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Uterine müllerian adenosarcoma with histiocytic (xanthomatous) mesenchymal component.

We present an endometrial Müllerian adenosarcoma in which the sarcomatous component showed prominent nests of foamy cells that accounted for 50% of the neoplastic mesenchyma. Such foamy cells showed occasional cytological atypias and immunohistochemical features of histiocytic (macrophagic differentiation in the absence of changes that could substantiate the presence of an inflammatory infiltration of foamy histiocytes. These facts suggest histiocytic differentiation from neoplastic mesenchymal cells. Such differentiation has been reported in association with malignant mixed mesodermal tumor, but not in Müllerian adenosarcoma.

Biomarkers, Tumor↗

Gynecologic malignancies.

The combination of cisplatin and cyclophosphamide remains the preferred regimen for the primary treatment of advanced stage epithelial ovarian cancer. Maximal dose intensity, particularly that of cisplatin, is generally accepted as critical for optimal results, but the concept has not yet been rigorously validated by prospective, randomized trials. Since higher doses of cisplatin are associated with renal and neurologic toxicity, the accumulating evidence of equivalent response rates with the less toxic platinum analogue, carboplatin, is encouraging. Salvage chemotherapy remains unsatisfactory, although the remarkable responses observed this year in heavily pre-treated and platinum-resistant patients with the novel new agent taxol is promising. Further trials with this unique drug in combination with other agents in previously untreated patients, as well as in salvage settings, is eagerly anticipated. Although experience with intraperitoneal therapy is rapidly accumulating, the precise role for this route of delivery has yet to be demonstrated in prospective trials. The management of early stage ovarian cancer has become increasingly clarified. Several trials have now demonstrated that a subgroup of patients at low risk for recurrence do well with surgery alone, while a high-risk subgroup clearly benefits from adjuvant therapy. The identification of optimal regimens awaits further trials. In cervical carcinoma, trials utilizing a variety of radiation-sensitizing agents have failed to demonstrate superiority over that of hydroxyurea, which has been shown to improve survival in advanced disease. Preliminary experience with neo-adjuvant regimens administered prior to surgery or radiation therapy is promising, but survival advantages utilizing this approach have yet to be demonstrated. In endometrial cancer, cisplatin was shown to achieve response rates similar to those attainable with single agent doxorubicin, and in uterine mixed mesodermal tumors, ifosfamide was found to have significant activity.

Antineoplastic Agents↗

Gynecologic Oncology Group experience with ifosfamide.

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II experience with ifosfamide/mesna in gynecologic malignancies: preliminary report of Gynecologic Oncology Group studies.

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Clinico-pathological profile of endometrial carcinoma in young women (under 40 years of age).

Twenty primary endometrial carcinomas in 40 year-old or younger women were collected from a series of 845 carcinomas and newly re-evaluated. The typical histological profile was well-differentiated adenocarcinoma (30%) or adenoacanthoma (35%); however, a case of adenosquamous carcinoma and an exceptional malignant mixed mesodermal tumor were also observed. No tendency for myometrial infiltration (M0) was displayed by 11 (55%) of the cases, while 6 were M1 and 3 were M2 infiltrating neoplasias. Adenomatous hyperplasia was associated with cancer in 53% of the 15 assessable cases. Histopathological diagnostic problems were elicited in 5 cases only. Typical Stein-Leventhal syndrome occurred in 7 patients (35%), while polycystic ovaries were observed in 15 cases (75%). Usually, the patients were obese (40%) and nulligravida (65%). All but one case were stage I disease. Prognosis seems to be excellent following surgery.

Adenocarcinoma↗

[Malignancy of the uterine body after radiotherapy for carcinoma of uterine cervix--report of 12 cases].

Twelve cases of malignancy of the uterine body occurred 5-19 years after radiotherapy for 8,704 cases of carcinoma of cervix-an incidence of 0.14%. 10 cases were malignant mixed mesodermal tumor and 2 endometrial carcinoma. The radiation dose varied from 5,500 to 12,000 rad to the area of uterine body. Eight patients had vaginal discharge and 4 were asymptomatic in the follow-up examination in which enlarged uterus was found in all except one. The tumor had extented out of the uterus in 6 patients. 6 of the 12 patients were diagnosed by endometrial biopsy before treatment. Eight patients were treated by operation, 3 by radiation and 1 was untreated. Eleven patients died within 3 years, one recurred in 4.5 years after treatment. It is believed that the malignant tumor of the uterine body is closely related to radiotherapy and the prognosis is poor. Therefore, in the follow-up examination, if vaginal discharge and enlarged uterus are found, endometrial biopsy should be done to ensure correct diagnosis and early operation in order to obtain a better result.

Adenocarcinoma↗

[Cytogenetic study of endometrial carcinoma].

Cytogenetic studies were performed on endometrial specimens of four patients with hyperplasia. Six with adenocarcinoma and one with mixed mesodermal tumor. All 65 cells obtained from hyperplasia specimens excluding one cell, had a normal female karyotype. However, cells from five adenocarcinoma specimens had chromosomal abnormalities, though a specimen of a well differentiated adenocarcinoma showed a normal karyotype. A few numerical abnormalities which were clonal in origin, were noted in one case each. Three kinds of structural abnormalities involving chromosomes 1 were identified as clonal in origin; del (1) (p21), t. dic(1; 16) (p21; q24), and i (lq). Since carcinoma cells had two chromosomes 1 of normal morphology, the presence of the marker chromosome led to the partial trisomy or tetrasomy of the long arm of a chromosome 1, being characteristic of cells from adenocarcinoma of the endometrium. A successively transplantable tumor has been produced from a poorly differentiated carcinoma cells with the t. dic (1; 16) (p21; q24) marker chromosome. Histological and chromosomal examinations were performed in cells from the passage 1, 4 and 5 tumors in order to explore the role of this marker played in the formation of the endometrial carcinoma. Though the degree of differentiation status of tumor cells had been changed during transplantations, the t. dic (1; 16) (p21; q24) marker were observed consistently among these cells. This suggested that the rearrangement of chromosome 1 was not produced as a result of genetic instability due to tumor progression, but rather specifically associated with the endometrial carcinogenesis. None of karyotypic changes excluding the marker and the tetraploid was responsible for these phenotypic changes.

Adenocarcinoma↗

[Papillary adenofibroma of the uterus: fact or fancy? (author's transl)]].

This report deals with the morphological findings in the uterus of a 40 yrs old premenopausal woman, who complained of vaginal bleedings. Macroscopical and microscopical examinations revealed a hernia-like prolaps of a part of the wall of the tuba uterina across a hole in the myometrium of the fundus uteri. Vellios et al. (1973) describe a similar lesion but without paying attention to the prolaps of the tuba uterina into the cavum uteri. They interpretate the lesion as a papillary adenofibroma of the uterus and believe it to be the benign counterpart of the mixed mesodermal tumor of Müllerian duct origin. Based upon our histological findings we believe in a dysontogenetic or traumatic etiology of this rare lesion. The diagnosis of a papillary adenofibroma of the uterus therefore should only be made when the uterus and the adnexa in toto are available for histological examinations.

Adenofibroma↗

Malignant squamous cell elements in the ovarian cancer: report of 5 cases and review of the literature.

Five cases of ovarian cancer are presented in which malignant squamous cell elements were present. Three of the cases were adenosquamous carcinoma without composite endometriosis, mature cystic teratoma or with mixed mesodermal tumor. The other two cases were squamous cell carcinoma which arose in mature cystic teratoma, one of them being in situ carcinoma. Among cases of adenosquamous carcinoma, one composed predominantly of squamous cell element and foci of endometrioid adenocarcinoma was found. In this case, transitional figures between the two components were found. In other cases of adenosquamous carcinoma, components of adeno- and squamous cell carcinoma were intermingled in each carcinoma cell nests. Thus a large variety of histogenesis and microscopic figures were seen in malignant squamous cell elements in the ovarian cancer.

Adult↗

Uterine sarcoma: the Hacettepe hospital experience of 88 consecutive patients.

The treatment modalities of 88 consecutive patients with uterine sarcomas were reviewed retrospectively in the hope of offering a more rational therapy especially in early stage disease. Of the patients, 47 had Leiomyosarcoma (LMS) (53.4%), 28 had Malignant Mixed Mesodermal Tumor (MMMT) (31.8%) and 8 had Endometrial Stromal Sarcoma (ESS) (9.0%). The patients with uterine sarcoma constituted 7.8% of all patients with uterine malignancies during the study period (88/1124). The mean age of this series at diagnosis was 49.2 years. This figure was 45.1, 53.2 and 35.3 for LMS, MMMT and ESS, respectively. The surgical procedure employed was total abdominal hysterectomy and bilateral salpingoophorectomy (TAH + BSO) in 53 (58.9%) patients and 35 patients underwent TAH + BSO and pelvic and paraaortic lymphadenectomy. The overall incidence of lymph node metastases was 28.5% (4/14) for MMMT and 5.8% (1/17) for LMS cases, respectively. The overall 3-year survival rate of this series was 29.5% (23/88). This figure was found to be 59.4% (22/37) for stage I disease and 27.2 (3/11) for stage II disease; The stage I patients with and without adjuvant therapy had similar survival rates. This study confirms that due to the existence of a substantial risk of lymph node metastasis, a complete surgical staging is necessary in the management of uterine sarcomas particularly of MMMT type. Another deserving finding is the failure to detect any therapeutic effect of adjuvant therapy in stage I patients.

Female↗

Primary sarcoma of the ovary: report of five cases and review of the literature.

Primary ovarian sarcomas are rare and usually behave very aggressively. Over a ten-year period (1987-1996) five cases of primary ovarian sarcoma were managed at the Soroka Medical Center, Beer-Sheva, Israel. Four patients had malignant mullerian-mixed mesodermal tumor (MMMMT): two had Stage IIIC tumor with chondrosarcoma being the predominant sarcomatous element, one had Stage IIIC tumor with high-grade endometrioid stromal sarcoma (ESS) being the predominant sarcomatous element and one had Stage IC tumor with rhabdomyosarcoma being the predominant sarcomatous element. One patient had Stage IA leiomyosarcoma (LMS). All four patients with MMMMT received postoperative adjuvant chemotherapy, whereas the patient with LMS did not. The four patients with MMMMT died of their disease 10, 10, 13 and 25 months, respectively, after initial surgery. The patient with LMS died of intercurrent disease 21 months after initial surgery. It is concluded that most patients with primary ovarian sarcoma present with extraovarian disease and the prognosis is poor. The mainstay of treatment is debulking surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy and extirpation of tumor masses. The benefit of postoperative adjuvant chemotherapy and/or radiotherapy is still a subject of debate and has yet not been established.

Aged↗

Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients: a phase II study.

Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Eight patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74% were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24%, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14% response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50+ response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of >24 months. Of evaluable patients, 34% had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22% of the patients. Hypertension, which responded to medications, was seen in 18% of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30% in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.

Adult↗

Amyloid-like material in odontogenic tumors.

Various types of odontogenic tumors (epithelial, mesodermal, and mixed tumors) were studied for the presence of amyloid material. Highman's Congo red and Wolman's standard toluidine blue methods were used for diagnosing amyloid. Of all types of odontogenic tumors studied, only the calcifying epithelial odontogenic tumors contained material that might be interpreted as amyloid-like.

Adult↗

Extrauterine mesodermal (müllerian) adenosarcoma: a clinicopathologic analysis of five cases.

Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (müllerian) mixed tumor previously described to occur in the uterus and designated müllerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of müllerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (müllerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave.

Adult↗

Mixed osteoclastic/pleomorphic giant cell tumor of the pancreas: a case report.

BACKGROUND: Mixed giant cell tumor (MGCT) of the pancreas is a rare malignant neoplasm. The tumor contains pleomorphic giant cells (PGC), pleomorphic mononuclear cells (PMC) and osteoclastic giant cells (OGC). We describe the first fine needle aspiration biopsy (FNAB) diagnosis of this tumor. CASE: A 76-year-old woman was discovered (on imaging studies) to have an apparently inoperable mass in the head of the pancreas. Computed tomography-guided FNAB showed a malignant neoplasm with features of an MGCT. PGC/PMC, OGC and spindle cells were present. The PGC/PMC expressed epithelial antigens, pancytokeratin, CAM 5.2, AE1/AE3 and epithelial membrane antigen (EMA). The spindle cells focally stained for EMA. OGC were negative for the epithelial antigens. OGC, PGC/PMC and the spindle cells were positive for the mesenchymal marker vimentin. CONCLUSION: FNAB was instrumental in making the diagnosis of a rare pancreatic tumor, MGCT. Immunocytochemistry was helpful in making a definitive diagnosis and suggested that MGCT is a carcinosarcoma like neoplasm. The morphology and immunocytochemical profile raise the possibility that osteoclastic giant cell tumor and pleomorphic giant cell tumor may be different morphologic and biologic expressions of the same tumor.

Aged↗

Lack of expression of c-kit protein (CD117) in mesenchymal tumors of the uterus and ovary.

c-kit is a proto-oncogene that codes for a transmembrane tyrosine kinase receptor (CD117). The gene product KIT is constitutively overexpressed in mastocytosis and gastrointestinal stromal tumors. Recently the use of the tyrosine kinase inhibitors, such as STI-571, has resulted in the successful treatment of bcr-abl-positive leukemias and gastrointestinal stromal tumors. In gastrointestinal stromal tumors, immunostaining for c-kit is diffusely positive. Because the expression of c-kit in mesenchymal tumors of the uterus and ovary has not been previously studied, we evaluated its expression in 38 of these tumors by immunohistochemistry. The number of positive labeled/total tumors were as follows: 0/8 malignant mullerian mixed tumors, 4/7 ovarian fibrosarcomas, 0/1 clear-cell ovarian sarcoma, 0/4 uterine leiomyosarcomas, 1/10 low-grade endometrial stromal sarcomas, 0/2 high-grade endometrial stromal sarcomas, and 3/6 endometrial stromal nodules. In all positive cases, no more than 5% of the cells were labeled. In conclusion, unlike gastrointestinal stromal tumors, mesenchymal tumors of the uterus and ovary rarely express c-kit. Therefore, it is unlikely that patients with these tumors will benefit from treatment with the currently available tyrosine kinase inhibitors.

Biomarkers, Tumor↗