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A case of uterine rupture resulting from tumor penetration of the myometrium in a patient with malignant mixed mesodermal tumor is described; the first in the literature known to the authors. Notable features include rapid progression of disease, hemoperitoneum, and diffuse intraoperative bleeding controlled by radiographic embolization.
A case of mesodermal (Müller) mixed tumor of the ovary is described. The tumor consisted of the endometrial component with benign epithelial structures, stromal sarcoma, rhabdomyosarcoma, and elements of undifferentiated sarcoma. By its histological structure the tumor may be classified as one of the variants of mesodermal (Müller) mixed tumor of the heterologous adenosarcoma type.
BACKGROUND: Tamoxifen treatment of breast cancer is associated with an increased risk of endometrial cancer, but tamoxifen-related risks of endometrial cancer are unclear in premenopausal women, in long-term users of tamoxifen, and in women for whom several years have passed since ending treatment. We conducted a case-control study in Britain to investigate these risks. METHODS: We compared treatment information on 813 case patients who had endometrial cancer after their diagnosis for breast cancer and 1067 control patients who had breast cancer but not subsequent endometrial cancer. We assessed risk by conditional logistic regression analysis. All statistical tests were two-sided. RESULTS: Overall, tamoxifen treatment, compared with no treatment, was associated with an increased risk of endometrial cancer (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.8 to 3.0). Risk increased statistically significantly (P(trend)<.001) with duration of treatment (for > or =5 years of treatment compared with no treatment, OR = 3.6, 95% CI = 2.6 to 4.8). As an indication of background levels of treatment, 16% of control patients received 5 years or more of treatment. Risk of endometrial cancer adjusted for treatment duration did not diminish in follow-up to at least 5 years after the last treatment ended. Risk of endometrial cancer was not associated with the daily dose of tamoxifen and was comparable in pre- and postmenopausal women. Ever treatment with tamoxifen was associated with a much greater risk of Mullerian and mesodermal mixed endometrial tumors (OR = 13.5, 95% CI = 4.1 to 44.5) than of adenocarcinoma (OR = 2.1, 95% CI = 1.6 to 2.7) or clear cell and papillary serous tumors (OR = 3.1, 95% CI = 0.8 to 17.9). CONCLUSIONS: There is an increasing risk of endometrial cancer associated with longer tamoxifen treatment, extending well beyond 5 years. The increased risk of endometrial cancer associated with tamoxifen treatment should be considered clinically for both premenopausal and postmenopausal women during treatment and for at least 5 years after the last treatment.
A total of forty nine cases of uterine sarcomas were seen in Georgetown University Hospital and Lombardi Cancer Center between 1956 and 1978. The peak incidence (35%) was in the age group of 60-70 year-olds. Forty-one percent of all patients presented with postmenopausal bleeding. Preoperative diagnosis was made in less than half of the cases before laparotomy. Endometrial biopsy or curettage was the most commonly used preoperative diagnostic tool. Stages II and III were less commonly seen than I and IV at the time of initial diagnosis. Leiomyosarcoma was the commonest sarcoma in stage I while mixed mesodermal tumors were commoner in advanced stages. Mixed mesodermal tumors of the homologous variety comprised 35% of all cases. The longest survivals in this series are 22 1/2 years (leiomyosarcoma stage I), 21 years (mixed mesodermal sarcoma stage III), and 13 years (mixed mesodermal sarcoma stage I). Retrospective analysis is done to compare the results of different modalities of treatment.
Clinicopathologic studies of 16 homologous and 19 heterologous malignant mesodermal (Mullerian) mixed tumors of the corpora uteri showed that homologous tumors were more common in black women than in white women; in the former, tumors were diagnosed at a younger age and in more advanced stages than in the latter. Fifty-five percent of women with clinical stage I disease had a higher surgicopathologic stage. The most significant prognostic factors were pathologic extent of disease and vascular invasion in the myometrium. There was no difference in outcome between homologous and heterologous tumors. Initial surgery for staging is essential for the adequate evaluation and treatment of these patients.
Ovarian carcinoma commonly has an insidious onset. By the time the diagnosis is made, advanced disease is usually present. Rarely does a patient have acute symptoms which require immediate medical attention and lead to the correct diagnosis. A 40-year-old white female presented with lower abdominal pain, nausea, and light-headedness. Physical examination revealed a markedly tender lower abdomen with the right lower quadrant slightly more tender than the left. Hemoglobin level was noted to have decreased 2.6 g/dl over 16 hr. At exploratory laparotomy, 1500 cc of blood and a ruptured right ovarian mass were found. Pathologic analysis revealed a malignant mixed mesodermal tumor of the right ovary and an endometrioma of the left ovary. In conclusion, ovarian carcinoma may present as an acute abdomen because of intra-abdominal hemorrhage. It should be part of the differential diagnosis in a woman with an acute surgical abdomen and a hemoperitoneum.
Mixed mesodermal tumors (MMT) of the ovary are rare and have a poor prognosis. This ovarian malignancy usually occurs in postmenopausal women. We report an unusual ovarian MMT in a young woman given treatment similar to one used for ovarian germ cell malignancies. We believe this is the youngest patient reported with an homologous MMT of the ovary.
Ten cases of endometrial small cell neuroendocrine carcinoma are described. The ages of the patients ranged from 50 to 75 years (mean, 64 years). Most of the tumors were bulky, intraluminal masses that invaded at least half of the myometrial wall. Small cells were the only malignant element in two tumors. In the other eight, there were admixed elements of adenocarcinoma (five), adenosquamous carcinoma (two), or heterologous mesodermal mixed tumor (one). Histologic examination of metastatic deposits in six cases revealed solely small cells in all but one. Immunohistochemical evidence of neuroendocrine differentiation was demonstrated in all tumors using the markers chromogranin, synaptophysin, leu-7, or neuron-specific enolase. Six of these tumors were originally interpreted as mesodermal mixed tumors with a homologous, stromal-type sarcomatous component at initial pathologic examination, but were reclassified as carcinoma. Clinical follow-up of these 10 patients and an additional seven well-documented patients reported in the literature provided strong evidence for the aggressive nature of this neoplasm. Endometrial small cell neuroendocrine carcinoma is a rare, but aggressive neoplasm that can commonly be mistaken for a homologous-type mesodermal mixed tumor.
A human oncodevelopmental protein (ODP) with a molecular size of 28 kDa was isolated, employing malignant ascitic fluid of an advanced mixed mesodermal tumor of the uterus, by anti-ODP coupled Affi-Gel 10 column chromatography, followed by preparative PAGE. The final preparation obtained with this procedure gave a single band exhibiting reactivity with an anti-ODP antibody on analytical sodium dodecyl sulfate-PAGE. The sequence of the first 20 N-terminal amino acids of this protein is identical with those of both the cystic fibrosis protein and Ca-binding protein MRP8 except at position 17, for which no result was obtained. Sequence analysis suggested that the protein shows 90% sequence homology with both these proteins.
We have examined a panel of gynecological sarcomas for microsatellite instability. The genomic DNA from 11 of 44 sarcomas contained somatic alterations in the lengths of one or more di-, tri-, tetra-, or pentanucleotide microsatellite sequence markers, and 6 of these cases had alterations in two or more markers. In addition, di-, tri-, and tetranucleotide microsatellites were found to be highly unstable in single cell clones of two cell lines derived from a uterine mixed mesodermal tumor. Since such instability is characteristic of cells defective in postreplication mismatch repair, we examined mismatch repair activity in extracts made from these lines. Both extracts were repair deficient, while an extract of another gynecological sarcoma cell line not exhibiting microsatellite instability was repair proficient. The repair deficiency was complemented by a colon tumor cell extract that was defective in the hMLH1 protein but not by an extract defective in hMSH2 protein. This suggested that the defect in the uterine sarcoma line could be in hMSH2. Subsequent analysis of the gene revealed a 2-bp deletion in exon 14, leading to premature truncation of the hMSH2 protein at codon 796 and no detectable wild-type gene present. These data suggest that the microsatellite instability observed in these cell lines, and possibly in a significant number of gynecological sarcomas, is due to defective postreplication mismatch repair. There was no apparent correlation with microsatellite instability and clinical outcome.
The objective of the study was to assess the usefulness of magnetic resonance (MR) imaging in distinguishing malignant from benign conditions in patients with an abnormal uterine cavity. Fifty-four patients that were suspected of having abnormal uterine cavities were retrospectively evaluated by using MR imaging. The diagnosis of an abnormal uterine cavity included a thickened endometrium, and/or a endometrial mass, and/or a submucosal mass. Threshold values to classify the uterine cavity as abnormal on sagittal T2-weighted images were >10 mm for premenopausal women and >5 mm for postmenopausal women. Malignancy was diagnosed when lesions invaded the myometrial/junctional zone, and/or lesion enhancement was lower than that of the adjacent myometrium. The results found that histology confirmed 18 malignant and 37 benign lesions. Twelve of 15 endometrial carcinomas and 3 malignant mixed mesodermal tumors (MMMT) were correctly characterized as malignant on enhanced T1-weighted images; whereas 6 of 15 endometrial carcinomas and 3 MMMT were correctly characterized on T2-weighted images. Thirty-four of 37 benign cases were correctly characterized as not malignant on enhanced T1-weighted images. One of 14 submucosal leiomyomas, one endometrial stromal metaplasia, and one of ten pathologically normal endometria were misdiagnosed on enhanced T1-weighted images but were correctly diagnosed on T2-weighted images. The overall sensitivity, specificity, and accuracy for distinguishing malignant from benign central uterine masses were 83%, 92%, and 89% for enhanced T1-weighted image, and 50%, 97%, and 82% for T2-weighted image, respectively. We came to the conclusion that in diagnosing patients with abnormal uterine cavity, MR imaging may help differentiate malignant from benign disorders.
It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.
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.
Intrauterine aspiration (Vakutage), endocervical aspiration cytology and vaginal, ectocervical and endocervical (VCE) smears were used as outpatient procedures for diagnosis of endometrial cancer and hyperplasias in 840 patients. The results of the three technics were correlated with D&C or hysterectomy specimens. Ninety-three percent of the malignant lesions (82 adenocarcinomas, 5 mixed mesodermal tumors, 5 mixed adenosquamous carcinomas and 5 metastatic adenocarcinomas) were diagnosed by the Vakutage sample but only 67% by the VCE smears and 68% by endocervical aspiration cytology. The diagnostic accuracy of Vakutage in 50 cases of cystic hyperplasia was 88% (as compared to 14% for VCE smears and endocervical aspiration cytology) and 89% in 90 cases of adenomatous hyperplasias (as compared to 20% for the other two technics). Endometrial polyps were diagnosed exclusively from the Vakutage tissue sample in 83% of the 42 cases.
We examined the cervicovaginal cytology (PAP) findings in a series of 21 endometrial and 2 cervical carcinosarcomas (CS) [malignant mixed mullerian (mesodermal) tumors] (MMMT). Initial cytology diagnosis was positive for cancer in 14 of 23 cases (sensitivity of 61%); however, CS was correctly identified only 2 times. The remaining 12 cancer diagnoses were carcinomas: 10 adenocarcinomas (4 endometrial, 1 cervical, and 5 adenocarcinomas not otherwise specified), 1 squamous carcinoma, and 1 poorly differentiated carcinoma. Seventeen smears were available for review, all 8 false negative, one unsatisfactory, and 8 of 14 true positive smears. One false negative smear showed rare clusters diagnostic of adenocarcinoma. The remaining 7 false negative smears showed 3 high grade squamous dysplasias (two with additional findings: one showed atypical spindle cells and the other showed endometrial stromal cells), 2 extensive repair changes, and 2 negatives. The unsatisfactory smear showed atypical spindle cells. Review of the 8 true positive smears confirmed malignant spindle cells in the two cases originally identified as CS by cytology and in 3 other cases originally identified as adenocarcinoma. Of 9 smears positive for cancer available for review, 4 showed only carcinoma cells. PAP positive for cancer was associated with high stage at presentation (P less than .025) and recurrent disease (P less than .001) (even among stage I or II patients, P less than .025). PAP positive for cancer showed no association with depth of myometrial invasion, size, grade, or histologic type of carcinosarcoma. The results of this study demonstrate the importance of consultative cytology reporting in which recommendations for appropriate biopsy are included in the report.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed müllerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases.
A rare case of aggressive ovarian tumor in a 38-year-old female is described. Cytological diagnosis of the intraoperative smears was difficult because of the presence of the epithelial and non-epithelial components. The latter consisted of two types: spindle cells and roundish undifferentiated cells with multinuclear forms. Histologically, it was a malignant mesodermal (Mullerian) mixed tumor. Round mesenchymal cells expressed desmin and vimentin while spindle cells expressed myoglobin. Non-epithelial component was verified as leiomyosarcoma and rhabdomyosarcoma. Cells of the epithelial component expressed cytokeratins and epithelial membrane antigen.
Endometrial stromal tumors may pose a problem in diagnosis when they appear as metastatic lesions without a known primary tumor. To determine the usefulness of electron microscopy in identifying them in these situations, optimally fixed low-grade stromal sarcomas (five), normal endometrial specimens (six), and malignant mesodermal mixed tumors (four) were studied. The endometrial stromal sarcomas had a general resemblance to normal proliferative endometrial stroma, being composed of undifferentiated cells, fibroblasts, and myofibroblasts. One stromal tumor showed evidence of partial epithelial differentiation. One of the four malignant mesodermal mixed tumors had a fibrosarcomalike component, but there was insufficient resemblance to normal endometrial stroma to indicate a relationship between the two. Together with a review of the literature, this study indicates that electron microscopy is useful in the diagnosis of low-grade endometrial stromal tumors by demonstrating characteristic cellular findings as well as a lack of features specific for other round cell and spindle cell neoplasms.