Charles J. Dunton

Poor prognosis associated with thrombocytosis in patients with cervical cancer

The medical records of 113 patients treated with radiation therapy for invasive cervical cancer between 1975 and 1985 were retrospectively reviewed. Patients with thrombocytosis (platelet count > 400,000/μ1) were compared with those with normal platelet counts. Thrombo‐cytosis was present at the initiation of therapy in 20 (17.7%) of the 113 patients. The 5‐year cumulative survival rate for the 93 patients with normal platelet counts was 65%, whereas it was 25% for the 20 with thrombocytosis (P < 0.0001, log‐rank test). Using Coxs proportional hazards model, thrombocytosis continued to correlate strongly with poor survival even when adjusted for histo‐logic type, patient age, and disease stage (P < 0.001). Thrombocytosis is an independent indicator of poor prognosis in patients with cervical cancer.

Use of computerized morphometric analyses of endometrial hyperplasias in the prediction of coexistent cancer

Abstract OBJECTIVE: Our purpose was to determine whether computerized morphometric analysis is predictive of coexistent cancer in uteri that show endometrial hyperplasia in curettings or biopsy specimens. STUDY DESIGN: Forty-five patients with endometrial hyperplasia and 10 patients with well-differentiated cancers diagnosed from curettings or biopsy specimens and treated by hysterectomy at Thomas Jefferson University Hospital between 1989 and 1993 were identified from the pathology department archives. Curettings were analyzed by computerized morphometric analysis at the Free University Hospital in Amsterdam. Pathologists performing the morphometric analyses were blinded to the pathologic diagnoses obtained by examining the hysterectomy specimens. The histopathologic classification of the hysterectomy specimens were used as the end point. RESULTS: Twelve of 45 patients with endometrial hyperplasia (26.7%) by preoperative histopathologic classification showed coexistent carcinoma at hysterectomy. All instances of carcinoma occurred in patients with atypical hyperplasia. Sensitivity of morphometric analysis to predict carcinoma was 100%, with a specificity of 88.5%. The positive predictive value was 83.3%, and the negative predictive value was 100%. A blinded reanalysis of the quantitative analysis in 16 patients showed good reproducibility of this technique ( r = 0.93). CONCLUSIONS: Morphometric analysis is useful for predicting which patients with endometrial hyperplasia have coexistent carcinomas. Computerized morphometric analysis may be useful in therapeutic decision making for complex atypical hyperplasia. (AM J OBSTET GYNECOL 1996;174:1518-21.)

Endometrial hyperplasia and the risk of carcinoma

Recent reports suggest that atypical endometrial hyperplasia diagnosed by biopsy or curettage is accompanied by a higher than expected risk of coexistent invasive cancer. In order to test this hypothesis we reviewed the pathology and clinical history of all patients at our institution who underwent hysterectomy for endometrial hyperplasia with or without cytologic atypia. We found 24 patients of 45 with a preoperative diagnosis of hyperplasia with cytologic atypia, and 21 with simple or complex hyperplasia without atypia. No cancers were found at surgery in the latter group nor were any significant historical differences found between the two groups. Of the patients with atypia, 12/24 (50%) had an endometrial carcinoma and nine patients (37.5%) were stage IB or greater. This is a significantly greater risk than previously reported in the literature. Endometrial hyperplasia with cytologic atypia may carry a higher risk of coexistent invasive endometrial carcinoma than previously believed. Methods to identify those patients at highest risk should be determined.

Uterine Papillary Serous Carcinoma: A Review

Uterine papillary serous carcinoma, a histologic subtype of endometrial cancer, is characterized by a propensity for deep myometrial invasion, upper abdominal spread, and poor prognosis. We reviewed its histologic and clinical characteristics and compared them to those of endometrial adenocarcinoma with papillary features.

Endometrial cancer in polyps associated with tamoxifen use

We report 5 cases of carcinoma arising within tamoxifen-associated endometrial polyps. In 4 of 5 cases there were no other changes within the endometrium. Given these findings, the sonohysterographic differentiation between a polypoid structure and thickened endometrium does not eliminate the need for histologic sampling of the uterine cavity.

Quantitative Image Analysis of Mib-1 Reactivity in Inflammatory, Hyperplastic, and Neoplastic Endocervical Lesions

SummaryThe diagnosis of endocervical neoplasia can be difficult as it is sometimes mimicked by proliferative or reactive glands. MIB-1 is a proliferation marker that can aid in the diagnosis of squamous intraepithelial lesions (SIL) of the cervix and vulva, but its potential value in the diagnosis of endocervical lesions has not been fully explored. Ten formalin-fixed, paraffin-embedded cases of each of the following were obtained: morphologically normal endocervical glands from patients with cervical SIL, endocervicitis. microglandular hyperplasia (MGH), and endocervical adenocarcinomas (eight in situ, two invasive). Microwave unmasking of antigens was performed prior to immunohistochemical staining for MIB-1 using the avidin/biotin peroxidase method. Labeling indexes were calculated for 34 specimens (10 adenocarcinoma, 8 each of the other diagnoses) using image analysis (Samba 4000). There was diffuse MIB-1 reactivity in adenocarcinoma (labeling index 57–96%, mean 80%), minimal focal reactivity in normal glands underlying SIL (labeling index 0.8–4.3%. mean 2.4%). moderate spotty reactivity in MGH (labeling index 2.9–18.4%, mean 8.5%). and minimal to focally diffuse reactivity in endocervicitis (labeling index 1.0–13.3%. mean 5.7%). These data indicate that the percentage and distribution of MIB-1-reactive endocervical cells can be of diagnostic utility in distinguishing neoplastic glands from those of endocervicitis and MGH.

Cytogenetic study of botryoid rhabdomyosarcoma of the uterine cervix

We report a case of sarcoma botryoides of the uterine cervix occurring in a 19-year-old woman. By light microscopy the tumor showed round and spindle cells with hyperchromatic nuclei and, focally, a cambium layer subjacent to the surface epithelium and surrounding endocervical glands. Strap-shaped cells with and without cross-striations and small foci of immature cartilage were also present. Immunohistochemical studies showed positive staining within the tumor cells for myoglobin, desmin, vimentin, muscle-specific actin and CD56. By electron microscopy, tumor cells showed cytoplasmic filaments in an alternating pattern of thick and thin filaments. Chromosomal analysis demonstrated deletion of the short arm of chromosome 1, and trisomies 13 and 18. To our knowledge, this is the first reported case of sarcoma botryoides of the endocervix with chromosomal analysis.

Stereotactic irradiation: Potential new treatment method for brain metastases resulting from ovarian cancer

Stereotactic irradiation (radiosurgery) is a method of precisely focusing well-defined beams of radiation at small intracranial targets. The technique has been applied to the treatment of brain lesions that are benign (e.g., arteriovenous malformations, meningiomas, pituitary adenomas) and malignant (e.g., gliomas, metastases). This paper introduces preliminary data suggesting the possible value of radiosurgery in the management of ovarian cancer metastatic to the brain. Among 32 women with ovarian cancer metastatic to the brain treated with whole brain irradiation, nine (29%) experienced a complete radiographic response, compared with two of the five patients (40%) treated with radiosurgery. The 2-year survival rate was 60% among those treated with radiosurgery and 15% among those who received whole brain irradiation without radiosurgical boost. Stereotactic irradiation may be of clinical benefit to select patients with brain metastases resulting from ovarian cancer. A prospective randomized trial has been implemented by the Radiation Therapy Oncology Group (RTOG 95-08) to determine whether such observations are reproducible on a national scale.

Concomitant Irradiation and Dose-escalating Carboplatin for Locally Advanced Carcinoma of the Uterine Cervix: An Updated Report

The combination of radiotherapy and carboplatin is associated with high response rates among women who have cervical cancer. To improve control rates for patients who have locally advanced carcinoma of the uterine cervix, oncologists have explored combinations of radiotherapy and chemotherapy. Carboplatin is an analogue of cisplatin, with similar efficacy against cervix cancer and a toxicity profile that is theoretically appealing for this group of patients because it is not nephrotoxic. Fifteen women with International Federation of Gynecology and Obstetrics (FIGO) stages IB2 through IIIB or recurrent carcinoma of the cervix were treated with megavoltage irradiation and weekly intravenous carboplatin (7 women, 60 mg/m2; 8 women, 90 mg/m2). Response was documented among all patients treated at 60 mg/m2 (three complete responses, four partial responses) and in 6 women treated with 90 mg/m2 (four complete responses, two partial responses). The two nonresponders in the series presented with recurrent glassy cell carcinoma of the cervix. All patients completed the planned course of therapy without the need for treatment interruption. At 60 mg/m2, one dose of carboplatin was withheld because of grade 2 thrombocytopenia. At 90 mg/m2, one case of grade 2 leukopenia was documented. The leukocyte counts remained within normal limits for all 3 patients who were irradiated through extended portals that encompassed the paraaortic nodes (2 women, 60 mg/m2; 1 woman, 90 mg/m2). To date, 2 of 7 patients treated at the lower dose level have died of disease (one local progression and distant failure at 11 months, one distant failure alone at 6 months). The remaining patients treated at 60 mg/m2 are alive at a median of 24 months (range, 21-37 months). Among those treated at the higher dose level, 1 patient is alive with local and distant failure at 14 months, and 1 woman succumbed to local and distant disease at 4 months. The remainder are alive at a median follow-up of 6 months (range, 2-10 months). The regimen was unsuccessful in salvaging women with recurrent glassy cell carcinoma. We conclude that the combination of radiotherapy and carboplatin can be safely delivered at both of the chemotherapy schedules studied. The regimen should not be offered to women who have recurrent glassy cell tumors. To prove the efficacy of this approach, phase III testing should be considered that compares the combination of agents to irradiation alone.

Randomized pilot study comparing rates of endocervical cell recovery between conventional pap smears and liquid-based cytology in a pregnant population

Objective. To determine whether liquid-based cytology improves Pap smear adequacy, as defined by the presence of endocervical cells, compared with conventional cytology during pregnancy. Materials and Methods. A randomized pilot study was conducted between May 2001 and May 2002. Patients presenting for their first prenatal visit were randomized to receive either a conventional Pap smear or a liquid-based smear (ThinPrep). Rates of endocervical cell recovery and cytologic results were compared between the groups. Results. Eighty-one patients were enrolled in the study. There were no differences between the groups in age (p = .40), parity (p = .62), gestational age (p = .14), history of abnormal pap (p = .08), previous treatment of neoplasia (p = 1.00), and tobacco use (p = .67). Adequacy of the standard pap versus the liquid-based smear was not different between the two groups (90.5% vs 82.1%, respectively;p = .34). Conclusions. The results of this pilot study show that rates of endocervical cell recovery in a pregnant population are not statistically different using conventional or liquid-based cytology. Further research is indicated to assess the utility of the more expensive ThinPrep technology in this population.