Chromosome analysis and comparison of the benign cystic and malignant squamous component of an ovarian teratoma.

Teratoma, the most common ovarian germ-cell tumor, presumably arises from a single germ cell and is composed of tissues representing all germ layers (ectoderm, mesoderm, and endoderm). Benign cystic teratomas (dermoid cyst) represent over 95% of ovarian teratomas and are comprised of entirely mature adult tissues. When malignant, almost all mature teratomas contain squamous carcinoma. We report for the first time the karyotypic comparison of an ovarian teratoma in a 36-year-old female with tissue separately taken from the benign cystic and malignant squamous components. The malignant squamous component revealed two distinct karyotypic populations: one diploid and the other polyploid. Both, however, demonstrated two common markers. The polyploid population also demonstrated numerous additional abnormalities with multiple copies of chromosome 20. Though many of the chromosomal aberrations were unique to the benign component, several karyotypes showed the same markers noted in the malignant squamous component. The significance of this finding is that it may serve to identify those histologically benign teratomas destined to undergo malignant transformation.

Karyotypic analysis of 32 malignant epithelial ovarian tumors.

The identification of recurrent specific cytogenetic findings in various malignancies has provided an improved means to diagnose and treat patients. To date, no characteristic markers have been found for epithelial ovarian cancer. This is due, in part, to several contributory factors, including the inability to identify optimal growth conditions for culture and the fact that most analyses of advanced-stage tumors are obtained from malignant effusions rather than from solid tissue. In addition, many reports include previously treated patients. In this study, 32 untreated solid epithelial ovarian tumors, including 8 tumors of low malignant potential (LMP), were obtained from primary and metastatic sites at initial surgical staging. Using a 2-culture plastic technique for tissue growth, we achieved a 96% short-term culture success rate. Only 4 normal 46,XX karyotypes were identified. Diploid or near-diploid genomes were associated with few cytogenetic alterations. Complex karyotypic morphologies were consistently associated with advanced or poorly differentiated tumors. Nonrandom cytogenetic aberrations most commonly involved chromosomes 1 and 6. A novel translocation, t(1;6)(p10;p10), was identified in both a metastatic LMP tumor and a poorly differentiated invasive tumor. This cytogenetic rearrangement can potentially be regarded as a clinically relevant early marker for tumorogenesis. Finally, karyotypes from both primary and metastatic sites were subject to a comparative analysis in 11 patients. In 4 cases, greater chromosomal complexity was associated with the primary site.

The accuracy of a frozen section diagnosis of borderline ovarian malignancy.

While the accuracy of frozen section in the diagnosis of invasive ovarian neoplasms has been previously addressed, the frozen section diagnosis of borderline ovarian tumors has been less well characterized. The distinction between benign and borderline lesions is critical to the proper operative management of these patients. The records of 48 patients that had a frozen section diagnosis of borderline ovarian malignancy during surgical exploration between 1986 and 1993 were reviewed. Thirty-one patients were Stage I, 2 patients were Stage II, 10 patients were Stage III, and 5 patients were unstaged. Clarifying phrases were used frequently in the frozen section report, and these terms were categorized as "rule out" borderline tumor, borderline tumor, and "at least" borderline tumor. Of 33 cases with a frozen section report of borderline or at least borderline malignancy, no case were subsequently found to be benign. Errors in the intraoperative management could have occurred in 3 of 48 cases (6.25%), when benign neoplasms were thought to be of borderline malignancy on frozen section. However, in each of these cases, the clarifying term rule out was used, indicating the equivocal nature of the frozen section findings. Thirteen of the 48 patients (27.1%) were found to have a focus of invasive cancer within a borderline tumor on final pathologic review; the primary tumors in these 13 cases ranged in maximal diameter from 5 to 26 cm and were of varying histologic types. The level of experience of the pathologist responsible for the frozen section did not influence the accuracy of frozen section determination noted in this study. A frozen section evaluation identifying a borderline ovarian malignancy is accurate in excluding the presence of benign pathology. It is crucial to understand the meaning of specific clarifying terms used in frozen section diagnoses.

Foreign body reaction (gossypiboma) masking as recurrent ovarian cancer.

Surgical is an absorbable sterile mesh composed of oxidized cellulose used to control capillary or venous bleeding. Although the manufacturer recommends its removal after hemostasis is achieved, in clinical practice it is usually left in situ to reabsorb spontaneously, usually with no untoward effect. We report the first case of foreign body reaction (gossypiboma) masking as recurrent malignancy discovered 13 months post-cytoreductive surgery for ovarian carcinoma.

A single clonal abnormality of chromosome 1 found in an adenocarcinoma of the uterus.

Adenocarcinomas usually have a complex genome comprised of multiple chromosomal alterations. These neoplasms rarely express a single genomic change. We report the first case of an endometrial adenocarcinoma demonstrating a single genomic variation in chromosome 1 associated with a 2 1/2-year survival. The finding of this anomaly may be important in determining the etiology and clinical behavior of uterine malignancies.

Treatment of primary ovarian angiosarcoma with ifosfamide and doxorubicin.

Angiosarcoma originating in the female genital tract is exceedingly rare with only 15 cases of angiosarcoma of the ovary described to date. All have been highly aggressive tumors, and no response to treatment has ever been reported. A case of primary ovarian angiosarcoma is described in which a short remission was achieved with intensive chemotherapy using ifosfamide and doxorubicin.

Endometrial adenocarcinoma.

Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for some 36,000 cases of invasive cancer each year. Hyperplastic lesions of the endometrium follow a continuum, with the risk of progression to carcinoma being related to the severity of the disorder. Risk factors associated with the development of adenocarcinoma include hyperplasia, obesity, menstrual abnormalities, diabetes, hypertension, prior pelvic irradiation, sequential oral contraceptive use, diet, and exogenous estrogen use. There is also some evidence of genetic predisposition, and some data indicating the possibility of specific genetic abnormalities and activation of oncogenes as factors determining the etiology of the disease. At this time there is no accepted screening test for endometrial carcinoma, though the role of immunochemistry techniques for screening and follow-up has just begun to be realized. Dilatation and curettage along with hysteroscopy remain the major means of diagnosis. A variety of prognostic variables including tumor cell type, histologic grade, depth of myometrial invasion, status of peritoneal cytology, presence of disease in preformed vascular spaces, presence of adnexal metastases, and presence of cervical involvement have been defined. Although the treatment plan for each patient must be individualized, the mainstay of treatment remains total abdominal hysterectomy with bilateral salpingo-oophorectomy. Metastatic and recurrent disease is usually treated with hormonal therapy and systemic chemotherapy. Radiation therapy like surgery in recurrent disease is only applicable for the treatment of local recurrences.

A formula for predicting the risk of a positive second-look laparotomy in epithelial ovarian cancer: implications for a randomized trial.

OBJECTIVE: To develop a formula to predict the risk of a positive second-look laparotomy. METHODS: A retrospective review was performed on 89 patients who underwent second-look surgery following a complete clinical remission after cis-platin- or carboplatin-based chemotherapy. Logistic regression was used to develop a formula to predict the probability of a positive second look based on age, stage, grade of tumor, residual disease after initial surgery, and histologic type. RESULTS: We identified three groups based on estimated probabilities: low probability (0.25 or less), intermediate probability (0.26-0.74), and high probability (0.75 or more). The low-probability group had an 8% chance of a positive second look, the high-probability group had an 82% chance of a positive second look, and the intermediate-probability group had the correct outcome predicted only 61% of the time. Survival curves paralleled these results and were significantly different for each group. CONCLUSIONS: Using known prognostic factors, a formula can aid in implementation of a randomized clinical trial to test the efficacy of second-look laparotomy. This formula could exclude patients not suitable for randomization and give the investigator a better idea of the expected survival of various subgroups.

Postmenopausal bleeding from unusual endometrial polyps in women on chronic tamoxifen therapy.

There are recent reports of postmenopausal bleeding from endometrial polyps in women receiving tamoxifen therapy for breast cancer. We describe four additional patients who presented with vaginal bleeding, and emphasize the pathology. These polyps demonstrated cystically dilated glands in all cases and stromal decidualization in two; in one instance, metastatic breast carcinoma was present in the polyp. The mechanisms by which tamoxifen may affect the development of these polyps are discussed.

The ability to evaluate prognostic variables on frozen section in hysterectomies performed for endometrial carcinoma.

The purpose of this study was to evaluate the ability of the pathologist to assess intraoperatively the hysterectomy specimen in patients with endometrial carcinoma. The past few years have seen the definition of prognostic variables that predict the ultimate outcome of patients with endometrial carcinoma. As a result, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system to take into account such prognostic factors as grade, depth of myometrial penetration by tumor, cervical involvement, adnexal metastasis, peritoneal cytology, and involvement of pelvic and para-aortic lymph nodes. The need for node evaluation has led to considerable controversy as to whether all hysterectomies for Stage I disease should be performed by gynecologic oncologists. To help predict which patients will need node sampling, several published studies have shown that determination of depth of myometrial penetration can be accomplished by gross evaluation of the uterine specimen, and even more accurately on frozen section. These studies recorded excellent results, but were limited to evaluation by pathologists with specific expertise in gynecologic pathology. The current study evaluated the ability to assess tumor grade, depth of invasion, and presence of cervical invasion by intra-operative evaluation of sixty hysterectomy specimens from patients with clinical Stage I disease. The gross and frozen section reports used for this study were produced by anatomic pathologists ranging in experience level from lecturer to professor, with varying levels of experience in gynecologic pathology. Our results indicate that the level of experience of the pathologist does not affect the ability to accurately assess the specimen for the parameters described. This, in turn, allows the surgeon to correctly determine the need for lymph node sampling in 94% of cases.

Endocervical carcinoma.

The past two decades have seen an increase in the incidence of endocervical carcinoma. Numerous studies have increased understanding of these tumors; hormonal therapy, human papilloma virus, and other cofactors have been implicated in the etiology of endocervical carcinoma. Early diagnosis is difficult: precursor lesions to adenocarcinoma in situ are still poorly defined and understood, and there may be a rapid transit time from in situ to invasive carcinoma. The definition of microinvasive adenocarcinoma is not uniformly agreed upon, and at this time the recommendation is not to use the term. Histologic typing and grading of adenocarcinoma may be useful in the prediction of prognosis for patients. Therapy is based upon stage of disease, the most beneficial results being obtained from either radical surgery or combination surgery and radiation therapy.

Residual trophoblastic tissue as a source of highly atypical cells in the postpartum cervicovaginal smear.

A cervicovaginal smear containing atypical cells, which were interpreted as dysplastic cells, was obtained from a women one-year postpartum. These cells were seen singly, in small groups and in clusters embedded in an amorphous pink matrix. They had amphophilic cytoplasm and increased nuclear/cytoplasmic ratios, as well as hyperchromatic nuclei with variably prominent nucleoli, features that are characteristic of trophoblastic cells. No evidence of dysplasia was seen on subsequent colposcopic examination or cervical biopsy. Endocervical curettage yielded fragments of exfoliated endometrium and residual trophoblastic tissue associated with a placental implantation site. Although involution of the placental site is generally complete by six to seven weeks postpartum, maternal-fetal tissue may in fact continue to be exfoliated for several months or longer after delivery. If seen on a cervicovaginal smear, these cells can be highly atypical and may be mistaken as dysplastic or malignant. The cytologic features that characterize trophoblasts and their persistence in postpartum cervicovaginal smears are discussed.

Database management for a gynecologic oncology service.

With the ready availability of powerful desktop computers, the ability to manage large clinical databases has become practical. A computer can enhance the capability of a gynecologic oncology service to catalog, recall, and analyze data about patients, tumors, and therapies. While commercially available database packages can be used for this purpose, we have developed a custom database for tracking the clinical activity of a busy gynecologic oncology service. The system catalogs data about patients, admissions, tumors, and therapeutic modalities and uses this information to generate several useful reports. The reports are used for daily patient care, fellow and resident case statistics, and clinical research. What is unique about the system is that it is optimized for ease of use. The development of this tumor registry, its user friendliness, and advantages over a manual recordkeeping system are described. Unlike other tumor registries, our system is utilized on a daily basis for patient care. Therefore, the data being entered have an immediate usefulness in addition to being simultaneously added to the tumor register for retrospective clinical research. One may hypothesize that it would be useful if all gynecologic oncology services used a common computerized tumor registry that could allow for the sharing of information on a national or global scale.

Is chromosome 10 a primary chromosomal abnormality in endometrial adenocarcinoma?

Seven cases of endometrial adenocarcinoma (EC) are reported. Two of these cases exhibited diploid chromosome ranges and showed simple rearrangements involving a chromosomal abnormality of chromosome 10. In four cases, the chromosome number ranged between 50 and 70; rearrangements were more complex, with many abnormalities such as homogeneously stained regions, minutes, dicentrics, and ring chromosomes. In one case, two subpopulations of cells were detected, one in a diploid chromosome range with chromosome 10 altered, and the second, very pleomorphic. These abnormalities are probably due to the evolution of a destabilized genome and represent a consequence of the advanced stage of the disease. The importance of simple abnormalities as clues to the primary chromosomal change, and the possibility that chromosome 10 represents the primary chromosomal alteration event in EC, are discussed.

Cytogenetics of an endometrial adenocarcinoma cell line and its implications.

Despite the fact that adenocarcinoma of the endometrium is currently the most common gynecologic malignancy in the United States, few chromosomal studies have been done to date characterizing this disease. HEC-1A, a cell line used by many laboratories as a reference cell line for endometrial carcinoma, has never been subjected to definitive karyotyping. For this reason, with the use of improved banding techniques, this has now been accomplished, and several consistent abnormalities have been identified. There was a marker chromosome formed from an insertion of 2q21, probably representing an insertion of the lacking chromosome 14. In addition, there was a translocation to the telomeric region of 1p; and trisomies of 3, 7, and 17. Many of these abnormalities are known to consistently be associated with other primary malignancies. In addition, the chromosomes in which trisomy is noted carry genes associated with epidermal growth factor and estrogen receptors, which also bear marked homology to known oncogenes. It would appear that further detailed studies of various grades and stages of endometrial carcinoma, as well as histologic types and "precursor lesions," may lead to an understanding of those chromosomal changes associated with disease initiation and progression.

Atypia in cervical cytology as a risk factor for intraepithelial neoplasia.

All Papanicolaou smears obtained during the years 1977 to 1982 were reported by a descriptive cytologic interpretation instead of a numerical report. All smears showing "atypia" were reviewed and found to fall into one of three categories: inflammatory atypia, squamous atypia, and endocervical atypia. Patients with the latter two categories and those with persistent inflammatory atypia after specific therapy underwent colposcopy and directed biopsies if indicated. Colposcopically directed biopsies revealed that 29% of patients with atypical Papanicolaou smears had underlying cervical intraepithelial neoplasia. There was no statistically significant difference in the incidence of underlying cervical intraepithelial neoplasia among patients in each of the three categories of atypia. Of those with intraepithelial neoplasia, 35% had lesions of greater severity than grade 1 cervical intraepithelial neoplasia. We conclude that all patients with squamous, endocervical, and persistent inflammatory atypia on Papanicolaou smear should undergo colposcopic evaluation to rule out intraepithelial neoplasia.

A case of endometrioid carcinoma of the ovary associated with pregnancy.

This is the second report of endometrioid carcinoma of the ovary associated with an intrauterine pregnancy. The previous report presented six cases, making this the seventh. Characteristics of the tumor are reviewed, as are the guidelines for the management of ovarian carcinoma complicating pregnancy.