John L. Currie

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.

Epidemiology of adenocarcinoma of the cervix.

There is general evidence that the incidence of adenocarcinoma of the cervix has been rising, particularly among younger women. The determinants of these trends, however, remain largely unknown. We have reviewed the epidemiology of adenocarcinoma of the cervix using descriptive data from cancer registration and clinical series and two main sources of analytical data: clinical studies comparing cervical adenocarcinoma (AC) and squamous carcinoma (SC) and formal case-control and cohort epidemiological studies. In both the United States and northern Europe there is evidence of the rising frequency of AC in absolute and relative terms as compared to SC. These trends are generally restricted to younger women: under-age-35 AC incidence approximately doubled from the early 1970s to the early 1980s. Available data, although scanty, consistently show that the frequency of cervical adenocarcinoma rises with the number of partners and with decreasing age at first intercourse, suggesting a potential role for sexually transmitted (viral) factors. In clinical series, nulliparity was reported more frequently in AC than in SC cases but an inconsistent association was found in three formal epidemiological studies. Similarities with the epidemiology of endometrial cancer are also suggested from the association with overweight, while a possible relation with hypertension and diabetes is based on clinical series only and hence more difficult to interpret. Thus, adenocarcinoma of the cervix appears to share epidemiological characteristics with both adenosquamous cancer of the cervix and adenocarcinoma of the endometrium, although uncertainties in classification and registration leave several questions unanswered.

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.

Uterine stromal sarcoma cell line: A cytogenetic and electron microscopic study

Uterine sarcomas constitute approximately 3% of all malignant uterine corpus tumors. Of these, the tumors that originate solely in the stromal elements of the uterine wall are relatively infrequent and have not been well characterized cytogenetically. We report data from a low-grade endometrial stromal sarcoma both at the time of resection and after months in long-term tissue culture. Cytogenetic analysis showed a clonal population of cells with an abnormal karyotype of 46,XX,del(5)(q31.1),der(7)t(6;7)(p21;p22) which remained unchanged in long-term culture. Electron microscopy suggests that these cells are similar to other neoplastic cells in having immature-appearing nuclei surrounded by a relatively mature cytoplasm (with well-developed organelles). Determination of the specificity of these observations must await study of additional stromal sarcomas.

Cytogenetic and FISH analysis of endometrial carcinoma

Endometrial cancer is a common gynecologic tumor, yet reports of cytogenetic studies are few. We studied chromosomes from seven primary specimens of endometrial cancer. Six had abnormal chromosomes; five had a diploid-hyperdiploid modal number and one was triploid. One specimen had a normal karyotype. Chromosome 1 was frequently involved in abnormalities (five tumors) with i(1q) in two tumors, and one tumor each had der(7)t(1;7)(q12;p11) and +add (1)(p13). One additional tumor had trisomy 1 in the single cell which could be fully analyzed. Trisomy 7 was noted in two tumors, and trisomy 10 in one. Because trisomies of these chromosomes have been reported in other cases of endometrial cancer, we used fluorescent in situ hybridization (FISH) with centromere probes to determine the prevalence of trisomies 7 and 10 in these specimens. No additional tumors were found to have trisomies 7 or 10 by FISH. Our data, in combination with published literature, suggest that additional copies of 1q or portions of 1q constitute the primary change in this tumor. Extra copies of genes in this region may play an important role in tumorigenesis in endometrial carcinoma.

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.

HPV-16 viral transcripts in vulvar neoplasia: Preliminary studies

Specific human papillomavirus (HPV) types are strongly associated with intraepithelial neoplasia and invasive cancer of the cervix. In contrast, the role of HPVs in the pathogenesis of invasive carcinoma of the vulva is poorly understood. We have employed in situ hybridization for the detection of subgenomic transcripts in four vulvar specimens to elucidate the role of HPV type 16 in the development and progression of vulvar cancer. These analyses revealed that the transcripts of the E6-E7 region were more abundant than those of the L1-L2 region in vulvar neoplastic tissues. The transcripts from early and late region of HPV-16 continued to increase with the differentiation of the epithelial cells in both the warty and the basaloid types of vulvar precancerous lesions. This pattern persisted in invasive warty carcinoma but not in basaloid invasive carcinoma; the transcripts in basaloid carcinoma were distributed in an even and discrete pattern. In contrast to earlier studies, L1-L2-region transcripts, as well as viral capsid protein, were detected in focal areas of well-differentiated cells of invasive warty carcinoma. These findings suggest that expression of HPV-16 is regulated by the degree of cellular differentiation.

Chromosome abnormalities in primary endometrioid ovarian carcinoma

Specific and recurrent chromosome abnormalities may occur in regions of the genome that are involved in the conversion of normal cells to those with tumorigenic potential. Ovarian cancer is the primary cause of death among patients with gynecologic malignancies. We performed cytogenetic analysis in a subgroup of epithelial ovarian tumors, the endometrioid tumors, which are histologically indistinguishable from endometrial carcinoma of the uterus. We studied 10 endometrioid tumors to determine the degree of cytogenetic similarity between these two carcinomas. Six of 10 endometrioid tumors showed a near-triploid modal number, and one had a tetraploid modal number. Eight of the 10 contained structural chromosome abnormalities, of which the most frequent were 1p-- (5 tumors), 6q-- (4 tumors), 19q+ (4 tumors), and chromosome 3 rearrangements (4 tumors). These cytogenetic results resemble those reported for papillary ovarian tumors and differ from those of endometrial carcinoma of the uterus. We conclude that despite the histologic similarities between the endometrioid and endometrial carcinomas, the genetic abnormalities in the genesis of these tumors differ significantly.

Squamous cell carcinoma of the vulva in pregnancy.

Two women presenting with invasive squamous cell cancer of the vulva during pregnancy are reported. The first patient was successfully treated by radical vulvectomy 2 weeks after cesarean section delivery; the second patient died of disseminated cancer despite radical vulvectomy and postoperative radiation therapy. In the second case the diagnosis was not established until 3 months after delivery. Only 12 cases of invasive squamous cell vulvar cancer during pregnancy have been previously reported. Liberal use of punch biopsy for any suspicious vulvar lesions is mandatory to enhance the potential for early diagnosis and successful treatment.