Human immunodeficiency virus testing in patients with invasive cervical carcinoma: a prospective trial of the gynecologic oncology group.

To determine the frequency of positive human immunodeficiency virus (HIV) serostatus among North American women 50 years of age or younger with invasive cervical cancer and to define their tolerance to treatment. Consenting patients with newly diagnosed invasive cervical cancer, age 50 or younger were tested by enzyme-linked immunosorbent assay. The study design anticipated that approximately 3% of patients would be HIV positive. After the accrual of 913 eligible and evaluable patients, interim analysis revealed that only 9/913 ( approximately 1%) patients were HIV seropositive, indicating that it would not be feasible to achieve the study objective. The study was closed to further accrual. Between 1994 and 1997, the frequency of positive HIV serostatus among North American women with newly diagnosed cervical cancer was quite low. As a consequence, no evaluation of response to treatment or treatment tolerance can be made.

Promotion of neovascularization around hollow fiber bioartificial organs using biologically active substances.

A limiting factor of the long-term function of bioartificial organs is oxygen delivery to the encapsulated tissue. This study determined whether incorporation of endothelial cell growth factor (ECGF) into the alginate core of a hollow fiber bioartificial organ will induce neovascularization around the hollow fiber. Polyethersulfone (PES) and polyvinylidine difluoride (PVDF) hollow fibers were examined. Endothelial cell growth factor was incorporated into sodium alginate, extruded into the lumen of hollow fibers, and cured in calcium chloride. Samples without ECGF were fabricated and used as controls. Hollow fibers were implanted into 16 rats. For each rat, two implants were placed subcutaneously and two intraperitoneally, one with and one without ECGF at each site. Implants were placed on opposite sides of each animal. Implants were removed 65 days later and examined using immunohistochemical methods and light microscopy to determine the extent of neovascularization. A total of 64 implants were used. Most intraperitoneal implants were found free floating but were encased within a 100-microm thick avascular fibrotic reaction. This finding was independent from the presence of ECGF. Hollow fibers without ECGF, implanted subcutaneously, also had an avascular fibrotic reaction surrounding each implant. Subcutaneous implants with incorporation of ECGF within the alginate core had marked neovascularization within the fibrotic overgrowth that surrounded these implants. This was most prevalent in hollow fibers, with the thin separation layer facing the fiber lumen irrespective of limiting pore size. Potent angiogenic factors, such as ECGF, incorporated into diffusion chamber bioartificial organs can promote neovascularization around the subcutaneously implanted hollow fiber and may improve oxygen delivery to the tissue encapsulated within devices based on this technology.

Primary ovarian sarcoma: analysis of prognostic variables and the role of surgical cytoreduction.

BACKGROUND: Data regarding the value of cytoreduction and cell histology in ovarian sarcomas are limited. The goal of this study was to assess the value of surgical cytoreduction, preoperative CA 125 levels, stage, histology, and platinum-based chemotherapy in the primary treatment of ovarian sarcomas. METHODS: A retrospective analysis of 47 women with primary ovarian sarcomas was performed. RESULTS: Forty-one patients (87%) presented with advanced stage disease (International Federation of Gynecology and Obstetrics Stage III or IV). Optimal surgical cytoreduction (< 1 cm residual tumor burden) was achieved in 25 patients (53%). Forty patients (85%) had a malignant mixed müllerian tumor whereas 7 patients had a pure sarcoma. Eighteen women with mixed müllerian tumors had homologous tumors and 22 had heterologous elements. Patients treated with platinum-based chemotherapy were significantly more likely to have a response (P = 0.008) compared with those treated with other regimens. Treatment with platinum-based chemotherapy also showed a survival advantage (P = 0.03). Preoperative CA 125 levels were elevated (> 35 U/mL) in 93% of patients with ovarian sarcomas. A preoperative CA 125 level < 75 U/mL was significantly associated with better survival (P = 0.01). In univariate analysis, other significant predictors of improved survival were early stage (P = 0.04), homologous tumors (P < 0.05), and optimal surgical cytoreduction (P < 0.001). In multivariate analysis of various prognostic variables, optimal surgical cytoreduction (P < 0.001) was the most significant factor, followed by histologic subtype (P < 0.02). CONCLUSIONS: Ovarian sarcomas are rare malignancies with a poor prognosis. All women with suspected ovarian carcinoma or sarcoma should have a preoperative CA 125 level taken. Surgical cytoreduction to a residual tumor burden of < or = 1 cm improves outcome and should be the goal of surgery. Although the optimal consolidation chemotherapy regimen remains unknown, platinum should be included as part of the regimen.

Nasopharyngeal teratoma. Report of a case with prenatal diagnosis and postnatal management.

BACKGROUND: Oral teratomas are rare entities. CASE: A patient was referred for elevations in the maternal serum alpha-fetoprotein. On ultrasound examination, a cyst was seen protruding from the fetal mouth. Postnatally, a teratoma was found to be filling the neonate's oral cavity. CONCLUSION: This case illustrates problems in determining the etiology of head and neck masses antenatally. It also shows that teratomas can appear to regress and yield positive amniotic fluid alpha-fetoprotein and acetyl-cholinesterase. The appropriate perinatal management of this potentially devastating disorder includes preparation for establishing an airway following delivery.

Cytomorphologic characteristics of thermal injury related to endocervical brushing following loop electrosurgical excision procedure (LEEP).

Loop electrosurgical excision procedure (LEEP) is gaining popularity in the United States as an alternative to other ablative and cone methods of treatment for preneoplastic conditions of the uterine cervix. The major advantage is that it is an outpatient procedure using local anesthesia. Post-LEEP evaluation of the endocervical canal can be accomplished by either endocervical curettage or cytobrush. We reviewed the immediate post-LEEP cytobrushes from 33 patients. Artifact related to the procedure was seen in all cases and included: 1) elongated endocervical cells with cytoplasmic "tails" and streaming nuclei ("taffy pulled"); 2) loose cellular aggregates with coalesced cytoplasm and "hockey stick" nuclei; 3) sheets of cells with frothy cytoplasm and shrunken thumbprinted nuclei; 4) nuclear enlargement; and 5) smudgy nuclear chromatin. The background ranged from bloody coagulum to watery proteinaceous material. Original diagnoses were negative in 25 cases. Eleven (44%) were considered abnormal on review. Of these, four were interpreted as having squamous intraepithelial lesions (SIL), one was atypical squamous cells of undetermined significance (ASCUS), and six had atypical glandular cells of undetermined significance (AGUS). It was not always possible to grade the degree of dysplasia. There was review agreement with 14 negatives, one SIL, one ASCUS, and one unsatisfactory specimen. Three AGUS were upgraded to SIL, and one unsatisfactory specimen was considered atypical on review. In conclusion it is possible to separate artifact from actual pathology on post-LEEP cytobrush specimens. Recognition of the characteristic changes seen on cytologic specimens obtained immediately following diathermy loop treatment will allow accurate identification of true abnormalities.

p53 expression in placentas with hydropic change and hydatidiform moles.

Hydatidiform moles result from abnormal fertilization and have been divided into partial and complete forms based on morphologic, cytogenetic, and clinical features. Little is known about their pathogenesis or malignant transformation. We applied an immunohistochemical marker for the p53 tumor suppressor gene product to placentas with hydropic change and hydatidiform moles to determine whether abnormal p53 gene product accumulation occurs in molar gestations. Ploidy of these placentas was determined by flow cytometry and fluorescence in situ hybridization. The mean percentages of p53-positive cells was determined by counting 200 cytotrophoblastic and proliferating trophoblastic cells. The staining intensity was graded on a scale of 1+ (faint) to 3+ (strong). The mean percentage of p53-positive cells for the placentas were as follows: 8.9% +/- 10.5 for hydropic change; 28.0% +/- 13.2 for partial mole; and 41.0% +/- 19.6 for complete mole. There was a significant difference in p53 expression between hydropic change and partial mole (P = 0.05) and hydropic change and complete mole (P = 0.0008). Although there was a difference between partial mole and complete mole, this did not reach statistical significance (P = 0.15). Hydatidiform moles exhibited 2+ to 3+ staining intensity, whereas hydropic placentas exhibited weaker intensity (1-2+). The finding of p53 gene product overaccumulation in partial and complete moles suggests that p53 gene mutations or alternatively, post-transcriptional changes in the p53 gene product occur resulting in inactivation and stabilization of the protein. This may play a role in uncontrolled trophoblastic proliferation and neoplastic transformation.

Obesity and prognosis in endometrial cancer.

OBJECTIVE: We tested the null hypothesis that morbid obesity as measured by the Quetelet index has no influence on survival in endometrial cancer. STUDY DESIGN: A retrospective study of 492 women with endometrial carcinoma was performed. Age, height, weight, Quetelet index, stage, cell type, grade, node status, peritoneal cytologic findings, and depth of myometrial invasion were analyzed for influence on survival. RESULTS: Mean Quetelet index was 34 (range 16 to 89). Quetelet index was < 30 in 45% of patients, 30 to 40 in 33%, and > 40 in 22%. Five percent of those with a Quetelet index > 40 had positive nodes, but 64% of patients with a Quetelet index > 40 did not have lymph node sampling done. Lack of sampling of lymph nodes in the entire group had no adverse effect on survival. In a proportional hazards regression model for time from diagnosis to death from disease, grade, node status, myometrial invasion, and stage had highly significant effects. When Quetelet index was analyzed as a continuous variable, as Quetelet index increased, time to recurrence was significantly increased (p = 0.0136), and significance was approached for survival (p = 0.0645). Quetelet index was strongly related to grade (p = 0.013), depth of myometrial invasion (p = 0.031), negative cytologic findings (p = 0.004), and stage (p = 0.011) with obese patients having better differentiated, less invasive tumors of lower stage with negative washings. CONCLUSIONS: Morbid obesity positively affects survival in endometrial carcinoma. This effect is accounted for by the association of obesity with less aggressive disease. Morbid obesity is not associated with increased death from other causes. Lack of sampling of negative lymph nodes does not adversely affect survival.

Evaluation of Ki-67 (MIB-1) in placentas with hydropic change and partial and complete hydatidiform mole.

The separation of complete from partial hydatidiform mole and of partial mole from placentas with hydropic change on gross and microscopic evaluation can be difficult, and ploidy provides important diagnostic information. We applied an immunohistochemical marker of proliferation, Ki-67 (MIB-1), to 10 complete moles, 11 partial moles, and 8 placentas with hydropic change to determine whether growth fraction differs in these three placentas and can aid in diagnosis. Ploidy was confirmed using flow cytometry and fluorescence in situ hybridization with probes to chromosomes 7 and 2. The Ki-67-determined growth fractions (number of positive cells/total number of cells) for villous stromal cells, cytotrophoblast, and proliferating trophoblast were evaluated separately by counting 200 cells of each population. Growth fraction on stroma did not differ among the three entities. Mean percent growth fraction for cytotrophoblast was 13.3% for hydropic change, 14.6% in partial moles and 38.7% in complete moles (P = .004 hydropic change to complete moles, P = .003 partial moles to complete moles). There was no significant difference between hydropic change and partial mole. Mean percent growth fraction for proliferating trophoblast was 38.5% in hydropic change, 25.9% in partial moles, and 67.1% in complete moles (P = .08 hydropic change to complete moles, P = .004 partial moles to complete moles). Again, no significant difference was identified between hydropic change and partial moles. Ploidy analysis using fluorescence in situ hybridization and flow cytometry confirmed diploidy in hydropic change and complete moles and triploidy in partial moles. Ki-67 may be useful in separating complete moles from partial moles but not partial moles from hydropic change.

Histopathologic prognostic factors in early stage cervical carcinoma.

The pathologist makes extensive assessments in cases of early stage carcinoma of the cervix. The following parameters are known to affect prognosis: capillary-lymphatic space invasion, depth of invasion, size of gross tumor, histologic type, grade (in adenocarcinoma), involvement by tumor of pelvic or para-aortic lymph nodes, and lymphoid response and immune status. These findings, along with clinical stage, best predict tumor behavior. Other observations are under investigation to evaluate their usefulness.

Detection of chromosomal abnormalities in the dysmorphic fetus using fluorescence in situ hybridization: evaluation for monosomy X genotype.

The cytogenetic abnormalities of dysmorphic fetuses who died in utero cannot be analyzed reliably by karyotyping. To overcome this obstacle, the authors applied fluorescence in situ hybridization (FISH) to formalin-fixed, paraffin-embedded tissue of two female infants and 13 female fetuses whose phenotypic features suggested possible Turner's syndrome. Previous cytogenetic evaluation of the amnionic fluid showed five were 45,XO karyotype; two were 46,XX karotype; and eight were of unknown karyotype. Karyotyping had been attempted on four of the unknown cases without success. The copy number of X chromosomes were correctly identified by FISH in all previously karyotyped cases. Of the remaining eight cases with unknown karyotype, three appeared to be XX, and five cases were identified as monosomy XO, confirming the suspicion of Turner's syndrome genotype. FISH is useful for confirming suspected Turner's syndrome genotypes in infants and macerated fetuses in which a karyotype cannot be obtained otherwise.

Postoperative radiation therapy in clinical stage I endometrial cancer: corpus, cervical, and lower uterine segment involvement--patterns of failure.

PURPOSE: To evaluate involvement of the lower uterine segment (LUS) in adenocarcinoma of the endometrium and to identify patterns of treatment failure. MATERIALS AND METHODS: Two hundred four patients, aged 29-92 years, with endometrial carcinoma underwent surgery. Postoperative radiation therapy was administered for adverse histologic criteria, including deep myometrial invasion, high grade, or LUS involvement. RESULTS: The incidence of tumor involvement of the LUS was 19%; of the cervix, 14%; and of the corpus, 67%. Distant metastasis occurred in 3% of patients with LUS involvement and in 17% of patients with cervical involvement. The local recurrence rate was 50% among patients with LUS involvement with no other risk factors and no postoperative radiation therapy and was 3% among those who underwent radiation therapy (P = .023). CONCLUSION: Early local-regional spread may be the primary mechanism of treatment failure in tumor invasion of the LUS. Aggressive local management, including postoperative radiation therapy, may be necessary.

Ploidy analysis by flow cytometry and fluorescence in situ hybridization in hydropic placentas and gestational trophoblastic disease.

Placentas with hydropic change may be hydropic degeneration (HD) or gestational trophoblastic disease (GTD), partial (PM) or complete (CM) hydatidiform mole. The separation of HD from PM and PM from CM by histological findings may be problematic in some cases and can be clarified with ploidy analysis. Fluorescence in situ hybridization (FISH) using a probe to chromosome 7 (D7Z1) was applied to tissue cut from paraffin blocks from 10 histologically representative cases each of HD, PM, and CM on which ploidy had been previously confirmed by flow cytometry from paraffin embedded tissue. Villous stromal cells and nonproliferative trophoblast were examined for number of signals/cell and percentage of cells/placenta with three hybridization signals. The mean number of hybridization signals/cell was HD 1.14; PM 1.79; and CM 1.17, with statistical significance between HD and PM (P < .0001), and PM and CM (P < .0001). The mean percentage of cells/placenta with three hybridization signals was HD 1.10%, PM 23.1%, and CM 2.11%, with statistical significance between HD and PM (P < .0001), and PM and CM (P < .0001). In addition, there was no overlap in the mean percentage of cells with three hybridization signals between HD and PM, and PM and CM. Chromosome 2 probe (D2Z1) was applied to tissues that had three chromosome 7 signals to exclude trisomy, and in all cases three signals were present confirming triploidy in PM. FISH can identify diploid and triploid hydropic placentas in paraffin-embedded tissue to assist in differentiating HD from PM, and PM from CM.

Adenomyoepithelioma of the breast: fine-needle aspiration biopsy and histologic findings.

Adenomyoepithelioma is an uncommon tumor of the breast which clinically presents as a discrete nodule and histologically is composed of lumenal spaces lined by a mixture of epithelial and myoepithelial cells. It has a spectrum of histologic appearances which are gradually gaining wider recognition. There are, however, only a few descriptions of the fine-needle aspiration biopsy (FNAB) findings in adenomyoepithelioma. We report the FNAB and histologic features of a mammary adenomyoepithelioma which contained a prominent epithelial component including a focus of marked epithelial atypia. This expands the spectrum of FNAB findings which have been reported in adenomyoepithelioma.

Liver transplant after massive spontaneous hepatic rupture in pregnancy complicated by preeclampsia.

BACKGROUND: Spontaneous hepatic rupture associated with preeclampsia is a rare but life-threatening situation. Several different surgical treatments have been described, depending on the severity of the rupture. Liver transplantation has become the mainstay for patients with end-stage liver disease. Transplantation in the setting of liver trauma or massive parenchymal disruption is not well defined. To our knowledge, this treatment has not been reported for spontaneous hepatic rupture in pregnancy. CASE: Massive, spontaneous hepatic rupture occurred in a patient at 36 weeks' gestation as a result of severe preeclampsia. Conventional surgical therapies were unsuccessful in controlling the massive hemorrhage. As a life-saving measure, the patient underwent total hepatectomy with the creation of an end-to-side portcaval shunt, thereby rendering the patient anhepatic. The patient was listed as urgently needing a liver for transplantation through the United Network for Organ Sharing. A suitable donor liver was located approximately 8 hours after the emergency hepatectomy. The patient underwent orthotopic liver transplantation after being maintained in an anhepatic state for almost 13 hours. The patient was discharged on postoperative day 41, suffering only from some ischemic lower extremity neuropathy secondary to hypovolemic hypotension occurring during the hepatectomy procedure. CONCLUSION: In the reported case, spontaneous hepatic rupture resulted in a massive hemorrhage that could not be controlled by previously reported techniques and required total hepatectomy followed by liver transplantation.

Histiocytosis X of the vulva with a confusing clinical and pathologic presentation. A case report.

Histiocytosis X (HX) is a rare disorder of Langerhans cells and most commonly occurs in children. We report a case of HX of the vulva in a 76-year-old woman that clinically simulated a yeast infection of the vulva but histologically resembled an amelanotic melanoma. We briefly report the clinical and pathologic features of this case, which responded to vincristine followed by vinblastine and was in complete remission after nine months.

Female genital tract cancer.

BACKGROUND: Site-specific cancer frequencies and incidence rates are reported regularly by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, but not by histologic type within site. This report reviews data for 160,977 histologically or cytologically confirmed invasive and in situ cancers of the female genital tract. METHODS: Data were supplied by the SEER program for histologically confirmed cases of uterine corpus, uterine cervix, ovary, vulva, vagina, fallopian tube, and placental cancers diagnosed between 1973 and 1987. Histologic types were reviewed for race, age at diagnosis, incidence, stage, and survival. RESULTS: There were 89,943 invasive and 71,034 in situ neoplasms. Squamous carcinoma was the most common invasive malignancy of the cervix (77.1%), vulva (74.4%), and vagina (70.8%). Adenocarcinoma was the most frequent malignancy in the uterine corpus (81.5%) and ovary (86.6%), with these percentages reaching 91.6% for corpus and 86.9% for ovary if adenosquamous carcinoma and adenocarcinoma with squamous metaplasia are included. Cervical carcinoma in situ accounted for 91.0% of all in situ cancers. In situ cancers made up 78.5% of all cervical cancers, 35.1% of vaginal cancers, and 50.4% of vulvar cancers. CONCLUSIONS: There are dominant histologic groups in each female genital tract site that are largely responsible for incidence and survival statistics. Within the groups, however, there are subtypes with differing features. Epidemiologic studies may provide more definite information by considering the effect of these subtypes in examining risk factors.

Hamartoma of the tongue in an infant with a primary diagnosis of ectrodactyly-ectodermal dysplasia-cleft lip and palate syndrome.

We describe a case of an unusual tongue hamartoma associated with ectrodactyly-ectodermal dysplasia-clefting syndrome in a 3-month-old white female infant. The lesion was composed of a mixture of salivary glands, adipose tissue, smooth muscle and skeletal muscle in a haphazard fashion. Lingual hamartomas are rare and can present a clinical differential diagnostic problem. We review the literature on this unique combination of malformations.

An unusual extrauterine variant of adenosarcoma with multiple recurrences over 16 years.

An unusual extrauterine (pelvic) variant of adenosarcoma is presented. A benign-appearing epithelium resembling fallopian tube epithelium is integrally mixed with malignant stroma that in all areas sampled is low-grade leiomyosarcoma. The tumor has behaved as a low-grade malignancy with four local recurrences over a 16-year period. Extrauterine adenosarcomas have rarely been reported in the literature; and one in which the stromal component is histologically all of smooth muscle differentiation is more unusual.