Ovarian Carcinosarcoma and Concurrent Serous Tubal Intraepithelial Carcinoma With Next-Generation Sequencing Suggesting an Origin From the Fallopian Tube.

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 of mixed Mullerian tumour of the uterus.

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.

CNS metastasis secondary to malignant-mixed Müllerian tumor: case report and review of therapeutics.

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.

Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.

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.

[Metastatic collision tumour. A case report]. / Tumor metastásico de colisión. Informe de un caso.

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.

Resection of an intramedullary high cervical metastasis from a malignant mixed Muellerian tumour.

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.

Malignant mixed Müllerian tumor of the fallopian tube: a case report.

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.

Presence of a sarcomatous component outside the ovary is an adverse prognostic factor for primary ovarian malignant mixed mesodermal/mullerian tumors: a clinicopathologic study of 47 cases.

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.

Paclitaxel-ifosfamide-carboplatin combination chemotherapy regimen in advanced uterine and adnexal malignant mixed Mullerian tumours.

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.

Intracardiac metastasis of a Malignant Mixed Mullerian tumor (MMMT): progressive dyspnoea due to obstruction of the left atrium and the left ventricle without left ventricular dysfunction or primary lung disease.

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.

Biopsy-proven cerebellar metastasis from a malignant mixed mullerian tumor (MMMT) of the uterus: case report.

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.

Extra genital heterologous malignant mixed mullerian tumor of primary peritoneal origin.

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.

CT imaging of a primary malignant mixed mullerian tumor arising from the peritoneum.

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.

Retrospective analysis of 105 cases with uterine sarcoma.

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.

Incidence and management of pleural effusions after diaphragm peritonectomy or resection for advanced mullerian cancer.

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 tumors.

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.

Pancreatic metastasis of an ovarian malignant mixed Mullerian tumor identified by EUS-guided fine needle aspiration and Trucut needle biopsy.

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.