined by Reagan and coworkers. These patients were computermatched for age, disease stage, and lesion size to 25 patients with large cell nonkeratinizing cancer and 25 patients with keratinizing squamous cell cancer. Morphometric analyses of nuclear size and maximum nuclear diameter were performed on all cases without knowledge of cell type. Small cell cancers were characterized by a nuclear area of 160 μ2 or less and a maximum nuclear diameter of 16.2 μ, which was significantly lower than that for large cell tumors. Thirty‐three percent of the small cell carcinomas stained positively for the neuroendocrine markers (neuron‐specific enolase [NSE] and chromogranin [CGR]), whereas the remainder contained only epithelial markers such as cytokeratin (CYK) and epithelial membrane antigen (EMA). Small cell cancers were associated with a high frequency of lymph‐vascular space invasion and a diminished lymphoplasmacytic response. Patients with small cell cancer had a significantly higher recurrence rate, particularly to extrapelvic sites, than the matched patients with large cell cancers, and their survival was lower. Clinical trials to determine the efficacy of adjuvant chemotherapy in the treatment of small cell cervical cancer are needed.

Endometrioid carcinoma of the ovary and endometriosis: The association in postmenopausal women☆

Histologic material from 42 patients with endometrioid carcinomas of the ovary was reviewed. Ovarian endometriosis was present in 11 cases (26%) and 8 of these patients were postmenopausal. The exact site of transition from benign to malignant epithelium was observed in 4 cases. The clinical characteristics of patients with associated endometriosis were not significantly different from those without this finding except that endometriosis was present only in patients with Grade 1 or Grade 2 carcinomas. These data suggest that ovarian endometriosis in the postmenopausal patient has the potential to undergo malignant transformation and, when detected, should be removed surgically.

Combined radiation therapy and extrafascial hysterectomy in the treatment of stage IB barrel‐shaped cervical cancer

Seventy‐five patients with bulky barrel‐shaped Stage IB cervical cancers, treated at the University of Kentucky from 1965 to 1981, were the subjects of this investigation. Thirty‐two of these patients were treated with radiation therapy alone and 43 were treated with radiation followed by extrafascial hysterectomy. There were no significant differences in age, gravidity, or tumor cell type between the two treatment groups. Patients were seen at regular intervals from 2 to 11 years after treatment and none were lost to follow‐up. Recurrent cancer was noted in 47% of patients treated by radiation alone as compared to 16% of those treated with combined therapy (P < 0.01). The incidence of pelvic recurrence was reduced from 19% to 2% and extrapelvic recurrence from 16% to 7% in patients treated by combination therapy. No rectal or urinary tract fistulae were noted after extrafascial hysterectomy. The findings of this study suggest that the use of extrafascial hysterectomy following radiation therapy in patients with bulky Stage IB cervical cancer causes a significant reduction in tumor recurrence without producing an increase in treatment‐related complications.

Clonal chromosome abnormalities in 54 cases of ovarian carcinoma

As a prelude to assessing the relationship of chromosome alterations to clinical outcome in ovarian carcinoma, we report on the cytogenetic analysis on short-term cultures from 54 patients. All patients had histopathologically confirmed malignancy, with the majority of cases demonstrating serous ovarian adenocarcinomas. Structural alterations were evident in 52 cases, whereas numeric changes were identified in 13 cases. The most notable numeric abnormalities were loss of the X-chromosome (9/13 total cases) and +7 (3/9 diploid cases). Structural alterations most frequently involved chromosomes 1, 3, 6, 7, 11, and 12. Chromosomal breakpoints were shown to cluster in several chromosomal banding regions, including 1p36, 1p11-q21, 3p23-p10, 7p (especially 7p22), 11p, 11q, 12p13-q12, and 12q24. The frequency of structural alterations involving the following chromosome arms was found to be significantly increased: 1p (p < 0.01), 7p (p < 0.01), 11p (p < 0.01), 11q (p < 0.05), and 12p (p < 0.05). An analysis of the net gain or loss of chromosome segments was also performed, with the most consistent tendency observed being over-representation of 1q and chromosome 7, deletion of 1p, and loss of the X chromosome.

Genetic alterations on chromosome 17 distinguish different types of epithelial ovarian tumors

Epithelial tumors of the ovary are the most common ovarian tumors of adult women. They exist in several different histological patterns and exhibit varying degrees of aggressiveness. Molecular genetic studies in epithelial ovarian cancer have shown that loss of heterozygosity (LOH) for regions of chromosome 17 is a common event, probably reflecting the inactivation of one or more tumor suppressor genes present on this chromosome. We examined 87 sporadic epithelial ovarian tumors of different grade and histological type at 16 loci on this chromosome and found that 35% of them showed LOH for chromosome 17. Of these, 84% showed LOH for all informative markers, suggesting that loss of the entire chromosome 17 homologue may have occurred. Interestingly, chromosome 17 loss was observed frequently in serous tumors (49%), was less common in endometrioid tumors (15%), and was rare in mucinous tumors (4%) (P = .01 and P = .0002, respectively). Our findings support the concept that the histological subtypes of epithelial ovarian cancer may be the result of different molecular genetic events.

Prognostic parameters in invasive vulvar cancer.

Prognostic parameters were studied in 66 patients with invasive squamous cell vulvar cancer treated with radical vulvectomy and bilateral inguinal and femoral lymph node dissection. Patients with metastases in regional lymph nodes had a 46% survival for 3 or more years compared to 76.3% in patients without evidence of nodal spread. The presence of lymph nodal metastases correlated directly with stage, lesion size, depth of invasion, and the presence of lymph-vascular space involvement with tumor. However, even the best prognostic groups had a 30% incidence of positive nodes. No patient with less than 5 mm of stromal invasion without vascular involvement had positive nodes. These preliminary data suggest that careful observation of vascular space invasion by tumor cells together with measurement of the depth of stromal invasion may help define a group of patients with vulvar cancer that can be treated conservatively. Further studies are needed to confirm these findings in larger numbers of patients.