Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells.

The c-Mos gene product is a component of the cytostatic factor and, as such, stabilizes the maturation-promoting factor causing cell-cycle blockade at metaphase II in unfertilized eggs. The potential role of c-Mos in regulating cell-cycle progression and cell death in somatic cells remains unknown. We studied whether paclitaxel-induced M-phase arrest and apoptosis are associated with c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells. The first cellular effect observed with continuous exposure to 50 ng/ml paclitaxel (ID50) was mitotic arrest with an increase in the accumulation of cyclin B1 and stimulation of cdc2/cyclin B1 kinase in a time-dependent manner during a 36-h incubation. DNA fragmentation determined by agarose gel electrophoresis and quantitation of [3H]thymidine-prelabeled genomic DNA was a later event, first detected at 24 h and peaking at 48 h (later time points were not studied). Induction of the c-Mos gene expression and activation were determined by Western blot analysis, immunoprecipitation using a polyclonal anti-mos antibody, reverse transcription-PCR assay, and 32P-ATP incorporation into c-Mos protein or the substrate of glutathione S-transferase mitogen-activated protein kinase kinase, respectively. Both induction and activation were clearly detected after 24 h of exposure to paclitaxel concentrations of >50 ng/ml, coinciding with drug-induced apoptosis. Mitogen-activated protein kinase activation preceded c-Mos gene induction. Paclitaxel-induced c-Mos gene expression was completely abrogated by cycloheximide and actinomycin D. Mos gene expression was also induced in SKOV3 cells that were treated with vinblastine but not in those that were treated with camptothecin, etoposide, or cisplatin. We concluded that tubulin-disturbing agents induce c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells and that such an effect occurs after mitotic blockade and coincides with drug-induced apoptosis.

MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.

A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.

Tumor epidermal growth factor receptor studies in patients with non-small-cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852.

PURPOSE: Tumor tyrosine kinase activity associated with the epidermal growth factor receptor (EGFR) and localization of anti-EGFR monoclonal antibody RG 83852 were studied in patients with non-small-cell lung cancer (NSCLC) and head and neck cancer. PATIENTS AND METHODS: Fifteen patients were treated with escalating doses of RG 83852 by continuous intravenous infusion for 5 days. Fresh tumor specimens were obtained 24 hours after therapy in 10 patients (of whom five had a pretherapy sample taken). Tumor EGFR tyrosine kinase activity was determined in fresh tumor samples by autophosphorylation of EGFR isolated in immunocomplexes with RG 83852. Tumor EGFR saturation with RG 83852 was assessed semiquantitatively by comparing the EGFR tyrosine kinase activity in immunocomplexes of tumor specimens obtained after therapy with total EGFR tyrosine kinase activity assessed by exogenous addition of RG 83852 to tumor lysates. Modulation of EGFR tyrosine kinase activity after the administration of RG 83852 was assessed by comparing EGFR tyrosine kinase activity from the same malignant lesion obtained before and after therapy. Tumor localization of RG 83852 and EGFR saturation were also assessed by immunohistochemistry. RESULTS: No significant side effects were observed up to a total dose of 600 mg/m2. Based on tyrosine kinase activity, a high degree of EGFR saturation (> or = 50%) was observed at doses > or = 200 mg/m2, and EGFR saturation was estimated to be 100% at a dose level of 600 mg/m2 both in tumor tissue and skin used as surrogate EGFR-positive tissue. Immunohistochemistry studies showed that RG 83852 localized in tumor tissue and skin, but not in stroma, at doses > or = 400 mg/m2, and high EGFR saturation was observed at 600 mg/m2. Tumor EGFR tyrosine kinase activity was studied in five patients (four with EGFR-positive tumors) before and 24 hours post-therapy; a threefold to fourfold upregulation of EGFR tyrosine kinase activity in posttherapy specimens was observed in two patients. Moderate upregulation of EGFR itself was suggested in both of these patients and in two additional patients by immunohistochemistry. CONCLUSION: RG 83852 causes no toxic effects at doses that result in high tumor EGFR saturation. Treatment with RG 83852 may enhance EGFR tyrosine kinase activity and/or EGFR expression. Because high EGFR expression by tumors has been associated with increased sensitivity to cytotoxic therapy, the suggestion of antibody-mediated upregulation of EGFR by agents such as RG 83852 may prove useful in enhancing chemotherapeutic efficacy.

Treatment of endometrial carcinoma with radiation therapy alone.

PURPOSE: To review the results of treatment with radiotherapy alone in 152 patients with adenocarcinoma of the endometrium who had medical or surgical contraindications to hysterectomy. METHODS AND MATERIALS: We reviewed the records of all patients who were treated with radiotherapy alone for uterine carcinoma at The University of Texas M. D. Anderson Cancer Center between 1960 and 1986. One hundred fifty-two cases were analyzed. Most patients had multiple medical problems. One hundred sixteen patients were treated with intracavitary radiotherapy alone. A combination of external beam and intracavitary radiotherapy was used for 10 patients with Stage I disease who had unusually large cavities, 10 patients with Stage II disease, and 13 of 15 patients with Stage III or IV disease. Histologic material was reviewed in 91 cases. RESULTS: Ten years after treatment, these patients were twice as likely to have died of intercurrent illness as of uterine cancer. The 5-year disease-specific survival rate of patients with Stage I disease was 87%. The disease-specific survival of patients with Stage II disease was 88%, which was not significantly different from that of Stage I patients. Stage III and IV patients had a significantly poorer disease-specific survival rate of 49% at 5 years. Intrauterine recurrence occurred in 14% of the patients with Stage I or II disease. Salvage treatment was attempted in 5 of the 10 patients who had isolated intrauterine recurrences of Stage I disease and was successful in all cases. Extrauterine pelvic recurrence developed in only 3% of Stage I and II patients. Of 82 Stage I and II carcinomas that were available for pathologic review, 17 (21%) were clear-cell or papillary serous variants. The disease-specific survival rate of patients with Stage I or II papillary serous carcinomas was 43%, significantly poorer than that of patients with endometrioid carcinomas. Seven patients experienced acute anesthesia-related complications; none were fatal. Five patients had serious late complications of radiation therapy. CONCLUSION: Radical radiotherapy achieved acceptable DSS and local control rates in patients with medically or surgically inoperable uterine carcinoma. However for patients with localized disease, such treatment is justified only when the operative risk exceeds the 10-15% uterine recurrence rate expected with radiation alone.

ASTRO Research Fellowship: apoptosis as a predictor of tumor response to radiation in stage IB cervical carcinoma. American Society for Therapeutic Radiology and Oncology.

PURPOSE: Levels of apoptosis predict for tumor responsiveness to radiation in various animal systems. To investigate the potential role of apoptosis as a predictor of response in human tumors, a retrospective review was undertaken of patients with adenocarcinoma of the cervix whose primary lesion at presentation measured at least 4 cm and who underwent definitive radiation therapy. A previous report had indicated that roughly half this group of patients should have a long-term relapse free survival. METHODS AND MATERIALS: Pretreatment biopsy specimens of 44 patients with Stage IB adenocarcinoma of the cervix, whose primary lesion at presentation measured at least 4 cm in greatest dimension, were scored for apoptosis by two independent investigators without knowledge of the treatment outcome, and the results were averaged. Actuarial methods were used to assess overall survival, disease-free survival, determinate survival, and local control as a function of the baseline level of apoptosis. Patients ranged in age from 21 to 87 years and were treated with definitive radiotherapy between 1964 and 1989. Follow-up for the surviving patients ranged from 1 to 278 months, with a mean of 101 months. RESULTS: Patients whose tumors had a baseline level of apoptosis above the median value (2%) had a better overall survival than those with lower levels of apoptosis (p = 0.056). A similar trend for disease-free survival (p = 0.32) and determinate survival (p = 0.27) did not reach statistical significance, perhaps because of the small number of patients. Because only 6 of the 44 patients (13%) had a local tumor failure, it was not possible to establish a correlation between the pretreatment level of apoptosis and the local tumor control by radiation. CONCLUSION: The baseline level of apoptosis predicted for survival in patients with Stage IB cervical adenocarcinoma. Further investigation of the measurement of apoptosis as a potential predictive assay is warranted in other human tumor systems.

Malignant peripheral nerve sheath tumor of the pleura with epithelial and rhabdomyoblastic differentiation: report of a case clinically simulating mesothelioma.

A primary malignant peripheral nerve sheath tumor (MPNST) of the pleura that clinically mimicked a malignant mesothelioma in a 57-year-old man is described. Histologically, the tumor had features similar to those described in cases of the so-called epithelioid MPNST. A unique finding in this case was the demonstration of keratin expression in the epithelioid component of the tumor, as well as the presence of rhabdomyoblasts. This is the first example of an MPNST with heterologous elements arising in the pleura. Immunohistochemical and ultrastructural studies were important in differentiating this tumor from other malignancies with sarcomatoid and epithelioid features involving the pleura.

High-stage endometrioid carcinoma of the ovary. Prognostic significance of pure versus mixed histologic types.

We retrospectively reviewed 80 cases of endometrioid carcinoma of the ovary: 68 pure endometrioid tumors and 12 predominantly endometrioid carcinomas (> 50%) mixed with either papillary serous or undifferentiated carcinoma. Each group had 11 cases of stage III or IV tumors, which were studied to determine whether the overall prognosis was affected by grade, histology, number of mitoses, residual tumor after surgery, and patient's age. Prognosis was significantly affected only by a mixed histologic pattern. The 5- and 10-year survival rates and the median survival time for pure endometrioid carcinomas were much better than those for mixed endometrioid carcinomas (63% and 45% and > 86 months versus 8% and 0% and 18 months, respectively). Recurrent tumors in cases of mixed endometrioid carcinoma were pure serous or undifferentiated carcinomas, whereas those in cases of pure endometrioid carcinoma were either endometrioid or high-grade carcinoma. Our results show that the presence of even a small component of serous or undifferentiated carcinoma in an otherwise predominantly endometrioid carcinoma significantly affects the prognosis. Thus pathologists should thoroughly sample all endometrioid carcinomas, especially high-stage tumors, to ensure that no serous or undifferentiated component is present.

Calcium oxalate crystals in breast biopsies. The missing microcalcifications.

Most calcifications detected by mammography and specimen radiography are readily identified by histologic sections stained with hematoxylin and eosin (H&E) or the von Kossa stain. However, calcifications composed of calcium oxalate crystals are not always seen in sections stained with H&E or with von Kossa. To study the incidence of calcium oxalate crystals in breast biopsies, we used polarized light microscopy to review 153 needle-localization breast biopsies. Birefringent crystals were observed in 19 cases (17 benign and 2 malignant), but typical calcium phosphate microcalcifications were revealed by H&E in only 16 of these 19 cases. Multiple H&E sections through the blocks of the remaining three cases did not reveal typical microcalcifications. These crystals did stain with silver nitrate/rubeanic acid with 5% acetic acid pretreatment but failed to stain with von Kossa and alizarin red at pH 4.2. This suggested that they were composed of calcium oxalate. Analytical electron microscopy performed in one of the three cases without typical microcalcifications demonstrated only a calcium peak of energy-dispersive x-ray analysis and an electron-diffraction pattern compatible with calcium oxalate monohydrate. We conclude that discrepancies between the amount of microcalcifications seen on the mammogram or on the x-ray film of the specimen or the paraffin blocks and the amount of microcalcifications seen on the H&E slides may be explained by the presence of calcium oxalate crystals. These crystals are detected with specimen radiography but are not easily seen on H&E slides unless polarized light microscopy is used. Polarized light microscopy and silver nitrate/rubeanic acid with 5% acetic acid pretreatment should be used for breast biopsy specimens when typical microcalcifications are not seen on H&E-stained sections.

Low-stage clear-cell carcinoma of the endometrium.

Clear-cell carcinoma (CCC) of the endometrium is a relatively rare malignancy that is considered to be one of the most aggressive types of endometrial carcinoma. To evaluate the behavior of low-stage (stages I and II) CCC of the endometrium, we retrospectively reviewed 17 such cases seen at The University of Texas M.D. Anderson Cancer Center from 1963 to 1990. Patients' ages ranged from 52 to 81 years. Fifteen cases were pure CCC, and two cases were predominantly CCC with a focus of endometrioid adenocarcinoma FIGO grade I. All patients have been followed-up for at least 3 years. At the time of the study, six patients were alive without disease, one patient was alive with disease, five had died of other causes, and five had died of disease. The estimated survival rate was 71%. Estimated 5-year survival rates for endometrioid adenocarcinoma FIGO grade III and uterine papillary serous carcinoma are 73 and 39%, respectively. We conclude that patients with low-stage CCC of the endometrium have a survival rate similar to that of patients with endometrioid adenocarcinoma FIGO grade III and better than that of patients with uterine papillary serous carcinoma of similar stages.

Endometrioid carcinoma of the ovary with a prominent spindle-cell component, a source of diagnostic confusion. A report of 14 cases.

Fourteen endometrioid carcinomas of the ovary with a prominent component of spindle-shaped epithelial cells are reported. Eleven were initially misdiagnosed as sexcord stromal tumors, malignant mesodermal mixed tumors, tumors of probable wolffian origin, or metastatic carcinomas. All of the tumors, however, had one or more features establishing them as endometrioid carcinomas, including (a) glands typical of endometrioid adenocarcinoma, (b) foci of squamous differentiation, and (c) an adenofibromatous component. Six cases were examined immunohistochemically, and the epithelial nature of the spindle cells was supported by immunostaining for keratin and epithelial membrane antigen. The patients ranged in age from 42 to 89 years (mean, 61). Four cases were stage I, five stage II, and three stage III. Follow-up information was available in seven cases. Five patients were free of disease at 8, 11, 32, 56, and 103 months, and two patients were alive with disease at 10 and 20 months. The age of the patients, clinical presentation, tumor stage, and gross appearance were similar to those of typical endometrioid carcinomas. It is important that this tumor be distinguished from other ovarian neoplasms with a spindle-cell component because of differences in treatment and prognosis.

Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identify those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior. p27kip1 is an important inhibitor of the cell cycle that acts by binding and inactivating cyclin-dependent kinases (CDKs). The aim of this study was to determine the prognostic value of loss of p27 protein in invasive breast cancer. We performed an immunohistochemical study of 147 patients with T1 and T2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis comparing tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor, low or absent p27kip1 is a strong predictor of reduced disease-free survival. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival than either marker alone. This simple, reliable and inexpensive assay, particularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer evaluation to better identify high risk patients.

Endocervical type glands in urinary bladder: a clinicopathologic study of six cases.

The authors report six cases of glandular lesions made up of endocervical type glands in the urinary bladders of women aged 34 to 65 years (mean, 39 years). Two patients presented with dysuria, one with painless hematuria, one with complaints of pelvic discomfort and hematuria, and one with vaginal discharge. The sixth patient was asymptomatic, but on a routine gynecologic examination, a pelvic mass was found. On physical examination, three women had masses between the bladder and uterus. Four lesions were located in the posterior wall of the urinary bladder, one in the dome, and one in the trigone. Four patients underwent biopsy of the bladder lesion. One of these patients had undergone a hysterectomy 10 years earlier. One woman with a pelvic mass between the bladder and uterus underwent a hysterectomy, bilateral salpingo-oophorectomy, and partial cystectomy. The sixth patient had a transurethral resection of the bladder tumor and left oophorectomy. Histologically, all cases showed intermediate to large-sized irregularly shaped endocervical type glands in the muscularis propria of the urinary bladder. Some glands exhibited cystic dilatation and contained mucinous secretions. The glands elicited no desmoplastic tissue reaction. The intraluminal mucin frequently contained polymorphonuclear leukocytes. In all cases, the glands were lined by mucinous, tall, columnar cells and less commonly by flattened to cuboidal cells. Rare admixed ciliated cells were also observed. The lining epithelium was bland in five cases, but moderate nuclear atypia was seen in one case. Mitoses were not observed in any case. Associated lesions included endometrial type glands surrounded by elastotic stroma in one case, exuberant cystitis glandularis in one case, and a pseudodiverticulum of the bladder in one case. Review of the slides from the patient who had had a hysterectomy 10 years previously revealed endocervical adenocarcinoma in situ. Follow-up (mean = 30 months; range = 6 to 60 months) shows that all patients are alive and well, suggesting that the lesion is benign.

Mild ductal atypia after large-core needle biopsy of the breast: is surgical excision always necessary?

BACKGROUND: The aim of the current study was to identify a select group of patients with mild atypia who do not need surgical excision after large-core needle biopsy (LCNB) of the breast. METHODS: Nineteen (70%) of 27 patients with ductal atypia found on LCNB had subsequent surgical excision. These 19 patients were retrospectively assigned to 3 groups according to the severity of the atypia found, which was compared with the final pathologic specimen after surgical biopsy. RESULTS: Cancer was identified through surgical biopsy in 6 (32%) of 19 patients. The severity of atypia seen on the LCNB specimen strongly correlated with subsequent cancer identification (P<.01). Two (33%) of 6 patients in group 2 (true atypical ductal hyperplasia [ADH]) and 4 (80%) of 5 patients in group 3 (severe ADH, borderline ductal carcinoma in situ) had cancer after surgical biopsy. No cancer was found after surgical biopsy in 8 patients in group 1 (mild atypia, not meeting criteria for ADH). CONCLUSIONS: The results of this study suggest that surgical excision can be avoided after LCNB of the breast in patients with only mildly atypical lesions that do not meet criteria for ADH. Patients with true ADH should continue to have surgical excision.

Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience.

The records of 41 patients diagnosed with adenosarcoma of the female genital tract between 1982 and 1996 were reviewed. The median age at diagnosis is 51 years (range, 14-84). The most common symptom is vaginal bleeding (71%). Clinical signs at presentation include pelvic mass (37%), uterine polyps (29%), and enlarged uterus (22%). In 71% of patients, the tumor originates from the uterus. Other sites include ovary (15%), pelvis (12%), cervix (2%). A history of thyroid cancer, benign ovarian cyst, and polycystic ovarian disease is found more frequently than expected in this patient population, whereas no relationship to endometriosis is observed. Surgery is the mainstay of treatment, but platin-based chemotherapy given upfront in inoperable patient has definite efficacy. An overall response rate of 92.5% was observed after primary therapy (surgery with or without radiotherapy, and/or chemotherapy), with a median survival of 48 months (range, 1-174). Thirty-eight percent of patients had recurrent disease. The median time to recurrence is 12 months (range, 5-132). Although 60% of patients with recurrence achieved a complete remission after treatment, only 1 (8%) is alive without disease, and 3 (22%), with disease at the time of this analysis. In our series, histologic sarcomatous overgrowth is a predictor of poor prognosis (p<0.03), however myometrial invasion and stage of disease seem to be of less prognostic significance. Adenosarcoma is a tumor with a fair prognosis. Most tumor can be cured with surgery, but recurrence carries a bad prognosis.

Octreotide induced remission of a refractory small cell carcinoma of the endometrium.

This is the first report of remission obtained with octreotide in a woman diagnosed with recurrent small cell carcinoma of the endometrium with neuroendocrine features, refractory to a combination of etoposide, cisplatin, and radiation therapy. Stabilization of disease was obtained with a combination of tamoxifen and leuprolide depot. Regression of disease was then achieved by the addition of octreotide. The use of octreotide as an antitumor agent is reviewed.

Ovarian neuroendocrine carcinoma associated with a mucinous neoplasm.

We describe a rare case of a neuroendocrine carcinoma of the ovary in a 22-year-old woman who presented with abdominal pain and a pelvic mass. Exploratory laparotomy revealed a right ovarian tumor weighing 2100 g. A right salpingo-oophorectomy and an appendectomy were performed. There was no evidence intraoperatively or postoperatively of metastatic disease. Microscopic examination of the ovary revealed solid nests of tumor cells with a neuroendocrine appearance, high mitotic rate, necrosis, and vascular invasion; the tumor was associated with a predominantly borderline mucinous neoplasm with a small focus of mucinous carcinoma. Neuroendocrine differentiation was confirmed by Grimelius stains, immunohistochemical assays (chromogranin), and electron microscopy. The appendix was histologically unremarkable. The patient received a course of chemotherapy; 3 months after completing chemotherapy, she developed multiple liver metastases and died of disease a week later. To our knowledge, this case report is the second one involving a primary neuroendocrine carcinoma of the ovary occurring in association with a mucinous neoplasm. Mixed mucinous and neuroendocrine carcinoma of the ovary may represent a rare neoplasm with extremely aggressive behavior.

Undifferentiated carcinoma of the ovary.

Thirty-five cases of ovarian carcinomas, which had as the predominant histologic component solid areas of epithelial cells without differentiation into müllerian carcinomas, were reviewed. The patients' ages ranged from 39 to 72 years (mean age, 54 years). Two patients had clinical stage I disease, one had stage II, 26 had stage III, and six had stage IV. Microscopically, the malignant cells formed large groups or sheets with desmoplastic stroma around them. Foci of papillary serous carcinoma, unclassified adenocarcinoma, or transitional cell carcinoma were seen in 26 tumors, foci of necrosis were seen in 30 tumors, and vascular invasion was seen in seven tumors. Six of 13 carcinomas tested expressed CA125 reactivity, and 12 of 13 carcinomas reacted to B72.3 monoclonal antibody. The primary tumors were treated by aggressive surgical reduction in 32 patients and by multiple biopsy procedures in three patients. After the first operation, 30 patients had residual disease, smaller than 2 cm in five patients and larger than 2 cm in 23 patients. After surgery, 33 patients received chemotherapy; three of these 33 also received radiotherapy. One patient was treated with postsurgical radiotherapy only, and one patient refused further treatment. Thirty-four patients (97%) died of disease between 8 and 108 months (mean, 27 months) after initial surgery, 29 patients died in less than 32 months. Four patients (11%) survived more than 5 years: two patients with stage I disease who died at 82 and 102 months, one patient with stage II who died at 72 months, and one patient with stage III who has no evidence of disease after 116 months. Five-year survival of patients with undifferentiated ovarian carcinoma is worse than the reported survival of patients with serous carcinoma or ovarian carcinoma with a pattern resembling transitional cell carcinoma. The distinction between these three carcinomas that have solid areas carries prognostic significance.

Pathology of epithelial ovarian cancer.

Ovarian epithelial tumors can be benign, LMP, and malignant. The prognoses of these three types of tumors are entirely different. A frozen section has to be done on all ovarian tumors to determine if they are benign. All lesions that are LMP or malignant have to be surgically and pathologically staged. The stage of disease is the most important prognostic factor. Other prognostic indicators vary with the type of epithelial tumor and are discussed in the text.

Sarcoma botryoides of the uterine endocervix: long-term results of conservative surgery.

Sarcoma botryoides, a variant of embryonal rhabdomyosarcoma, is the most common neoplasm of the lower genital tract in girls under 16 years of age. This neoplasm more frequently has a vaginal location in patients younger than 4 years, whereas a cervical location has its peak incidence in the second decade. Although the recommended therapy has been radical surgery alone or combined with other modalities, the use of neoadjuvant chemotherapy has changed the surgical approach to one employing a less radical procedure such as a simple hysterectomy or local excision. We present the case of a 12-year-old girl diagnosed with an embryonal rhabdomyosarcoma of the endocervix who received vincristine-Adriamycin-cyclophosphamide combination chemotherapy followed by a simple hysterectomy. The patient exhibits no evidence of disease 8 years after the initial diagnosis.

Prolonged oral etoposide for advanced uterine leiomyosarcoma with pulmonary metastases: case report.

A patient who had a high grade uterine leiomyosarcoma with intraabdominal and pulmonary metastases at the time of diagnosis underwent supracervical hysterectomy, bilateral salpingo-oophorectomy and tumor reductive surgery. Induction chemotherapy achieved a partial response with small amount of residual disease. On achieving a plateau in the response to her induction chemotherapy, she was switched to prolonged oral etoposide at a dose of 50 mg/m2/day 21 days with a 7-day rest period between cycles. Follow up imaging revealed stable disease with a slight decrease in the size of the paraaortic lymphnodes. Prolonged oral etoposide may be considered in patients with advanced high grade leiomyosarcoma of the uterus.