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Background . Ovarian carcinosarcomas are rare aggressive biphasic tumors. Evidence suggests that these tumors are monoclonal and that the sarcoma component is derived from a stem cell undergoing divergent differentiation. Currently, there remains a paucity of data regarding its origin, with few reports suggesting an association with serous tubal intraepithelial carcinoma (STIC) by immunohistochemistry and genetics. Objective . We sought to determine the relationship of carcinosarcoma to high-grade serous carcinoma and STIC by investigating for similar mutation signatures through next-generation sequencing. Methodology. A case of carcinosarcoma with associated high-grade serous carcinoma and STIC was macrodissected, and next-generation sequencing was performed on each component separately. Results. The STIC, high-grade serous carcinoma component, and chondrosarcoma component were all diffusely positive for p53 and p16 by immunohistochemistry. Next-generation sequencing demonstrated an identical TP53 gene c.376-1G>A 5' splice site pathogenic mutation in all 3 components. Conclusions . Our findings suggest that carcinosarcomas may also originate from the fallopian tube.

Endobronchial metastasis occurs in only 2%-5% of non-pulmonary cancers. Here we report on an 84-year-old woman who presented with breathlessness and light-headedness while on holiday in Australia, 2 years post-treatment for endometrial cancer. Initial CT pulmonary angiogram identified a soft tissue mass in the left hemithorax. A chest radiograph performed after repatriation was consistent with a large left pleural effusion, but bedside ultrasound showed a lobulated mass involving the left hemidiaphragm. A pleural procedure in the traditional 'triangle of safety' would have resulted in inadvertent puncture of the underlying mass. Serial imaging confirmed the mass was rapidly progressing, and metastatic malignant mixed Mullerian endometrial carcinoma was diagnosed by endobronchial biopsy. A tunnelled intrapleural catheter was inserted for symptom relief, and the patient deteriorated and died at home 2 weeks later. To our knowledge, this is the first case of endobronchial metastasis from malignant mixed Mullerian tumour of the uterus., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This paper reviews CNS involvement secondary to malignant-mixed Müllerian tumor or uterine carcinosarcoma, a rare aggressive biphasic Müllerian tumor. We report a cerebellar metastasis with epithelial and mesenchymal components, demonstrating heterologous rhabdomyogenic and chondroblastic differentiation. The patient had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy for palliation of symptomatic chemotherapy-resistant node-positive disease. CNS involvement is rare, and prognostically poor, and suggestively poorer in predominantly sarcomatous metastases. Multimodal therapy is indicated; in solitary metastases, surgical resection or stereotactic radiosurgery is included, followed by whole brain radiotherapy. In unresectable brain metastases, stereotactic radiosurgery and whole brain radiotherapy warrant consideration in up to 2-3 metastases. In multiple metastases, palliative steroid therapy or cranial irradiation may be considered. Combination or platinum-based chemotherapy (i.e., ifosfamide-paclitaxel or carboplatin-paclitaxel) is indicated in all stages, with a role in both disease cure and control-directed management. Targeted therapeutics have thus far not demonstrated significant clinical efficacy.

The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131 (P=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required., (Published by Elsevier Inc.)

Background: Collision tumours are extremely rare. They are defined by the presence of two tumours of different histological origin in the same organ., Clinical Case: A 71 year old female with history of a carcinoid tumour removed 20 years ago without any recurrence. The patient was admitted with intestinal occlusion symptoms secondary to a right flank abdominal tumour. An exploratory laparotomy was performed, removing the tumor and applying optimal debulking. The histopathological study reported bilateral ovary adenocarcinoma, as well as metastatic collision tumour of two histological types: well differentiated adenocarcinoma and a mixed malignant mesodermic Mullerian tumor. The patient was treated with adjuvant chemotherapy with poor results (death in 24 months)., Conclusions: The presence of collision tumours is extremely rare. There are no statistics or specific treatment reported. Diagnosis is made with histopathology. At the moment, no similiar cases have been reported., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.)

We present a 66-year-old female patient with a high cervical intramedullary metastasis from a malignant mixed Muellerian tumour (MMMT; carcinosarcoma) with concomitant syringomyelia. She was admitted to our clinic with symptoms of cervical myelopathy. MRI revealed an intramedullary tumour of 2.6cm×1.2cm at the cervical vertebral body C2. We performed a laminectomy on C2 followed by a dorsal median myelotomy from C1 to C3 to resect the tumour. The surgical intervention removed the tumour completely and resolved the syringomyelia. During the 36months of follow-up, the patient presented in a stable condition with no evidence of tumour recurrence. To our knowledge, this is the first report of an intramedullary metastasis of a MMMT., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Primary ovarian malignant mixed mesodermal tumors are uncommon. There exist few data in the literature on the significance of the sarcomatous component (SC) in these tumors. Here we investigated this aspect in 47 such tumors, with particular interest in whether the presence of SC outside the ovary confers a worse prognosis. We correlated various features of the SC (homologous vs. heterologous, type of heterologous SC, extent/percentage, mitotic count, necrosis, whether or not SC is present outside the ovary) with disease-specific survival (DSS) using the Kaplan-Meier method and log-rank test. We also correlated other clinicopathologic parameters with DSS: age, stage, tumor size, tumor laterality, type of the carcinomatous component (CC), lymph node status, vascular invasion, and degree of surgical debulking. The mean age was 69.0 years (range, 43 to 89 y). The tumor was located in the left and right ovary in 18 and 24 patients, respectively (laterality could not be determined in 5 cases). The mean tumor size was 13.6 cm. Surgical debulking was optimal in 28, suboptimal in 6, and unclear in 13 patients. FIGO stage was I in 1 patient, II in 5 patients, III in 40 (IIIA in 1, IIIB in 11, IIIC in 28), and IV in 1 patient. Node metastasis and vascular invasion were noted in 6/17 and 29/47 patients, respectively. The mean percentage of SC was 29% (median 20%; range, 1% to 90%). The SC was heterologous in 34 (72%) and homologous in 13 (28%) patients. The mitotic figures per 10 HPF in SC were 33 (0 to 128). Tumor necrosis was present in 45/47 cases (mean 10%; range, 1% to 40%, only in CC in 14, only in SC in 2, in both SC and CC in 29). The CC was high-grade serous in 27 patients, endometrioid in 2, mixed high-grade serous and endometrioid in 17, and mixed high-grade serous and clear cell carcinoma in 1 patient. The extraovarian tumor contained only CC in 17 cases, only SC in 1 case, and both SC and CC in 28 cases. The median follow-up was 29 months (range, 1 to 183 mo): 6 patients were lost to follow-up, 3 died postoperatively, 29 died from disease, 2 died from other causes, and 7 were still alive (14 to 183 mo). The DSS rate at 1, 2, and 5 years was 75%, 56%, and 21%, respectively. Presence of SC outside the ovary was a significant adverse prognostic factor (P=0.03), whereas other parameters were not. After adjusting for FIGO stage, presence of SC outside the ovary was still a significant adverse prognosticator for stage III patients (P=0.003), whereas others were not. Therefore, our findings showed that presence of SC outside the ovary was a significant adverse prognostic factor. We advocate listing the specific extraovarian tumor component (SC and/or CC) in the pathology report for primary ovarian malignant mixed mesodermal tumors.

Malignant mixed Müllerian tumor (MMMT) of the female genital tract is uncommon and extremely rare in the Fallopian tube. We describe a case of primary MMMT of the Fallopian tube with carcinomatous and heterologous mesenchymal components in a 60-year-old woman. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, pelvic and paraaortic lymph node dissection, and resection of intrapelvic metastases. The tumor formed a large polypoid mass within the right Fallopian tube and had penetrated the wall to the paraovarian space. Microscopic examination revealed two components of poorly differentiated adenocarcinoma and high-grade sarcoma with chondromatous differentiation. The patient received six courses of adjuvant chemotherapy with ifomide and cisplatin and is currently in remission. Although MMMT in the Fallopian tube shows poor prognosis, primary cytoreductive surgery with platinum-based combination chemotherapy may improve survival.

Background: Malignant mixed Mullerian tumours (MMMTs) of the uterus and adnexa represent aggressive gynaecologic malignancies with a high rate of loco-regional and distant failure. For that reason, we evaluated the paclitaxel-ifosfamide-carboplatin (TICb) combination in patients with advanced MMMTs., Methods: Female patients with advanced MMMTs, WHO-PS 0-2, no prior chemotherapy for systemic disease, unimpaired haemopoietic and organ function were eligible. Chemotherapy was administered at the following doses; paclitaxel: 175 mg m(-2) on day 1, ifosfamide: 2.0 g m(-2) day(-1)--days 1 and 2, and carboplatin at a target area under the curve 5 on day 2, with prophylactic G-CSF from day 3., Results: Forty patients of a median age 61 (45-72) years, performance status 0-2 with advanced MMMTs of the uterus (n=34), tubes (n=2) or ovary (n=4) have entered and all were evaluable for response and toxicity. Responses were as follows: 27 out of 40 (67.5%) evaluable patients responded, with 11 complete responses and 16 partial responses, while 10 had stable disease, and 3 developed progressive disease. The median response duration was 9 months (range, 4-40 months), median progression-free survival 13 months (range, 3-42 months), while median overall survival 18 months (range, 4-48 months). Grade 3/4 neutropenia was recorded in 22 out of 40 (55%)--with 13 developing grade 4 (≤7 days) and 7 out of 40 (17.5%) of patients at least one episode of febrile neutropenia., Conclusion: In this study, it appears that the TICb combination, yielded important activity with manageable toxicity in females with advanced MMMTs warranting further randomised comparison with current standard regimens.

Brain metastasis from a malignant mixed Mullerian tumor (MMMT) of the uterus is rare. To our knowledge only three similar cases have been reported in the literature. In this report, the authors present the case of a 57-year-old woman with biopsy-proven cerebellar metastasis from a uterine MMMT. One month after complete resection, the mass showed rapid local recurrence. Attention should be paid to the possibility of unusual brain metastasis from a uterine MMMT, which could have an aggressive clinical course.

Malignant Mixed Mullerian tumors (MMMT) are rare gynecological tumors. Even with surgical treatment, chemotherapy, and/or radiotherapy, outcome is poor. MMMTs are known to metastasize to the liver, the abdomen, and the lungs. One case of an ocular metastasis has been reported. In a 61-year-old female patient who had undergone surgical resection of a Mullerian tumor of the uterus 26 months prior to being admitted to our department, we found an obstructing left atrial mass. Histopathologic assessment of this lesion after surgical resection revealed a Mullerian tumor metastasis. Immediately after surgery, the patient was asymptomatic, but was readmitted 4 months later with dyspnoea. Echocardiography and CT revealed new masses in the left atrium and left ventricle. On a literature review, we did not find any description of left atrial and left ventricular occluding metastases of MMMT.

The case of an extragenital heterologous malignant mixed müllerian tumor (MMMT) of primary peritoneal origin occurring in a 76-year-old female is presented. A large tumor was seen between the uterus and rectosigmoid occupying the entire pelvis. The uterus, fallopian tubes and ovaries were uninvolved. The tumor was composed of carcinomatous areas showing endometrioid and serous papillary differentiation and sarcomatous areas showing cartilaginous differentiation. The extragenital primary MMMTs of the female peritoneum are thought to originate from the secondary müllerian system. This case is presented for its rarity. To the best our knowledge, this is the first case of extragenital MMMT of primary peritoneal origin in Indian literature.

Primary peritoneal malignant mixed mullerian tumors are very rare. We report the case of a patient presenting with pain in the right upper quadrant of the abdomen and in whom the physical examination demonstrated a peritoneal mass. Computed tomography (CT) confirmed the presence of a mass, with invasion of adjacent organs.

To evaluate the role of adjuvant therapy in survival and to identify important prognostic factors in uterine sarcoma. One hundred five patients with uterine sarcoma have been retrospectively researched to evaluate the results in this tumor group. 43.8% had leiomyosarcoma, 28.6% had endometrial stromal sarcoma and 27.6% had a malign Mullarian mixed tumor while the distribution according to the histological subgroups were found to be 42.6,16.2 and 41.2% in grade I, II and III tumors respectively. 38.1% of the patients had Radiotherapy, 18.1% had chemotherapy and 12.4% had chemoradiotherapy in addition to surgery. The distant metastases rate is 30% and the local recurrence is 16.2%. All the local recurrences and 90% of the distant metastases have occurred within the first two years. The disease free survival and overall survival rates at 3rd and 5th years are 54.46, 49.88, 54.63 and 51.09% all respectively. In our series, univariate analysis for overall survival demonstrated statistical significance for radical surgery, grade, stage, age, menopausal status and presence of RT in treatment modality, but; histology, number of mitosis, tumor size demonstrated no significance. Our data favors treatment for uterine sarcoma with radical surgery plus radiotherapy alone over 54 Gy or with chemotherapy.

Objectives: Diaphragm peritonectomy or resection is an effective way to cytoreduce diaphragm disease but frequently results in sympathetic pleural effusions. Our objective was to determine the incidence and management of effusions that developed after diaphragm surgery in patients with advanced mullerian cancer., Methods: We reviewed the records of all patients with stage IIIC-IV epithelial ovarian, fallopian tube, or peritoneal cancer who had diaphragm peritonectomy or resection as part of optimal primary cytoreduction at our institution from 2000-2003. All patients had preoperative and serial postoperative chest X-rays to detect and follow pleural effusions. Factors evaluated included the presence and size of preoperative and postoperative effusions, their laterality, and subsequent need for thoracentesis and/or chest tube placement for symptomatic effusions., Results: Of the 215 patients who had primary cytoreduction during the study period, 59 (27%) underwent diaphragm peritonectomy or resection. In addition to standard cytoreduction, 31 (53%) of these 59 patients had diaphragm surgery alone, while 28 (47%) had diaphragm surgery in combination with other upper abdominal resections. Laterality of diaphragm surgery was as follows: right only, 43 (73%); left only, 2 (3%); and bilateral, 14 (24%). Intraoperative chest tubes were placed in 7 (12%) patients. In the remaining 12 patients with preoperative effusions, postoperative effusions on the same side as the diaphragm surgery increased in 6 patients (50%), and 3 patients (25%) required postoperative thoracentesis or chest tube. In the remaining 40 patients without preoperative effusions, ipsilateral effusions developed in 24 patients (60%), and 5 patients (13%) required postoperative chest tubes. The overall rate of new or increased ipsilateral effusions was 58%; the overall rate of postoperative thoracentesis or chest tube placement was 15%. In 75% of the patients, thoracentesis or chest tubes were placed within 5 days of surgery (median, 3 days; range, 2-24)., Conclusions: More than half of patients developed ipsilateral pleural effusions after diaphragm peritonectomy for cytoreduction. Most were managed conservatively without requiring a chest tube or thoracentesis. The incidence of symptomatic effusions was not high enough to recommend routine chest tube placement at the time of diaphragm peritonectomy or resection.

Malignant mixed Mullerian tumours (MMMTs) are rare neoplasms, highly aggressive and with an extremely poor prognosis, usually arising in elderly postmenopausal women and presenting at an advanced stage. MMMTs derive from the mullerian mesodermus that differentiates in epithelial and stromal elements, both malignant elements. The clinic pathological features of 3 uterine MMMTs are reported here. The patients ranged in age from 25 to 69 years. The initial manifestations were mainly bloody discharge, abdominal pain and increase of the volume of the uterus. Treatment in 2 patients was hysterectomy with double ooforectomy, and resection of the pelvic mass was the treatment in the third case. Adjuvant radio chemotherapy was administrated in 2 of the 3 cases. Follow-up revealed recurrent pelvic tumour in 1 patient at 59 months, and breast metastases at 20 months in the second one. Because of the high incidence of recurrence and poor prognosis of these tumours, they should be studied and managed by a multidisciplinary team composed by surgeons, oncologists, radiotherapists and pathologists.

Context: Malignant mixed Mullerian tumors are rare ovarian neoplasms that account for less than 2% of ovarian malignancies. They have a generally poor prognosis and often develop recurrent disease. To our knowledge, this is the first report of a malignant mixed Mullerian tumor with metastasis to the pancreas. The metastatic tumor was identified by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and Trucut needle biopsy of the pancreas., Case Report: We describe a 69-year-old female with concomitant Duke's C adenocarcinoma of the colon and stage III-C malignant mixed Mullerian tumor that presented with malignant ascites, increasing abdominal girth and a pancreatic head mass. EUS revealed an 11 cm cystic mass in the head of the pancreas that was characterized as a carcinosarcoma/malignant mesodermal mixed tumor by EUS-FNA and Trucut needle biopsy. The tumor was morphologically identical to the surgical specimen of her ovarian mass. The patient was treated with palliative chemotherapy and a three-month follow up CT scan did not reveal any new metastatic lesions., Conclusion: The pancreas is a rare site of metastasis and more commonly seen in renal cell carcinoma, melanoma or lung tumors; amongst others. Although ovarian adenocarcinoma has been reported as a primary site of pancreatic metastasis, it has not been previously described originating from a mixed Mullerian tumor of the ovary presenting as a cystic pancreatic head mass.

The central nervous system is traditionally considered as an uncommon site for metastatic disease from the female genital tract, and cerebral metastasis as the primary manifestation of an occult gynecological malignancy is even more rare. Here, we report the case of a 61-year-old female who presented with neurological symptoms of confusion, headache, cerebellar ataxia and right-sided weakness. Magnetic resonance imaging of the brain revealed two solid lesions in the frontal lobe and the left cerebellar hemisphere. Endometrial biopsy of a uterine mass detected during search for the primary lesion showed malignant mixed Müllerian tumor (MMMT). The patient refused surgery. Cranial radiotherapy for progressive cerebral disease led to resolution of her neurological symptoms. Two months after the diagnosis of MMMT the patient died from local complications of advanced pelvic disease. At autopsy, only the epithelial component of the tumor had metastasized to the brain. Attention should be paid to possibility of unusual distant metastases associated to MMMT in order to avoid delay in diagnosis and treatment of these patients.

Despite numerous studies documenting reduction of pelvic relapses after adjuvant pelvic radiotherapy stage I and II uterine sarcomas, improved survival remains unproven. This retrospective report analyzes patterns of failure, survival, and toxicity in 42 women with stage I and 7 patients with stage II uterine sarcomas treated from 1972 through 1998 to identify patients likely to benefit from pelvic or abdominal radiotherapy and chemotherapy. Four of these patients also received adjuvant chemotherapy. There were 20 leiomyosarcomas, 18 homologous mixed mullerian tumors, and 11 heterologous mixed mullerian tumors. Disease-free survivals for mixed mullerian tumors were 65% at 5 years and 61% at 15 years. Disease-free survivals for leiomyosarcomas were 40% at 5 years and 40% at 15 years. There were 14 distant only, 5 distant and abdominal, 1 abdominal, 1 distant and pelvic, and 2 unknown initial sites of failure. Acute toxicity was acceptable as measured by a median 1-kg weight loss from radiotherapy and a 2% rate of failure to complete therapy. Chronic toxicity consisted of 3 small bowel obstructions and 1 sigmoid colon obstruction. In conclusion, the efficacy of adjuvant pelvic radiation is demonstrated by the absence of any isolated pelvic failures. Although the frequent occurrence of peritoneal failures suggests a role for prophylactic abdominal radiation for mixed mullerian tumors, more effective systemic therapy is necessary to substantially increase the chance of cure for women with early-stage uterine sarcomas.

Objective: The present review analyzes patients with advanced uterine sarcomas with the goal of identifying patients likely to benefit from larger volumes and higher dosages of radiotherapy., Methods: A retrospective review was performed of medical records of all patients receiving adjuvant radiotherapy for advanced uterine sarcomas from 1978 to 1997 at the University of Minnesota., Results: Nineteen women with advanced uterine sarcomas received adjuvant radiotherapy. Seven also received adjuvant chemotherapy. Three patients had FIGO stage IIIA, 1 stage IIIB, 5 stage IIIC, and 12 stage IVB. Patients with mixed mullerian tumors had overall and disease-free survivals of 31% at 1 year and 23% at 5 years. For leiomyosarcomas, overall survival was 67% at 1 year and 33% at 5 years, but relapse-free survival was 33% at 1 and 5 years. First sites of failure were three pelvic and abdominal, one abdominal only, one abdominal and distant, two pelvic and distant, one pelvic, abdominal, and distant, five distant only, and one unknown. No Grade 3 or 4 toxicity occurred., Conclusion: Ongoing technical advancements in radiotherapy offer more precise radiation delivery, particularly to the peritoneal cavity. Although abdominal failures are common in women with mixed mullerian tumors, translation of higher radiation dosage to cure is unproven, and the majority of failures have a distant component. Until effective systemic therapy is developed, the prognosis of uterine sarcomas with any spread beyond the uterus will remain poor.

Non-puerperal uterine inversion due to uterine sarcoma is a rare entity often diagnosed at the time of surgery. Patients may present with pelvic pain, vaginal discharge, or hemodynamic shock. Clinically, the diagnosis may be suspected if there is a large vaginal mass and difficulty in palpating the cervix. Four surgical procedures have been described to manage non-puerperal uterine inversion, two by the abdominal route and two by the vaginal route. The Haultain procedure performed abdominally is preferred for uterine sarcomas as it facilitates reversion of the uterus vaginally or excision of the pedicle and removal of the prolapsed tumor vaginally. We describe a patient with this condition managed by the Haultain procedure.

Ovarian endocervical-type (müllerian) mucinous tumors and tumors composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and indifferent cells with abundant eosinophilic cytoplasm reported to date have been primarily limited to borderline and microinvasive types, with only one report of a disease-related death. The clinicopathologic features of 54 endocervical-type and mixed cell-type mucinous tumors, defined as tumors with papillary architecture resembling serous tumors but containing endocervical-type mucinous epithelium, were evaluated. Thirty-four tumors (64%) were classified as atypical proliferative (borderline) tumors based on the absence of stromal invasion and the absence of micropapillary architecture measuring >5 mm. Five tumors (9%) qualified as intraepithelial carcinoma based on the presence of marked cytologic atypia or a complex cribriform growth pattern involving the epithelium covering the surface of papillae or lining cystic spaces. Eight tumors (15%) with stromal invasion < or =5 mm were classified as microinvasive carcinoma. Seven tumors (13%) with either stromal invasion (five tumors) or micropapillary architecture measuring >5 mm (two tumors) were classified as carcinoma. Sixteen tumors (30%) were bilateral, and endosalpingiosis was identified in 41% of cases. Serous-type differentiation was present in all cases. Of the 29 patients with atypical proliferative tumors, intraepithelial carcinomas, and microinvasive carcinomas for whom follow-up was available, there were no disease-related deaths. In contrast, of the seven patients whose tumors had either stromal invasion or micropapillary architecture >5 mm, two stage III patients died of disease (one with frank invasion and one with a micropapillary tumor that lacked stromal invasion). One other stage III patient with a noninvasive micropapillary carcinoma was alive with disease at 84 months. The remaining four patients (three stage I and one stage III) were alive with no evidence of disease. In summary, most endocervical-type atypical proliferative tumors are stage I and benign. The presence of either intraepithelial carcinoma or microinvasion has no adverse effect on behavior. Rare endocervical-type mucinous tumors demonstrate histologically malignant features and aggressive behavior that warrant designation as carcinoma. As with serous tumors, micropapillary architecture without frank invasion in endocervical-type mucinous tumors is associated with disease recurrence and death when presenting as advanced-stage disease. All the tumors in this study were composed of a heterogeneous population of cells, consisting mainly of serous (ciliated) and endocervical-type mucinous cells. In addition, they all contained endometrioid-type cells, hobnail cells, and indifferent cells with abundant eosinophilic cytoplasm to a varying degree. Accordingly, it appears that tumors that feature endocervical-type mucinous cells are rarely if ever pure but almost invariably of mixed cell type. Despite containing mucinous epithelium, the papillary architecture, serous-type differentiation, association with endosalpingiosis, frequent bilaterality, size, and clinical behavior of endocervical-type mucinous tumors closely resemble serous tumors. We therefore recommend the term "seromucinous" for these tumors, which acknowledges both their serous and mucinous features.

Background: The authors report the gynaecological pathology of surgical interest occurring in an Emergency Department in the first half of 2000 and occasionally found during an operation in women who presented a pelvic mass or abdominal pain., Methods: Six women, average age of 50 years, reached the Emergency Department: five of them were operated with an emergency procedure., Results: Of the 6 cases, 1 patient was affected by uterine mass, 1 by uterine-ovarian mass and 3 by ovarian mass; in one patient, affected by ovarian tumour, another intervention was necessary for intestinal metastasis., Conclusions: The authors have considered the clinical aspect of the abdominal masses, the age of the patients, the diagnostic laboratory and instrumental implications, the surgical approach and the histological result, referring to literature. Their contribution is related to the need for an appropriate surgical approach in emergency where it may, sometimes, solve or, at least, stabilize an uncertain clinical case, thanks to the implicit basic knowledge of multidisciplinary surgical technique.

The aim of this study was to retrospectively analyze the clinical and pathologic data of a series of patients presenting to our unit with uterine malignant mixed Müllerian tumors (MMMT) to attempt to identify prognostic factors and relate them to survival. Thirty-seven patients diagnosed with MMMT of the uterus from 1988 through 2000 were identified from the gynecological tumor registry. Data was abstracted and analyzed. The effect of a variety of clinical, histopathologic, and surgical variables on recurrence and survival were analyzed by univariate and multivariate analyses. Patients tended to be postmenopausal, overweight, hypertensive, and presented with abnormal bleeding. Preoperatively 28 (76%) were thought to have clinical stage I-II disease. Nine (32%) were upstaged based on surgical data. Five (56%) of these patients were found to have gross extrauterine disease and four (44%) were found subsequently to have microscopic extrauterine disease. Twenty (54%) patients underwent lymph node dissection and positive nodes were found in seven (35%) patients. Nine patients underwent omentectomy and disease was found in three (33%). Peritoneal washings were positive in three of 16 patients (19%). At the completion of primary surgery, 27 (75%) patients had no residual disease. Twelve (44%) of these patients had recurrence of disease. Median disease-free interval prior to first recurrence was 15 months. Median overall survival was 30 months. Log-rank analysis performed on multiple variables, including stage, age, residual disease, and depth of myometrial invasion showed a statistically significant association with overall survival probability. Only stage remained a significant independent variable predictive of overall survival (P = 0.034). We found that stage was an independent prognostic factor for overall survival in patients with uterine MMMT. Age, depth of myometrial invasion, and residual tumor were significant prognostic factors on univariate analysis. These factors may be a guide in order to select a group of high risk patients that may benefit from adjuvant therapy.

Objective: The aim of this study was to provide the management and outcome of three patients who presented with uterine Müllerian adenosarcoma associated with extrauterine metastases., Methods: A retrospective study of three patients who were referred to our hospital was performed. One patient was referred because of vaginal metastatic deposits that were noted during investigations for primary infertility. The other two were referred because of abnormal vaginal bleeding; one of these had a large polyp protruding through her cervix into the vagina., Results: In two patients the preoperative diagnosis and extent of their disease were known while in the third patient the diagnosis was only made postoperatively. All patients had a type II radical abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Two patients were given three cycles of neoadjuvant chemotherapy and pelvic irradiation over 12 weeks. Both of these patients had their diagnosis made preoperatively and the chemotherapy consisted of 240 mg/m(2) carboplatin and 80 mg/m(2) farmorubicin per cycle. The pelvic irradiation consisted of daily fractions of 1.8-Gy irradiation to a total of 45 Gy over the first 6 weeks. The other patient was given the same regime postoperatively. All patients are still alive and free of disease between 34 and 56 months., Conclusion: Radical surgery, chemotherapy, and irradiation provide a management option with seemingly favorable outcome for patients with uterine Müllerian adenosarcoma associated with extrauterine metastases., (Copyright 2000 Academic Press.)

Two cases of uterine carcinosarcoma developing after long-term tamoxifen (TAM) treatment are presented. The patients, 67 and 72 years old, were treated with TAM for 6 and 7 years, continuously. They both developed an heterologous malignant mixed Mullerian tumor (mmMt). At laparotomy, an advanced stage of disease was found with peritoneal spread. In spite of the surgical and the postoperative treatment, they both died of disease, 3 and 10 months later. There are only 10, well documented, similar cases reported. Another 7 were identified in series of uterine malignancies developing after TAM treatment. Considerable evidence suggests that mmMt represents an epithelial cancer with sarcomatous dedifferentiation. Prolonged (> 5 years) TAM treatment may represent a causative factor in the development of this highly lethal disease (80% of the reported patients had a dismal prognosis). Large uterine polyps with special histological features, may represent an intermediate step in the tumor formation. Close follow-up of the patients is warranted.

Myasthenia gravis is a neurologic disorder characterized by intermittent muscle weakness which improves after anticholinesterase medication. The pathogenesis of myasthenia gravis is associated with production of autoantibodies to nicotinic acetylcholine receptor in the motor end plate. Most patients do not have an underlying neoplasm, but in 10-15% of the cases, a thymoma may be detected. Apart from thymoma, no other tumor type or organ has consistently been associated with myasthenia gravis. We describe an unusual case of myasthenia gravis in a patient with malignant mixed Mullerian tumor of the uterine corpus. Initial histology revealed malignant mixed Mullerian tumor of a predominant carcinomatous element. At that time, there were no symptoms of muscle weakness. Intraabdominal metastases were detected later, concommitantly with symptoms of muscle weakness and the diagnosis of myasthenia gravis. Histology of the metastases disclosed an exclusive mesenchymal element with striated muscle differentiation. To the best of our knowledge this case is the first report of myasthenia gravis in a patient with malignant mixed Mullerian tumor of the uterine corpus. We propose that the mechanism contributing to myasthenia gravis in this patient was closely associated with the evolving histology and with the nature of the tumor, so that antibodies produced to muscle-like epitopes exposed by malignant cells could have cross-reacted with acetylcholine nicotinic receptors and caused myasthenia gravis.

A case of alpha-fetoprotein production by a uterine malignant mixed müllerian tumour is described. The patient was a 68 year old woman who developed intraabdominal recurrence of a stage 1 uterine tumour which had been treated surgically seven years previously. Her serum alpha-fetoprotein was raised at 21,000 micrograms/l (normal < 10 micrograms/l) and staining with immunoperoxidase confirmed that the tumour was the site of alpha-fetoprotein production. The patient was treated with combination chemotherapy but died two weeks after the first course. This is believed to be only the second such case reported.

Four patients with metastatic ovarian mixed Müllerian sarcoma (2 homologous, 2 heterologous) were treated with mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy. Two of four patients had optimal debulking. Three of four patients responded to chemotherapy, with two complete responses of 34- and 46-month duration. The MAID regimen appears to be active in patients with ovarian sarcoma.

Two autopsy cases (69 and 87-year-old women) of malignant mixed müllerian tumor (MMMT) following radiation therapy for uterine cervical cancer sixteen and twenty years ago respectively were reported. They were admitted due to abdominal pain and diagnosed as ileus. In the first case, CT examination revealed a tumor measuring about 8 x 10 cm in size in the uterine posterior wall. Recurrence of the uterine cancer was suspected and hysterooophorectomy combined with sigmoidectomy was performed. In the second case, artificial anus formation was performed because of sigmoid stricture by the invasion of the tumor. Histologically, tumors in both cases were composed of carcinomatous and sarcomatous components including heterologous elements such as cartilage. The patients died of extensive spreads and metastasis in the liver and alimentary tract.

Fifteen ovarian malignant mixed müllerian tumors (MMMT) of the ovary are reported in an attempt to identify morphologic factors of prognostic interest. Several features were correlated to survival: histologic subtype and nuclear and histologic grades of the epithelial component; histologic subtype, grade, and mitotic rate of the mesenchymal component; necrosis and epithelial-to-mesenchymal ratio. The epithelial component was mainly of endometrioid (four cases) and serous (four cases) types. The mesenchymal component was largely heterologous, of which five were of chondromatous and five of rhabdomyoblastic differentiation. This latter differentiation was further demonstrated by electron microscopy (two cases) and immunohistochemistry (four cases). Ten tumors showed hyaline droplets that stained for alpha 1-antitrypsin in two cases. Eight patients died of their disease, 13 days to 32 months after diagnosis (median, 5 months). Seven were alive 3 to 49 months (median, 10 months) after initial therapy. No morphologic factor was found to correlate with survival, but a tendency was observed for ovarian MMMTs with a high epithelial nuclear grade, a predominance of the mesenchymal component, or a rhabdomyoblastic mesenchymal component to be associated with more aggressive behavior. The histologic appearance of metastases did not correlate with prognosis.